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Anaplastic Large Cell Lymphoma PowerPoint Presentation

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On : Feb 24, 2014

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  • Slide 1 - ANAPLASTIC LARGE CELL LYMPHOMA:- a clinico-pathological perspective Lymphoma Meeting – The Alfred Hospital Monday 14th April, 2008 Dr Andrew Guirguis Clinical Haematology Registrar
  • Slide 2 - Outline of presentation Classification Features (including immunophenotype) Clinical features (including prognostic features) Rx modalities Chemo Role of transplantation Novel therapies
  • Slide 3 - Classification One of the T cell lymphomas – nodal (-ve prognostic factor) Haematology 2006 – Therapy of peripheral T/NK neoplasms
  • Slide 4 - And yet many difficulties remain…. What comprises anaplastic large cell lymphoma? Much variation within studies Multiple variants in studies – small cell, large cell, histiocytic, Hodgkin’s like etc Expresses CD30 and EMA (epithelial membrane antigen) – Benharroch et al B-cell antigens – to be included or not to be?? 2 main types:- 1’ systemic* 1’ cutaneous Other:- HIV related, those with lymphomatoid papulosis, mycosis fungoides, Hodgkin’s etc
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  • Slide 6 - Primary systemic ALCL:- Large lymphoid cell neoplasm – pleomorphic nuclei with multiple nucleoli and abundant cytoplasm +ve for CD30 and T cell antigens Not limited to the skin Hallmark cell- Warnke et al
  • Slide 7 - Variants Common type Small cell variant Lymphohistiocytic Hodgkin’s disease like variant (? Nodular sclerosis)** B cell specific activation protein Reclassified by WHO
  • Slide 8 - Immunophenotype T cell markers – including HLA DR, CD25 60% - CD3 / CD 43 / CD45RO Cytogenetics – most have TCR rearrangement; not seen in 20-30% 2;5 translocation – anaplastic lymphoma kinase*
  • Slide 9 - Translocation (2;5) Discovered in late 80s – 20-50% Results in fusion protein of NPM gene and anaplastic lymphoma kinase (ALK)** - activation of TK domain End result:- increased cell proliferation and reduced apoptosis Associated with better prognosis Highly specific to ALCL of T/null type. Rarely seen in other lymphoma types May be fused to other proteins other than NPM ALK protein – more common in children + young adults
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  • Slide 11 - JCO – Molecular Biology of ALCL (Ki +ve) – Kutok et al 2002
  • Slide 12 - Re-classification:- 1’ systemic ALK +ve 1’ systemic ALK –ve 1’ cutaneous ALK -ve Haematology 2001 – T cell and NK cell disorders
  • Slide 13 - Haematology 2001 – T cell and NK cell disorders
  • Slide 14 - Clinically speaking… 2% of all NHL (2nd most common T-cell lymphoma) Occurs in 30s with M > F Bimodal distribution Extranodal involvement
  • Slide 15 - Prognostic factors ALK CD56 +ve International prognostic index Survivin expression Inhibitor of apoptosis family – irrespective of ALK expression – Schlette et all (JCO 2003) High BCL2 expression Caspase 3 (component of pro-death pathways) - +ve
  • Slide 16 - Rx options Much data looks at ALCL under the umbrella of T cell lymphomas Distinction is important Progress is impaired by rarity of the disease, chemoresistance of lymphoma other than ALCL ALK +ve and lack of RCT No clear consensus re optimal Rx
  • Slide 17 - Haematology 2001 – T cell and NK cell disorders
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  • Slide 19 - 2. Risk stratification More well defined in children Not as clear in adults Studies in the adult population to date have not performed this step well!!
  • Slide 20 - Specific Rx Much data in paediatric population:- Trials:- SFOP HM89/91; NHL-BFM90, UKCCSG, AIEOP, POG etc BFM (Berlin Frankfurt Munster) – excellent results using B-cell type Rx – EFS 5yrs of 76%. Cytoreductive phase then stratification according to stage. APO strategy – 70% EFS for advanced stage disease. Anthracycline containing. Induction phase then maintenance.
  • Slide 21 - What about the big people? Usual Rx is multiagent anthracycline containing regimen (5ysr is 60-93% if ALK +ve vs 11-46% for ALK –ve disease) Outcome is inferior to children Poorer Px:- ALK –ve, High IPI, CD56 or survivin +ve
