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Slide 1 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE
Slide 2 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma
Slide 3 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared
Slide 4 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment!
Slide 5 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65)
Slide 6 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning)
Slide 7 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting
Slide 8 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE!
Slide 9 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy
Slide 10 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more
Slide 11 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year
Slide 12 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates
Slide 13 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993
Slide 14 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000
Slide 15 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type:
Slide 16 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type: Approximately 1.5 million people worldwide are living with non-Hodgkin’s lymphoma (NHL) It is estimated that 300,000 people die each year from the disease
Slide 17 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type: Approximately 1.5 million people worldwide are living with non-Hodgkin’s lymphoma (NHL) It is estimated that 300,000 people die each year from the disease Facts and Figures *US statistics Ries LAG, et al. SEER Cancer Statistics Review, 1975-2000, National Cancer Institute. Bethesda, MD Cancer Facts & Figures 2004, www.cancer.org 1 new case of lymphoma is diagnosed every 9 minutes* 1 in 50 people will develop lymphoma* 81% increase in incidence of NHL between 1973-1990 Overall survival at 5 years is 50%-60% for all non-Hodgkin’s lymphomas
Slide 18 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type: Approximately 1.5 million people worldwide are living with non-Hodgkin’s lymphoma (NHL) It is estimated that 300,000 people die each year from the disease Facts and Figures *US statistics Ries LAG, et al. SEER Cancer Statistics Review, 1975-2000, National Cancer Institute. Bethesda, MD Cancer Facts & Figures 2004, www.cancer.org 1 new case of lymphoma is diagnosed every 9 minutes* 1 in 50 people will develop lymphoma* 81% increase in incidence of NHL between 1973-1990 Overall survival at 5 years is 50%-60% for all non-Hodgkin’s lymphomas Lymphoma: Current Challenges Continued increase in incidence 3-4% increase in annual incidence of NHL over last 2-3 decades Diverse disease made up of numerous subtypes. Careful patient selection necessary to maximize treatment benefit Despite improvements in outcomes over the past decade, some subgroups of NHL, in particular, remain difficult to treat Development of newer treatment strategies critical to improving outcomes Müller A et al. Ann Hematol. 2005;84:1-12; Hagemeister FB. New agents in the treatment of lymphomas: which ones will succeed. Available at: www.cmeinteractive.cancerconsultants.com/ShowArticle.aspx?ArticleID=2.
Slide 19 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type: Approximately 1.5 million people worldwide are living with non-Hodgkin’s lymphoma (NHL) It is estimated that 300,000 people die each year from the disease Facts and Figures *US statistics Ries LAG, et al. SEER Cancer Statistics Review, 1975-2000, National Cancer Institute. Bethesda, MD Cancer Facts & Figures 2004, www.cancer.org 1 new case of lymphoma is diagnosed every 9 minutes* 1 in 50 people will develop lymphoma* 81% increase in incidence of NHL between 1973-1990 Overall survival at 5 years is 50%-60% for all non-Hodgkin’s lymphomas Lymphoma: Current Challenges Continued increase in incidence 3-4% increase in annual incidence of NHL over last 2-3 decades Diverse disease made up of numerous subtypes. Careful patient selection necessary to maximize treatment benefit Despite improvements in outcomes over the past decade, some subgroups of NHL, in particular, remain difficult to treat Development of newer treatment strategies critical to improving outcomes Müller A et al. Ann Hematol. 2005;84:1-12; Hagemeister FB. New agents in the treatment of lymphomas: which ones will succeed. Available at: www.cmeinteractive.cancerconsultants.com/ShowArticle.aspx?ArticleID=2. Non-Hodgkin Lymphoma: Incidence Follicular lymphoma (22%) Small lymphocytic lymphoma (6%) Marginal zone B-cell lymphoma MALT type (5%) Marginal zone B-cell lymphoma nodal type (1%) Lymphoplasmacytic lymphoma (1%) Diffuse B-cell lymphoma (31%) Composite lymphomas (13%) Peripheral T-cell (6%) Mantle cell (6%) Other subtypes with a frequency ≤ 2% (9%) Armitage et al. J Clin Oncol. 1998;16:2780-2795.
Slide 20 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type: Approximately 1.5 million people worldwide are living with non-Hodgkin’s lymphoma (NHL) It is estimated that 300,000 people die each year from the disease Facts and Figures *US statistics Ries LAG, et al. SEER Cancer Statistics Review, 1975-2000, National Cancer Institute. Bethesda, MD Cancer Facts & Figures 2004, www.cancer.org 1 new case of lymphoma is diagnosed every 9 minutes* 1 in 50 people will develop lymphoma* 81% increase in incidence of NHL between 1973-1990 Overall survival at 5 years is 50%-60% for all non-Hodgkin’s lymphomas Lymphoma: Current Challenges Continued increase in incidence 3-4% increase in annual incidence of NHL over last 2-3 decades Diverse disease made up of numerous subtypes. Careful patient selection necessary to maximize treatment benefit Despite improvements in outcomes over the past decade, some subgroups of NHL, in particular, remain difficult to treat Development of newer treatment strategies critical to improving outcomes Müller A et al. Ann Hematol. 2005;84:1-12; Hagemeister FB. New agents in the treatment of lymphomas: which ones will succeed. Available at: www.cmeinteractive.cancerconsultants.com/ShowArticle.aspx?ArticleID=2. Non-Hodgkin Lymphoma: Incidence Follicular lymphoma (22%) Small lymphocytic lymphoma (6%) Marginal zone B-cell lymphoma MALT type (5%) Marginal zone B-cell lymphoma nodal type (1%) Lymphoplasmacytic lymphoma (1%) Diffuse B-cell lymphoma (31%) Composite lymphomas (13%) Peripheral T-cell (6%) Mantle cell (6%) Other subtypes with a frequency ≤ 2% (9%) Armitage et al. J Clin Oncol. 1998;16:2780-2795. Low Public Awareness of Lymphoma According to a study of lymphoma patients carried out in 2003: Prior to diagnosis almost all respondents (97.5%) had been unaware of non-Hodgkin’s lymphoma Many patients with non-Hodgkin’s lymphoma do not have an accurate understanding of the disease Up to 35% of respondents were vague about the body parts affected by non-Hodgkin’s lymphoma Half of respondents were unaware of their specific diagnosis
Slide 21 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type: Approximately 1.5 million people worldwide are living with non-Hodgkin’s lymphoma (NHL) It is estimated that 300,000 people die each year from the disease Facts and Figures *US statistics Ries LAG, et al. SEER Cancer Statistics Review, 1975-2000, National Cancer Institute. Bethesda, MD Cancer Facts & Figures 2004, www.cancer.org 1 new case of lymphoma is diagnosed every 9 minutes* 1 in 50 people will develop lymphoma* 81% increase in incidence of NHL between 1973-1990 Overall survival at 5 years is 50%-60% for all non-Hodgkin’s lymphomas Lymphoma: Current Challenges Continued increase in incidence 3-4% increase in annual incidence of NHL over last 2-3 decades Diverse disease made up of numerous subtypes. Careful patient selection necessary to maximize treatment benefit Despite improvements in outcomes over the past decade, some subgroups of NHL, in particular, remain difficult to treat Development of newer treatment strategies critical to improving outcomes Müller A et al. Ann Hematol. 2005;84:1-12; Hagemeister FB. New agents in the treatment of lymphomas: which ones will succeed. Available at: www.cmeinteractive.cancerconsultants.com/ShowArticle.aspx?ArticleID=2. Non-Hodgkin Lymphoma: Incidence Follicular lymphoma (22%) Small lymphocytic lymphoma (6%) Marginal zone B-cell lymphoma MALT type (5%) Marginal zone B-cell lymphoma nodal type (1%) Lymphoplasmacytic lymphoma (1%) Diffuse B-cell lymphoma (31%) Composite lymphomas (13%) Peripheral T-cell (6%) Mantle cell (6%) Other subtypes with a frequency ≤ 2% (9%) Armitage et al. J Clin Oncol. 1998;16:2780-2795. Low Public Awareness of Lymphoma According to a study of lymphoma patients carried out in 2003: Prior to diagnosis almost all respondents (97.5%) had been unaware of non-Hodgkin’s lymphoma Many patients with non-Hodgkin’s lymphoma do not have an accurate understanding of the disease Up to 35% of respondents were vague about the body parts affected by non-Hodgkin’s lymphoma Half of respondents were unaware of their specific diagnosis Cause-specific Survival of NHL Study Patients (1974–1995) Cumulative survival (%) Time (years) 100 80 60 40 20 0 0 5 10 15 20 25 30 Aggressive NHL Indolent NHL
Slide 22 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type: Approximately 1.5 million people worldwide are living with non-Hodgkin’s lymphoma (NHL) It is estimated that 300,000 people die each year from the disease Facts and Figures *US statistics Ries LAG, et al. SEER Cancer Statistics Review, 1975-2000, National Cancer Institute. Bethesda, MD Cancer Facts & Figures 2004, www.cancer.org 1 new case of lymphoma is diagnosed every 9 minutes* 1 in 50 people will develop lymphoma* 81% increase in incidence of NHL between 1973-1990 Overall survival at 5 years is 50%-60% for all non-Hodgkin’s lymphomas Lymphoma: Current Challenges Continued increase in incidence 3-4% increase in annual incidence of NHL over last 2-3 decades Diverse disease made up of numerous subtypes. Careful patient selection necessary to maximize treatment benefit Despite improvements in outcomes over the past decade, some subgroups of NHL, in particular, remain difficult to treat Development of newer treatment strategies critical to improving outcomes Müller A et al. Ann Hematol. 2005;84:1-12; Hagemeister FB. New agents in the treatment of lymphomas: which ones will succeed. Available at: www.cmeinteractive.cancerconsultants.com/ShowArticle.aspx?ArticleID=2. Non-Hodgkin Lymphoma: Incidence Follicular lymphoma (22%) Small lymphocytic lymphoma (6%) Marginal zone B-cell lymphoma MALT type (5%) Marginal zone B-cell lymphoma nodal type (1%) Lymphoplasmacytic lymphoma (1%) Diffuse B-cell lymphoma (31%) Composite lymphomas (13%) Peripheral T-cell (6%) Mantle cell (6%) Other subtypes with a frequency ≤ 2% (9%) Armitage et al. J Clin Oncol. 1998;16:2780-2795. Low Public Awareness of Lymphoma According to a study of lymphoma patients carried out in 2003: Prior to diagnosis almost all respondents (97.5%) had been unaware of non-Hodgkin’s lymphoma Many patients with non-Hodgkin’s lymphoma do not have an accurate understanding of the disease Up to 35% of respondents were vague about the body parts affected by non-Hodgkin’s lymphoma Half of respondents were unaware of their specific diagnosis Cause-specific Survival of NHL Study Patients (1974–1995) Cumulative survival (%) Time (years) 100 80 60 40 20 0 0 5 10 15 20 25 30 Aggressive NHL Indolent NHL Other reasons for incidence of NHL Many are age-related Auto-immune disease Environmental chemicals
