Is allogeneic stem cell transplantation for myelofibrosis still indicated at the time of molecular markers and JAK inhibitors era?

Eur J Haematol. 2017 Jul;99(1):60-69. doi: 10.1111/ejh.12891. Epub 2017 May 5.

Abstract

Objective: The role of allogenic stem cell transplantation (ASCT) is still debated in myelofibrosis (MF).

Methods: A retrospective analyzed was performed to compare the outcome of 71 patients with intermediate-2 or high-risk Dynamic International Prognosis Scoring System+ (DIPSS+) primary (PMF) or secondary (SMF) myelofibrosis with an indication of ASCT as they ultimately underwent the procedure (n=34) or not (n=37).

Results: Five-year overall survival (OS) was not statistically different between both groups (allograft: 52% vs no allograft: 34%, P=.12). However, progression to myelodysplastic syndrome or acute myeloid leukemia at 5 years was significantly lower in transplanted patients (14% vs 50%, P=.01). In univariate analysis, 5-year OS was significantly higher for transplanted vs non-transplanted patients with unfavorable karyotype (75% vs 0%, P=.001), SMF (71% vs 20%, P=.001) or high DIPSS+ score (46% vs 15%, P=.03). There was also a trend for better 5-year OS in allografted patients with high JAK2V617F burden (>65%) (75% vs 8%, P=.07). Interestingly, the survival of patients who did not proceed to ASCT was dramatically increased by the use of ruxolitinib.

Conclusions: Not all intermediate-2/high-risk DIPSS+ MF patients benefit from ASCT, especially since the introduction of JAK2 inhibitors.

Keywords: JAK inhibitor; JAK2; allogeneic transplantation; calreticuline; intent-to-treat analysis; myeloproliferative leukemia virus; primary myelofibrosis; secondary myelofibrosis.

MeSH terms

  • Adult
  • Aged
  • Biomarkers
  • Female
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Janus Kinase 2 / genetics
  • Janus Kinase Inhibitors / administration & dosage
  • Janus Kinase Inhibitors / adverse effects
  • Janus Kinase Inhibitors / therapeutic use*
  • Male
  • Middle Aged
  • Molecular Targeted Therapy
  • Mutation
  • Primary Myelofibrosis / diagnosis
  • Primary Myelofibrosis / genetics
  • Primary Myelofibrosis / mortality*
  • Primary Myelofibrosis / therapy*
  • Prognosis
  • Retrospective Studies
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • Biomarkers
  • Janus Kinase Inhibitors
  • Janus Kinase 2