Posttransplantation cyclophosphamide mediates effective reconstitution of memory B cells after allogeneic hematopoietic cell transplantation

Eur J Haematol. 2024 Nov;113(5):651-663. doi: 10.1111/ejh.14280. Epub 2024 Jul 28.

Abstract

Objectives: Impaired B-cell reconstitution after allogeneic hematopoietic cell transplantation (allo-HCT) contributes to the pathogenesis of chronic graft-versus-host disease (cGVHD). Therefore, methods to consistently achieve effective B cell lymphogenesis are required. We assessed the long-term effects of posttransplantation cyclophosphamide (PTCy) use on immune reconstitution in clinical settings, an emerging strategy to suppress allogeneic immunological inflammation early after allo-HCT and prevent subsequent GVHD.

Methods: We comprehensively analyzed peripheral immune cell subsets and measured serum immunoglobulin G (IgG) or cytokine levels in 39 patients who survived for >1 year after allo-HCT.

Results: The absolute counts of B1 and IgM memory B cells were significantly lower in patients with severe cGVHD than in those without. The absolute count and percentage (among total CD19+ B cells) of switched memory B cells and serum IgG levels were significantly higher in patients transplanted with PTCy than in those transplanted with conventional GVHD prophylaxis. Interestingly, increased percentages of switched memory B cells and serum IgG levels were observed only in patients transplanted with PTCy and not in those transplanted with umbilical cord blood.

Conclusions: PTCy administration can mediate favorable memory B-cell reconstitution long after allo-HCT and may therefore suppress cGVHD.

Keywords: chronic graft‐versus‐host disease; cord blood stem cell transplantation; cyclophosphamideimmune reconstitution; memory B cells.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Cyclophosphamide* / therapeutic use
  • Cytokines / metabolism
  • Female
  • Graft vs Host Disease* / etiology
  • Graft vs Host Disease* / prevention & control
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Immune Reconstitution
  • Immunoglobulin G* / blood
  • Immunoglobulin G* / immunology
  • Immunologic Memory
  • Immunosuppressive Agents / therapeutic use
  • Lymphocyte Count
  • Male
  • Memory B Cells* / immunology
  • Middle Aged
  • Transplantation, Homologous*
  • Young Adult

Substances

  • Cyclophosphamide
  • Immunoglobulin G
  • Cytokines
  • Immunosuppressive Agents