Successful allogeneic stem cell transplantation with nonmyeloablative conditioning in patients with relapsed hematologic malignancy following autologous stem cell transplantation

The use of myeloablative preparative therapy and allogeneic stem cell trans plantation (alloSCT) as salvage therapy for adult patients with relapsed he matologic malignancy after autologous stem cell transplantation (autoSCT) i s generally unsuccessful due to very high treatment-related mortality rates . We evaluated the outcome of HLA-matched related donor alloSCT following n onmyeloablative preparative therapy in 13 patients (median age, 38 years) w ith relapsed hematologic malignancies (Hodgkin's disease, n = 4; Hodgkin's disease and advanced myelodysplastic syndrome, n = 1; non-Hodgkin's lymphom a, n = 6; multiple myeloma, n = 2) after initial autoSCT Median time from a utoSCT to alloSCT was 12 months (range, 3-24 months); 6 patients had chemot herapy-refractory disease following autoSCT, 6 were in untreated relapse, a nd 1 had a partial response from salvage chemotherapy. Preparative therapy consisted of cyclophosphamide, 150-200 mg/kg; peritransplantation anti-thym ocyte globulin; thy mic irradiation (in patients who had not received previ ous mediastinal irradiation); and a very short course of cyclosporine as GV HD prophylaxis. All patients achieved initial mixed chimerism as defined by greater than 1% donor peripheral white blood cells. Seven patients, who ha d no evidence of GVI-m, received prophylactic DLI beginning 5 to 6 weeks af ter transplantation for conversion of mixed chimerism to full donor hematop oiesis and to optimize a graft-versus-tumor effect. Six patients showed con version to full donor chimerism and 1 lost the graft. Grade II or greater a cute GVHD occurred in 9 patients. Seven patients achieved a complete respon se; 6 had no response. The median survival time of the 13 patients is curre ntly 10 months (range, 3-39 months), with an overall survival probability a t 2 years of 45% (95% confidence interval [CI], 19%-73%) and a disease-free survival probability at 2 years of 37.5% (95 % CI, 12%-65%). Thus, this no vel nonmyeloablative alloSCT strategy followed by prophylactic DLI was well tolerated and can result in durable disease-free survival among patients w ith advanced hematologic malignancies after a failed autoSCT. Further follo w-up and evaluation of additional patients are required to conclusively est ablish the role of this strategy in the treatment of hematologic malignanci es after an autologous transplantation.