1. Correlation of somatic mutations with outcome after FLAMSA-busulfan sequential conditioning and allogeneic stem cell transplantation in patients with myelodysplastic syndromes.
- Author
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Christopeit, Maximilian, Badbaran, Anita, Alawi, Malik, Zabelina, Tatjana, Zeck, Gaby, Wolschke, Christine, Ayuk, Francis, and Kröger, Nicolaus
- Subjects
HEMATOPOIETIC stem cell transplantation ,MYELODYSPLASTIC syndromes ,BONE marrow transplantation ,GENETIC mutation ,CANCER chemotherapy - Abstract
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 TP53 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). RUNX1, GATA2, TET2, and CEBPA were the genes most frequently found mutated. TP53, 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 TP53. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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