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Blood. 2017 Mar 30;129(13):1763-1767. doi: 10.1182/blood-2016-10-747170. Epub 2017 Jan 12.

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

Author information

1
Department of Medicine, Hematology Service, and.
2
Department of Epidemiology-Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.
3
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Biostatistics Center, Boston, MA.
4
Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Center, East Melbourne, Australia.
5
Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY.
6
Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, Australia.
7
Department of Hematology, Mayo Clinic, Rochester, MN.
8
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
9
Section of Hematology/Oncology, University of Chicago, Chicago, IL.
10
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
11
Section on Hematology and Oncology, Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC.
12
Health Informatics Institute, University of South Florida, Tampa, FL.
13
Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN.
14
Department of Hematology, Rambam Medical Center, Haifa, Israel.
15
Division of Hematology and Oncology, University of Alabama School of Medicine, Birmingham, AL.
16
Division of Hematology, Stanford University School of Medicine, Stanford, CA.
17
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and.
18
Cancer Research Foundation, Chappaqua, NY.

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 ± 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/μL vs <20 000/μL. In this large cohort of APL patients, high white blood cell count emerged as an independent predictor of early HD.

PMID:
28082441
PMCID:
PMC5374291
DOI:
10.1182/blood-2016-10-747170
[Indexed for MEDLINE]
Free PMC Article

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