  • Slide 22 - Prospective trial – non randomised (1991-97) N = 36 Rx:- MOPP / EBV / CAD hybrid scheme (mechlorethamine substituted by CCNU alternate cycles, vindesine, melphalan, PNL; then D8 – epidoxorubicin, vincristine + procarbazine; D15 – vinblastine + bleo Chemo each 28 days for 6 cycles +/- XRT Median f’up – 35mo. Max – 7.3yrs Remission rate 78% (CR) for CRT +/- XRT. At 74mo – 69%. No significant difference if XRT used or not! T phenotype treated with CRT + XRT – better survival than B-ALCL. Limitations:- Included B-cell ALCL?? (Haralambieva et al – BJH 2000) No distinction b/w ALK +ve and ALK -ve
  • Slide 23 - What is becoming apparent… ALK+ve do better than ALK-ve (10yr follow-up 82% vs 28% - Falini et al). Of +ve pts – low-intermediate risk IPI vs high/intermediate risk
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  • Slide 25 - Primary Cutaneous ALCL Features:- limited to skin, no extracutaneous disease Histopathology:- large lymphoid cell neoplasm Immunophenotyping:- -ve ALK and EMA; CD30 +ve, CD4+ve Older adults* Solitary lesion or often localised Px favourable long term* Rx:- localised Important to rule out systemic disease with cutaneous spread – 5ysr 29-44% vs 90-100%. If ALK +ve – look for evidence of systemic disease
  • Slide 26 - Should we transplant? Autologous transplant – role in first relapse is accepted as std of care (PARMA study – favour SCT over platinum based chemo) How about CR1? Controversial ? Transplant earlier in those with adverse prognostic factors Again data is difficult to assess – ALCL not looked at alone. PTCL often looked at as one entity*
  • Slide 27 - Autologous hematopoietic SCT in peripheral T cell lymphoma using uniform high dose regimen – Smith et al – BMT 07 N=32 (PTCL unspecified 11 and ALCL 21). ASCT for 1’ refractory disease (no response to Rx or progression) or relapse 6 pts in CR1/PR1, 8 for 1’ refractory; 17 for relapsed, 1 uknown CR1/PR1 patients – all received anthracycline based chemo For relapse – salvage chemo given Transplant – busulfan (1mg/kg QID x 14), etoptoside (60mg/kg IV), cyclophos (60mg/kg IV for 2 days)
  • Slide 28 - Results:- Median follow-up 30 mo 5ysr OS 34%; RFS 18% - very poor! No significant difference b/w OS and RFS – for ALCL and PTCL-us No significant difference b/w OS based on disease status at time of transplant. Limitations:- ? Too small ALK status not looked at. Fanin et al – 64 ALCL pts – inferior survival in those transplanted post relapse or refractory ALCL cf first remission. Again no’s too small and ? ALK status
  • Slide 29 - Present recommendations? If ALK +ve – do not routinely transplant in CR1. If relapse – salvage chemo and SCT. Esp not recommended if IPI is low. For ALK+ve and high IPI – consider stem cell support. ALK-ve pts – consider early SCT
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  • Slide 31 - Allogeneic transplants Case reports in children Would expect fewer relapses Higher mortality rates during conditioning.
  • Slide 32 - Newer agents ? ALK inhibitors (Blood 06) ? SGN30 – antiCD30 (JCO 07 – Ansell et al – Phase I/II studies)
  • Slide 33 - References:- 1. Dx + Rx of childhood NHL – ASH 07 – Reiter 2. Should adolescents with NHL be treated as old children or young adults? Sandlund – ASH Haem 07 3. T cell and NK cell lymphoproliferative disorders – Haem 01 4. Therapy of peripheral T / NK neoplasm’s – Haem 06 5. Aggressive Peripheral T cell lymphomas – Haem 05 6. Auto hematopoietic SCT in peripheral T cell lymphoma using uniform high dose regimen – Smith et al – BMT 2007 7. Clinical characteristics, Rx outcome and survival of 36 adult pts with 1’ ALCL, Haematologica 1999 8. Phase I/II study of an anti-CD30 monoclonal antibody in HL + ALCL CD30 anaplastic large cell lymphoma:- a review of its histopathologic, genetic and clinical features. 9. 1’ systemic CD30+ve anaplastic LCL in the adult: sequential intensive Rx with F-MACHOP regimen +/- XRT and ABMT – Fanin et al – Blood 1996

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