Autografting followed by nonmyeloablative immunosuppressive chemotherapy and allogeneic peripheral-blood hematopoietic stem-cell transplantation as treatment of resistant Hodgkin's disease and non-Hodgkin's lymphoma

Purpose: To investigate the use of a nonmyeloablative fludarabine-based imm unosuppressive regimen to allow engraftment of HLA-sibling donors' mobilize d stem cells and induction of a graft-versus-lymphoma effect for patients w ith advanced resistant Hodgkin's disease and non-Hodgkin's lymphoma. Patients and Methods: Fifteen patients with Hodgkin's disease (n = 10) and non-Hodgkin's lymphoma (n = 5) were studied. All patients received cyclopha sphamide and granulocyte colony-stimulating factor to mobilize autologous h ematopoietic stem cells (HSCs). Subsequently, they received high-dose thera py with carmustine, etoposide, cytarabine, and melphalan and reinfusion of HSCs. At a median of 61 days after engraftment, patients were given fludara bine 30 mg/m(2) with cyclophosphamide 300 mg/m(2) daily for 3 days. Donor-m obilized HSC collections were prepared for fresh infusion and were not T-ce ll depleted. Methotrexate and cyclosporine were used to prevent graft rejec tion and as graft-versus-host disease (GVHD) prophylaxis. Results: Combined treatment was well tolerated. After mini-allografting, he matologic recovery was prompt. Thirteen patients had 100% donor cell engraf tment. Eleven patients achieved complete remission (CR) after the combined procedure. Nine patients, who were in partial remission after autografting, achieved CR after mini-allografting. Seven patients developed greater than or equal to grade 2 acute GVHD (aGVHD) and two developed extensive chronic GVHD (cGVHD). Three patients who received the highest number of donor lymp hocyte infusions (DLIs) developed grade 3 GVHD (two patients) and extensive cGVHD (one patient). Ten patients are currently alive, and five are in con tinuous CR. Seven patients received DLI, with five CRs. Five patients died: one of progressive disease, two of progressive disease combined with aGVHD or cGVHD, one of extensive cGVHD, and one of infection. Conclusion: Fludarabine/cyclophosphamide was well tolerated and allowed con sistent engraftment in lymphoma allografted patients. Response rates were h igh in this group of refractory and heavily pretreated patients. This dual procedure seems to be mast promising in patients with end-stage malignant l ymphomas. (C) 2000 by American Society of Clinical Oncology.