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Role of Nonmyeloablative Allogeneic Stem-Cell Transplantation After Failure of Autologous Transplantation in Patients With Lymphoproliferative Malignancies

From the CR (UK) Department of Medical Oncology, Christie Hospital, Manchester; Department of Hematology, University College, London Hospital, Department of Hematology, Guy’s Hospital, and Department of Hematology, St George’s Hospital, London; Department of Hematology, Glasgow Royal Infirmary, Glasgow; Department of Hematology, University Hospital; and Department of Hematology, Heartlands Hospital, Birmingham, United Kingdom.

Address reprint requests to Rajesh Chopra, MD, CR (UK) Department of Medical Oncology, Christie Hospital, Wilmslow Rd, Manchester M20 4BX, United Kingdom; email: rchopra{at}picr.man.ac.uk

PURPOSE: Conventional allogeneic stem-cell transplantation (SCT) after a prior failed autograft is associated with a transplant-related mortality rate of 50% to 80%. The aim of the current study was to evaluate the safety and efficacy of sibling, HLA-matched, nonmyeloablative allogeneic SCT with donor lymphocyte infusion (DLI) in patients with lymphoid malignancy after failure of autologous SCT.

PATIENTS AND METHODS: A total of 38 patients with refractory, progressive, or relapsed disease after autologous SCT were entered onto this study. The conditioning regimen consisted of the humanized monoclonal antibody CAMPATH-1H, fludarabine, and melphalan. Fifteen of 35 assessable patients received DLI after SCT.

RESULTS: Sustained neutrophil engraftment was achieved in 37 recipients, and platelet engraftment was achieved in 35 patients. The estimated transplant-related mortality was 7.9% at day 100 and 20% at 14 months, the median duration of follow-up. Eight patients experienced grade I/II acute graft-versus-host disease (GVHD) after transplantation, but no grade III/IV GVHD was observed in this setting. However, grade III/IV GVHD occurred in seven patients who received DLI. The actuarial overall survival at 14 months was 53%, with a progression-free survival of 50%. DLI produced a further response in three of 15 recipients.

CONCLUSION: Nonmyeloablative allogeneic SCT after CAMPATH-1H–containing conditioning is a relatively safe option compared with conventional allogeneic transplantation for patients who have failed previous autologous SCT. The low incidence of early GVHD enabled the subsequent administration of DLI to improve further clinical responses in this poor-risk group of lymphoma and myeloma patients.

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