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Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders.

Pérez-Simón, José A
; 
Kottaridis, Panagiotis D
; 
Martino, Rodrigo
; 
Craddock, Charles
; 
Caballero, Dolores
; 
Chopra, Rajesh
; 
García-Conde, Javier
; 
Milligan, Donald W
; 
Schey, Stephen
; 
Urbano-Ispizua, Alvaro
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Abstract
Although nonmyeloablative conditioning regimen transplantations (NMTs) induce engraftment of allogeneic stem cells with a low spectrum of toxicity, graft-versus-host disease (GVHD) remains a significant cause of morbidity and mortality. In vivo T-cell depletion, using alemtuzumab, has been shown to reduce the incidence of GVHD. However, this type of maneuver, although reducing GVHD, may have an adverse impact on disease response, because NMTs exhibit their antitumor activity by relying on a graft-versus-malignancy effect. To explore the efficacy of alemtuzumab compared with methotrexate (MTX) for GVHD prophylaxis, we have compared the results in 129 recipients of a sibling NMT enrolled in 2 prospective studies for chronic lymphoproliferative disorders. Both NMTs were based on the same combination of fludarabine and melphalan, but the United Kingdom regimen (group A) used cyclosporin A plus alemtuzumab, whereas the Spanish regimen (group B) used cyclosporin A plus MTX for GVHD prophylaxis. Patients receiving alemtuzumab had a higher incidence of cytomegalovirus (CMV) reactivation (85% versus 24%, P <.001) and a significantly lower incidence of acute GVHD (21.7% versus 45.1%, P =.006) and chronic GVHD (5% versus 66.7%, P <.001). Twenty-one percent of patients in group A and 67.5% in group B had complete or partial responses 3 months after transplantation (P <.001). Eighteen patients in group A received donor lymphocyte infusions (DLIs) to achieve disease control. At last follow-up there was no difference in disease status between the groups with 71% versus 67.5% (P =.43) of patients showing complete or partial responses in groups A and B, respectively. No significant differences were observed in event-free or overall survival between the 2 groups. In conclusion, alemtuzumab significantly reduced GVHD but its use was associated with a higher incidence of CMV reactivation. Patients receiving alemtuzumab often required DLIs to achieve similar tumor control but the incidence of GVHD was not significantly increased after DLI.
Authors
Pérez-Simón, José A
Kottaridis, Panagiotis D
Martino, Rodrigo
Craddock, Charles
Caballero, Dolores
Chopra, Rajesh
García-Conde, Javier
Milligan, Donald W
Schey, Stephen
Urbano-Ispizua, Alvaro
Parker, Anne
Leon, Angel
Yong, Kwee
Sureda, Anna
Hunter, Ann
Sierra, Jordi
Goldstone, Anthony H
Linch, David C
San Miguel, Jesus F
Mackinnon, Stephen
Affiliation
Department of Hematology, Hospital Universitairo de Salamanca, Paseo de San Vicente s/n, 37007 Salamanca, Spain. pesimo@usal.es
Description
Date
2002-11-01
Publisher
Collections
All Paterson Institute for Cancer Research
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Keywords
Graft vs Tumour Effect
Cancer Antibodies
Haematologic Cancer
Type
Article
Citation
Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders. 2002, 100 (9):3121-7 Blood
Journal Title
Journal ISSN
Volume Title
URI
http://hdl.handle.net/10541/84355
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