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

作者:Panagiotis D. Kottaridis, Donald William Milligan, Rajesh Kumar Chopra, Ronjon K. Chakraverty, Suparno Chakrabarti, Stephen Paul Robinson, Karl S. Peggs, Stephanie Verfuerth, Ruth Pettengell, Judith C. W. Marsh, Stephen Schey, Premini Mahendra, Gareth John Morgan, G Hale, Herman Waldmann, M C Ruiz de Elvira, Catherine D. Williams, Stephen Devereux, David C. Linch, Anthony H. Goldstone, Stephen Mackinnon · 发表于:Blood · 年份:2000 · DOI:10.1182/blood.v96.7.2419 · 被引用次数:503 · 研究领域:Hematopoietic Stem Cell Transplantation、Polyomavirus and related diseases、Renal Transplantation Outcomes and Treatments

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 nonrelapse mortality was ...