Slide 23 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type: Approximately 1.5 million people worldwide are living with non-Hodgkin’s lymphoma (NHL) It is estimated that 300,000 people die each year from the disease Facts and Figures *US statistics Ries LAG, et al. SEER Cancer Statistics Review, 1975-2000, National Cancer Institute. Bethesda, MD Cancer Facts & Figures 2004, www.cancer.org 1 new case of lymphoma is diagnosed every 9 minutes* 1 in 50 people will develop lymphoma* 81% increase in incidence of NHL between 1973-1990 Overall survival at 5 years is 50%-60% for all non-Hodgkin’s lymphomas Lymphoma: Current Challenges Continued increase in incidence 3-4% increase in annual incidence of NHL over last 2-3 decades Diverse disease made up of numerous subtypes. Careful patient selection necessary to maximize treatment benefit Despite improvements in outcomes over the past decade, some subgroups of NHL, in particular, remain difficult to treat Development of newer treatment strategies critical to improving outcomes Müller A et al. Ann Hematol. 2005;84:1-12; Hagemeister FB. New agents in the treatment of lymphomas: which ones will succeed. Available at: www.cmeinteractive.cancerconsultants.com/ShowArticle.aspx?ArticleID=2. Non-Hodgkin Lymphoma: Incidence Follicular lymphoma (22%) Small lymphocytic lymphoma (6%) Marginal zone B-cell lymphoma MALT type (5%) Marginal zone B-cell lymphoma nodal type (1%) Lymphoplasmacytic lymphoma (1%) Diffuse B-cell lymphoma (31%) Composite lymphomas (13%) Peripheral T-cell (6%) Mantle cell (6%) Other subtypes with a frequency ≤ 2% (9%) Armitage et al. J Clin Oncol. 1998;16:2780-2795. Low Public Awareness of Lymphoma According to a study of lymphoma patients carried out in 2003: Prior to diagnosis almost all respondents (97.5%) had been unaware of non-Hodgkin’s lymphoma Many patients with non-Hodgkin’s lymphoma do not have an accurate understanding of the disease Up to 35% of respondents were vague about the body parts affected by non-Hodgkin’s lymphoma Half of respondents were unaware of their specific diagnosis Cause-specific Survival of NHL Study Patients (1974–1995) Cumulative survival (%) Time (years) 100 80 60 40 20 0 0 5 10 15 20 25 30 Aggressive NHL Indolent NHL Other reasons for incidence of NHL Many are age-related Auto-immune disease Environmental chemicals Lymphomas associated with host susceptibility factors Enteropathy – associated T-cell Lymphoma - Genetics - Gliadin allergy Extranodal and systemic EBV + T/Non-Hodgkin’s Lymphoma - Genetics Hepatosplenic T-cell Lymphoma - Immunosuppression + chronic autogenic stimulation Burkitt - Malaria + HIV Post transplant Lymphoma - Iatrogenic immunosuppression
Slide 24 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type: Approximately 1.5 million people worldwide are living with non-Hodgkin’s lymphoma (NHL) It is estimated that 300,000 people die each year from the disease Facts and Figures *US statistics Ries LAG, et al. SEER Cancer Statistics Review, 1975-2000, National Cancer Institute. Bethesda, MD Cancer Facts & Figures 2004, www.cancer.org 1 new case of lymphoma is diagnosed every 9 minutes* 1 in 50 people will develop lymphoma* 81% increase in incidence of NHL between 1973-1990 Overall survival at 5 years is 50%-60% for all non-Hodgkin’s lymphomas Lymphoma: Current Challenges Continued increase in incidence 3-4% increase in annual incidence of NHL over last 2-3 decades Diverse disease made up of numerous subtypes. Careful patient selection necessary to maximize treatment benefit Despite improvements in outcomes over the past decade, some subgroups of NHL, in particular, remain difficult to treat Development of newer treatment strategies critical to improving outcomes Müller A et al. Ann Hematol. 2005;84:1-12; Hagemeister FB. New agents in the treatment of lymphomas: which ones will succeed. Available at: www.cmeinteractive.cancerconsultants.com/ShowArticle.aspx?ArticleID=2. Non-Hodgkin Lymphoma: Incidence Follicular lymphoma (22%) Small lymphocytic lymphoma (6%) Marginal zone B-cell lymphoma MALT type (5%) Marginal zone B-cell lymphoma nodal type (1%) Lymphoplasmacytic lymphoma (1%) Diffuse B-cell lymphoma (31%) Composite lymphomas (13%) Peripheral T-cell (6%) Mantle cell (6%) Other subtypes with a frequency ≤ 2% (9%) Armitage et al. J Clin Oncol. 1998;16:2780-2795. Low Public Awareness of Lymphoma According to a study of lymphoma patients carried out in 2003: Prior to diagnosis almost all respondents (97.5%) had been unaware of non-Hodgkin’s lymphoma Many patients with non-Hodgkin’s lymphoma do not have an accurate understanding of the disease Up to 35% of respondents were vague about the body parts affected by non-Hodgkin’s lymphoma Half of respondents were unaware of their specific diagnosis Cause-specific Survival of NHL Study Patients (1974–1995) Cumulative survival (%) Time (years) 100 80 60 40 20 0 0 5 10 15 20 25 30 Aggressive NHL Indolent NHL Other reasons for incidence of NHL Many are age-related Auto-immune disease Environmental chemicals Lymphomas associated with host susceptibility factors Enteropathy – associated T-cell Lymphoma - Genetics - Gliadin allergy Extranodal and systemic EBV + T/Non-Hodgkin’s Lymphoma - Genetics Hepatosplenic T-cell Lymphoma - Immunosuppression + chronic autogenic stimulation Burkitt - Malaria + HIV Post transplant Lymphoma - Iatrogenic immunosuppression HIV – associated Lymphomas DLBC Primary CNS Lymphoma Burkitt Primary Effusion Lymphoma 600 fold increase for immunoblastic Lymphoma 14 fold xs for low grade Non-Hodgkin’s Lymphoma Hodgkin’s Lymphoma
Slide 25 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type: Approximately 1.5 million people worldwide are living with non-Hodgkin’s lymphoma (NHL) It is estimated that 300,000 people die each year from the disease Facts and Figures *US statistics Ries LAG, et al. SEER Cancer Statistics Review, 1975-2000, National Cancer Institute. Bethesda, MD Cancer Facts & Figures 2004, www.cancer.org 1 new case of lymphoma is diagnosed every 9 minutes* 1 in 50 people will develop lymphoma* 81% increase in incidence of NHL between 1973-1990 Overall survival at 5 years is 50%-60% for all non-Hodgkin’s lymphomas Lymphoma: Current Challenges Continued increase in incidence 3-4% increase in annual incidence of NHL over last 2-3 decades Diverse disease made up of numerous subtypes. Careful patient selection necessary to maximize treatment benefit Despite improvements in outcomes over the past decade, some subgroups of NHL, in particular, remain difficult to treat Development of newer treatment strategies critical to improving outcomes Müller A et al. Ann Hematol. 2005;84:1-12; Hagemeister FB. New agents in the treatment of lymphomas: which ones will succeed. Available at: www.cmeinteractive.cancerconsultants.com/ShowArticle.aspx?ArticleID=2. Non-Hodgkin Lymphoma: Incidence Follicular lymphoma (22%) Small lymphocytic lymphoma (6%) Marginal zone B-cell lymphoma MALT type (5%) Marginal zone B-cell lymphoma nodal type (1%) Lymphoplasmacytic lymphoma (1%) Diffuse B-cell lymphoma (31%) Composite lymphomas (13%) Peripheral T-cell (6%) Mantle cell (6%) Other subtypes with a frequency ≤ 2% (9%) Armitage et al. J Clin Oncol. 1998;16:2780-2795. Low Public Awareness of Lymphoma According to a study of lymphoma patients carried out in 2003: Prior to diagnosis almost all respondents (97.5%) had been unaware of non-Hodgkin’s lymphoma Many patients with non-Hodgkin’s lymphoma do not have an accurate understanding of the disease Up to 35% of respondents were vague about the body parts affected by non-Hodgkin’s lymphoma Half of respondents were unaware of their specific diagnosis Cause-specific Survival of NHL Study Patients (1974–1995) Cumulative survival (%) Time (years) 100 80 60 40 20 0 0 5 10 15 20 25 30 Aggressive NHL Indolent NHL Other reasons for incidence of NHL Many are age-related Auto-immune disease Environmental chemicals Lymphomas associated with host susceptibility factors Enteropathy – associated T-cell Lymphoma - Genetics - Gliadin allergy Extranodal and systemic EBV + T/Non-Hodgkin’s Lymphoma - Genetics Hepatosplenic T-cell Lymphoma - Immunosuppression + chronic autogenic stimulation Burkitt - Malaria + HIV Post transplant Lymphoma - Iatrogenic immunosuppression HIV – associated Lymphomas DLBC Primary CNS Lymphoma Burkitt Primary Effusion Lymphoma 600 fold increase for immunoblastic Lymphoma 14 fold xs for low grade Non-Hodgkin’s Lymphoma Hodgkin’s Lymphoma Lymphoma associated with Infectious Agents Nasal, cutaneous NK/T EBV Adult T-cell leukaemia Lymphoma HTLV1 Marginal zone H.pylori, campylobacter, Hepatitis C Primary effusion Lymphoma HHV-8/KSHV
Slide 26 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type: Approximately 1.5 million people worldwide are living with non-Hodgkin’s lymphoma (NHL) It is estimated that 300,000 people die each year from the disease Facts and Figures *US statistics Ries LAG, et al. SEER Cancer Statistics Review, 1975-2000, National Cancer Institute. Bethesda, MD Cancer Facts & Figures 2004, www.cancer.org 1 new case of lymphoma is diagnosed every 9 minutes* 1 in 50 people will develop lymphoma* 81% increase in incidence of NHL between 1973-1990 Overall survival at 5 years is 50%-60% for all non-Hodgkin’s lymphomas Lymphoma: Current Challenges Continued increase in incidence 3-4% increase in annual incidence of NHL over last 2-3 decades Diverse disease made up of numerous subtypes. Careful patient selection necessary to maximize treatment benefit Despite improvements in outcomes over the past decade, some subgroups of NHL, in particular, remain difficult to treat Development of newer treatment strategies critical to improving outcomes Müller A et al. Ann Hematol. 2005;84:1-12; Hagemeister FB. New agents in the treatment of lymphomas: which ones will succeed. Available at: www.cmeinteractive.cancerconsultants.com/ShowArticle.aspx?ArticleID=2. Non-Hodgkin Lymphoma: Incidence Follicular lymphoma (22%) Small lymphocytic lymphoma (6%) Marginal zone B-cell lymphoma MALT type (5%) Marginal zone B-cell lymphoma nodal type (1%) Lymphoplasmacytic lymphoma (1%) Diffuse B-cell lymphoma (31%) Composite lymphomas (13%) Peripheral T-cell (6%) Mantle cell (6%) Other subtypes with a frequency ≤ 2% (9%) Armitage et al. J Clin Oncol. 1998;16:2780-2795. Low Public Awareness of Lymphoma According to a study of lymphoma patients carried out in 2003: Prior to diagnosis almost all respondents (97.5%) had been unaware of non-Hodgkin’s lymphoma Many patients with non-Hodgkin’s lymphoma do not have an accurate understanding of the disease Up to 35% of respondents were vague about the body parts affected by non-Hodgkin’s lymphoma Half of respondents were unaware of their specific diagnosis Cause-specific Survival of NHL Study Patients (1974–1995) Cumulative survival (%) Time (years) 100 80 60 40 20 0 0 5 10 15 20 25 30 Aggressive NHL Indolent NHL Other reasons for incidence of NHL Many are age-related Auto-immune disease Environmental chemicals Lymphomas associated with host susceptibility factors Enteropathy – associated T-cell Lymphoma - Genetics - Gliadin allergy Extranodal and systemic EBV + T/Non-Hodgkin’s Lymphoma - Genetics Hepatosplenic T-cell Lymphoma - Immunosuppression + chronic autogenic stimulation Burkitt - Malaria + HIV Post transplant Lymphoma - Iatrogenic immunosuppression HIV – associated Lymphomas DLBC Primary CNS Lymphoma Burkitt Primary Effusion Lymphoma 600 fold increase for immunoblastic Lymphoma 14 fold xs for low grade Non-Hodgkin’s Lymphoma Hodgkin’s Lymphoma Lymphoma associated with Infectious Agents Nasal, cutaneous NK/T EBV Adult T-cell leukaemia Lymphoma HTLV1 Marginal zone H.pylori, campylobacter, Hepatitis C Primary effusion Lymphoma HHV-8/KSHV A Cancer in Disguise Symptoms are commonly seen in other, less serious illnesses, such as influenza or other viral infections and are often overlooked Symptoms can appear anywhere in the body
Slide 27 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type: Approximately 1.5 million people worldwide are living with non-Hodgkin’s lymphoma (NHL) It is estimated that 300,000 people die each year from the disease Facts and Figures *US statistics Ries LAG, et al. SEER Cancer Statistics Review, 1975-2000, National Cancer Institute. Bethesda, MD Cancer Facts & Figures 2004, www.cancer.org 1 new case of lymphoma is diagnosed every 9 minutes* 1 in 50 people will develop lymphoma* 81% increase in incidence of NHL between 1973-1990 Overall survival at 5 years is 50%-60% for all non-Hodgkin’s lymphomas Lymphoma: Current Challenges Continued increase in incidence 3-4% increase in annual incidence of NHL over last 2-3 decades Diverse disease made up of numerous subtypes. Careful patient selection necessary to maximize treatment benefit Despite improvements in outcomes over the past decade, some subgroups of NHL, in particular, remain difficult to treat Development of newer treatment strategies critical to improving outcomes Müller A et al. Ann Hematol. 2005;84:1-12; Hagemeister FB. New agents in the treatment of lymphomas: which ones will succeed. Available at: www.cmeinteractive.cancerconsultants.com/ShowArticle.aspx?ArticleID=2. Non-Hodgkin Lymphoma: Incidence Follicular lymphoma (22%) Small lymphocytic lymphoma (6%) Marginal zone B-cell lymphoma MALT type (5%) Marginal zone B-cell lymphoma nodal type (1%) Lymphoplasmacytic lymphoma (1%) Diffuse B-cell lymphoma (31%) Composite lymphomas (13%) Peripheral T-cell (6%) Mantle cell (6%) Other subtypes with a frequency ≤ 2% (9%) Armitage et al. J Clin Oncol. 1998;16:2780-2795. Low Public Awareness of Lymphoma According to a study of lymphoma patients carried out in 2003: Prior to diagnosis almost all respondents (97.5%) had been unaware of non-Hodgkin’s lymphoma Many patients with non-Hodgkin’s lymphoma do not have an accurate understanding of the disease Up to 35% of respondents were vague about the body parts affected by non-Hodgkin’s lymphoma Half of respondents were unaware of their specific diagnosis Cause-specific Survival of NHL Study Patients (1974–1995) Cumulative survival (%) Time (years) 100 80 60 40 20 0 0 5 10 15 20 25 30 Aggressive NHL Indolent NHL Other reasons for incidence of NHL Many are age-related Auto-immune disease Environmental chemicals Lymphomas associated with host susceptibility factors Enteropathy – associated T-cell Lymphoma - Genetics - Gliadin allergy Extranodal and systemic EBV + T/Non-Hodgkin’s Lymphoma - Genetics Hepatosplenic T-cell Lymphoma - Immunosuppression + chronic autogenic stimulation Burkitt - Malaria + HIV Post transplant Lymphoma - Iatrogenic immunosuppression HIV – associated Lymphomas DLBC Primary CNS Lymphoma Burkitt Primary Effusion Lymphoma 600 fold increase for immunoblastic Lymphoma 14 fold xs for low grade Non-Hodgkin’s Lymphoma Hodgkin’s Lymphoma Lymphoma associated with Infectious Agents Nasal, cutaneous NK/T EBV Adult T-cell leukaemia Lymphoma HTLV1 Marginal zone H.pylori, campylobacter, Hepatitis C Primary effusion Lymphoma HHV-8/KSHV A Cancer in Disguise Symptoms are commonly seen in other, less serious illnesses, such as influenza or other viral infections and are often overlooked Symptoms can appear anywhere in the body Diagnosis of NHL Physical examination Chest X-ray Ultrasound CT scan & PET Scan Bone marrow biopsy Blood test, incl. cell surface marker phenotype Sometimes: Cytogenetics Gene rearrangement Liver biopsy MRI
Slide 28 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type: Approximately 1.5 million people worldwide are living with non-Hodgkin’s lymphoma (NHL) It is estimated that 300,000 people die each year from the disease Facts and Figures *US statistics Ries LAG, et al. SEER Cancer Statistics Review, 1975-2000, National Cancer Institute. Bethesda, MD Cancer Facts & Figures 2004, www.cancer.org 1 new case of lymphoma is diagnosed every 9 minutes* 1 in 50 people will develop lymphoma* 81% increase in incidence of NHL between 1973-1990 Overall survival at 5 years is 50%-60% for all non-Hodgkin’s lymphomas Lymphoma: Current Challenges Continued increase in incidence 3-4% increase in annual incidence of NHL over last 2-3 decades Diverse disease made up of numerous subtypes. Careful patient selection necessary to maximize treatment benefit Despite improvements in outcomes over the past decade, some subgroups of NHL, in particular, remain difficult to treat Development of newer treatment strategies critical to improving outcomes Müller A et al. Ann Hematol. 2005;84:1-12; Hagemeister FB. New agents in the treatment of lymphomas: which ones will succeed. Available at: www.cmeinteractive.cancerconsultants.com/ShowArticle.aspx?ArticleID=2. Non-Hodgkin Lymphoma: Incidence Follicular lymphoma (22%) Small lymphocytic lymphoma (6%) Marginal zone B-cell lymphoma MALT type (5%) Marginal zone B-cell lymphoma nodal type (1%) Lymphoplasmacytic lymphoma (1%) Diffuse B-cell lymphoma (31%) Composite lymphomas (13%) Peripheral T-cell (6%) Mantle cell (6%) Other subtypes with a frequency ≤ 2% (9%) Armitage et al. J Clin Oncol. 1998;16:2780-2795. Low Public Awareness of Lymphoma According to a study of lymphoma patients carried out in 2003: Prior to diagnosis almost all respondents (97.5%) had been unaware of non-Hodgkin’s lymphoma Many patients with non-Hodgkin’s lymphoma do not have an accurate understanding of the disease Up to 35% of respondents were vague about the body parts affected by non-Hodgkin’s lymphoma Half of respondents were unaware of their specific diagnosis Cause-specific Survival of NHL Study Patients (1974–1995) Cumulative survival (%) Time (years) 100 80 60 40 20 0 0 5 10 15 20 25 30 Aggressive NHL Indolent NHL Other reasons for incidence of NHL Many are age-related Auto-immune disease Environmental chemicals Lymphomas associated with host susceptibility factors Enteropathy – associated T-cell Lymphoma - Genetics - Gliadin allergy Extranodal and systemic EBV + T/Non-Hodgkin’s Lymphoma - Genetics Hepatosplenic T-cell Lymphoma - Immunosuppression + chronic autogenic stimulation Burkitt - Malaria + HIV Post transplant Lymphoma - Iatrogenic immunosuppression HIV – associated Lymphomas DLBC Primary CNS Lymphoma Burkitt Primary Effusion Lymphoma 600 fold increase for immunoblastic Lymphoma 14 fold xs for low grade Non-Hodgkin’s Lymphoma Hodgkin’s Lymphoma Lymphoma associated with Infectious Agents Nasal, cutaneous NK/T EBV Adult T-cell leukaemia Lymphoma HTLV1 Marginal zone H.pylori, campylobacter, Hepatitis C Primary effusion Lymphoma HHV-8/KSHV A Cancer in Disguise Symptoms are commonly seen in other, less serious illnesses, such as influenza or other viral infections and are often overlooked Symptoms can appear anywhere in the body Diagnosis of NHL Physical examination Chest X-ray Ultrasound CT scan & PET Scan Bone marrow biopsy Blood test, incl. cell surface marker phenotype Sometimes: Cytogenetics Gene rearrangement Liver biopsy MRI The greatest increase is in skin Lymphoma
