In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation

P D Kottaridis, D W Milligan, R Chopra, R K Chakraverty, S Chakrabarti, S Robinson, K Peggs, S Verfuerth, R Pettengell, J C W Marsh, S Schey, P Mahendra, G J Morgan, G Hale, H Waldmann, M C R de Elvira, C D Williams, S Devereux, D C Linch, A H GoldstoneS Mackinnon

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477 Citations (Scopus)

Abstract

A novel nonmyeloablative conditioning regimen was investigated in 44 patients with hematologic malignancies. The median patient age was 41 years. Many of the patients had high-risk features, including 19 patients with a previous failed transplant. Recipient conditioning consisted of CAMPATH-1H, 20 mg/day on days -8 to -4; fludarabine, 30 mg/m(2) on days -7 to -3; and melphalan, 140 mg/m(2) on day -2. Thirty-six recipients received unmanipulated granculocyte colony-stimulating factor-mobilized peripheral blood stem cells from HLA-identical siblings, and 8 received unmanipulated marrow from matched unrelated donors. GVHD prophylaxis was with cyclosporine A alone for 38 patients and cyclosporine A plus methotrexate for 6 sibling recipients. Forty-two of the 43 evaluable patients had sustained engraftment. Results of chimerism analysis using microsatellite polymerase chain reaction indicate that 18 of 31 patients studied were full-donor chimeras while the other patients were mixed chimeras in one or more lineages. At a median follow-up of 9 months (range 3 to 29 months), 33 patients remain alive in complete remission or with no evidence of disease progression. Seven patients relapsed or progressed post-transplantation, and 4 of them subsequently died. Four patients died of regimen-related complications. There were no cases of grades III-IV acute GVHD. Only 2 patients developed grade II acute GVHD, and only 1 had chronic GVHD. The estimated probability of non-relapse mortality was 11%. Although longer follow-up is needed to establish the longterm remission rates, this study demonstrates that this nonmyeloablative preparative regimen is associated with durable engraftment, minimal toxicity, and low incidence of GVHD. (Blood. 2000;96:2419-2425) (C) 2000 by The American Society of Hematology.
Original languageEnglish
Pages (from-to)2419 - 2425
Number of pages7
JournalBlood
Volume96
Issue number7
Publication statusPublished - 1 Oct 2000

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