Adult Acute leukemia Matthew Seftel August 21 2007 mseftel@cancercare.mb.ca
Principles 3 cases Diagnosis and classification of acute leukemia (AL) Therapy Emergencies Remission induction BMT Complications Palliation
leukemia
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
Hematopoiesis 101 Marrow Myeloid Stem cell Progenitor cell Lymphoid Stem cell Red cell Neutrophil Basophil Lymphocyte Plasma cell Platelets Eosinophil Monocyte Blood
Hematopoiesis 201 Lymphoid stem cell Pre-B B Lymphocyte T Lymphocyte Grans / Monos PSC CFU- GEMM BFU-E CFU-E Erythrocytes Mega Platelets
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
Leukemia incidence SEER: http://seer.cancer.gov/csr/ - accessed August 2007
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
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
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?
Blood
Marrow
Case 1 Diagnosis? Confirmatory tests? Immediate Rx? Definitive Rx?
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
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
APML survival Ades L et al, J Clin Oncol 2006
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
Case 2 Blood
Case 2 Marrow
Case 2 Diagnosis? Confirmatory tests? Immediate Rx? Definitive Rx?
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
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
Case 2 Therapy 7 +3 remission induction Well until Day 16 38.8C, rash, pulmonary infiltrate Work-up? Treatment?
Survival for elderly AML: UK Goldstone AH et al Blood 98:1302-1311 (2001)
AML: survival over time * 1970s 1990s <60 yrs 10% >50% >60yrs 5% 15% * 5 year survival
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
Case 3 Marrow aspirate
Case 3 Flow cytometry
Case 3 Karyotype
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
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
Case 3 Blood film 2 months ago
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
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
Overall survival for adult ALL in Manitoba 1. 00 By r egi men 0. 75 0. 50 Other 0. 25 89-1 Palliative 0. 00 0 50 100 150 200 250 300 Mont hs p- val ue<0. 0001 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
Therapeutic choices in AL Chemo Auto Allo-related Allo-UD Availability ++++ +++ ++ + Relapse risk ++++ +++ ++ + Safety ++++ +++ ++ + Infertility + +++ +++ +++ Preserves +++ ++ + + Other Rx options
Conclusions Diagnosis and classification of acute leukemia (AL) Therapy Emergencies Remission induction BMT Complications Palliative