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Prepublished online as a Blood First Edition Paper on July 5, 2002July 12, 2002; DOI 10.1182/blood-2002-03-0701.
Submitted March 5, 2002
Accepted June 12, 2002
Non-myeloablative transplants with or without CAMPATH-1H: comparison between two prospective studies in patients with lymphoproliferative disorders
Jose A Perez-Simon*, Panagiotis D Kottaridis, Rodrigo Martino, Charles Craddock, Dolores Caballero, Raj Chopra, Javier Garcia-Conde, Don W Milligan, Stephen Schey, Alvaro Urbano-Ispizua, Anne Parker, Angel Leon, Kwee Yong, Ana Sureda, Ann Hunter, Jordi Sierra, Anthony H Goldstone, David C Linch, Jesus F San Miguel, and Stephen Mackinnon
Spanish and UK Collaborative Groups for non-myeloablative transplantation, Paseo de San Vicente, Spain
Spanish and UK Collaborative Groups for non-myeloablative transplantation, London, United Kingdom
* Corresponding author; email: pesimo{at}usal.es.
Although non-myeloablative conditioning regimen transplants (NMT) induce engraftment of allogeneic stem cells with a low spectrum of toxicity, GVHD remains a significant cause of morbidity and mortality. In vivo-T cell depletion, using CAMPATH-1H, has been shown to reduce the incidence of GVHD. However this type of maneuvers whilst reducing GVHD may have an adverse impact on disease response, since NMT exhibit their antitumour activity by relying on a graft versus malignancy effect. In order to explore the efficacy of CAMPATH-1H as compared to methotrexate (MTX) for GVHD prophylaxis we have compared the results of 129 recipients of a sibling NMT enrolled in two pospective studies for chronic lymphoproliferative disorders. Both NMT were based on the same combination of fludarabine and melphalan but the UK regimen (group A) used Cyclosporine A plus CAMPATH-1H whilst the Spanish regimen (group B) used Cyclosporine A plus MTX for GVHD prophylaxis. Patients receiving CAMPATH-1H had a higher incidence of CMV reactivation (85% vs 24%, p<0.001) and a significantly lower incidence of aGVHD (23.1% vs 45.1%, p=0.006) and cGVHD (5% vs 66.7%, p<0.001). Twenty-one percent (group A) and 67.5% (group B) of patients achieved CR or PR 3 months after transplant (p<0.001). Eighteen patients in group A received donor lymphocyte infusions (DLI) in order to achieve disease control. At last follow up there was no difference in disease status between the groups with 71% vs 67.5% (p=0.43) of patients reaching CR or PR in groups A and B, respectively. No significant differences were observed in event free or overall survival between both groups. In conclusion, CAMPATH-1H significantly reduced GVHD but its use was associated with a higher incidence of CMV reactivation. Patients receiving CAMPATH-1H often required DLI in order to achieve similar tumour control but the incidence of GVHD was not significantly increased after DLI.
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