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KMT2A Rearrangement in AML Linked with Early Mortality, Increased Risk of Bleeding


By Cecilia Brown - March 23, 2023

Acute myeloid leukemia (AML) with rearrangement of the gene encoding lysine methyltransferase 2a (KMT2A) is associated with a higher rate of early mortality and an increased risk of bleeding and coagulopathy compared with normal karyotype AML.

Daniel Nguyen, MD, PhD, of the McGovern Medical School at the University of Texas Health Science Center at Houston and the University of Texas MD Anderson Cancer Center and colleagues conducted the research and published their findings in Cancer.

They conducted the study because AML with KMT2A rearrangement is “characterized by chemotherapy resistance and high rates of relapse.”

“However, additional causes of treatment failure or early mortality have not been well defined in this entity,” Dr. Nguyen and colleagues wrote.

They conducted a retrospective analysis to compare the causes and rates of early morality after induction treatment in patients with AML who had a KMT2A rearrangement (n=172) and those with normal karyotypes (n=522).

The 60-day mortality rate was around twice as high in patients with KMT2A rearrangement (15%) compared with those who had a normal karyotype (7%; P=.04). Patients with KMT2A rearrangement had a significantly higher occurrence of major bleeding events (P=.005) and total bleeding events than those with diploid AML.

Nearly all (93%) evaluable patients with KMT2A rearrangement exhibited overt disseminated intravascular coagulopathy, compared with 54% of patients who had a normal karyotype before death (P=.03).

Furthermore, a multivariate analysis showed KMT2A rearrangement (odds ratio [OR], 3.5; 95% CI, 1.4-10.4; P=.03) and a monocytic phenotypic (OR, 3.2; 95% CI, 1.1-9.4; P=.04) were the only independent predictors of any bleeding event in patients who died within 60 days.

“In conclusion, early recognition and aggressive management of disseminated intravascular coagulopathy and coagulopathy are important considerations that could mitigate the risk of death during induction treatment in KMT2A [rearrangement] AML,” Dr. Nguyen and colleagues wrote.


Nguyen D, Kantarjian HM, Short NJ, et al. Early mortality in acute myeloid leukemia with KMT2A rearrangement is associated with high risk of bleeding and disseminated intravascular coagulation. Cancer. 2023. doi:10.1002/cncr.34728


Original Source: KMT2A Rearrangement in AML Linked with Early Mortality, Increased Risk of Bleeding | Blood Cancers Today

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