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Acute Promyelocytic Leukemia Matthew Volk Morning Report 5/21/2010.

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Presentation on theme: "Acute Promyelocytic Leukemia Matthew Volk Morning Report 5/21/2010."— Presentation transcript:

1 Acute Promyelocytic Leukemia Matthew Volk Morning Report 5/21/2010

2 Epidemiology  Incidence of all AML is 3-5/100k  APL represents 5-10% of AML  In total new ALP cases/year  Incidence of APL is highest in young adults

3 Classification  WHO Classification of AML AML with recurrent genetic abnormalities  APL with t(15;17)(q22,q12); PML-RARA (previously known as AML M3 by FAB) AML with MDS-related features Therapy-related AML and MDS AML not otherwise specified

4 Pathogenesis q22 q12 #15#17 Chromosome t(15,17)(q22,q12) PML RARa PML RARa

5 Pathogenesis  Defining abnormality is a translocation of retinoic acid receptor alpha 95% PML-RARa – t(15;17) <5% PLZF-RARa – t(11;17)  Physiologic quantities of retinoic acid no longer sufficient to allow for cell differentiation

6 Presentation  Pancytopenia Anemia - weakness Neutropenia – severe infections Thrombocytopenia – mucosal or GI bleeding, ecchymosis.  Coagulopathy Severe bleeding  Promyelocytes in peripheral blood

7 Peripheral Smear Hypergranular morphology (75%) Microgranular varient (25%)

8 Bone Marrow Biopsy Aspirate above (hypergranular morphology) shows multiple Auer rods (“faggot cells”)

9 Cytogenetics  Karyotype Detects translocation variant  FISH or immunostaining Fast – often within 2-4 hours Immunostaining is inexpensive and can be done at smaller centers  RT-PCR Can detect residual disease “Gold Standard”

10 Supportive Therapy  Severe Cytopenias Transfuse irradiated blood products Note: pRBCs can worsen coagulopathy  Neutropenic Fever Start broad spectrum abx (vanc/ceftaz)  Tumor Lysis - rare with APL replete electrolytes, hydrate, allopurinol, rasburicase

11 Supportive Therapy  Coagulopathy/DIC – very common with APL Maintain platelets >20-30k Maintain fibrinogen > mg/dl Avoid invasive procedures if possible Start ATRA at preliminary diagnosis

12 Induction Chemotherapy  Good functional status – ATRA with an anthracycline + cytarabine Often “7+3” with daily ATRA  Elderly/frail patients – ATRA with arsenic trioxide  Bone marrow performed either at count recovery or day 90

13 Hyperleukocytosis  Can develop after initiation of ATRA Develops in 50% of patients induced with single-agent ATRA High risk if initial WBC count >10  Treatment Cytotoxic chemotherapy Hydroxyurea may help Prophylactic steroids to prevent differentiation syndrome

14 Differentiation Syndrome  Develops 2-21 days post induction with ATRA Up to 25% incidence Fever, peripheral edema, pulmonary infiltrates, renal/hepatic failure, serositis with effusions  Treatment Dexamathasone 10mg iv q12h x 3 days Hold ATRA for severe symptoms

15 Consolidation/Maintenance  Consolidation – optimal regimen still undefined ATRA + anthracycline +/- cytarabine Additional cycles of arsenic trioxide Goal: negative RT-PCR on marrow  Maintenance therapy Intermittent ATRA + 6-MP + MTX (1 yr) Follow with RT-PCR (3 yrs)

16 Prognosis  Chronic remission achieved in % of patients Platelet count WBC count 3-yr relapse- free survival Low Risk>40<1098% Intermediate<40<1089% High Risk<40>1070%

17 References  Jurcic, J et al. Diagnosis and Treatment of Acute Promyelocytic Leukemia. Current Oncology Reports 2007, 9:  MKSAP14 Hematology/Oncology  Sanz, M. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood, 2009, 113:  Scaglioni PP et al. The theory of APL revisited. Curr Top Microbiol Immunol. 2007;313: Scaglioni PP  Uptodate Online – “Clinical manifestations, pathologic features, and diagnosis of APL in Adults” and “Initial Treatment of APL in Adults” 5/2010

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