title: Correlation of somatic mutations with outcome after FLAMSA-busulfan sequential conditioning and allogeneic stem cell transplantation in patients with myelodysplastic syndromes.
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.
authors.affiliation: Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Christopeit
authors.affiliation: Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Badbaran
authors.affiliation: Bioinformatics Service Facility, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Malik
authors.initials: M
authors.lastname: Alawi
authors.affiliation: Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Zabelina
authors.affiliation: Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Gaby
authors.initials: G
authors.lastname: Zeck
authors.affiliation: Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Wolschke
authors.affiliation: Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Francis
authors.initials: F
authors.lastname: Ayuk
authors.affiliation: Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015415:Biomarkers; D001853:Bone Marrow / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D011379:Prognosis; D012074:Remission Induction; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D015415:Biomarkers
keywords: allogeneic stem cell transplantation; molecular diagnostics; myelodysplastic syndromes; next-generation sequencing