Two Mutations Prognostic of Survival in Acute Myeloid Leukemia Regardless of Hematopoietic Stem Cell Transplantation

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Internal tandem duplications in FLT3 and mutations in CEBPA were independently prognostic of overall survival in patients with acute myeloid leukemia.
Internal tandem duplications in FLT3 and mutations in CEBPA were independently prognostic of overall survival in patients with acute myeloid leukemia.

Of the various genetic mutations associated with acute myeloid leukemia (AML), internal tandem duplications in FLT3 (FLT3-ITD) and mutations in CEBPA were found to be predictors of prognosis in patients with AML regardless of whether they had undergone hematopoietic stem cell transplantation (HSCT), according to study findings published in Biology of Blood and Marrow Transplantation.

Researchers in China assessed the effects of cytogenetic changes and gene mutations on clinical outcomes in 977 patients with AML who were enrolled at the First Affiliated Hospital of Soochow University in China between 2006 and 2016.

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Subsets of these patients had mutations previously associated with AML, including mutations in CEBPA (16.4%), FLT3-ITD (18.5%), NPM1 (17.9%), FLT3-TKD (3.9%), DNMT3A (8.6%), and C-KIT (8.8%). Nearly half (49.2%) had undergone consolidation HSCT.

Adverse karyotype (P =.001, hazard ratio [HR] 1.48), receiving nonstandard first-line induction chemotherapy (P =.003, HR 1.45), and the presence of FLT3-ITD (P <.001, HR 1.90) were prognostic of inferior overall survival (OS). The presence of a mutation in CEBPA (P <.001, HR 0.42) or undergoing HSCT (P <.001, HR 0.35) was associated with superior OS.

In addition, the presence of FLT3-ITD was an independent risk factor for poor disease-free survival (P <.001; HR 2.11), while undergoing HSCT was an independent factor for superior disease-free survival (P =.046; HR 0.74).

Patients who underwent HSCT for consolidation experienced a better prognosis than patients who received chemotherapy as consolidation, suggesting that undergoing HSCT may allow patients to overcome the negative prognosis associated with abnormal karyotype at initial diagnosis.

Reference

1. Wang H, Chu TT, Han SY, et al. FLT3-ITD and CEBPA mutations predict prognosis in acute myeloid leukemia irrespective of hematopoietic stem cell transplantation [published online November 29, 2018]. Biol Blood Marrow Transplant. doi:10.1016/j.bbmt,2018.11.031

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