Allogeneic Stem Cell Transplantation Combined With Transfusion of Mesenchymal Stem Cells in Primary Myelofibrosis: A Multicenter Retrospective Study

BACKGROUND: Allogeneic stem cell transplantation (allo-SCT) remains the only effective curative therapy for primary myelofibrosis. Utilization and efficacy of allo-SCT are limited by lethal complications, including engraftment failure, and acute (aGVHD) and chronic graft-versus-host disease (cGVHD). Several clinical trials have explored the use of mesenchymal stem cells (MSCs) in allo-SCT to prevent hematopoietic stem cell (HSC) engraftment failure and control GVHD. METHODS: Clinical data of 17 patients with primary myelofibrosis who underwent allo-SCT combined with ex vivo expanded MSC transfusion in four centers from February 2011 to December 2018 were retrospectively analyzed. RESULTS: All patients received myeloablative conditioning regimen. The median number of transplanted nucleated cells (NCs) per kilogram body weight was 11.18 × 10(8) (range: 2.63–16.75 × 10(8)), and the median number of CD34(+) cells was 4.72 × 10(6) (range: 1.32–8.4 × 10(6)). MSCs were transfused on the day of transplant or on day 7 after transplant. The median MSC infusion number was 6.5 × 10(6) (range: 0.011–65 × 10(6)). None of the patients experienced primary or secondary graft failure in the study. The median time to neutrophil engraftment was 13 days (range: 11–22 days), and the median time to platelet engraftment was 21 days (range: 12–184 days). The median follow-up time was 40.3 months (range: 1.8–127.8 months). The estimated relapse-free survival (RFS) at 5 years was 79.1%, and overall survival (OS) at 5 years was 64.7%. Analysis showed that the cumulative incidence of aGVHD grade II to IV was 36% (95% CI: 8%–55%) and that of grade III to IV was 26% (95% CI: 0%–45%) at day 100. The cumulative incidence of overall cGVHD at 2 years for the entire study population was 63% (95% CI: 26%–81%). The cumulative incidence of moderate to severe cGVHD at 2 years was 17% (95% CI: 0%–42%). Seven patients died during the study, with 5 patients succumbing from non‐relapse causes and 2 from disease relapse. CONCLUSION: The findings of the study indicate that allo-SCT combined with MSC transfusion may represent an effective treatment option for primary myelofibrosis.