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• W2912870107 abstract "Introduction Allogeneic hematopoietic stem cells transplant (HSCT) is a curative treatment for acute myeloid leukemia (AML). The persistence of disease-associated somatic mutations following HSCT for myelodysplastic syndrome has been shown to be associated with a high risk of disease progression. While a recent study in AML found that the presence of somatic mutations at day 21 post-HSCT is associated with higher risk of relapse, there is paucity of data at a later time point. We hypothesized that persistence of mutations at day 100 resulted in increased relapse rates and inferior outcomes than in patients who had cleared their mutations. Methods All adult patients with AML, diagnosed in 2016-2017, who underwent allogeneic HSCT, were included in the study. Somatic mutations in diagnostic and post-transplantation bone marrow specimens were detected by a 97-gene next generation sequencing (NGS) assay. Baseline characteristics including age, sex, risk stratification, type of transplant, conditioning regimen and presence of acute and chronic graft-versus-host disease (GHVD) were collected. We evaluated somatic mutations in bone marrow samples obtained 100 days after transplantation (T+100). Results We identified 32 patients, four had no detectable mutations in the diagnostic bone marrow NGS and were excluded from the analysis. Most patients were >60 years with male-predominance (68%). Fourteen (50%) patients fell into the poor-risk AML category. Twenty eight (87.5%) patients had at least one mutation in the diagnostic bone marrow; the mean number of mutations at diagnosis was 3 (1-11). FLT3, NPM1, RUNX1, TET2, RAS and ASXL-1 were the most common mutations. Eighteen patients (64%) underwent matched unrelated HSCT and 15 (54%) had reduced-intensity conditioning (RIC) chemotherapy. Twenty three (82%) out of 28 patients had no detectable mutations in the day 100 bone marrow. All five patients with persistent mutations at T+ 100 had evidence of disease relapse. The T+100 bone marrow demonstrated evidence of relapse in two patients while the other three relapsed after a median of 6.53 months from transplant. This compared to a relapse rate of 17% in patients with no detectable mutations at T+100 (p=0.001, Fisher-Exact test). Median progression-free survival (PFS) was longer in patients who had no mutations at day 100 compared to those with persistent mutations (15.03 months vs. 5.50 months). Conclusions Our data show, that the persistence of somatic mutations at T+100 after allogeneic HCT can predict relapse. While the number of patients in this study is limited, the signal observed is significant and expansion of this analysis to a larger study is warranted, as identification of this high-risk population for relapse potentially allows for the initiation of early post-transplantation intervention strategies." @default.
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• W2912870107 date "2019-03-01" @default.
• W2912870107 modified "2023-09-27" @default.
• W2912870107 title "Clinical Outcomes and Persistence of Somatic Mutations in Acute Myeloid Leukemia Patients after Transplantation" @default.
• W2912870107 doi "https://doi.org/10.1016/j.bbmt.2018.12.378" @default.
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