Allogeneic hematopoietic transplantation as adoptive immunotherapy. Induction of graft-versus-malignancy as primary therapy.
An immune-mediated graft-versus-malignancy effect is important to prevent relapse after allogeneic bone marrow transplant for a range of hematologic malignancies and potentially some solid tumors. Graft-versus-leukemia (GVL) effects as seen in response to donor lymphocyte infusions have been most prominent against indolent malignancies including chronic myelogenous leukemia, chronic lymphocytic leukemia, and low-grade lymphoma. Acute myelogenous leukemia and multiple myeloma may also respond. An alternative strategy for allogeneic transplantation is to avoid the toxicity of high-dose chemoradiotherapy and use a relatively nontoxic, nonablative preparative regimen to achieve engraftment, allowing subsequent infusion of additional donor lymphocytes to mediate GVL. Fludarabine-based nonablative chemotherapy agents, using standard dose combinations, produce moderate myelosuppression but are sufficiently immunosuppressive to allow engraftment of an allogeneic hematopoietic transplant and generation of graft-versus-malignancy effects.
Champlin
R
R
Department of Blood and Marrow Transplantation, University of Texas M.D. Anderson Cancer Center, Houston, USA. rchampli@mdacc.tmc.edu
Khouri
I
I
Kornblau
S
S
Marini
F
F
Anderlini
P
P
Ueno
N T
NT
Molldrem
J
J
Giralt
S
S
D000951:Antigens, Neoplasm; D020350:Graft vs Tumor Effect; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016219:Immunotherapy, Adoptive; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
D000951:Antigens, Neoplasm