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Slide 1 - Acute Leukemia Leukaemia Rakesh Biswas MD, Professor, Department of Medicine, People's College of Medical Sciences, Bhanpur, Bhopal, India
Slide 2 - A 16 year old girlExtreme pallorgum bleeds, Purpura,With Lymphadenopathy and Hepatosplenomegaly
Slide 3 - Possible causes: Investigations and treatment
Slide 4 - Only a week later, D was ill again, with a fever, severe headache, and extreme lethargy.
Slide 5 - During a sunny spring weekend, D would go outside to play, only to return minutes later exhausted, flopping herself onto the sofa to rest
Slide 6 - Leukemia Group of malignant disorders of the hematopoietic tissues characteristically associated with increased numbers of white cells in the bone marrow and / or peripheral blood
Slide 7 - Once inside the van and on our way out of the clinic parking lot, she asked, "Dad, what is leukemia?" "Can I die from this?"
Slide 8 - Classification Classified based on cell type involved and the clinical course 1. Acute : ALL AML 2. Chronic : CLL CML
Slide 9 - Subclassification ALL Common type( pre-B) B-cell T-cell Undifferentiated
Slide 10 - After the oncologist performed a bone marrow aspiration to confirm the diagnosis of leukemia, we learned specifically what type it was and the count. "D had acute lymphoblastic leukemia, early pre-B cell.
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Slide 13 - Myelomono
Slide 14 - Ref-Harrison’s Principle of Internal Medicine
Slide 15 - CLL B-cell: common T-cell: rare
Slide 16 - CML Ph +ve Ph –ve, BCR-abl +ve Ph –ve, BCR-abl -ve Eosinophilic Leukemia Ph: Philadelphia chromosome BCR: Breakpoint cluster region; abl : Abelson oncogene
Slide 17 - Acute Myeloid Leukemia ( AML) Malignant transformation of a myeloid precursor cell ; usually occurs at a very early stage of myeloid development Rare in childhood & incidence increases with age
Slide 18 - Etiology Unknown / De-novo !! In majority Predisposing factors: Ionizing radiation exposure Previous chemotherapy : alkylating agents Occupational chemical exposure : benzene Genetic factors: Down’s Syndrome, Bloom’s, Fanconi’s Anemia Viral infection ( HTLV-1) Immunological : hypogammaglobulinemia Acquired hematological condition -Secondary
Slide 19 - Epidemiology M > F ALL which predominantly affects younger individuals AML – adults and the elderly Median age gp-65yrs Geographical variation-none
Slide 20 - Clinical features General : Onset is abrupt & stormy (usually present within 3 months) Bone marrow failure (anemia, infection ,bleeding) Bone pain & tenderness
Slide 21 - Specific: M2 : Chloroma:-presents as a mass lesion ‘tumor of leukemic cells’ M3 : DIC M4/M5 : Infiltration of soft tissues, gum infiltration, skin deposits ,Meningeal involvement-headache, vomiting, eye symptoms
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Slide 23 - Skin Infiltration with AML (Leukemia Cutis)
Slide 24 - Diagnosis Blood count : WBC usually elevated (50,000- 1,00,000 / cmm ); may be normal or low; often anemia & thrombocytopenia Blood film : (as above) Blast cells
Slide 25 - P. Smear AML
Slide 26 - Bone marrow aspirate & trephine: Hypercellular, blast cells ( > 20%), presence of Auer rods - AML type Cytochemistry : Special stains to differentiate AML from ALL ; Positivity with Sudan black & Myeloperoxidase (MPO) in AML
Slide 27 - Jemshidi trephine & Salah aspiration needle
Slide 28 - Auer Rods in Leukemia cells
Slide 29 - MPO (right) & Sudan black (left) showing intense localised positivity in blasts
Slide 30 - Confirmation: Immunophenotyping Molecular genetics Cytogenetics: Chromosomal abnormalities
Slide 31 - Other Inv: Coagulation screen, fibrinogen, D- dimer RFT, LFT LDH, Uric acid Urine CXR ECG, ECHO
Slide 32 - Management I. Supportive care : Anemia – red cell transfusion Thrombocytopenia – platelet concentrates Infection – broad spectrum IV antibiotics Hematopoietic growth factors : GM-CSF, G-CSF Barrier nursing Indwelling central venous catheter
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Slide 34 - Metabolic problems : Monitoring hepatic / renal / hematologic function; Fluid & electrolyte balance, nutrition Hyperuricemia- hydration, Allopurinol Psychological support
Slide 35 - The white blood cell count in her peripheral blood was about 550,000. Her bone marrow was packed with leukemia blasts."
