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

Eur J Haematol. 2016 Sep;97(3):288-96. doi: 10.1111/ejh.12724. Epub 2016 Feb 15.

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.

Keywords: allogeneic stem cell transplantation; molecular diagnostics; myelodysplastic syndromes; next-generation sequencing.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers
  • Bone Marrow / pathology
  • DNA Mutational Analysis
  • Female
  • Graft vs Host Disease / etiology
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Mutation*
  • Myelodysplastic Syndromes / diagnosis
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / mortality
  • Myelodysplastic Syndromes / therapy*
  • Prognosis
  • Remission Induction
  • Transplantation Conditioning*
  • Transplantation, Homologous

Substances

  • Biomarkers