Adult Acute leukemia. Matthew Seftel. August

Transcription

1 Adult Acute leukemia Matthew Seftel August

2 Principles 3 cases Diagnosis and classification of acute leukemia (AL) Therapy Emergencies Remission induction BMT Complications Palliation

3 leukemia

4 Hematological malignancy Myeloid Lymphoid Chronic myeloid disorders Acute myeloid leukemia (AML) Acute lymphoblastic leukemia (ALL) Other Lymphoid disorders Myeloproliferative disorders Chronic myeloid leukemia (CML) Chronic lymphocytic Leukemia (CLL) Multiple myeloma Myelodysplasia Lymphoma

5 Hematopoiesis 101 Marrow Myeloid Stem cell Progenitor cell Lymphoid Stem cell Red cell Neutrophil Basophil Lymphocyte Plasma cell Platelets Eosinophil Monocyte Blood

6 Hematopoiesis 201 Lymphoid stem cell Pre-B B Lymphocyte T Lymphocyte Grans / Monos PSC CFU- GEMM BFU-E CFU-E Erythrocytes Mega Platelets

7 Examples of malignant counterparts ALL B Lymphocyte CML Pre-B T Lymphocyte PSC CFU- GEMM BFU-GM Burkitt Lymphoma AML Grans / Monos Erythrocytes BFU-E CFU-E Mega Platelets

8 Leukemia incidence SEER: - accessed August 2007

9 AML classification FAB (1976) WHO (2002) M0 - undifferentiated M1 - without maturation M2 - with maturation M3 - promyelocytic M4 - myelomonocytic M5 - monocytic M6 - erythroleukemia M7 - megakaryoblastic Recurrent cytogenetic abnormalities t(15;17) t(8;21) Inv(16) 11q23 Multilineage dysplasia Therapy related Alkylator Topoisomerase Other AML NOS

10 ALL classification (WHO) Precursor B lymphoblastic leukaemia/ lymphoma (precursor B - ALL) Precursor T lymphoblastic leukaemia/ lymphoma (precursor T - ALL) Harris N et al, J Clin Oncol 1999

11 55 year man Case 1 2 w bruising, gum bleeding PMH: HTN Meds: ASA, HCTZ WBC 3 x 10 9 /l, HB 62g/l, platelets 48x10 9 /l ANC 1.1x10 9 /l Differential diagnosis?

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14 Blood

15 Marrow

16 Case 1 Diagnosis? Confirmatory tests? Immediate Rx? Definitive Rx?

17 Hematological malignancy Myeloid Lymphoid Chronic myeloid disorders Acute myeloid leukemia (AML) Acute lymphoblastic leukemia (ALL) Other Lymphoid disorders Myeloproliferative disorders Chronic myeloid leukemia (CML) Chronic lymphocytic Leukemia (CLL) Multiple myeloma Myelodysplasia Lymphoma

18 AML classification FAB (1976) WHO (2002) M0 - undifferentiated M1 - without maturation M2 - with maturation M3 - promyelocytic M4 - myelomonocytic M5 - monocytic M6 - erythroleukemia M7 - megakaryoblastic Recurrent cytogenetic abnormalities t(15;17) t(8;21) Inv(16) 11q23 Multilineage dysplasia Therapy related Alkylator Topoisomerase Other AML NOS

19 APML survival Ades L et al, J Clin Oncol 2006

20 72 year woman Case 2 PMH breast cancer 1998 surgery, adjuvant AC 1 month fatigue, fever, back pain 38.2 * C, pallor, gingival swelling WBC 43 x 10 9 /l, HB 88g/l, platelets 21x10 9 /l Blasts 38 x10 9 /l, ANC 1.1x10 9 /l, MCV 104fl

21 Case 2 Blood

22 Case 2 Marrow

23 Case 2 Diagnosis? Confirmatory tests? Immediate Rx? Definitive Rx?

24 Hematological malignancy Myeloid Lymphoid Chronic myeloid disorders Acute myeloid leukemia (AML) Acute lymphoblastic leukemia (ALL) Other Lymphoid disorders Myeloproliferative disorders Chronic myeloid leukemia (CML) Chronic lymphocytic Leukemia (CLL) Multiple myeloma Myelodysplasia Lymphoma

25 AML classification FAB (1976) WHO ( 2002) M0 - undifferentiated M1 - without maturation M2 - with maturation M3 - promyelocytic M4 - myelomonocytic M5 - monocytic M6 - erythroleukemia M7 - megakaryoblastic Recurrent cytogenetic abnormalities t(15;17) t(8;21) Inv(16) 11q23 Multilineage dysplasia Therapy related Alkylator Topoisomerase Other AML NOS

26 Case 2 Therapy 7 +3 remission induction Well until Day C, rash, pulmonary infiltrate Work-up? Treatment?

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29 Survival for elderly AML: UK Goldstone AH et al Blood 98: (2001)

30 AML: survival over time * 1970s 1990s <60 yrs 10% >50% >60yrs 5% 15% * 5 year survival

31 Case 3 55 year old social worker Fatigue, aches and pains x 1 month 37.8C, pale, splenomegaly WBC 2.6x10 9 /l, Hb 92g/l, Plts 110x10 9 /l LDH 600IU 4 healthy sibs

32 Case 3 Marrow aspirate

33 Case 3 Flow cytometry

34 Case 3 Karyotype

35 Hematological malignancy Myeloid Lymphoid Chronic myeloid disorders Acute myeloid leukemia (AML) Acute lymphoblastic leukemia (ALL) Other Lymphoid disorders Myeloproliferative disorders Chronic myeloid leukemia (CML) Chronic lymphocytic Leukemia (CLL) Multiple myeloma Myelodysplasia Lymphoma

36 ALL classification (WHO) Precursor B lymphoblastic leukaemia/ lymphoma (precursor B - ALL) Precursor T lymphoblastic leukaemia/ lymphoma (precursor T - ALL) Harris N et al, J Clin Oncol 1999

37 Case 3 Blood film 2 months ago

38 Examples of malignant counterparts ALL B Lymphocyte CML Pre-B T Lymphocyte PSC CFU- GEMM BFU-GM Burkitt Lymphoma AML Grans / Monos Erythrocytes BFU-E CFU-E Mega Platelets

39 Case 3 Received NCIC AL.4 regimen Acute tumor lysis syndrome on day 2 Complete remission at day 28 Imatinib mesylate x 2 months Reversion to chronic phase CML Sibling allo-bmt 2 months later In CR 1 year later with chronic GVHD

40 Overall survival for adult ALL in Manitoba By r egi men Other Palliative Mont hs p- val ue< STRATA: r egi men=all89_1 Censor ed r egi men=all89_1 regimen=ot her r egi men Censor ed r egi men=ot her r egi men regimen=pal l i at i ve

41 Therapeutic choices in AL Chemo Auto Allo-related Allo-UD Availability Relapse risk Safety Infertility Preserves Other Rx options

42 Conclusions Diagnosis and classification of acute leukemia (AL) Therapy Emergencies Remission induction BMT Complications Palliative