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 t(15,17)(q22,q12) q12 q22 #15 #17 Chromosome PML 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 Coagulopathy
Anemia - weakness
Neutropenia – severe infections
Thrombocytopenia – mucosal or GI bleeding, ecchymosis.
Coagulopathy
Severe bleeding
Promyelocytes in peripheral blood

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

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

9. Cytogenetics Karyotype FISH or immunostaining RT-PCR
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 Neutropenic Fever
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 Treatment
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 80-95% of patients
Platelet count
WBC count
3-yr relapse-free survival
Low Risk
>40
<10
98%
Intermediate
<40
89%
High Risk
>10
70%

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