Efficacy and safety of mesenchymal stem cells treatment for multidrug-resistant graft-versus-host disease after haploidentical allogeneic hematopoietic stem cell transplantation

Abstract

Purpose: Graft- versus-host disease (GVHD) is an important complication after human leukocyte antigen (HLA) haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT), which may lead to poor prognosis. Our study intends to identify the efficacy and safety of mesenchymal stem cells (MSCs) for multidrug-resistant (MDR)-GVHD after HID HSCT. Methods: MDR-GVHD was referring to GVHD remaining no response to at least two types of therapy, and hUCB-MSCs were given at the dose of (1.0–2.0) × 106/kg once a week. Results: A total of 21 patients were enrolled in this retrospective study (acute GVHD (aGVHD): n = 14, chronic GVHD (cGVHD): n = 7). The median dose of MSCs was 1.2 × 106 cells/kg (range, 0.8–1.8 × 106) cells/kg, and the median numbers of infusion were 2 (range, 1–7) and 3 (range, 2–12) for MDR-aGVHD and MDR-cGVHD patients, respectively. In MDR-aGVHD patients, the overall response rate (ORR) was 57.1%, including 50.0% complete response (CR) and 7.1% partial response (PR), and the median time to response was 49.5 days (range, 16–118) days. The 2-year probability of overall survival after MSCs was 64.3%. Five patients (35.7%) developed infections after MSCs, and no obvious hematologic toxicities were observed. Five MDR-aGVHD patients died after MSCs treatments because of GVHD progression ( n = 1), severe infection (bacterial central nervous system infection: n = 1; fungal pneumonia: n = 2), and poor graft function ( n = 1). In MDR-cGVHD patients, three patients (42.9%) achieved PR after MSCs and the median time to response was 56 days (22–84) days. The ORRs for moderate and severe cGVHD were 50.0% and 33.3%, respectively. Four MDR-cGVHD patients died after MSCs treatments because of GVHD progression ( n = 2), severe fungal pneumonia ( n = 1), and relapse ( n = 1). Conclusion: MSCs treatment may be safe and effective for MDR-GVHD after HID HSCT.

Basiliximab for steroid‐refractory acute graft‐versus‐host disease: A real‐world analysis

“…Several studies have reported that low‐dose methotrexate treatment was tolerable and effective for GVHD 33–35 . The safety of mesenchymal stem cell infusion for SR‐aGVHD was acceptable, 36,37 although its efficacy was controversial 38–41 . Thus, whether these two methods could further improve the efficacy of basiliximab treatment is of the utmost interest.…”

“…[33][34][35] The safety of mesenchymal stem cell infusion for SR-aGVHD was acceptable, 36,37 although its efficacy was controversial. [38][39][40][41] Thus, whether these two methods could further improve the efficacy of basiliximab treatment is of the utmost interest.…”

Efficacy and safety of ruxolitinib in steroid-refractory graft-versus-host disease: A meta-analysis

“…Thus far, there are many clinical studies focused on ruxolitinib for SR-GVHD treatment, and Li et al (19) had conducted a meta-analysis for ruxolitinib as the treatment for SR-GVHD in adults; however, only studies published before January 2019 were enrolled. Since 2019, many important research studies for ruxolitinib in SR-GVHD have been published (15,16,(20)(21)(22)(23)(24)(25)(26)(27)(28). In addition, this meta-analysis did not include children, whereas several studies focused on ruxolitinib for treatment of SR-GVHD in children have been published since 2019 (29)(30)(31)(32).…”

A Predicted Model for Refractory/Recurrent Cytomegalovirus Infection in Acute Leukemia Patients After Haploidentical Hematopoietic Stem Cell Transplantation

“…ATG, cyclosporine A (CSA), mycophenolate mofetil, and short-term methotrexate were administered to prevent GVHD ( Supplementary Methods ) ( Wang et al., 2019 ). Protocol for GVHD and minimal residual disease therapy had been reported in detail ( Liu et al., 2020 ; Zhao et al., 2021 ; Fan et al., 2021 ; Shen et al., 2021 ; Mo et al., 2022 ; Shen et al., 2022 ; Shen et al., 2022 ).…”