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

Qingyuan Wang; Na Xu; Yu Wang; Xi Zhang; Limin Liu; Huifen Zhou; Hong Wang; Xiang Zhang; Xiaowen Tang; Chengcheng Fu; Miao Miao; Depei Wu

doi:10.3389/fonc.2021.792142

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

Front Oncol. 2022 Jan 24:11:792142. doi: 10.3389/fonc.2021.792142. eCollection 2021.

Authors

Qingyuan Wang^{1

2

3}, Na Xu⁴, Yu Wang^{5

6

7}, Xi Zhang⁸, Limin Liu^{1

2

3}, Huifen Zhou^{1

2

3}, Hong Wang^{1

2

3}, Xiang Zhang^{1

2

3}, Xiaowen Tang^{1

2

3}, Chengcheng Fu^{1

2

3}, Miao Miao^{1

2

3}, Depei Wu^{1

2

3}

Affiliations

¹ National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China.
² Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
³ Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, China.
⁴ Nanfang Hospital, Southern Medical University, Guangzhou, China.
⁵ Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Beijing, China.
⁶ Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.
⁷ Collaborative Innovation Center of Hematology, Peking University, Beijing, China.
⁸ Xinqiao Hospital, Army Military Medical University, Chongqing, China.

Abstract

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 × 10⁸ (range: 2.63-16.75 × 10⁸), and the median number of CD34⁺ cells was 4.72 × 10⁶ (range: 1.32-8.4 × 10⁶). MSCs were transfused on the day of transplant or on day 7 after transplant. The median MSC infusion number was 6.5 × 10⁶ (range: 0.011-65 × 10⁶). 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.

Keywords: allogeneic stem cell transplantation; graft failure; mesenchymal stem cells; overall survival; primary myelofibrosis.