Reduced-intensity transplantation with in vivo T-cell depletion and adjuvant dose-escalating donor lymphocyte infusions for chemotherapy-sensitive myeloma: limited efficacy of graft-versus-tumor activity.
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 adjuva...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2003
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| _version_ | 1797091497108045824 |
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| author | Peggs, K Mackinnon, S Williams, C D'Sa, S Thuraisundaram, D Kyriakou, C Morris, E Hale, G Waldmann, H Linch, D Goldstone, A Yong, K |
| author_facet | Peggs, K Mackinnon, S Williams, C D'Sa, S Thuraisundaram, D Kyriakou, C Morris, E Hale, G Waldmann, H Linch, D Goldstone, A Yong, K |
| author_sort | Peggs, K |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T03:33:58Z |
| format | Journal article |
| id | oxford-uuid:bbaa6b36-c255-40c8-a263-b757ef67b23d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:33:58Z |
| publishDate | 2003 |
| record_format | dspace |
| spelling | oxford-uuid:bbaa6b36-c255-40c8-a263-b757ef67b23d2022-03-27T05:18:35ZReduced-intensity transplantation with in vivo T-cell depletion and adjuvant dose-escalating donor lymphocyte infusions for chemotherapy-sensitive myeloma: limited efficacy of graft-versus-tumor activity.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:bbaa6b36-c255-40c8-a263-b757ef67b23dEnglishSymplectic Elements at Oxford2003Peggs, KMackinnon, SWilliams, CD'Sa, SThuraisundaram, DKyriakou, CMorris, EHale, GWaldmann, HLinch, DGoldstone, AYong, KReduced-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. |
| spellingShingle | Peggs, K Mackinnon, S Williams, C D'Sa, S Thuraisundaram, D Kyriakou, C Morris, E Hale, G Waldmann, H Linch, D Goldstone, A Yong, K Reduced-intensity transplantation with in vivo T-cell depletion and adjuvant dose-escalating donor lymphocyte infusions for chemotherapy-sensitive myeloma: limited efficacy of graft-versus-tumor activity. |
| title | Reduced-intensity transplantation with in vivo T-cell depletion and adjuvant dose-escalating donor lymphocyte infusions for chemotherapy-sensitive myeloma: limited efficacy of graft-versus-tumor activity. |
| title_full | Reduced-intensity transplantation with in vivo T-cell depletion and adjuvant dose-escalating donor lymphocyte infusions for chemotherapy-sensitive myeloma: limited efficacy of graft-versus-tumor activity. |
| title_fullStr | Reduced-intensity transplantation with in vivo T-cell depletion and adjuvant dose-escalating donor lymphocyte infusions for chemotherapy-sensitive myeloma: limited efficacy of graft-versus-tumor activity. |
| title_full_unstemmed | Reduced-intensity transplantation with in vivo T-cell depletion and adjuvant dose-escalating donor lymphocyte infusions for chemotherapy-sensitive myeloma: limited efficacy of graft-versus-tumor activity. |
| title_short | Reduced-intensity transplantation with in vivo T-cell depletion and adjuvant dose-escalating donor lymphocyte infusions for chemotherapy-sensitive myeloma: limited efficacy of graft-versus-tumor activity. |
| title_sort | reduced intensity transplantation with in vivo t cell depletion and adjuvant dose escalating donor lymphocyte infusions for chemotherapy sensitive myeloma limited efficacy of graft versus tumor activity |
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