TP53 and IDH2 Somatic Mutations Are Associated With Inferior Overall Survival After Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrome

Clin Lymphoma Myeloma Leuk. 2017 Nov;17(11):753-758. doi: 10.1016/j.clml.2017.06.003. Epub 2017 Jun 16.


Background: Next-generation sequencing has identified somatic mutations that are prognostic of cancer.

Patients and methods: We evaluated the incidence and prognostic significance of somatic mutations in 89 myelodysplastic syndrome (MDS) patients who received an allogeneic hematopoietic cell transplantation. Next-generation sequencing was performed on paraffin embedded bone marrow, which was obtained at a median of 31 days before initiating the preparative regimen.

Results: The 3 most common subtypes of MDS were refractory anemia with excess blasts (RAEB)-1 (35%), RAEB-2 (29%), and refractory cytopenia with multilineage dysplasia (18%). Most patients (91%) received a myeloablative regimen of fludarabine with intravenous busulfan. Somatic mutations (> 0) were identified in 39 (44%) of analyzed samples. The 6 most commonly identified gene mutations were ASXL1 (8%), DNMT3A (8%), RUNX1 (7%), KRAS (6%), IDH2 (4%), and TP53 (4%). The low incidence of mutations in our study sample might be explained by tissue source and stringent variant-calling methodology. Moreover, we speculate that the low incidence of mutations might, perhaps, also be explained by previous azacitidine treatment in 82% of cases. Multivariate analysis identified TP53 (hazard ratio [HR], 3.82; 95% confidence interval [CI], 1.12-13.09; P = .03) and IDH2 mutations (HR, 4.74; 95% CI, 1.33-16.91; P = .02) as predictors of inferior 3-year overall survival.

Conclusion: This study furthers implementation of clinical genomics in MDS and identifies TP53 and IDH2 as targets for pre- or post-transplant therapy.

Keywords: Next-generation sequencing; Non-relapse mortality; Post-transplant outcomes; Post-transplant relapse; Progression-free survival.

MeSH terms

  • Adult
  • Aged
  • Female
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Male
  • Middle Aged
  • Mutation
  • Myelodysplastic Syndromes / pathology
  • Myelodysplastic Syndromes / surgery*
  • Myelodysplastic Syndromes / therapy*
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous / methods*
  • Tumor Suppressor Protein p53 / genetics*
  • Young Adult


  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • IDH2 protein, human
  • Isocitrate Dehydrogenase