Slide 29 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type: Approximately 1.5 million people worldwide are living with non-Hodgkin’s lymphoma (NHL) It is estimated that 300,000 people die each year from the disease Facts and Figures *US statistics Ries LAG, et al. SEER Cancer Statistics Review, 1975-2000, National Cancer Institute. Bethesda, MD Cancer Facts & Figures 2004, www.cancer.org 1 new case of lymphoma is diagnosed every 9 minutes* 1 in 50 people will develop lymphoma* 81% increase in incidence of NHL between 1973-1990 Overall survival at 5 years is 50%-60% for all non-Hodgkin’s lymphomas Lymphoma: Current Challenges Continued increase in incidence 3-4% increase in annual incidence of NHL over last 2-3 decades Diverse disease made up of numerous subtypes. Careful patient selection necessary to maximize treatment benefit Despite improvements in outcomes over the past decade, some subgroups of NHL, in particular, remain difficult to treat Development of newer treatment strategies critical to improving outcomes Müller A et al. Ann Hematol. 2005;84:1-12; Hagemeister FB. New agents in the treatment of lymphomas: which ones will succeed. Available at: www.cmeinteractive.cancerconsultants.com/ShowArticle.aspx?ArticleID=2. Non-Hodgkin Lymphoma: Incidence Follicular lymphoma (22%) Small lymphocytic lymphoma (6%) Marginal zone B-cell lymphoma MALT type (5%) Marginal zone B-cell lymphoma nodal type (1%) Lymphoplasmacytic lymphoma (1%) Diffuse B-cell lymphoma (31%) Composite lymphomas (13%) Peripheral T-cell (6%) Mantle cell (6%) Other subtypes with a frequency ≤ 2% (9%) Armitage et al. J Clin Oncol. 1998;16:2780-2795. Low Public Awareness of Lymphoma According to a study of lymphoma patients carried out in 2003: Prior to diagnosis almost all respondents (97.5%) had been unaware of non-Hodgkin’s lymphoma Many patients with non-Hodgkin’s lymphoma do not have an accurate understanding of the disease Up to 35% of respondents were vague about the body parts affected by non-Hodgkin’s lymphoma Half of respondents were unaware of their specific diagnosis Cause-specific Survival of NHL Study Patients (1974–1995) Cumulative survival (%) Time (years) 100 80 60 40 20 0 0 5 10 15 20 25 30 Aggressive NHL Indolent NHL Other reasons for incidence of NHL Many are age-related Auto-immune disease Environmental chemicals Lymphomas associated with host susceptibility factors Enteropathy – associated T-cell Lymphoma - Genetics - Gliadin allergy Extranodal and systemic EBV + T/Non-Hodgkin’s Lymphoma - Genetics Hepatosplenic T-cell Lymphoma - Immunosuppression + chronic autogenic stimulation Burkitt - Malaria + HIV Post transplant Lymphoma - Iatrogenic immunosuppression HIV – associated Lymphomas DLBC Primary CNS Lymphoma Burkitt Primary Effusion Lymphoma 600 fold increase for immunoblastic Lymphoma 14 fold xs for low grade Non-Hodgkin’s Lymphoma Hodgkin’s Lymphoma Lymphoma associated with Infectious Agents Nasal, cutaneous NK/T EBV Adult T-cell leukaemia Lymphoma HTLV1 Marginal zone H.pylori, campylobacter, Hepatitis C Primary effusion Lymphoma HHV-8/KSHV A Cancer in Disguise Symptoms are commonly seen in other, less serious illnesses, such as influenza or other viral infections and are often overlooked Symptoms can appear anywhere in the body Diagnosis of NHL Physical examination Chest X-ray Ultrasound CT scan & PET Scan Bone marrow biopsy Blood test, incl. cell surface marker phenotype Sometimes: Cytogenetics Gene rearrangement Liver biopsy MRI The greatest increase is in skin Lymphoma NHL and occupation
Slide 30 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type: Approximately 1.5 million people worldwide are living with non-Hodgkin’s lymphoma (NHL) It is estimated that 300,000 people die each year from the disease Facts and Figures *US statistics Ries LAG, et al. SEER Cancer Statistics Review, 1975-2000, National Cancer Institute. Bethesda, MD Cancer Facts & Figures 2004, www.cancer.org 1 new case of lymphoma is diagnosed every 9 minutes* 1 in 50 people will develop lymphoma* 81% increase in incidence of NHL between 1973-1990 Overall survival at 5 years is 50%-60% for all non-Hodgkin’s lymphomas Lymphoma: Current Challenges Continued increase in incidence 3-4% increase in annual incidence of NHL over last 2-3 decades Diverse disease made up of numerous subtypes. Careful patient selection necessary to maximize treatment benefit Despite improvements in outcomes over the past decade, some subgroups of NHL, in particular, remain difficult to treat Development of newer treatment strategies critical to improving outcomes Müller A et al. Ann Hematol. 2005;84:1-12; Hagemeister FB. New agents in the treatment of lymphomas: which ones will succeed. Available at: www.cmeinteractive.cancerconsultants.com/ShowArticle.aspx?ArticleID=2. Non-Hodgkin Lymphoma: Incidence Follicular lymphoma (22%) Small lymphocytic lymphoma (6%) Marginal zone B-cell lymphoma MALT type (5%) Marginal zone B-cell lymphoma nodal type (1%) Lymphoplasmacytic lymphoma (1%) Diffuse B-cell lymphoma (31%) Composite lymphomas (13%) Peripheral T-cell (6%) Mantle cell (6%) Other subtypes with a frequency ≤ 2% (9%) Armitage et al. J Clin Oncol. 1998;16:2780-2795. Low Public Awareness of Lymphoma According to a study of lymphoma patients carried out in 2003: Prior to diagnosis almost all respondents (97.5%) had been unaware of non-Hodgkin’s lymphoma Many patients with non-Hodgkin’s lymphoma do not have an accurate understanding of the disease Up to 35% of respondents were vague about the body parts affected by non-Hodgkin’s lymphoma Half of respondents were unaware of their specific diagnosis Cause-specific Survival of NHL Study Patients (1974–1995) Cumulative survival (%) Time (years) 100 80 60 40 20 0 0 5 10 15 20 25 30 Aggressive NHL Indolent NHL Other reasons for incidence of NHL Many are age-related Auto-immune disease Environmental chemicals Lymphomas associated with host susceptibility factors Enteropathy – associated T-cell Lymphoma - Genetics - Gliadin allergy Extranodal and systemic EBV + T/Non-Hodgkin’s Lymphoma - Genetics Hepatosplenic T-cell Lymphoma - Immunosuppression + chronic autogenic stimulation Burkitt - Malaria + HIV Post transplant Lymphoma - Iatrogenic immunosuppression HIV – associated Lymphomas DLBC Primary CNS Lymphoma Burkitt Primary Effusion Lymphoma 600 fold increase for immunoblastic Lymphoma 14 fold xs for low grade Non-Hodgkin’s Lymphoma Hodgkin’s Lymphoma Lymphoma associated with Infectious Agents Nasal, cutaneous NK/T EBV Adult T-cell leukaemia Lymphoma HTLV1 Marginal zone H.pylori, campylobacter, Hepatitis C Primary effusion Lymphoma HHV-8/KSHV A Cancer in Disguise Symptoms are commonly seen in other, less serious illnesses, such as influenza or other viral infections and are often overlooked Symptoms can appear anywhere in the body Diagnosis of NHL Physical examination Chest X-ray Ultrasound CT scan & PET Scan Bone marrow biopsy Blood test, incl. cell surface marker phenotype Sometimes: Cytogenetics Gene rearrangement Liver biopsy MRI The greatest increase is in skin Lymphoma NHL and occupation CAUTION Is the rise apparent and not real? Are we just better at finding and diagnosing?
Slide 31 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type: Approximately 1.5 million people worldwide are living with non-Hodgkin’s lymphoma (NHL) It is estimated that 300,000 people die each year from the disease Facts and Figures *US statistics Ries LAG, et al. SEER Cancer Statistics Review, 1975-2000, National Cancer Institute. Bethesda, MD Cancer Facts & Figures 2004, www.cancer.org 1 new case of lymphoma is diagnosed every 9 minutes* 1 in 50 people will develop lymphoma* 81% increase in incidence of NHL between 1973-1990 Overall survival at 5 years is 50%-60% for all non-Hodgkin’s lymphomas Lymphoma: Current Challenges Continued increase in incidence 3-4% increase in annual incidence of NHL over last 2-3 decades Diverse disease made up of numerous subtypes. Careful patient selection necessary to maximize treatment benefit Despite improvements in outcomes over the past decade, some subgroups of NHL, in particular, remain difficult to treat Development of newer treatment strategies critical to improving outcomes Müller A et al. Ann Hematol. 2005;84:1-12; Hagemeister FB. New agents in the treatment of lymphomas: which ones will succeed. Available at: www.cmeinteractive.cancerconsultants.com/ShowArticle.aspx?ArticleID=2. Non-Hodgkin Lymphoma: Incidence Follicular lymphoma (22%) Small lymphocytic lymphoma (6%) Marginal zone B-cell lymphoma MALT type (5%) Marginal zone B-cell lymphoma nodal type (1%) Lymphoplasmacytic lymphoma (1%) Diffuse B-cell lymphoma (31%) Composite lymphomas (13%) Peripheral T-cell (6%) Mantle cell (6%) Other subtypes with a frequency ≤ 2% (9%) Armitage et al. J Clin Oncol. 1998;16:2780-2795. Low Public Awareness of Lymphoma According to a study of lymphoma patients carried out in 2003: Prior to diagnosis almost all respondents (97.5%) had been unaware of non-Hodgkin’s lymphoma Many patients with non-Hodgkin’s lymphoma do not have an accurate understanding of the disease Up to 35% of respondents were vague about the body parts affected by non-Hodgkin’s lymphoma Half of respondents were unaware of their specific diagnosis Cause-specific Survival of NHL Study Patients (1974–1995) Cumulative survival (%) Time (years) 100 80 60 40 20 0 0 5 10 15 20 25 30 Aggressive NHL Indolent NHL Other reasons for incidence of NHL Many are age-related Auto-immune disease Environmental chemicals Lymphomas associated with host susceptibility factors Enteropathy – associated T-cell Lymphoma - Genetics - Gliadin allergy Extranodal and systemic EBV + T/Non-Hodgkin’s Lymphoma - Genetics Hepatosplenic T-cell Lymphoma - Immunosuppression + chronic autogenic stimulation Burkitt - Malaria + HIV Post transplant Lymphoma - Iatrogenic immunosuppression HIV – associated Lymphomas DLBC Primary CNS Lymphoma Burkitt Primary Effusion Lymphoma 600 fold increase for immunoblastic Lymphoma 14 fold xs for low grade Non-Hodgkin’s Lymphoma Hodgkin’s Lymphoma Lymphoma associated with Infectious Agents Nasal, cutaneous NK/T EBV Adult T-cell leukaemia Lymphoma HTLV1 Marginal zone H.pylori, campylobacter, Hepatitis C Primary effusion Lymphoma HHV-8/KSHV A Cancer in Disguise Symptoms are commonly seen in other, less serious illnesses, such as influenza or other viral infections and are often overlooked Symptoms can appear anywhere in the body Diagnosis of NHL Physical examination Chest X-ray Ultrasound CT scan & PET Scan Bone marrow biopsy Blood test, incl. cell surface marker phenotype Sometimes: Cytogenetics Gene rearrangement Liver biopsy MRI The greatest increase is in skin Lymphoma NHL and occupation CAUTION Is the rise apparent and not real? Are we just better at finding and diagnosing? New diagnostic and therapeutic areas in Lymphoma PET scanning - diagnosis - activity - prognosis Immunohistochemistry Targeted therapies - eg Rituximab Stem cell transplantation
