Abstract |
Reduced-intensity conditioning regimens allow application of allogeneic stem cell transplantation to greater numbers of patients with myeloma by reducing transplantation-related mortality. We prospectively evaluated the role of an approach incorporating in vivo T-cell depletion and subsequent adjuvant donor lymphocyte infusions (DLIs) as part of front-line therapy for chemotherapy-sensitive multiple myeloma. Twenty patients with HLA-matched related (n = 12) or unrelated (n = 8) donors entered the study. None had previously undergone autologous transplantation. Acute graft-versus-host disease (GVHD) following transplantation was minimal (3 grade II and no grade III or IV). Nonrelapse mortality rate was relatively low (15%) compared with conventional myeloablative allogeneic transplantation series, although it remained significantly higher than in the autologous setting. Disease responses by 6 months posttransplantation were modest (2 in complete remission, 4 in partial remission, 2 were minimally responsive, 6 had no change, 3 had progressive disease, and 3 were not evaluable). Fourteen patients received escalating-dose DLI for residual/progressive disease. Three developed acute GVHD and 2 developed limited chronic GVHD. Seven demonstrated further disease responses, which appeared to be more common in those developing GVHD (5 of 5 versus 2 of 9; P =.02). All responses were associated with conversion from mixed to full donor T-cell chimerism. Response durations were disappointing (5 <12 months) and progression often occurred despite persisting full donor chimerism. Two-year estimated overall survival and current progression-free survival rates (intention to treat with DLI from 6 months) were 71% and 30%, respectively. The current approach incorporating T-cell depletion appears excessively immunosuppressive despite attempts to restore immune function with DLI. Dose escalation failed to allow convincing dissociation of graft-versus-myeloma from GVHD. Attempts to hasten immune reconstitution and to focus and amplify appropriate components of allogeneic T-cell responses will be required to increase complete remission rates and response durations.
|
Authors | Karl S Peggs, Stephen Mackinnon, Catherine D Williams, Shirley D'Sa, Dharsha Thuraisundaram, Charalampia Kyriakou, Emma C Morris, Geoff Hale, Herman Waldmann, David C Linch, Anthony H Goldstone, Kwee Yong |
Journal | Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
(Biol Blood Marrow Transplant)
Vol. 9
Issue 4
Pg. 257-65
(Apr 2003)
ISSN: 1083-8791 [Print] United States |
PMID | 12720218
(Publication Type: Clinical Trial, Journal Article)
|
Copyright | Copyright 2003 American Society for Blood and Marrow Transplantation |
Topics |
- Adult
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use, toxicity)
- Female
- Graft Survival
- Graft vs Tumor Effect
- Hematopoietic Stem Cell Transplantation
(adverse effects, methods, mortality)
- Humans
- Infections
(chemically induced)
- Lymphocyte Depletion
- Lymphocyte Transfusion
- Male
- Middle Aged
- Multiple Myeloma
(complications, mortality, therapy)
- Survival Analysis
- T-Lymphocytes
- Transplantation Chimera
- Transplantation Conditioning
(methods)
- Transplantation, Homologous
- Treatment Outcome
|