Co-transplantation of mesenchymal stem cells makes haploidentical HSCT a potential comparable therapy with matched sibling donor HSCT for patients with severe aplastic anemia

Zenghui Liu; Xiaoxiong Wu; Shunqing Wang; Linghui Xia; Haowen Xiao; Yonghua Li; Hongbo Li; Yuping Zhang; Duorong Xu; Danian Nie; Yongrong Lai; Bingyi Wu; Dongjun Lin; Xin Du; Zujun Jiang; Yang Gao; Xuekui Gu; Yang Xiao

doi:10.1177/2040620720965411

Co-transplantation of mesenchymal stem cells makes haploidentical HSCT a potential comparable therapy with matched sibling donor HSCT for patients with severe aplastic anemia

Ther Adv Hematol. 2020 Oct 29:11:2040620720965411. doi: 10.1177/2040620720965411. eCollection 2020.

Authors

Zenghui Liu¹, Xiaoxiong Wu², Shunqing Wang³, Linghui Xia⁴, Haowen Xiao⁵, Yonghua Li⁵, Hongbo Li⁶, Yuping Zhang³, Duorong Xu⁷, Danian Nie⁸, Yongrong Lai⁹, Bingyi Wu¹⁰, Dongjun Lin¹¹, Xin Du¹², Zujun Jiang⁵, Yang Gao⁵, Xuekui Gu¹³, Yang Xiao¹⁴

Affiliations

¹ Guangzhou University of Chinese Medicine; The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
² First Affiliated Hospital of PLA General Hospital, Beijing, China.
³ Guangzhou First People's Hospital, Guangzhou, China.
⁴ Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁵ General Hospital of Guangzhou Military Command, Guangzhou, China.
⁶ The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
⁷ First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
⁸ Second Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
⁹ First Affiliated Hospital of Guangxi Medical University, Nanning, China.
¹⁰ Affiliated Zhujiang Hospital of Southern Medical University, Guangzhou, China.
¹¹ Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
¹² Shenzhen Second People's Hospital, Shenzhen, China.
¹³ Department of Hematology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, No 16, Jichang Road, Guangzhou, Guangdong Province, 510405, PR China.
¹⁴ Stem Cell Translational Medicine Center, The Second Affiliated Hospital of Guangzhou Medical University, No. 250, Changgang East Road, Guangzhou, Guangdong Province, 510260, PR China.

Abstract

The application of haploidentical hematopoietic stem cell transplantation (HSCT) with mesenchymal stem cell (MSC) infusion as a treatment regimen for severe aplastic anemia (SAA) has been reported to be efficacious in single-arm trials. However, it is difficult to assess without comparing the results with those from a first-line, matched-sibling HSCT. Herein, we retrospectively reviewed 91 patients with acquired SAA. They received HSCT from haploidentical donors combined with MSC transfer (HID group). We compared these patients with 103 others who received first-line matched-sibling HSCT (MSD group) to evaluate relative treatment efficacy. Compared with the patients in the MSD group, those in the HID group presented with higher incidences of grades II-IV and III-IV acute graft versus host disease (aGvHD) and chronic graft versus host disease (cGvHD) (p < 0.05). However, the incidence of myeloid and platelet engraftment, graft failure, poor graft function, and extensive cGvHD were comparable for both groups. The median follow-up was 36.6 months and the 3-year overall survival rate was similar for both groups (83.5% versus 79.1%). Univariate and multivariate analyses revealed that time intervals greater than 4 months from diagnosis to transplantation, experienced graft failure, poor graft function, or grade III-IV aGvHD were significantly associated with adverse outcomes. All HID patients received MSC co-transplantation with hematopoietic stem cells. However, the infused MSCs were derived from umbilical cord (UC-MSC group; 43 patients) or bone marrow (BM-MSC group; 48 patients) and were administered at different medical centers. We first compared the outcomes between the two groups and detected that the BM-MSC group exhibited lower incidences of grade III-IV aGvHD and cGvHD (p < 0.05). This study suggests that co-transplantation of hematopoietic and MSCs significantly reduces the risk and incidence of graft rejection and may effectively improve overall survival in patients with SAA even in the absence of closely related histocompatible donor material.

Keywords: co-transplantation; haploidentical HSCT; mesenchymal stem cells.