Preliminary characterization of functional residual host-type T lymphocytes following conditioning for allogeneic HLA-matched bone marrow transplantation (BMT).
Host T lymphocytes which escape the effects of chemoradiotherapy may proliferate and lead to graft rejection, particularly in recipients of T cell-depleted bone marrow (BM) allografts. We studied the efficacy of several conditioning regimens including a new immunosuppressive regimen--total lymphoid irradiation (TLI) plus conventional chemotherapy and total body irradiation (TBI)--in abrogating residual host T lymphocytes as assessed by their ability to grow in vitro. A total of 38 patients were evaluated, 29 with hematologic malignancies, six with severe aplastic anemia (AA) and three with beta-thalassemia major (TM), of whom 32 were transplanted with HLA-identical T cell-depleted allogeneic BM from sibling donors. The median observation period was 15 months (range 3-21) posttransplant. Peripheral blood mononuclear cells (PBMC) taken from each patient on the day of transplant were cultured with interleukin 2 (IL-2) + phytohemagglutinin + irradiated donors' PBMC. Survival of cells for less than 2 weeks in vitro without proliferation was observed in 20 of 29 cases with malignancies and was considered negative. In this group only two leukemia (L) patients rejected the graft. Limited cell growth (less than or equal to 3 weeks) was seen in four L patients, two of whom showed early graft failure. Vigorous T cell growth (greater than 5 weeks, 62-96% CD4+ cells) was noted in eight cases (two L, four AA, two TM; none received TBI). In this group, sustained engraftment was observed in 7/7 patients who were treated with cyclosporin A (CSA) post grafting. Overall, we could demonstrate no clear correlation between graft failure and cell growth in vitro. The proliferating cells exhibited considerable cytotoxic activity in vitro against several tumor cell lines and were susceptible to pharmacological doses of CSA. The low incidence of continuous T cell proliferation in vitro in PBMC of L patients suggests that a combination of TLI, TBI and cyclophosphamide (CY) is highly effective in abrogating the host T cells and subsequent graft rejection. Since a rather small number of patients was included in this study, further studies are needed to determine the possible value of the in vitro T cell proliferation assay as a means for predicting graft failure.
D000293:Adolescent; D000328:Adult; D001853:Bone Marrow / Q000187:drug effects; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D003524:Cyclosporins / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D006085:Graft Survival; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D007376:Interleukin-2; D008213:Lymphocyte Activation / Q000187:drug effects / Q000528:radiation effects; D008212:Lymphocyte Depletion; D008875:Middle Aged; D010641:Phenotype; D011292:Premedication; D013601:T-Lymphocytes / Q000145:classification* / Q000276:immunology; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
D003524:Cyclosporins; D006680:HLA Antigens; D007376:Interleukin-2