Dose-escalated donor lymphocyte infusions following reduced intensity transplantation: toxicity, chimerism, and disease responses
- 15 February 2004
- journal article
- clinical trial
- Published by American Society of Hematology in Blood
- Vol. 103 (4) , 1548-1556
- https://doi.org/10.1182/blood-2003-05-1513
Abstract
Data on the application of donor lymphocyte infusions (DLIs) following reduced-intensity transplantation (RIT) remain limited. Persistence of host antigen-presenting cells might increase the efficacy or toxicity of cellular immunotherapies. We report the results of dose-escalating DLIs in 46 patients undergoing RIT, who received a total of 109 infusions to treat mixed chimerism or residual or progressive disease. Diagnoses were myeloma (n = 19), Hodgkin lymphoma (n = 13), non-Hodgkin lymphoma (n = 10), and other (n = 4). Thirty-two had an HLA-matched family donor and 14 an unrelated donor. Grades II to IV graft-versus-host disease (GVHD) occurred in 5 sibling and 7 unrelated donor recipients. GVHD was more common (P = .002), occurred at lower T-cell doses, and was more severe in the unrelated donor cohort. Conversion from mixed to multilineage full donor chimerism occurred in 30 of 35 evaluable patients. Presence of mixed chimerism in the granulocyte lineage at the time of DLI did not predict for chimerism response or GVHD. Disease responses occurred in 63% of patients with myeloma and 70% of those with Hodgkin lymphoma and were not predicted by changes in chimerism. These data support the presence of clinically relevant graft-versus-Hodgkin activity and indicate that DLI may be associated with a significantly increased toxicity in unrelated compared to sibling donor transplant recipients receiving identical treatment protocols.Keywords
This publication has 28 references indexed in Scilit:
- Donor lymphocyte infusions mediate superior graft-versus-leukemia effects in mixed compared to fully allogeneic chimeras: a critical role for host antigen–presenting cellsBlood, 2002
- The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantationBlood, 2002
- Unrelated Donor Leukocyte Infusions to Treat Relapse after Unrelated Donor Bone Marrow TransplantationLeukemia & Lymphoma, 2002
- Induction of stable long-term mixed hematopoietic chimerism following nonmyeloablative conditioning with T cell-depleting antibodies, cyclophosphamide, and thymic irradiation leads to donor-specific in vitro and in vivo toleranceTransplantation and Cellular Therapy, 2001
- Prevention of Graft Versus Host Disease by Inactivation of Host Antigen-Presenting CellsScience, 1999
- Lymphohematopoietic graft-vs.-host reactions can be induced without graft-vs.-host disease in murine mixed chimeras established with a cyclophosphamide-based nonmyeloablative conditioning regimenTransplantation and Cellular Therapy, 1999
- Adoptive immunotherapy for relapse of chronic myeloid leukemia after allogeneic bone marrow transplant: equal efficacy of lymphocytes from sibling and matched unrelated donorsBone Marrow Transplantation, 1998
- Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation.Journal of Clinical Oncology, 1997
- Bone marrow transplants from HLA-identical siblings in advanced Hodgkin's disease.Journal of Clinical Oncology, 1996
- Graft-versus-host-related immunosuppression is induced in mixed chimeras by alloresponses against either host or donor lymphohematopoietic cells.The Journal of Experimental Medicine, 1988