Slide 32 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type: Approximately 1.5 million people worldwide are living with non-Hodgkin’s lymphoma (NHL) It is estimated that 300,000 people die each year from the disease Facts and Figures *US statistics Ries LAG, et al. SEER Cancer Statistics Review, 1975-2000, National Cancer Institute. Bethesda, MD Cancer Facts & Figures 2004, www.cancer.org 1 new case of lymphoma is diagnosed every 9 minutes* 1 in 50 people will develop lymphoma* 81% increase in incidence of NHL between 1973-1990 Overall survival at 5 years is 50%-60% for all non-Hodgkin’s lymphomas Lymphoma: Current Challenges Continued increase in incidence 3-4% increase in annual incidence of NHL over last 2-3 decades Diverse disease made up of numerous subtypes. Careful patient selection necessary to maximize treatment benefit Despite improvements in outcomes over the past decade, some subgroups of NHL, in particular, remain difficult to treat Development of newer treatment strategies critical to improving outcomes Müller A et al. Ann Hematol. 2005;84:1-12; Hagemeister FB. New agents in the treatment of lymphomas: which ones will succeed. Available at: www.cmeinteractive.cancerconsultants.com/ShowArticle.aspx?ArticleID=2. Non-Hodgkin Lymphoma: Incidence Follicular lymphoma (22%) Small lymphocytic lymphoma (6%) Marginal zone B-cell lymphoma MALT type (5%) Marginal zone B-cell lymphoma nodal type (1%) Lymphoplasmacytic lymphoma (1%) Diffuse B-cell lymphoma (31%) Composite lymphomas (13%) Peripheral T-cell (6%) Mantle cell (6%) Other subtypes with a frequency ≤ 2% (9%) Armitage et al. J Clin Oncol. 1998;16:2780-2795. Low Public Awareness of Lymphoma According to a study of lymphoma patients carried out in 2003: Prior to diagnosis almost all respondents (97.5%) had been unaware of non-Hodgkin’s lymphoma Many patients with non-Hodgkin’s lymphoma do not have an accurate understanding of the disease Up to 35% of respondents were vague about the body parts affected by non-Hodgkin’s lymphoma Half of respondents were unaware of their specific diagnosis Cause-specific Survival of NHL Study Patients (1974–1995) Cumulative survival (%) Time (years) 100 80 60 40 20 0 0 5 10 15 20 25 30 Aggressive NHL Indolent NHL Other reasons for incidence of NHL Many are age-related Auto-immune disease Environmental chemicals Lymphomas associated with host susceptibility factors Enteropathy – associated T-cell Lymphoma - Genetics - Gliadin allergy Extranodal and systemic EBV + T/Non-Hodgkin’s Lymphoma - Genetics Hepatosplenic T-cell Lymphoma - Immunosuppression + chronic autogenic stimulation Burkitt - Malaria + HIV Post transplant Lymphoma - Iatrogenic immunosuppression HIV – associated Lymphomas DLBC Primary CNS Lymphoma Burkitt Primary Effusion Lymphoma 600 fold increase for immunoblastic Lymphoma 14 fold xs for low grade Non-Hodgkin’s Lymphoma Hodgkin’s Lymphoma Lymphoma associated with Infectious Agents Nasal, cutaneous NK/T EBV Adult T-cell leukaemia Lymphoma HTLV1 Marginal zone H.pylori, campylobacter, Hepatitis C Primary effusion Lymphoma HHV-8/KSHV A Cancer in Disguise Symptoms are commonly seen in other, less serious illnesses, such as influenza or other viral infections and are often overlooked Symptoms can appear anywhere in the body Diagnosis of NHL Physical examination Chest X-ray Ultrasound CT scan & PET Scan Bone marrow biopsy Blood test, incl. cell surface marker phenotype Sometimes: Cytogenetics Gene rearrangement Liver biopsy MRI The greatest increase is in skin Lymphoma NHL and occupation CAUTION Is the rise apparent and not real? Are we just better at finding and diagnosing? New diagnostic and therapeutic areas in Lymphoma PET scanning - diagnosis - activity - prognosis Immunohistochemistry Targeted therapies - eg Rituximab Stem cell transplantation The Rationale for Transplant in Lymphoma Auto Dose Conventional Allo DOSE ALLO EFFECT Mini-Allo DOSE ALLO EFFECT
Slide 33 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type: Approximately 1.5 million people worldwide are living with non-Hodgkin’s lymphoma (NHL) It is estimated that 300,000 people die each year from the disease Facts and Figures *US statistics Ries LAG, et al. SEER Cancer Statistics Review, 1975-2000, National Cancer Institute. Bethesda, MD Cancer Facts & Figures 2004, www.cancer.org 1 new case of lymphoma is diagnosed every 9 minutes* 1 in 50 people will develop lymphoma* 81% increase in incidence of NHL between 1973-1990 Overall survival at 5 years is 50%-60% for all non-Hodgkin’s lymphomas Lymphoma: Current Challenges Continued increase in incidence 3-4% increase in annual incidence of NHL over last 2-3 decades Diverse disease made up of numerous subtypes. Careful patient selection necessary to maximize treatment benefit Despite improvements in outcomes over the past decade, some subgroups of NHL, in particular, remain difficult to treat Development of newer treatment strategies critical to improving outcomes Müller A et al. Ann Hematol. 2005;84:1-12; Hagemeister FB. New agents in the treatment of lymphomas: which ones will succeed. Available at: www.cmeinteractive.cancerconsultants.com/ShowArticle.aspx?ArticleID=2. Non-Hodgkin Lymphoma: Incidence Follicular lymphoma (22%) Small lymphocytic lymphoma (6%) Marginal zone B-cell lymphoma MALT type (5%) Marginal zone B-cell lymphoma nodal type (1%) Lymphoplasmacytic lymphoma (1%) Diffuse B-cell lymphoma (31%) Composite lymphomas (13%) Peripheral T-cell (6%) Mantle cell (6%) Other subtypes with a frequency ≤ 2% (9%) Armitage et al. J Clin Oncol. 1998;16:2780-2795. Low Public Awareness of Lymphoma According to a study of lymphoma patients carried out in 2003: Prior to diagnosis almost all respondents (97.5%) had been unaware of non-Hodgkin’s lymphoma Many patients with non-Hodgkin’s lymphoma do not have an accurate understanding of the disease Up to 35% of respondents were vague about the body parts affected by non-Hodgkin’s lymphoma Half of respondents were unaware of their specific diagnosis Cause-specific Survival of NHL Study Patients (1974–1995) Cumulative survival (%) Time (years) 100 80 60 40 20 0 0 5 10 15 20 25 30 Aggressive NHL Indolent NHL Other reasons for incidence of NHL Many are age-related Auto-immune disease Environmental chemicals Lymphomas associated with host susceptibility factors Enteropathy – associated T-cell Lymphoma - Genetics - Gliadin allergy Extranodal and systemic EBV + T/Non-Hodgkin’s Lymphoma - Genetics Hepatosplenic T-cell Lymphoma - Immunosuppression + chronic autogenic stimulation Burkitt - Malaria + HIV Post transplant Lymphoma - Iatrogenic immunosuppression HIV – associated Lymphomas DLBC Primary CNS Lymphoma Burkitt Primary Effusion Lymphoma 600 fold increase for immunoblastic Lymphoma 14 fold xs for low grade Non-Hodgkin’s Lymphoma Hodgkin’s Lymphoma Lymphoma associated with Infectious Agents Nasal, cutaneous NK/T EBV Adult T-cell leukaemia Lymphoma HTLV1 Marginal zone H.pylori, campylobacter, Hepatitis C Primary effusion Lymphoma HHV-8/KSHV A Cancer in Disguise Symptoms are commonly seen in other, less serious illnesses, such as influenza or other viral infections and are often overlooked Symptoms can appear anywhere in the body Diagnosis of NHL Physical examination Chest X-ray Ultrasound CT scan & PET Scan Bone marrow biopsy Blood test, incl. cell surface marker phenotype Sometimes: Cytogenetics Gene rearrangement Liver biopsy MRI The greatest increase is in skin Lymphoma NHL and occupation CAUTION Is the rise apparent and not real? Are we just better at finding and diagnosing? New diagnostic and therapeutic areas in Lymphoma PET scanning - diagnosis - activity - prognosis Immunohistochemistry Targeted therapies - eg Rituximab Stem cell transplantation The Rationale for Transplant in Lymphoma Auto Dose Conventional Allo DOSE ALLO EFFECT Mini-Allo DOSE ALLO EFFECT PET+ve after 2# ABVD predictive of treatment failure in HL PET-2-ve: 2yr FFS 96% (n=161) PET-2+ve: 2yr FFS 14% (n=41) Gallamini et al, ASH 2006 (n=202)
Slide 34 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type: Approximately 1.5 million people worldwide are living with non-Hodgkin’s lymphoma (NHL) It is estimated that 300,000 people die each year from the disease Facts and Figures *US statistics Ries LAG, et al. SEER Cancer Statistics Review, 1975-2000, National Cancer Institute. Bethesda, MD Cancer Facts & Figures 2004, www.cancer.org 1 new case of lymphoma is diagnosed every 9 minutes* 1 in 50 people will develop lymphoma* 81% increase in incidence of NHL between 1973-1990 Overall survival at 5 years is 50%-60% for all non-Hodgkin’s lymphomas Lymphoma: Current Challenges Continued increase in incidence 3-4% increase in annual incidence of NHL over last 2-3 decades Diverse disease made up of numerous subtypes. Careful patient selection necessary to maximize treatment benefit Despite improvements in outcomes over the past decade, some subgroups of NHL, in particular, remain difficult to treat Development of newer treatment strategies critical to improving outcomes Müller A et al. Ann Hematol. 2005;84:1-12; Hagemeister FB. New agents in the treatment of lymphomas: which ones will succeed. Available at: www.cmeinteractive.cancerconsultants.com/ShowArticle.aspx?ArticleID=2. Non-Hodgkin Lymphoma: Incidence Follicular lymphoma (22%) Small lymphocytic lymphoma (6%) Marginal zone B-cell lymphoma MALT type (5%) Marginal zone B-cell lymphoma nodal type (1%) Lymphoplasmacytic lymphoma (1%) Diffuse B-cell lymphoma (31%) Composite lymphomas (13%) Peripheral T-cell (6%) Mantle cell (6%) Other subtypes with a frequency ≤ 2% (9%) Armitage et al. J Clin Oncol. 1998;16:2780-2795. Low Public Awareness of Lymphoma According to a study of lymphoma patients carried out in 2003: Prior to diagnosis almost all respondents (97.5%) had been unaware of non-Hodgkin’s lymphoma Many patients with non-Hodgkin’s lymphoma do not have an accurate understanding of the disease Up to 35% of respondents were vague about the body parts affected by non-Hodgkin’s lymphoma Half of respondents were unaware of their specific diagnosis Cause-specific Survival of NHL Study Patients (1974–1995) Cumulative survival (%) Time (years) 100 80 60 40 20 0 0 5 10 15 20 25 30 Aggressive NHL Indolent NHL Other reasons for incidence of NHL Many are age-related Auto-immune disease Environmental chemicals Lymphomas associated with host susceptibility factors Enteropathy – associated T-cell Lymphoma - Genetics - Gliadin allergy Extranodal and systemic EBV + T/Non-Hodgkin’s Lymphoma - Genetics Hepatosplenic T-cell Lymphoma - Immunosuppression + chronic autogenic stimulation Burkitt - Malaria + HIV Post transplant Lymphoma - Iatrogenic immunosuppression HIV – associated Lymphomas DLBC Primary CNS Lymphoma Burkitt Primary Effusion Lymphoma 600 fold increase for immunoblastic Lymphoma 14 fold xs for low grade Non-Hodgkin’s Lymphoma Hodgkin’s Lymphoma Lymphoma associated with Infectious Agents Nasal, cutaneous NK/T EBV Adult T-cell leukaemia Lymphoma HTLV1 Marginal zone H.pylori, campylobacter, Hepatitis C Primary effusion Lymphoma HHV-8/KSHV A Cancer in Disguise Symptoms are commonly seen in other, less serious illnesses, such as influenza or other viral infections and are often overlooked Symptoms can appear anywhere in the body Diagnosis of NHL Physical examination Chest X-ray Ultrasound CT scan & PET Scan Bone marrow biopsy Blood test, incl. cell surface marker phenotype Sometimes: Cytogenetics Gene rearrangement Liver biopsy MRI The greatest increase is in skin Lymphoma NHL and occupation CAUTION Is the rise apparent and not real? Are we just better at finding and diagnosing? New diagnostic and therapeutic areas in Lymphoma PET scanning - diagnosis - activity - prognosis Immunohistochemistry Targeted therapies - eg Rituximab Stem cell transplantation The Rationale for Transplant in Lymphoma Auto Dose Conventional Allo DOSE ALLO EFFECT Mini-Allo DOSE ALLO EFFECT PET+ve after 2# ABVD predictive of treatment failure in HL PET-2-ve: 2yr FFS 96% (n=161) PET-2+ve: 2yr FFS 14% (n=41) Gallamini et al, ASH 2006 (n=202) Hodgkin Lymphoma Normally 5 x less frequent than NHL More frequent also in HIV patients Now 2 subtypes - Classical - NLPH (nodular lymphocytic predominant)
