TP53-mutant variant allele frequency and cytogenetics determine prognostic groups in MDS/AML for transplantation

TP53突变变异等位基因频率和细胞遗传学决定MDS/AML移植的预后分组

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Abstract

Results after hematopoietic stem cell transplantation (HSCT) for TP53-mutated myeloid malignancies are disappointing. Several HSCT centers decline to perform HSCT for patients with TP53 mutation because of poor outcomes. In this study, we analyzed 240 patients with TP53-mutated myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) who underwent HSCT. We aimed to identify the patients who benefit most from HSCT. The primary outcome was progression-free survival (PFS). Of the cohort, 52% had AML and the median age was 62 years. AML and MDS outcomes were similar. We identified several favorable prognostic factors for PFS, including absence of complex cytogenetics/5q deletion/7q deletion, a lower variant allele frequency (VAF), a monohit status, and use of a matched-related donor. Using classification and regression tree analysis, we identified VAF and cytogenetics as the 2 most important prognostic factors. Patients with TP53mut VAF ≥ 50% had a 2-year PFS of 3%, and patients with TP53mut VAF < 50% and complex/5q/7q cytogenetic abnormalities had 2-year PFS of 22%. Patients with TP53mut VAF < 50% and without complex/5q/7q cytogenetics had 2-year PFS of 60%. These data inform clinical practice and help patients decide whether to pursue HSCT.

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