Immune reconstitution following bone marrow transplantation: comparison of recipients of T-cell depleted marrow with recipients of conventional marrow grafts

Abstract

The reconstitution of hematopoietic cells and in vitro assays of immunologic function have been followed in leukemic patients after conventional bone marrow transplantation (BMT) (N = 34) and T-cell depleted BMT (N = 52) from human leukocyte antigen (HLA)-identical sibling donors. No effects of the T-cell depletion could be seen on the recovery of myeloid or lymphoid cells as measured by the day to engraftment or by the absolute number of cells through day 100. Normal numbers of lytically active natural killer cells returned the earliest and were rapidly followed in both groups of patients by the appearance of circulating B cells and normalization of the responses to B-cell mitogens. However, the recovery of normal T-cell proliferative responses were more delayed in recipients of T-cell depleted grafts. Significant quantitative differences were seen only during the first 3 months after transplantation. Neither the number of CD3+ T cells nor the ratio of CD4:CD8 positive cells differed markedly between the two transplant groups. Mitogen-induced immunoglobulin production by peripheral blood lymphocytes (PBL) from patients following T-cell depleted BMT was quantitatively less than that of conventional marrow recipients through the first year, with low normal IgM production reached by 4 to 6 months in both groups. IgG production reached low normal 7 to 9 months after conventional BMT but did not remain at this level until 1 year following either type of transplant. Assessment of the incidence of infections from the day the absolute neutrophil count reached 500 until day 180 after transplant revealed no significant differences between the two groups; indeed, the overall nonleukemic mortality was higher in the recipients of conventional bone marrow. Thus, in our series, the removal of mature cells from the marrow graft did not affect the rate or degree of recovery of myeloid and lymphoid cells but did affect the regeneration of in vitro T-cell dependent functions. We noted early quantitative differences and a delay in the normalization of the T-cell functions measured rather than prolonged absolute deficiencies. The in vitro deficiencies did not result in significant clinically apparent differences between the two groups.

Early reconstitution of the T‐cell repertoire after non‐myeloablative peripheral blood stem cell transplantation is from post‐thymic T‐cell expansion and is unaffected by graft‐versus‐host disease or mixed chimaerism

“…Very early after transplant, all lymphocyte subsets measured were higher in NST patients; however, by 6 weeks, equivalent numbers of most T-cell subsets were achieved in TCD recipients despite a four log difference in the number of T cells infused at transplant. Our results are similar to those reported by Keever et al (1989), in which there were no quantitative differences in absolute counts of T cells between patients receiving T-cell-depleted and unmanipulated BMT, and Morecki et al (2001), who reported similar levels of lymphocyte subsets in myeloablative and low-intensity conditioning transplants.…”

Changes of isoagglutinin titres after ABO‐incompatible allogeneic stem cell transplantation

“…In our study, titres of isoagglutinins against ABO antigens absent both on recipient and donor RBCs decreased during the early post-transplant period, then rose subsequently at a median of 59 d posttransplant in most cases. This phenomenon of a posttransplant increase in isoagglutinin titres might reflect antibody production by donor-derived B-lymphocytes, and is consistent with other studies that showed reconstitution of B-lymphocyte number and function within 1-2 months after allogeneic stem cell transplantation (Noel et al, 1978;Ault et al, 1985;Keever et al, 1989). Unrelated stem cell transplantation and use of cyclosporine plus methotrexate for GVHD prophylaxis tended to be associated with delayed immunohaematological reconstitution compared with sibling transplantation and use of cyclosporine only respectively.…”

Immune reconstitution after haematopoietic cell transplantation in children: immunophenotype analysis with regard to factors affecting the speed of recovery

“…Ottinger et al (1996) observed a normalization of the B-cell count as late as 11 months post alloHCT in adults treated with GvHD prophylaxis of CsA and MTX. However, Keever et al (1989) reported an earlier time period of 6 months post alloBMT to normalization of B-cell count. In our group, the B-cell count returned to normal at 4-6 months after alloHCT.…”