Acute Promyelocytic Leukemia

Matthew VolkMorning Report5/21/2010

Epidemiology

Incidence of all AML is 3-5/100k APL represents 5-10% of AML In total 600-800 new ALP cases/year Incidence of APL is highest in young

adults

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

Pathogenesis

q22q12

#15 #17Chromosome

t(15,17)(q22,q12)

PML

RARa

PML

RARa

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

Presentation

Pancytopenia Anemia - weakness Neutropenia – severe infections Thrombocytopenia – mucosal or GI

bleeding, ecchymosis. Coagulopathy

Severe bleeding Promyelocytes in peripheral blood

Peripheral Smear

Hypergranular morphology(75%)

Microgranular varient(25%)

Bone Marrow Biopsy

Aspirate above (hypergranular morphology) shows multiple Auer rods (“faggot cells”)

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”

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

Supportive Therapy

Coagulopathy/DIC – very common with APL Maintain platelets >20-30k Maintain fibrinogen >100-150mg/dl Avoid invasive procedures if possible Start ATRA at preliminary diagnosis

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

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

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

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)

Prognosis

Chronic remission achieved in 80-95% of patients

Platelet count

WBC count

3-yr relapse-free survival

Low Risk >40 <10 98%

Intermediate <40 <10 89%

High Risk <40 >10 70%

References

Jurcic, J et al. Diagnosis and Treatment of Acute Promyelocytic Leukemia. Current Oncology Reports 2007, 9:337-334

MKSAP14 Hematology/Oncology Sanz, M. Management of acute promyelocytic leukemia:

recommendations from an expert panel on behalf of the European LeukemiaNet. Blood, 2009, 113:1875-1891

Scaglioni PP et al. The theory of APL revisited. Curr Top Microbiol Immunol. 2007;313:85-100.

Uptodate Online – “Clinical manifestations, pathologic features, and diagnosis of APL in Adults” and “Initial Treatment of APL in Adults” 5/2010