Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects
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Open Access
- 1 June 2001
- journal article
- clinical trial
- Published by American Society of Hematology in Blood
- Vol. 97 (11), 3390-3400
- https://doi.org/10.1182/blood.v97.11.3390
Abstract
Toxicities have limited the use of allogeneic hematopoietic cell transplantation (HCT) to younger, medically fit patients. In a canine HCT model, a combination of postgrafting mycophenolate mofetil (MMF) and cyclosporine (CSP) allowed stable allogeneic engraftment after minimally toxic conditioning with low-dose (200 cGy) total-body irradiation (TBI). These findings, together with the known antitumor effects of donor leukocyte infusions (DLIs), led to the design of this trial. Forty-five patients (median age 56 years) with hematologic malignancies, HLA-identical sibling donors, and relative contraindications to conventional HCT were treated. Immunosuppression involved TBI of 200 cGy before and CSP/MMF after HCT. DLIs were given after HCT for persistent malignancy, mixed chimerism, or both. Regimen toxicities and myelosuppression were mild, allowing 53% of eligible patients to have entirely outpatient transplantations. Nonfatal graft rejection occurred in 20% of patients. Grades II to III acute graft-versus-host disease (GVHD) occurred in 47% of patients with sustained engraftment. With median follow-up of 417 days, survival was 66.7%, nonrelapse mortality 6.7%, and relapse mortality 26.7%. Fifty-three percent of patients with sustained engraftment were in complete remission, including 8 with molecular remissions. This novel allografting approach, based on the use of postgrafting immunosuppression to control graft rejection and GVHD, has dramatically reduced the acute toxicities of allografting. HCT with the induction of potent graft-versus-tumor effects can be performed in previously ineligible patients, largely in an outpatient setting. Future protocol modifications should reduce rejection and GVHD, thereby facilitating studies of allogeneic immunotherapy for a variety of malignancies.Keywords
This publication has 40 references indexed in Scilit:
- Long-term follow-up of patients who achieved complete remission after donor leukocyte infusionsTransplantation and Cellular Therapy, 1999
- Mixed chimerism: Preclinical studies and clinical applicationsTransplantation and Cellular Therapy, 1999
- Mixed lymphohaemopoietic chimerism and graft-ver suslymphoma effects after non-myeloablative therapy and HLA-mismatched bone-marrow transplantationThe Lancet, 1999
- Solid Cancers after Bone Marrow TransplantationNew England Journal of Medicine, 1997
- Efficacy and Safety of Fluconazole Prophylaxis for Fungal Infections after Marrow Transplantation--A Prospective, Randomized, Double-Blind StudyThe Journal of Infectious Diseases, 1995
- Induction of Graft-versus-Host Disease as Immunotherapy for Relapsed Chronic Myeloid LeukemiaNew England Journal of Medicine, 1994
- Comparison of Autologous and Allogeneic Bone Marrow Transplantation for Treatment of High-Risk Refractory Acute Lymphoblastic LeukemiaNew England Journal of Medicine, 1987
- MARROW GRAFT REJECTION AND VENO-OCCLUSIVE DISEASE OF THE LIVER IN PATIENTS WITH APLASTIC ANEMIA CONDITIONED WITH CYCLOPHOSPHAMIDE AND CYCLOSPORINETransplantation, 1986
- Antileukemic Effect of Chronic Graft-versus-Host DiseaseNew England Journal of Medicine, 1981
- Antileukemic Effect of Graft-versus-Host Disease in Human Recipients of Allogeneic-Marrow GraftsNew England Journal of Medicine, 1979