Prediction of life-threatening and disabling bleeding in patients with AML receiving intensive induction chemotherapy

Jurjen Versluis, Manu Pandey, Yael Flamand, J. Erika Haydu, Roger Belizaire, Mark Faber, Rahul S. Vedula, Anne Charles, Kevin M. Copson, Shai Shimony, Alon Rozental, Pavan K. Bendapudi, Ofir Wolach, Elizabeth A. Griffiths, James E. Thompson, Richard M. Stone, Daniel J. DeAngelo, Donna Neuberg, Marlise R. Luskin, Eunice S. WangR. Coleman Lindsley*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Bleeding in patients with acute myeloid leukemia (AML) receiving intensive induction chemotherapy is multifactorial and contributes to early death. We sought to define the incidence and risk factors of grade 4 bleeding to support strategies for risk mitigation. Bleeding events were retrospectively assessed between day-14 and day 160 of induction treatment according to the World Health Organization (WHO) bleeding assessment scale, which includes grade 4 bleeding as fatal, life-threatening, retinal with visual impairment, or involving the central nervous system. Predictors were considered pretreatment or prior to grade 4 bleeding. Using multivariable competing-risk regression analysis with grade 4 bleeding as the primary outcome, we identified risk factors in the development cohort (n=341), which were tested in an independent cohort (n=143). Grade 4 bleeding occurred in 5.9% and 9.8% of patients in the development and validation cohort, respectively. Risk factors that were independently associated with grade 4 bleeding included baseline platelet count #40x109/L compared with .40x109/L, and baseline international normalized ratio of prothrombin time (PT-INR) .1.5 or 1.3 . 1.5 compared with #1.3. These variables were allocated points, which allowed for stratification of patients with low- and high-risk for grade 4 bleeding. Cumulative incidence of grade 4 bleeding at day160 was significantly higher among patients with high- vs low-risk (development: 31±7% vs 2±1%; P<.001; validation: 25±9% vs 7±2%; P=.008). In both cohorts, high bleeding risk was associated with disseminated intravascular coagulation (DIC) and proliferative disease. We developed and validated a simple risk model for grade 4 bleeding, which enables the development of rational risk mitigation strategies to improve early mortality of intensive induction treatment.

Original languageEnglish
Pages (from-to)2835-2846
Number of pages12
JournalBlood advances
Issue number9
StatePublished - 10 May 2022


FundersFunder number
American Society of Hematology-Amos Medical Faculty Development
Erasmus Medical Center Foundation-Daniel
National Institutes of HealthK08CA204734, T32HL066987
National Cancer InstituteP50CA206963
Edward P. Evans Foundation
Nederlandse Organisatie voor Wetenschappelijk Onderzoek


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