Slide 35 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type: Approximately 1.5 million people worldwide are living with non-Hodgkin’s lymphoma (NHL) It is estimated that 300,000 people die each year from the disease Facts and Figures *US statistics Ries LAG, et al. SEER Cancer Statistics Review, 1975-2000, National Cancer Institute. Bethesda, MD Cancer Facts & Figures 2004, www.cancer.org 1 new case of lymphoma is diagnosed every 9 minutes* 1 in 50 people will develop lymphoma* 81% increase in incidence of NHL between 1973-1990 Overall survival at 5 years is 50%-60% for all non-Hodgkin’s lymphomas Lymphoma: Current Challenges Continued increase in incidence 3-4% increase in annual incidence of NHL over last 2-3 decades Diverse disease made up of numerous subtypes. Careful patient selection necessary to maximize treatment benefit Despite improvements in outcomes over the past decade, some subgroups of NHL, in particular, remain difficult to treat Development of newer treatment strategies critical to improving outcomes Müller A et al. Ann Hematol. 2005;84:1-12; Hagemeister FB. New agents in the treatment of lymphomas: which ones will succeed. Available at: www.cmeinteractive.cancerconsultants.com/ShowArticle.aspx?ArticleID=2. Non-Hodgkin Lymphoma: Incidence Follicular lymphoma (22%) Small lymphocytic lymphoma (6%) Marginal zone B-cell lymphoma MALT type (5%) Marginal zone B-cell lymphoma nodal type (1%) Lymphoplasmacytic lymphoma (1%) Diffuse B-cell lymphoma (31%) Composite lymphomas (13%) Peripheral T-cell (6%) Mantle cell (6%) Other subtypes with a frequency ≤ 2% (9%) Armitage et al. J Clin Oncol. 1998;16:2780-2795. Low Public Awareness of Lymphoma According to a study of lymphoma patients carried out in 2003: Prior to diagnosis almost all respondents (97.5%) had been unaware of non-Hodgkin’s lymphoma Many patients with non-Hodgkin’s lymphoma do not have an accurate understanding of the disease Up to 35% of respondents were vague about the body parts affected by non-Hodgkin’s lymphoma Half of respondents were unaware of their specific diagnosis Cause-specific Survival of NHL Study Patients (1974–1995) Cumulative survival (%) Time (years) 100 80 60 40 20 0 0 5 10 15 20 25 30 Aggressive NHL Indolent NHL Other reasons for incidence of NHL Many are age-related Auto-immune disease Environmental chemicals Lymphomas associated with host susceptibility factors Enteropathy – associated T-cell Lymphoma - Genetics - Gliadin allergy Extranodal and systemic EBV + T/Non-Hodgkin’s Lymphoma - Genetics Hepatosplenic T-cell Lymphoma - Immunosuppression + chronic autogenic stimulation Burkitt - Malaria + HIV Post transplant Lymphoma - Iatrogenic immunosuppression HIV – associated Lymphomas DLBC Primary CNS Lymphoma Burkitt Primary Effusion Lymphoma 600 fold increase for immunoblastic Lymphoma 14 fold xs for low grade Non-Hodgkin’s Lymphoma Hodgkin’s Lymphoma Lymphoma associated with Infectious Agents Nasal, cutaneous NK/T EBV Adult T-cell leukaemia Lymphoma HTLV1 Marginal zone H.pylori, campylobacter, Hepatitis C Primary effusion Lymphoma HHV-8/KSHV A Cancer in Disguise Symptoms are commonly seen in other, less serious illnesses, such as influenza or other viral infections and are often overlooked Symptoms can appear anywhere in the body Diagnosis of NHL Physical examination Chest X-ray Ultrasound CT scan & PET Scan Bone marrow biopsy Blood test, incl. cell surface marker phenotype Sometimes: Cytogenetics Gene rearrangement Liver biopsy MRI The greatest increase is in skin Lymphoma NHL and occupation CAUTION Is the rise apparent and not real? Are we just better at finding and diagnosing? New diagnostic and therapeutic areas in Lymphoma PET scanning - diagnosis - activity - prognosis Immunohistochemistry Targeted therapies - eg Rituximab Stem cell transplantation The Rationale for Transplant in Lymphoma Auto Dose Conventional Allo DOSE ALLO EFFECT Mini-Allo DOSE ALLO EFFECT PET+ve after 2# ABVD predictive of treatment failure in HL PET-2-ve: 2yr FFS 96% (n=161) PET-2+ve: 2yr FFS 14% (n=41) Gallamini et al, ASH 2006 (n=202) Hodgkin Lymphoma Normally 5 x less frequent than NHL More frequent also in HIV patients Now 2 subtypes - Classical - NLPH (nodular lymphocytic predominant) Radiotherapy in Hodgkin’s Much less frequently used today Major problem with Breast Cancer after “Mantle” field Chemo more toxic short term but less toxic long term Fertility issues with new escalated chemo Issues of “Survivorship”
Slide 36 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type: Approximately 1.5 million people worldwide are living with non-Hodgkin’s lymphoma (NHL) It is estimated that 300,000 people die each year from the disease Facts and Figures *US statistics Ries LAG, et al. SEER Cancer Statistics Review, 1975-2000, National Cancer Institute. Bethesda, MD Cancer Facts & Figures 2004, www.cancer.org 1 new case of lymphoma is diagnosed every 9 minutes* 1 in 50 people will develop lymphoma* 81% increase in incidence of NHL between 1973-1990 Overall survival at 5 years is 50%-60% for all non-Hodgkin’s lymphomas Lymphoma: Current Challenges Continued increase in incidence 3-4% increase in annual incidence of NHL over last 2-3 decades Diverse disease made up of numerous subtypes. Careful patient selection necessary to maximize treatment benefit Despite improvements in outcomes over the past decade, some subgroups of NHL, in particular, remain difficult to treat Development of newer treatment strategies critical to improving outcomes Müller A et al. Ann Hematol. 2005;84:1-12; Hagemeister FB. New agents in the treatment of lymphomas: which ones will succeed. Available at: www.cmeinteractive.cancerconsultants.com/ShowArticle.aspx?ArticleID=2. Non-Hodgkin Lymphoma: Incidence Follicular lymphoma (22%) Small lymphocytic lymphoma (6%) Marginal zone B-cell lymphoma MALT type (5%) Marginal zone B-cell lymphoma nodal type (1%) Lymphoplasmacytic lymphoma (1%) Diffuse B-cell lymphoma (31%) Composite lymphomas (13%) Peripheral T-cell (6%) Mantle cell (6%) Other subtypes with a frequency ≤ 2% (9%) Armitage et al. J Clin Oncol. 1998;16:2780-2795. Low Public Awareness of Lymphoma According to a study of lymphoma patients carried out in 2003: Prior to diagnosis almost all respondents (97.5%) had been unaware of non-Hodgkin’s lymphoma Many patients with non-Hodgkin’s lymphoma do not have an accurate understanding of the disease Up to 35% of respondents were vague about the body parts affected by non-Hodgkin’s lymphoma Half of respondents were unaware of their specific diagnosis Cause-specific Survival of NHL Study Patients (1974–1995) Cumulative survival (%) Time (years) 100 80 60 40 20 0 0 5 10 15 20 25 30 Aggressive NHL Indolent NHL Other reasons for incidence of NHL Many are age-related Auto-immune disease Environmental chemicals Lymphomas associated with host susceptibility factors Enteropathy – associated T-cell Lymphoma - Genetics - Gliadin allergy Extranodal and systemic EBV + T/Non-Hodgkin’s Lymphoma - Genetics Hepatosplenic T-cell Lymphoma - Immunosuppression + chronic autogenic stimulation Burkitt - Malaria + HIV Post transplant Lymphoma - Iatrogenic immunosuppression HIV – associated Lymphomas DLBC Primary CNS Lymphoma Burkitt Primary Effusion Lymphoma 600 fold increase for immunoblastic Lymphoma 14 fold xs for low grade Non-Hodgkin’s Lymphoma Hodgkin’s Lymphoma Lymphoma associated with Infectious Agents Nasal, cutaneous NK/T EBV Adult T-cell leukaemia Lymphoma HTLV1 Marginal zone H.pylori, campylobacter, Hepatitis C Primary effusion Lymphoma HHV-8/KSHV A Cancer in Disguise Symptoms are commonly seen in other, less serious illnesses, such as influenza or other viral infections and are often overlooked Symptoms can appear anywhere in the body Diagnosis of NHL Physical examination Chest X-ray Ultrasound CT scan & PET Scan Bone marrow biopsy Blood test, incl. cell surface marker phenotype Sometimes: Cytogenetics Gene rearrangement Liver biopsy MRI The greatest increase is in skin Lymphoma NHL and occupation CAUTION Is the rise apparent and not real? Are we just better at finding and diagnosing? New diagnostic and therapeutic areas in Lymphoma PET scanning - diagnosis - activity - prognosis Immunohistochemistry Targeted therapies - eg Rituximab Stem cell transplantation The Rationale for Transplant in Lymphoma Auto Dose Conventional Allo DOSE ALLO EFFECT Mini-Allo DOSE ALLO EFFECT PET+ve after 2# ABVD predictive of treatment failure in HL PET-2-ve: 2yr FFS 96% (n=161) PET-2+ve: 2yr FFS 14% (n=41) Gallamini et al, ASH 2006 (n=202) Hodgkin Lymphoma Normally 5 x less frequent than NHL More frequent also in HIV patients Now 2 subtypes - Classical - NLPH (nodular lymphocytic predominant) Radiotherapy in Hodgkin’s Much less frequently used today Major problem with Breast Cancer after “Mantle” field Chemo more toxic short term but less toxic long term Fertility issues with new escalated chemo Issues of “Survivorship” Why Targeted Therapies? Need to improve outcomes for all types of lymphoma -Improve cure rate for aggressive lymphomas -Maintain remission for indolent disease -Eradicate minimal residual disease -Decrease relapse rate for all lymphoma Lymphoma frequently associated with deregulated cellular pathways of differentiation, proliferation or survival -Molecules involved in these aberrations provide rational targets for selective therapies Agents generally well tolerated and easily combined with other therapies (eg, chemotherapy, radiotherapy) Coiffier B. Semin Oncol. 2004;31(1 suppl 2):7-11.