Slide 36 - The next thing that occurred was a procedure called leukopheresis.This procedure lasted 4 hours and cut D’s white blood cell (WBC) count in half--to about 250,000.
Slide 37 - She was administered chemotherapy immediately following the leukopheresis procedure. The next day we learned that the chemo had produced an effect as well: The WBC had halved again--125,000.
Slide 38 - SPECIFIC THERAPHY: Chemotherapy : Induction: (4-6 wks) vincristine, prednisone, anthracycline, (idarubicin or daunorubicin) cyclophosphamide, and L-asparaginase
Slide 39 - Consolidation: (multiple cycles of intensive chemotherapy given over a 6 to 9 month period). Cytosine arabinoside, high-dose methotrexate, etoposide anthracycline, (idarubicin or daunorubicin)
Slide 40 - Maintenance phase:(18 to 24 months). LPs with intrathecal MTX every 3 months, Monthly vincristine, Daily 6-MP, and weekly MTX.
Slide 41 - At day 29 of the induction protocol D was declared to be in complete remission. We were all relieved with this news.
Slide 42 - Step two was the next phase of treatment called consolidation therapy. This entailed multiple combinations of drugs administered on a rotational basis (on various weeks) for the next six months.
Slide 43 - For instance, she would receive an infusion of methotrexate for a couple of days and then take 6-MP by mouth for a week. Another cycle included VM-26 (Teniposide) and Ara-C.
Slide 44 - Complete remission ( CR): < 5% blast cells in normocellular bone marrow Autologous BMT : Can be curative in younger patient (< 40-50 yrs)
Slide 45 - Exactly 5 months since her diagnosis, and 16 weeks of remission…"We're at the clinic. D has relapsed. Her white count is 27,000."
Slide 46 - The Consolidation protocol had been dropped and replaced with a new induction protocol. After the bone marrow aspiration to determine the extent of the leukemia relapse, she was given doxirubicin, vincristine and L-asparaginase.
Slide 47 - For several days following D‘s discharge from the bone marrow transplant unit, all of us loaf around the house and recuperate from our 90 day marathon…
Slide 48 - …the first 30 days representing Ds' relapse and the induction therapy to obtain a second remission
Slide 49 - Back in fighting form, D proceeds directly to the final 30 days of the marathon--the actual bone marrow transplant. BMT patients are in a delicate condition following discharge
Slide 50 - Looking back, the nine weeks or so--the post BMT discharge period--was a sublime time for us. D was home and was feeling pretty good.
Slide 51 - As D’s hair began to grow again, we rubbed her head every night at the dinner table, wondering what color it was going to be or if it was going to be curly or straight. We never found out.
Slide 52 - On Monday, March 1, 1999 we went to clinic and waited for the lab results. The results came back as we feared. D had relapsed. Her white count was 47,000. We were devastated.
Slide 53 - III. PALLIATIVE THERAPHY Chemo, RT, Blood product support
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Slide 55 - Prognosis Median survival without treatment is 5 weeks 30% 5-yr survival in younger patients with chemotherapy Disease which relapses during treatment or soon after the end of treatment has a poor prognosis
Slide 56 - Poor prognostic factors Increasing age Male sex High WBC count at diagnosis CNS involvement at diagnosis Cytogenetic abnormalities Antecedent hematological abnormalities (eg. MDS) No complete remission
Slide 57 - Two things that I will always remember about D: She was a collector of many things, trinket boxes, key rings. But she was first and foremost a collector of "FRIENDS."
Slide 58 - Among other things, she wrote: "Hair loss is a side effect of chemotherapy, and cancer is a side effect of life."
Slide 59 - Summary; Learning Points
Slide 60 - THANK YOU