Ruxolitinib during Allogeneic Stem Cell Transplantation (allo-SCT) in Primary Myelofibrosis (PMF) Recommendation

Introduction: Ruxolitinib is the first approved drug for treatment of myelofibrosis ,and also can improve survival outcomes by managing graft-versus-host disease. The aim of this work is to produce Ruxolitinib treatment recommendations during allogeneic stem cell transplantation (allo-SCT) in primary myelofibrosis (PMF).

Methods: A total of 13 patients with intermediate or high-risk myelofibrosis who received allogeneic hematopoietic stem cell transplantation from June 2017 to October 2019 at the Department of Hematology, Southern Hospital were selected.All patients were given a maximum tolerated dose of ruxolitinib for at least 2 months before transplantation, ruxolitinib was discontinued at a median of 7 days (around the start of conditioning) pre-HCT.Decitabine combined with BF conditioning protocol, CSA+MTX+ATG(7.5mg/kg,if Haploid donor)+ruxolitinib (5mg bid ;+6 to +60d) was used to prevent GVHD.Time to hematopoietic reconstruction, rate of improvement in myelofibrosis, change in spleen size, incidence of GVHD, and patient outcomes were observed.

Results: ⑴The median age of the 13 patients was 55 (21-57) years, 10 of whom were male and 3 female. By the MIPSS70 score scale ,11 patients were in the high-risk group and 2 were in the intermediate-risk group.Nine patients carried driver mutations and 3 were triple-negative.All patients received peripheral blood and bone marrow grafts, from a matched sibling donor in 3 patients and a haploidentical-related donor in 10 patient. (2) In 13 patients who received ruxolitinib bridging allogeneic hematopoietic stem cell transplantation,All patients engrafted neutrophils and platelet recovery. The median time to neutrophil engraftment was 12 (10-18) days,the median time to platelet engraftment was 20 (12-35) days; 7 patients developed acute GVHD (6 patients had grade I°and 1 patients had grade 2°) and the median time to acute GVHD was 46 (21-100) days. 6 patients developed chronic GVHD (5 patients were limited and 1 patient was extensive). (3) Three months after transplantation, spleen size improved in all eight patients with splenomegaly; myelofibrosis was stable or improved in all patients and four patients improved to grade 0 . (4) Follow up to July 2020, the non-relapse mortality rate(NRM) for all patients was 0, one patient had a positive MRD conversion and the relapse-free survival rate(RFS) was 92.31%.

Conclusions: Single-center, small-sample data suggest that the use of Decitabine combined with BF conditioning protocol ,and peri-transplant administration of ruxolitinib at 5mg bid dose is safe in myelofibrosis patients, no high relapse incidence founded.

Keywords: myelofibrosis, ruxolitinib, during allogeneic hematopoietic stem cell transplantation;