Allogeneic Stem Cell Transplantation Combined with Mesenchymal Stem Cells Transfusion in Primary Myelofibrosis-a Single-Center Retrospective Study

Background: There are multiple treatment options that may provide symptom relief and improvement in survival in patients with primary myelofibrosis. However, allogeneic stem cell transplantation (ASCT) remains the only potentially curative option. The use and effectiveness of ASCT are limited by lethal complications, i.e., engraftment failure, acute and chronic graft-versus-host disease. Several clinical trials have used mesenchymal stem cells (MSCs) in ASCT to prevent hematopoietic stem cell (HSC) engraftment failure and to control graft versus host disease (GVHD).

Objective:To evaluate the efficacy of MSCs transfusion in patients with primary myelofibrosis after allogeneic hematopoietic stem cell transplantation.

Methods:The clinical data of 11 patients with primary myelofibrosis underwent ASCT and MSCs transfusion were retrospectively analyzed.

Results:Among the 11 patients, 5 were male and 6 were female, with a median age of 34(20-48) years. Risk profile according the DIPSS-plus score was intermediate-1 risk(n=2) , intermediate-2 risk (n=2), and high risk (n=7). 7 of 11 patients were MF-3 and 4 cases were MF-2. Severe splenomegaly before transplantation were observed in 8 patients. Six patients were treated with ruxolitinib prior to ASCT. Among the 11 patients, 3 patients received HLA-identical sibling-ASCT, 2 received unrelated donor-ASCT and 6 received haploid ASCT from related donors. Median age of donor is 34 years old (range,20~48years old). All patients received myeloablative BuCy conditioning regime and GVHD prophylaxis consisted of cyclosporine A and MTX. Further GVHD prophylaxis consisted of ATG and MMF. All but 2 patients received peripheral blood stem cells (PBST)as graft source, the rest graft source were bone marrow (BM) plus PBST. The median number of transplanted NC cells was 12.27 (2.63 ~ 16.75) *10E8/Kg, and CD34+ cells was 5 (4.2 ~ 7.8) *10E6/Kg. BM-derived MSCs were transfused at +7d after stem cell transplantation. The median MSC infusion number was 6.5*10E6(6 ~ 65*10E6). All patients obtained hematopoietic reconstruction after transplantation, and chimerism analysis by short tandem repeat(STR) suggested complete chimerism. The median time to leukocyte engraftment was 12(range,11 ~ 20days) days and the median time to platelet engraftment was 18 days (range, 8-145 days). Leukocyte was continuously implanted in all patients whereas platelet was continuously implanted in 8 patients. Three patients did not experience any acute graft-versus-host disease (GVHD) .4 patients developed grade 1-2 acute GVHD and 4 developed grade 3-4 acute GVHD. Chronic GVHD was seen in 6 patients which were all limited disease. The median follow-up time was 24.3(1.7 ~ 48 months) months, and the expected 3-year overall survival rate was 61.4%. During the follow-up period, none relapse were observed.Four patients died, 2 of which died early after transplantation (2 months and 1.7 months). The causes of death were thrombotic microangiopathy and immunological cerebrovascular inflammation (this patient had congenital abnormalities of cerebrovascular development and had a long history of repeated epilepsy before transplantation). The other 2 patients died late after transplantation (12 months and 6.4 months) due to heart failure (the patient was with persistent atrial fibrillation before transplantation) and pulmonary infection.

Conclusion: Our results demonstrated that MSCs transfusion combined with allogeneic hematopoietic stem cell transplantation is an effective treatment for primary myelofibrosis.