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

Author:

Kottaridis Panagiotis D.1,Milligan Donald W.1,Chopra Rajesh1,Chakraverty Ronjon K.1,Chakrabarti Suparno1,Robinson Stephen1,Peggs Karl1,Verfuerth Stephanie1,Pettengell Ruth1,Marsh Judith C. W.1,Schey Stephen1,Mahendra Premini1,Morgan Gareth J.1,Hale Geoff1,Waldmann Herman1,de Elvira M. Carmen Ruiz1,Williams Catherine D.1,Devereux Stephen1,Linch David C.1,Goldstone Anthony H.1,Mackinnon Stephen1

Affiliation:

1. From the Departments of Hematology, University College London Hospital, London, England; Heartlands Hospital, Birmingham, England; Christie Hospital, Manchester, England; St George's Hospital, London, England; Guy's Hospital, London, England; Queen Elizabeth Hospital, Birmingham, England; Leeds General Infirmary, Leeds, England, and Therapeutic Antibody Centre, University of Oxford, Oxford, England.

Abstract

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/m2 on days −7 to −3; and melphalan, 140 mg/m2 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 11%. Although longer follow-up is needed to establish the long-term remission rates, this study demonstrates that this nonmyeloablative preparative regimen is associated with durable engraftment, minimal toxicity, and low incidence of GVHD.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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