Infusion of haploidentical hematopoietic stem cells combined with mesenchymal stem cells for treatment of severe aplastic anemia in adult patients yields curative effects

Cytotherapy. 2022 Feb;24(2):205-212. doi: 10.1016/j.jcyt.2021.09.014. Epub 2021 Nov 16.

Abstract

Background aims: Despite the great advances in immunosuppressive therapy for severe aplastic anemia (SAA), most patients are not completely cured. Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has been recommended as an alternative treatment in adult SAA patients. However, haplo-HSCT presents a higher incidence of graft failure and graft-versus-host disease (GVHD). The authors designed a combination of haplo-HSCT and umbilical cord-derived mesenchymal stem cells (UC-MSCs) for treatment of SAA in adult patients and evaluated its effects.

Methods: Adult patients (≥18 years) with SAA (N = 25) were given HLA-haploidentical hematopoietic stem cells (HSCs) combined with UC-MSCs after a conditioning regimen consisting of busulfan, cyclophosphamide, fludarabine and anti-thymocyte globulin and intensive GVHD prophylaxis, including cyclosporine, basiliximab, mycophenolate mofetil and short-term methotrexate. Additionally, the effects of the protocol in adult SSA patients were compared with those observed in juvenile SAA patients (N = 75).

Results: All patients achieved myeloid engraftment after haplo-HSCT at a median of 16.12 days (range, 11-26). The median time of platelet engraftment was 28.30 days (range, 13-143). The cumulative incidence of grade II acute GVHD (aGVHD) at day +100 was 32.00 ± 0.91%. No one had grade III-IV aGVHD at day +100. The cumulative incidence of total chronic GVHD was 28.00 ± 0.85%. The overall survival was 71.78 ± 9.05% at a median follow-up of 42.08 months (range, 2.67-104). Promisingly, the protocol yielded a similar curative effect in both young and adult SAA patients.

Conclusions: The authors' data suggest that co-transplantation of HLA-haploidentical HSCs and UC-MSCs may provide an effective and safe treatment for adult SAA.

Keywords: GVHD; SAA; UC-MSC; adult patients; haploidentical HSCT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Aplastic* / therapy
  • Graft vs Host Disease*
  • Hematopoietic Stem Cell Transplantation*
  • Hematopoietic Stem Cells
  • Humans
  • Mesenchymal Stem Cells*
  • Transplantation Conditioning