TY - JOUR
T1 - Early mortality in acute myeloid leukemia with KMT2A rearrangement is associated with high risk of bleeding and disseminated intravascular coagulation
AU - Nguyen, Daniel
AU - Kantarjian, Hagop M.
AU - Short, Nicholas J.
AU - Qiao, Wei
AU - Ning, Jing
AU - Cuglievan, Branko
AU - Daver, Naval G.
AU - DiNardo, Courtney D.
AU - Jabbour, Elias J.
AU - Kadia, Tapan M.
AU - Borthakur, Gautam
AU - Garcia-Manero, Guillermo
AU - Konopleva, Marina Y.
AU - Andreeff, Michael
AU - Ravandi-Kashani, Farhad
AU - Sasaki, Koji
AU - Issa, Ghayas C.
N1 - Publisher Copyright:
© 2023 American Cancer Society.
PY - 2023/6/15
Y1 - 2023/6/15
N2 - 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. Plain Language Summary: Acute myeloid leukemia (AML) with rearrangement of KMT2A 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. In this article, that KMT2A-rearranged AML is demonstrably associated with higher early mortality and an increased risk of bleeding and coagulopathy, specifically, disseminated intravascular coagulation, compared with normal karyotype AML. These findings emphasize the importance of monitoring and mitigating coagulopathy in KMT2A-rearranged leukemia similar to what is done in acute promyelocytic leukemia.
AB - 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. Plain Language Summary: Acute myeloid leukemia (AML) with rearrangement of KMT2A 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. In this article, that KMT2A-rearranged AML is demonstrably associated with higher early mortality and an increased risk of bleeding and coagulopathy, specifically, disseminated intravascular coagulation, compared with normal karyotype AML. These findings emphasize the importance of monitoring and mitigating coagulopathy in KMT2A-rearranged leukemia similar to what is done in acute promyelocytic leukemia.
KW - AML
KW - APL
KW - bleeding
KW - DIC
KW - early mortality
KW - KMT2A
KW - MLL
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U2 - 10.1002/cncr.34728
DO - 10.1002/cncr.34728
M3 - Article
C2 - 36892949
AN - SCOPUS:85150489098
SN - 0008-543X
VL - 129
SP - 1856
EP - 1865
JO - Cancer
JF - Cancer
IS - 12
ER -