A prospective observational study of immune reconstitution following transplantation with post‐transplant reduced‐dose cyclophosphamide from HLA ‐haploidentical donors

• DOI: 10.1111/tri.13494
• Publication Date: 2019-08-21T06:54:17Z
• Authors: Hirohisa Nakamae; Kazuki Fujii; Satoru Nanno; Hiroshi Okamura; Takahiko Nakane; Hideo Koh; Yasuhiro Nakashima; Mika Nakamae; Asao Hirose; Takanori Teshima; Masayuki Hino
• Keywords: Adult; Histocompatibility Testing; Hematopoietic Stem Cell Transplantation; Graft vs Host Disease; Middle Aged; Tissue Donors; 3. Good health; Killer Cells, Natural; 03 medical and health sciences; Immune Reconstitution; 0302 clinical medicine; Humans; Virus Activation; Prospective Studies; Cyclophosphamide; Aged

Allogeneic hematopoietic cell transplantation (HCT) from HLA-haploidentical donors with post-transplantation high-dose cyclophosphamide (PT/Cy-haplo) now predominates worldwide. However, to our knowledge, no prospective study has compared immune reconstitution after PT/Cy-haplo with that after conventional HCT. The mechanism by which chronic graft-versus-host disease (GVHD) is inhibited by PT/Cy-haplo also remains unknown. We prospectively compared immune recovery patterns of lymphocyte subsets among four groups of adult patients with hematological disease who received HCT from either HLA-matched related or HLA-matched unrelated donors, cord blood transplantation, or reduced-dose PT/Cy-haplo. Counts of CD4+ T-cell subsets, CD8+ T-cell subsets, and NK cells on days 30 and 60 were often lower in PT/Cy-haplo than those in HLA-matched related HCT. The immune recovery pace in PT/Cy-haplo subsequently caught up with that of the other grafts. The regulatory T cells (Tregs) to conventional CD4+ T-cell (Tcon) ratio was significantly higher until day 90 in PT/Cy-haplo. In multivariate analysis, a higher Tregs-to-Tcon ratio on day 60 was significantly associated with a lower incidence of chronic GVHD (P < 0.01). The preservation of Tregs by PT/Cy in the early phase might have resulted in a lower incidence of chronic GVHD.