Mesenchymal Stem Cells for Prophylaxis of Chronic Graft-vs-Host Disease After Haploidentical Hematopoietic Stem Cell Transplant

Author:

Huang Ruihao1,Chen Ting1,Wang Sanbin2,Wang Jishi3,Su Yi4,Liu Jing5,Zhang Yanqi6,Ma Xiangyu7,Wen Qin1,Kong Peiyan1,Zhang Cheng1,Gao Lei1,Zhong Jiang F.8,Gao Li1,Zhang Xi19

Affiliation:

1. Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University, Chongqing, China

2. Department of Hematology, 920th Hospital of Joint Logistics Support Force, Yunnan, China

3. Department of Hematology, Affiliated Hospital of Guizhou Medical University, Guizhou, China

4. Department of Hematology, the General Hospital of Western Theater Command, Sichuan, China

5. Department of Hematology, the Third Xiangya Hospital of Central South University, Hunan, China

6. Department of Health Statistics, College of Military Preventive Medicine, Army Medical University, Chongqing, China

7. Department of Epidemiology, College of Military Preventive Medicine, Army Medical University, Chongqing, China

8. Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles

9. Jinfeng Laboratory, Chongqing, China

Abstract

ImportanceChronic graft-vs-host disease (GVHD) limits the long-term benefit of haploidentical hematopoietic stem cell transplant (HSCT). This clinical trial evaluated repeated infusions of umbilical cord mesenchymal stem cells (MSCs) during the early stage (45 days and 100 days) after haplo-HSCT to prevent chronic GVHD.ObjectiveTo determine whether repeated infusions of MSCs during the early stage after haplo-HSCT decreases the incidence of severe chronic GVHD.Design, Setting, and ParticipantsThis open-label, multicenter, parallel randomized clinical trial was conducted from April 2016 to January 2022. Eligibility criteria included a diagnosis of acute leukemia and having a haploidentical, suitable related donor for HSCT. The median (range) follow-up time was 39.0 (1.5-67.0) months.InterventionsThe enrolled patients with a haploidentical relative for HSCT received the modified busulfan/cyclophosphamide + antithymocyte globulin modified regimen and standard GVHD prophylaxis. Patients were randomly chosen to receive MSCs (the MSC group) (1 × 106 cells/kg, every 2 weeks, starting from 45 days after transplant, 4 times total) or regular prophylaxis (control group).Main Outcome and MeasureThe cumulative incidence of severe chronic GVHD.ResultsOf 158 patients, 58 (36.7%) were female individuals; the median (range) age for the MSC and control groups was 28 (18-60) years and 28 (18-56) years, respectively. A total of 158 patients were screened, and 148 patients were randomly assigned to the MSC group (n = 74) or control group (n = 74) 1 day before MSCs infusion. The estimated 2-year cumulative incidence of severe chronic GVHD was 5.4% (95% CI, 1.8%-14.0%) in the MSC group and 17.4% (95% CI, 10.1%-28.5%) in the control group (hazard ratio [HR], 0.29; 95% CI, 0.10-0.88; P = .03). There was no difference between the MSC and control groups in the cumulative incidence of leukemia relapse (HR, 1.17; 95% CI, 0.55-2.47; P = .68). The cumulative incidence of stage II to IV acute GVHD in the MSC group was significantly lower than that in the control group (HR, 0.25; 95% CI, 0.09-0.67; P = .01). The MSC group had better GVHD-free and relapse-free survival rates than the control group (HR, 0.62; 95% CI, 0.39-0.98; P = .04).Conclusions and RelevanceThe results of this randomized clinical trial show that early repeated infusions of MSCs decreased the incidence and severity of chronic GVHD, and the incidence and severity of acute GVHD manifested as a better GVHD-free and relapse-free survival rate for patients after haplo-HSCT.Trial RegistrationChinese Clinical Trial Registry: ChiCTR-IIR-16007806

Publisher

American Medical Association (AMA)

Subject

Oncology,Cancer Research

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