Successful Allogeneic Stem Cell Transplantation with Nonmyeloablative Conditioning in Patients with Relapsed Hodgkin's Disease Following Autologous Stem Cell Transplantation

Abstract

Use of myeloablative preparative therapy and allogeneic stem cell transplantation (alloSCT) as salvage therapy for adult patients with relapsed hematologic malignancies after autologous stem cell transplantation (autoSCT) is generally unsuccessful due to very high treatment-related mortality rates. We report here the outcome of HLA-matched related donor alloSCT following nonmyeloablative preparative therapy in two patients with Hodgkin's disease, relapsed after autologous stem cell graft. Times from autoSCT to alloSCT were 9 and 11 months, respectively. Preparative therapy consisted of the following: oral busulfan, 4 mg/kg on days −6 and −5; intravenous (i.v.) cyclophosphamide, 350 mg/m 2 on days −4, −3 and, −2, and i.v. fludarabine, 30 mg/m 2 on days −4, −3, and −2; oral cyclosporin A (CyA) 5 mg/kg was begun on day −1 and i.v. methotrexate 5 mg/m 2 was delivered on days +1, +3, +5, and +11. Both patients achieved initial mixed chimerism as defined as >1% donor peripheral white blood cells and did not receive prophylactic donor lymphocyte infusions; both showed conversion to final full-donor chimerism. Stage I acute graft-vs.-host disease occurred in one patient and both achieved sustained complete response. One patient died on day 233 as a consequence of drug-induced pulmonary toxicity, whereas the other patient remains in continued complete remission 513 days after allograft. This nonmyeloablative alloSCT strategy was well tolerated, was completed entirely on an out-patient basis, and can result in durable disease-free survival among patients with Hodgkin's disease after failed autoSCT. Further follow-up and evaluation of additional patients are required to conclusively establish the role of this strategy in treatment of hematologic malignancies after autologous transplantation.