Slide 37 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type: Approximately 1.5 million people worldwide are living with non-Hodgkin’s lymphoma (NHL) It is estimated that 300,000 people die each year from the disease Facts and Figures *US statistics Ries LAG, et al. SEER Cancer Statistics Review, 1975-2000, National Cancer Institute. Bethesda, MD Cancer Facts & Figures 2004, www.cancer.org 1 new case of lymphoma is diagnosed every 9 minutes* 1 in 50 people will develop lymphoma* 81% increase in incidence of NHL between 1973-1990 Overall survival at 5 years is 50%-60% for all non-Hodgkin’s lymphomas Lymphoma: Current Challenges Continued increase in incidence 3-4% increase in annual incidence of NHL over last 2-3 decades Diverse disease made up of numerous subtypes. Careful patient selection necessary to maximize treatment benefit Despite improvements in outcomes over the past decade, some subgroups of NHL, in particular, remain difficult to treat Development of newer treatment strategies critical to improving outcomes Müller A et al. Ann Hematol. 2005;84:1-12; Hagemeister FB. New agents in the treatment of lymphomas: which ones will succeed. Available at: www.cmeinteractive.cancerconsultants.com/ShowArticle.aspx?ArticleID=2. Non-Hodgkin Lymphoma: Incidence Follicular lymphoma (22%) Small lymphocytic lymphoma (6%) Marginal zone B-cell lymphoma MALT type (5%) Marginal zone B-cell lymphoma nodal type (1%) Lymphoplasmacytic lymphoma (1%) Diffuse B-cell lymphoma (31%) Composite lymphomas (13%) Peripheral T-cell (6%) Mantle cell (6%) Other subtypes with a frequency ≤ 2% (9%) Armitage et al. J Clin Oncol. 1998;16:2780-2795. Low Public Awareness of Lymphoma According to a study of lymphoma patients carried out in 2003: Prior to diagnosis almost all respondents (97.5%) had been unaware of non-Hodgkin’s lymphoma Many patients with non-Hodgkin’s lymphoma do not have an accurate understanding of the disease Up to 35% of respondents were vague about the body parts affected by non-Hodgkin’s lymphoma Half of respondents were unaware of their specific diagnosis Cause-specific Survival of NHL Study Patients (1974–1995) Cumulative survival (%) Time (years) 100 80 60 40 20 0 0 5 10 15 20 25 30 Aggressive NHL Indolent NHL Other reasons for incidence of NHL Many are age-related Auto-immune disease Environmental chemicals Lymphomas associated with host susceptibility factors Enteropathy – associated T-cell Lymphoma - Genetics - Gliadin allergy Extranodal and systemic EBV + T/Non-Hodgkin’s Lymphoma - Genetics Hepatosplenic T-cell Lymphoma - Immunosuppression + chronic autogenic stimulation Burkitt - Malaria + HIV Post transplant Lymphoma - Iatrogenic immunosuppression HIV – associated Lymphomas DLBC Primary CNS Lymphoma Burkitt Primary Effusion Lymphoma 600 fold increase for immunoblastic Lymphoma 14 fold xs for low grade Non-Hodgkin’s Lymphoma Hodgkin’s Lymphoma Lymphoma associated with Infectious Agents Nasal, cutaneous NK/T EBV Adult T-cell leukaemia Lymphoma HTLV1 Marginal zone H.pylori, campylobacter, Hepatitis C Primary effusion Lymphoma HHV-8/KSHV A Cancer in Disguise Symptoms are commonly seen in other, less serious illnesses, such as influenza or other viral infections and are often overlooked Symptoms can appear anywhere in the body Diagnosis of NHL Physical examination Chest X-ray Ultrasound CT scan & PET Scan Bone marrow biopsy Blood test, incl. cell surface marker phenotype Sometimes: Cytogenetics Gene rearrangement Liver biopsy MRI The greatest increase is in skin Lymphoma NHL and occupation CAUTION Is the rise apparent and not real? Are we just better at finding and diagnosing? New diagnostic and therapeutic areas in Lymphoma PET scanning - diagnosis - activity - prognosis Immunohistochemistry Targeted therapies - eg Rituximab Stem cell transplantation The Rationale for Transplant in Lymphoma Auto Dose Conventional Allo DOSE ALLO EFFECT Mini-Allo DOSE ALLO EFFECT PET+ve after 2# ABVD predictive of treatment failure in HL PET-2-ve: 2yr FFS 96% (n=161) PET-2+ve: 2yr FFS 14% (n=41) Gallamini et al, ASH 2006 (n=202) Hodgkin Lymphoma Normally 5 x less frequent than NHL More frequent also in HIV patients Now 2 subtypes - Classical - NLPH (nodular lymphocytic predominant) Radiotherapy in Hodgkin’s Much less frequently used today Major problem with Breast Cancer after “Mantle” field Chemo more toxic short term but less toxic long term Fertility issues with new escalated chemo Issues of “Survivorship” Why Targeted Therapies? Need to improve outcomes for all types of lymphoma -Improve cure rate for aggressive lymphomas -Maintain remission for indolent disease -Eradicate minimal residual disease -Decrease relapse rate for all lymphoma Lymphoma frequently associated with deregulated cellular pathways of differentiation, proliferation or survival -Molecules involved in these aberrations provide rational targets for selective therapies Agents generally well tolerated and easily combined with other therapies (eg, chemotherapy, radiotherapy) Coiffier B. Semin Oncol. 2004;31(1 suppl 2):7-11. Targeting the Cell Surface slg DR CD19 CD20 CD22 B Lymphocyte
Slide 38 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type: Approximately 1.5 million people worldwide are living with non-Hodgkin’s lymphoma (NHL) It is estimated that 300,000 people die each year from the disease Facts and Figures *US statistics Ries LAG, et al. SEER Cancer Statistics Review, 1975-2000, National Cancer Institute. Bethesda, MD Cancer Facts & Figures 2004, www.cancer.org 1 new case of lymphoma is diagnosed every 9 minutes* 1 in 50 people will develop lymphoma* 81% increase in incidence of NHL between 1973-1990 Overall survival at 5 years is 50%-60% for all non-Hodgkin’s lymphomas Lymphoma: Current Challenges Continued increase in incidence 3-4% increase in annual incidence of NHL over last 2-3 decades Diverse disease made up of numerous subtypes. Careful patient selection necessary to maximize treatment benefit Despite improvements in outcomes over the past decade, some subgroups of NHL, in particular, remain difficult to treat Development of newer treatment strategies critical to improving outcomes Müller A et al. Ann Hematol. 2005;84:1-12; Hagemeister FB. New agents in the treatment of lymphomas: which ones will succeed. Available at: www.cmeinteractive.cancerconsultants.com/ShowArticle.aspx?ArticleID=2. Non-Hodgkin Lymphoma: Incidence Follicular lymphoma (22%) Small lymphocytic lymphoma (6%) Marginal zone B-cell lymphoma MALT type (5%) Marginal zone B-cell lymphoma nodal type (1%) Lymphoplasmacytic lymphoma (1%) Diffuse B-cell lymphoma (31%) Composite lymphomas (13%) Peripheral T-cell (6%) Mantle cell (6%) Other subtypes with a frequency ≤ 2% (9%) Armitage et al. J Clin Oncol. 1998;16:2780-2795. Low Public Awareness of Lymphoma According to a study of lymphoma patients carried out in 2003: Prior to diagnosis almost all respondents (97.5%) had been unaware of non-Hodgkin’s lymphoma Many patients with non-Hodgkin’s lymphoma do not have an accurate understanding of the disease Up to 35% of respondents were vague about the body parts affected by non-Hodgkin’s lymphoma Half of respondents were unaware of their specific diagnosis Cause-specific Survival of NHL Study Patients (1974–1995) Cumulative survival (%) Time (years) 100 80 60 40 20 0 0 5 10 15 20 25 30 Aggressive NHL Indolent NHL Other reasons for incidence of NHL Many are age-related Auto-immune disease Environmental chemicals Lymphomas associated with host susceptibility factors Enteropathy – associated T-cell Lymphoma - Genetics - Gliadin allergy Extranodal and systemic EBV + T/Non-Hodgkin’s Lymphoma - Genetics Hepatosplenic T-cell Lymphoma - Immunosuppression + chronic autogenic stimulation Burkitt - Malaria + HIV Post transplant Lymphoma - Iatrogenic immunosuppression HIV – associated Lymphomas DLBC Primary CNS Lymphoma Burkitt Primary Effusion Lymphoma 600 fold increase for immunoblastic Lymphoma 14 fold xs for low grade Non-Hodgkin’s Lymphoma Hodgkin’s Lymphoma Lymphoma associated with Infectious Agents Nasal, cutaneous NK/T EBV Adult T-cell leukaemia Lymphoma HTLV1 Marginal zone H.pylori, campylobacter, Hepatitis C Primary effusion Lymphoma HHV-8/KSHV A Cancer in Disguise Symptoms are commonly seen in other, less serious illnesses, such as influenza or other viral infections and are often overlooked Symptoms can appear anywhere in the body Diagnosis of NHL Physical examination Chest X-ray Ultrasound CT scan & PET Scan Bone marrow biopsy Blood test, incl. cell surface marker phenotype Sometimes: Cytogenetics Gene rearrangement Liver biopsy MRI The greatest increase is in skin Lymphoma NHL and occupation CAUTION Is the rise apparent and not real? Are we just better at finding and diagnosing? New diagnostic and therapeutic areas in Lymphoma PET scanning - diagnosis - activity - prognosis Immunohistochemistry Targeted therapies - eg Rituximab Stem cell transplantation The Rationale for Transplant in Lymphoma Auto Dose Conventional Allo DOSE ALLO EFFECT Mini-Allo DOSE ALLO EFFECT PET+ve after 2# ABVD predictive of treatment failure in HL PET-2-ve: 2yr FFS 96% (n=161) PET-2+ve: 2yr FFS 14% (n=41) Gallamini et al, ASH 2006 (n=202) Hodgkin Lymphoma Normally 5 x less frequent than NHL More frequent also in HIV patients Now 2 subtypes - Classical - NLPH (nodular lymphocytic predominant) Radiotherapy in Hodgkin’s Much less frequently used today Major problem with Breast Cancer after “Mantle” field Chemo more toxic short term but less toxic long term Fertility issues with new escalated chemo Issues of “Survivorship” Why Targeted Therapies? Need to improve outcomes for all types of lymphoma -Improve cure rate for aggressive lymphomas -Maintain remission for indolent disease -Eradicate minimal residual disease -Decrease relapse rate for all lymphoma Lymphoma frequently associated with deregulated cellular pathways of differentiation, proliferation or survival -Molecules involved in these aberrations provide rational targets for selective therapies Agents generally well tolerated and easily combined with other therapies (eg, chemotherapy, radiotherapy) Coiffier B. Semin Oncol. 