Early mortality in acute myeloid leukemia with KMT2A rearrangement is associated with high risk of bleeding and disseminated intravascular coagulation

Abstract

Background: Acute myeloid leukemia (AML) with rearrangement of lysine methyltransferase 2a gene (KMT2Ar) 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. Methods:In a retrospective analysis, causes and rates of early mortality following induction treatment were compared between a cohort of adults with KMT2Ar AML (N = 172) and an age-matched cohort of patients with normal karyotype AML (N = 522). Results:The 60-day mortality in patients with KMT2Ar AML was 15% compared with 7% with normal karyotype (p = .04). We found a significantly higher occurrence of major bleeding events (p = .005) and total bleeding events (p = .001) in KMT2Ar AML compared with diploid AML. Among evaluable patients with KMT2Ar AML, 93% exhibited overt disseminated intravascular coagulopathy compared with 54% of patients with a normal karyotype before death (p = .03). In a multivariate analysis, KMT2Ar and a monocytic phenotypic were the only independent predictors of any bleeding event in patients who died within 60 days (odds ratio, 3.5; 95% CI, 1.4-10.4; p = .03; odds ratio, 3.2; 95% CI, 1-1-9.4; p = .04, respectively). Conclusion: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 KMT2Ar AML.

Trying to outRun‐DIC in KMT2Ar AML: It's tricky

“…This simultaneous hyperfibrinogenesis and hyperfibrinolysis rapidly consumes the key clotting factors, resulting in consumptive coagulopathy with nearly fatal bleeding complications 9 . In this issue of Cancer , Nguyen and colleagues hypothesize that the early mortality in patients with KMT2A rearranged ( r ) AML is associated with high risk of bleeding and DIC akin to APL 10 . Like APL, KMT2A r AML is a relatively rare subset of AML marked by a characteristic translocation, in this case KMT2A on chromosome 11q23 is rearranged with various fusion partners.…”

“…9 In this issue of Cancer, Nguyen and colleagues hypothesize that the early mortality in patients with KMT2A rearranged (r) AML is associated with high risk of bleeding and DIC akin to APL. 10 Like APL, KMT2Ar AML is a relatively rare subset of AML marked by a characteristic translocation, in this case KMT2A on chromosome 11q23 is rearranged with various fusion partners. However, unlike APL, most cases of KMT2Ar AML are associated with a poor prognosis.…”