Acute Promyelocytic Leukemia - PowerPoint PPT Presentation

View by Category
About This Presentation
Title:

Acute Promyelocytic Leukemia

Description:

Acute Promyelocytic Leukemia Matthew Volk Morning Report 5/21/2010 Epidemiology Incidence of all AML is 3-5/100k APL represents 5-10% of AML In total 600-800 new ALP ... – PowerPoint PPT presentation

Number of Views:862
Avg rating:3.0/5.0
Slides: 18
Provided by: sbur1
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: Acute Promyelocytic Leukemia


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 600-800 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(1517)(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
PML
PML
q22
RARa
RARa
15
17
Chromosome
5
Pathogenesis
  • Defining abnormality is a translocation of
    retinoic acid receptor alpha
  • 95 PML-RARa t(1517)
  • lt5 PLZF-RARa t(1117)
  • 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
Microgranular varient (25)
Hypergranular morphology (75)
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 gt20-30k
  • Maintain fibrinogen gt100-150mg/dl
  • Avoid invasive procedures if possible
  • Start ATRA at preliminary diagnosis

12
Induction Chemotherapy
  • Good functional status ATRA with an
    anthracycline cytarabine
  • Often 73 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 gt10
  • 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 gt40 lt10 98
Intermediate lt40 lt10 89
High Risk lt40 gt10 70
17
References
  • Jurcic, J et al. Diagnosis and Treatment of Acute
    Promyelocytic Leukemia. Current Oncology Reports
    2007, 9337-334
  • MKSAP14 Hematology/Oncology
  • Sanz, M. Management of acute promyelocytic
    leukemia recommendations from an expert panel on
    behalf of the European LeukemiaNet. Blood, 2009,
    1131875-1891
  • Scaglioni PP et al. The theory of APL revisited.
    Curr Top Microbiol Immunol. 200731385-100.
  • Uptodate Online Clinical manifestations,
    pathologic features, and diagnosis of APL in
    Adults and Initial Treatment of APL in Adults
    5/2010
About PowerShow.com