Immune reconstitution following allogeneic stem cell transplantation in recipients conditioned by low intensity vs myeloablative regimen

We have investigated the immune status of patients with hematologic maligna ncies treated with a low intensity conditioning in preparation for allogene ic stem cell transplantation. Conditioning consisted of fludarabine, anti-T lymphocyte globulin and low-dose busulfan, followed by infusion of allogen eic blood stem cells. This protocol resulted in rapid engraftment and compl ete replacement of host with donor hematopoietic cells. Immunological param eters of these patients were compared to those patients who were conditione d by an aggressive myeloablative regimen. Distribution of cell surface mark ers of lymphocyte subsets from both groups of patients was similar, but dif ferent from that of normal control cells. Reduced intensity or non-myeloabl ative conditioning prior to allogeneic stein cell transplantation (NST), ha rdly lowered the normal T cell-dependent mitogenic response even during the early period following transplant, while the myeloablative treatments resu lted in a suppressed mitogenic reaction and in slow immune recovery. Reacti vity of non-MHC restricted cytotoxic T cells was also at a normal level in patients who were treated with NST. We conclude that stem cell engraftment following reduced conditioning may result in early reconstitution of immune responses assessed in vitro. We hypothesize that clinical application of N ST may lead to faster development of effective immune responses against res idual host-type malignant and abnormal non-malignant hematopoietic cells, a lthough the role of fludarabine on post-transplant infections remains to be investigated in a larger cohort of patients.