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
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
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