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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

From the Hematology and Autologous Stem Cell Transplantation Unit, Department of Hematology, Azienda Ospedale San Martino; Istituto Medicina Legale, Università di Genova, Genova; Centro Trasfusionale, Ospedale San Martino, Genova; Oncologia Medica, Ospedale San Carlo, Milano; Oncologia Medica, Ospedale Circolo di Varese, Varese; and Divisione Medicina, Ospedale Pietrasanta, Italy.

Address reprint requests to Angelo Michele Carella, Hematology and Stem Cell Transplant, Department of Hematology, Azienda Ospedaliera e Cliniche, Universitarie Convenzionate, Ospedale San Martino, Via Acerbi 10/22, 16148 Genoa, Italy; email amcarella@ smartino.ge.it.

PURPOSE: To investigate the use of a nonmyeloablative fludarabine-based immunosuppressive regimen to allow engraftment of HLA-sibling donors’ mobilized stem cells and induction of a graft-versus-lymphoma effect for patients with 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 cyclophosphamide and granulocyte colony-stimulating factor to mobilize autologous hematopoietic stem cells (HSCs). Subsequently, they received high-dose therapy with carmustine, etoposide, cytarabine, and melphalan and reinfusion of HSCs. At a median of 61 days after engraftment, patients were given fludarabine 30 mg/m² with cyclophosphamide 300 mg/m² daily for 3 days. Donor-mobilized HSC collections were prepared for fresh infusion and were not T-cell depleted. Methotrexate and cyclosporine were used to prevent graft rejection and as graft-versus-host disease (GVHD) prophylaxis.

RESULTS: Combined treatment was well tolerated. After mini-allografting, hematologic recovery was prompt. Thirteen patients had 100% donor cell engraftment. 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 grade 2 acute GVHD (aGVHD) and two developed extensive chronic GVHD (cGVHD). Three patients who received the highest number of donor lymphocyte infusions (DLIs) developed grade 3 GVHD (two patients) and extensive cGVHD (one patient). Ten patients are currently alive, and five are in continuous 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 consistent engraftment in lymphoma allografted patients. Response rates were high in this group of refractory and heavily pretreated patients. This dual procedure seems to be most promising in patients with end-stage malignant lymphomas.

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