Effect of pre-transplant JAK1/2 inhibitors and CD34 dose on transplant outcomes in myelofibrosis

Eur J Haematol. 2021 Nov;107(5):517-528. doi: 10.1111/ejh.13689. Epub 2021 Jul 27.

Abstract

Allogeneic hematopoeitic cell transplantation (allo-HCT) is the only curative treatment for myelofibrosis (MF). We evaluate the impact of various factors on survival outcomes post-transplant in MF. Data of 89 consecutive MF patients (primary 47%) who underwent allo-HCT between 2005 and 2018 was evaluated. Fifty-four percent patients had received JAK1/2 inhibitors (JAKi) pre-HCT. The median CD34 count was 7.1x106 cells/kg. Graft failure was seen in 10% of the patients. Grade 3-4 acute GVHD (aGVHD) and moderate/severe chronic graft versus host disease (cGVHD) occurred in 24% and 40% patients, respectively. Two-year overall survival (OS) and relapse free survival (RFS) were 51% and 43%, respectively. Cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) at 2 years were 11% and 46%, respectively. Higher CD34 cell dose (≤5 × 106 cells/kg vs 5-9 or ≥9 × 106 cells/kg) and lower pre-HCT ferritin (</=1000 ng/ml) were associated with better OS, RFS and lower NRM. Grade 3-4 aGVHD was associated with higher NRM. Use of pre-transplant JAKi was associated with lower incidence of grade 3-4 aGVHD. In summary, higher CD34 cell dose is associated with better allo-HCT outcomes in MF and pre-HCT JAKi use is associated with reduced risk of severe aGVHD. These two modifiable parameters should be considered during allo-HCT for MF.

Keywords: Allogeneic; CD34 count; Hematopoietic cell transplantation; JAK2 inhibitor; Myelofibrosis.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD34 / immunology*
  • Dose-Response Relationship, Immunologic
  • Female
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Janus Kinase 1 / antagonists & inhibitors*
  • Janus Kinase 2 / antagonists & inhibitors*
  • Male
  • Middle Aged
  • Primary Myelofibrosis / therapy*
  • Protein Kinase Inhibitors / pharmacology*
  • Survival Analysis
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • Antigens, CD34
  • Protein Kinase Inhibitors
  • JAK1 protein, human
  • JAK2 protein, human
  • Janus Kinase 1
  • Janus Kinase 2