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 malignancies treated with a low intensity conditioning in preparation for allogeneic stem cell transplantation. Conditioning consisted of fludarabine, anti-T lymphocyte globulin and low-dose busulfan, followed by infusion of allogeneic blood stem cells. This protocol resulted in rapid engraftment and complete replacement of host with donor hematopoietic cells. Immunological parameters of these patients were compared to those patients who were conditioned by an aggressive myeloablative regimen. Distribution of cell surface markers of lymphocyte subsets from both groups of patients was similar, but different from that of normal control cells. Reduced intensity or non-myeloablative conditioning prior to allogeneic stem cell transplantation (NST), hardly lowered the normal T cell-dependent mitogenic response even during the early period following transplant, while the myeloablative treatments resulted in a suppressed mitogenic reaction and in slow immune recovery. Reactivity 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 NST may lead to faster development of effective immune responses against residual host-type malignant and abnormal non-malignant hematopoietic cells, although the role of fludarabine on post-transplant infections remains to be investigated in a larger cohort of patients.
Morecki
S
S
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah University Hospital, Jerusalem, Israel.
Gelfand
Y
Y
Nagler
A
A
Or
R
R
Naparstek
E
E
Varadi
G
G
Engelhard
D
D
Akerstein
A
A
Slavin
S
S
D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000633:toxicity; D002066:Busulfan / Q000008:administration & dosage / Q000633:toxicity; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D002648:Child; D002675:Child, Preschool; D003602:Cytotoxicity, Immunologic; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000187:drug effects*; D007239:Infections / Q000139:chemically induced; D015979:Killer Cells, Lymphokine-Activated / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D019172:Transplantation Conditioning / Q000379:methods* / Q000592:standards; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000379:methods; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity
D000961:Antilymphocyte Serum; D010835:Phytohemagglutinins; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine