Determinants of fatal bleeding during induction therapy for acute promyelocytic leukemia in the ATRA era Journal Article


Authors: Mantha, S.; Goldman, D. A.; Devlin, S. M.; Lee, J. W.; Zannino, D.; Collins, M.; Douer, D.; Iland, H. J.; Litzow, M. R.; Stein, E. M.; Appelbaum, F. R.; Larson, R. A.; Stone, R.; Powell, B. L.; Geyer, S.; Laumann, K.; Rowe, J. M.; Erba, H.; Coutre, S.; Othus, M.; Park, J. H.; Wiernik, P. H.; Tallman, M. S.
Article Title: Determinants of fatal bleeding during induction therapy for acute promyelocytic leukemia in the ATRA era
Abstract: Acute promyelocytic leukemia (APL) is commonly complicated by a complex coagulopathy. Uncertainty remains as to which markers of bleeding risk are independent predictors. Drawing from 5 large clinical trials that included all-trans retinoic acid (ATRA) as part of induction, we assessed known determinants of bleeding at baseline and evaluated them as potential predictors of hemorrhagic death (HD) in the first 30 days of treatment. The studies included were ALLG APML3 (single arm of ATRA + idarubicin 6 prednisone), ALLG APML4 (single arm of ATRA + idarubicin + arsenic trioxide + prednisone), CALGB C9710 (single arm of ATRA + cytarabine + daunorubicin), Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) E2491 (intergroup I0129, consisting of daunorubicin + cytarabine vs ATRA), and SWOG S0521 (single-arm induction of ATRA + cytarabine + daunorubicin). A total of 1009 patients were included in the original trials, of which 995 had sufficient data to be included in our multivariate analysis. In this final cohort, there were 37 HD cases during the first 30 days following induction, for an estimated cumulative incidence of 3.7% (95% confidence interval [CI], 2.6% to 5.0%). Using multivariate Cox proportional hazards regression, the hazard ratio of HD in the first 30 days was 2.17 (95% CI, 0.84-5.62) for an ECOG performance status of 3-4 vs 0-2 and 5.20 (95% CI, 2.70-10.02) for a white blood cell count of >= 20 000/mu L vs < 20 000/mu L. In this large cohort of APL patients, high white blood cell count emerged as an independent predictor of early HD.
Keywords: chemotherapy; maintenance therapy; arsenic trioxide; remission; idarubicin; prognostic-factors; induction; consolidation; trans-retinoic acid; initial therapy; early death rate
Journal Title: Blood
Volume: 129
Issue: 13
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2017-03-30
Start Page: 1763
End Page: 1767
Language: English
ACCESSION: WOS:000397776800008
DOI: 10.1182/blood-2016-10-747170
PROVIDER: wos
PMCID: PMC5374291
PUBMED: 28082441
Notes: Article -- Source: Wos
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MSK Authors
  1. Martin Stuart Tallman
    408 Tallman
  2. Jae Hong Park
    132 Park
  3. Dan Douer
    80 Douer
  4. Debra Alyssa Goldman
    92 Goldman
  5. Sean McCarthy Devlin
    288 Devlin
  6. Simon H Mantha
    29 Mantha