2004;31(1 suppl 2):7-11. Targeting the Cell Surface slg DR CD19 CD20 CD22 B Lymphocyte Major Themes Effectiveness without toxicity. Dose escalation Exploitation of passive & active immunotherapy
Slide 39 - Issues in Haematological Malignancy 2010 Prof. A H Goldstone CBE AML ALL CML CLL Myeloma Lymphoma There is more that can be achieved almost everywhere and the PCTs and Insurance Companies are running scared The patient over 70 years starts to get proper treatment! AML – Acute Myeloid Leukaemia The elderly still do badly Targeted therapy anti CD33 (Mylotarg) RIC transplant for the older patient - (50-65) ALL – Acute Lymphoblastic Leukaemia Adults still do badly Kids 90% survival Adults 35% survival Antibody treatment arrives Rituximab may also be useful in ALL More transplant!- Unrelated donors transplant increasing RIC (reduced intensity conditioning) CML – Chronic Myeloid Leukaemia Arrival of tyrosine kinase inhibitors (TKIs) Imatinib (Glivec) “wonder drug” now produces 90% 10 year survival Probably needs to be continued indefinitely £25K/yr Very few patients now need transplanting CLL – Chronic Lymphocyte Leukaemia Strategy moves from “suppression” to induction of remission FCR (Fludarabine, Cyclophosphamide, Rituximab) More complex treatment, more immunosuppression, more commitment of patient Younger patients should be considered for transplant – this disease is sometime CURABLE! Myeloma Drugs begin to be effective Thalidomide Bortezomib (Velcade) Lenalidomide (Revlimid) Side effects are considerable and need close monitoring Outlook now increased from 2-3 yrs to 6-8 yrs Every patient of whatever age worthy of consideration of first line therapy So you thought Lymphoma was a rare disease – not any more Lymphoma is:- The most common blood cancer, more common than leukaemia and myeloma Most common cause of blood cancer death 5th leading cause of cancer death in men, 4th in women Causes 11% of childhood cancers Increasing 4%/year Non-Hodgkin’s Lymphoma Incidence and Mortality Rates Age-specific incidence rate (case numbers per 100,000 per year) for cases of NHL collected from geographically defined areas of the UK 1984-1993 Lymphoma – A growing problem Increasing incidence of NHL Non-Hodgkin's Lymphoma Hodgkin's Lymphoma Australian Institute of Health and Welfare 2000 The following table gives the estimated numbers of new cases and deaths for each common cancer type: Approximately 1.5 million people worldwide are living with non-Hodgkin’s lymphoma (NHL) It is estimated that 300,000 people die each year from the disease Facts and Figures *US statistics Ries LAG, et al. SEER Cancer Statistics Review, 1975-2000, National Cancer Institute. Bethesda, MD Cancer Facts & Figures 2004, www.cancer.org 1 new case of lymphoma is diagnosed every 9 minutes* 1 in 50 people will develop lymphoma* 81% increase in incidence of NHL between 1973-1990 Overall survival at 5 years is 50%-60% for all non-Hodgkin’s lymphomas Lymphoma: Current Challenges Continued increase in incidence 3-4% increase in annual incidence of NHL over last 2-3 decades Diverse disease made up of numerous subtypes. Careful patient selection necessary to maximize treatment benefit Despite improvements in outcomes over the past decade, some subgroups of NHL, in particular, remain difficult to treat Development of newer treatment strategies critical to improving outcomes Müller A et al. Ann Hematol. 2005;84:1-12; Hagemeister FB. New agents in the treatment of lymphomas: which ones will succeed. Available at: www.cmeinteractive.cancerconsultants.com/ShowArticle.aspx?ArticleID=2. Non-Hodgkin Lymphoma: Incidence Follicular lymphoma (22%) Small lymphocytic lymphoma (6%) Marginal zone B-cell lymphoma MALT type (5%) Marginal zone B-cell lymphoma nodal type (1%) Lymphoplasmacytic lymphoma (1%) Diffuse B-cell lymphoma (31%) Composite lymphomas (13%) Peripheral T-cell (6%) Mantle cell (6%) Other subtypes with a frequency ≤ 2% (9%) Armitage et al. J Clin Oncol. 1998;16:2780-2795. Low Public Awareness of Lymphoma According to a study of lymphoma patients carried out in 2003: Prior to diagnosis almost all respondents (97.5%) had been unaware of non-Hodgkin’s lymphoma Many patients with non-Hodgkin’s lymphoma do not have an accurate understanding of the disease Up to 35% of respondents were vague about the body parts affected by non-Hodgkin’s lymphoma Half of respondents were unaware of their specific diagnosis Cause-specific Survival of NHL Study Patients (1974–1995) Cumulative survival (%) Time (years) 100 80 60 40 20 0 0 5 10 15 20 25 30 Aggressive NHL Indolent NHL Other reasons for incidence of NHL Many are age-related Auto-immune disease Environmental chemicals Lymphomas associated with host susceptibility factors Enteropathy – associated T-cell Lymphoma - Genetics - Gliadin allergy Extranodal and systemic EBV + T/Non-Hodgkin’s Lymphoma - Genetics Hepatosplenic T-cell Lymphoma - Immunosuppression + chronic autogenic stimulation Burkitt - Malaria + HIV Post transplant Lymphoma - Iatrogenic immunosuppression HIV – associated Lymphomas DLBC Primary CNS Lymphoma Burkitt Primary Effusion Lymphoma 600 fold increase for immunoblastic Lymphoma 14 fold xs for low grade Non-Hodgkin’s Lymphoma Hodgkin’s Lymphoma Lymphoma associated with Infectious Agents Nasal, cutaneous NK/T EBV Adult T-cell leukaemia Lymphoma HTLV1 Marginal zone H.pylori, campylobacter, Hepatitis C Primary effusion Lymphoma HHV-8/KSHV A Cancer in Disguise Symptoms are commonly seen in other, less serious illnesses, such as influenza or other viral infections and are often overlooked Symptoms can appear anywhere in the body Diagnosis of NHL Physical examination Chest X-ray Ultrasound CT scan & PET Scan Bone marrow biopsy Blood test, incl. cell surface marker phenotype Sometimes: Cytogenetics Gene rearrangement Liver biopsy MRI The greatest increase is in skin Lymphoma NHL and occupation CAUTION Is the rise apparent and not real? Are we just better at finding and diagnosing? New diagnostic and therapeutic areas in Lymphoma PET scanning - diagnosis - activity - prognosis Immunohistochemistry Targeted therapies - eg Rituximab Stem cell transplantation The Rationale for Transplant in Lymphoma Auto Dose Conventional Allo DOSE ALLO EFFECT Mini-Allo DOSE ALLO EFFECT PET+ve after 2# ABVD predictive of treatment failure in HL PET-2-ve: 2yr FFS 96% (n=161) PET-2+ve: 2yr FFS 14% (n=41) Gallamini et al, ASH 2006 (n=202) Hodgkin Lymphoma Normally 5 x less frequent than NHL More frequent also in HIV patients Now 2 subtypes - Classical - NLPH (nodular lymphocytic predominant) Radiotherapy in Hodgkin’s Much less frequently used today Major problem with Breast Cancer after “Mantle” field Chemo more toxic short term but less toxic long term Fertility issues with new escalated chemo Issues of “Survivorship” Why Targeted Therapies? Need to improve outcomes for all types of lymphoma -Improve cure rate for aggressive lymphomas -Maintain remission for indolent disease -Eradicate minimal residual disease -Decrease relapse rate for all lymphoma Lymphoma frequently associated with deregulated cellular pathways of differentiation, proliferation or survival -Molecules involved in these aberrations provide rational targets for selective therapies Agents generally well tolerated and easily combined with other therapies (eg, chemotherapy, radiotherapy) Coiffier B. Semin Oncol. 2004;31(1 suppl 2):7-11. Targeting the Cell Surface slg DR CD19 CD20 CD22 B Lymphocyte Major Themes Effectiveness without toxicity. Dose escalation Exploitation of passive & active immunotherapy The ongoing management of the patient with active disease is vital Lymphoma, Myeloma + CLL are of major importance in this regard “Living with Cancer” has truly arrived in many haematological malignancies