Allogeneic stem cell transplantation in patients with myelofibrosis harboring the MPL mutation

Eur J Haematol. 2019 Dec;103(6):552-557. doi: 10.1111/ejh.13318. Epub 2019 Sep 16.

Abstract

Introduction: Primary and post-ET/PV myelofibrosis are myeloproliferative neoplasms harboring in most cases driving mutations in JAK2, CALR or MPL, and a variable number of additional mutations in other genes. Molecular analysis represents a powerful tool to guide prognosis and clinical management. Only about 10% of patients with myelofibrosis harbor alterations in MPL gene. No data are available about the transplantation outcome in the specific MPL-mutated group.

Patients: We collected the data of 18 myelofibrosis patients(primary: 14; post-ET: 4) transplanted in 4 EBMT centers (Hamburg, Paris, Essen, and Hannover) between 2005 and 2016.

Results: Before the transplant, we explored the molecular profile by NGS and reported the frequency of mutations occurring in a panel of genes including JAK2, MPL, CALR, U2AF1, SRSF2, SF3B1, ASXL1, IDH1, IDH2, CBL, DNMT3A, TET2, EZH2, TP53, IKZF1, NRAS, KRAS, FLT3, SH2B3, and RUNX1. The 1-year transplant-related mortality was 16.5%, 5-years overall survival and 5-y relapse-free survival 83.5%. The only relapse occurred in a patient who harbored mutations in both ASXL1 and EZH2 genes.

Conclusion: These retrospective data suggest that MPL-mutated myelofibrosis patients have a favorable outcome after allogeneic transplantation with very low rate of disease relapse (5.5%) in comparison with the available historical controls regarding myelofibrosis in all.

Keywords: bone marrow transplantation; molecular biology of myelopoiesis; myelofibrosis with myeloid metaplasia; transplantation.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Allografts
  • Disease-Free Survival
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Primary Myelofibrosis / genetics*
  • Primary Myelofibrosis / mortality*
  • Primary Myelofibrosis / therapy*
  • Receptors, Thrombopoietin / genetics*
  • Retrospective Studies
  • Survival Rate

Substances

  • Receptors, Thrombopoietin
  • MPL protein, human