Correlation of somatic mutations with outcome after FLAMSA‐busulfan sequential conditioning and allogeneic stem cell transplantation in patients with myelodysplastic syndromes

Allogeneic hematopoietic stem cell transplantation (allo‐ HSCT ) is a curative treatment option for myelodysplastic syndromes ( MDS ). Little is known about the prognostic impact of mutations, for example, in TP 53 specifically after allo‐ HSCT . We here describe the prognostic impact of mutations in a panel of 19 genes analyzed by amplicon‐based next‐generation‐sequencing in a uniformly treated patient cohort. Sixty‐two patients with a median age of 61 yr suffered from MDS with 0–20% bone marrow blasts. International Prognostic Score was intermediate 1 (15%) and higher (79%). Conditioning uniformly was performed using a sequential approach in which FLAMSA chemotherapy was followed by Busulfan‐based conditioning. Patients mostly were transplanted from an unrelated donor (77%), and 36% of patients received a graft from a mismatched donor. Median number of mutations was 2 (range 0–6). RUNX 1 , GATA 2 , TET 2 , and CEBPA were the genes most frequently found mutated. TP 53 , a factor previously reported to confer adverse prognostic impact after allogeneic stem cell transplantation, was mutated in samples from eight patients, one of which showed a silent mutation. With an estimated 5‐yr overall/disease‐free survival of 48 ± 7%/41 ± 7%, none of the mutations analyzed showed a prognostic impact in this analysis of the largest uniformly treated cohort thus far. This especially holds true for patients with a mutation in TP 53 .