Ruxolitinib Therapy during Hematopoietic Cell Transplantation for Myelofibrosis

Background :The beneficial effects of JAK 1/2 inhibitors (JAKi) ruxolitinib in MF patients have led to control of disease related symptoms,but ruxolitinib has been limited by their inability to deplete the malignant stem cell clones. Allogeneic hematopoietic cell transplantation (HCT) is currently the only treatment with proven curative potential for myelofibrosis (MF). Previous research suggested pre-HCT ruxolitinib may improve post-HCT outcome because of ruxolitinib accelerate engraftment, improve graft function, decrease the risk and severity of graft-versus-host disease (GVHD). However,HCT in PMF with higher non-relapse mortality (NRM),In the present study, we aimed to prospectively assess the effects of Rux therapy during HCT period(NCT04526223).

Objective Preliminarily investigate the safety and efficacy of ruxolitinib in myelofibrosis patients during the peri-transplantation period.

Method: To prospectively analyze the clinical data of 26 patients with myelofibrosis who were used DAC bridge BF as conditioning treatment and treated with ruxolitinib(5mg bid +6d to +60d) during the peri-transplantation period.

Results: 26 patients were eligible if they had primary myelofibrosis (PMF) as defined by the 2008 World Health Organization classification or secondary MF as defined by the IWG for Myeloproliferative Neoplasms Research and Treatment criteria and met the criteria for Intermediate-1 (Int-1), Int-2, or high-risk disease by the DIPSS scoring system at the time of enrollment. Patients consenting to treatment with Rux for at least 8 weeks prior to HCT and could receive Rux (5mg bid +6d to +60d) during the peri-transplantation period. DAC bridge BF as Myeloablative regiment, There have been no episodes of cytokine release syndrome and all patients achieved sustained engraftment. Neutrophil reconstitution was obtained in 26 patients with a median time of 15 (10 to 31) d; platelet reconstitution was obtained in 26 patients with a median time of 26(12 to 68) d. Acute GVHD occurred in 26 patients (46.15%) , of which 1(3.8%) were ш°; chronic GVHD occurred in 9 patients (34.6%), 1 patients with extensive chronic GVHD. There patients relapsed and two patients died because of resistance to alvage treatment . With a median follow-up 336 (70-993) days，no patient died of non-relapse mortality (NRM)., overall survival is 92.3% (95% CI: 0.73, 0.97) and DFS is 88.5% (95% CI: 0.63, 0.96) at1 year post-HCT.

Conclusion: This study demonstrates that Ruxolitinib therapy during HCT is well tolerated and suggests that during-HCT Rux may improve post-HCT outcome.

Keywords: Ruxolitinib;Hematopoietic Cell Transplantation;Myelofibrosis