Allogeneic cell therapy for patients who relapse after autologous stem cell transplantation

Allogeneic donor leukocytes can be used after nonmyeloablative conditioning to exploit their graft-versus-tumor (GVT) activity in the setting of reduc ed conditioning-regimen toxicity. This approach may be particularly useful for patients who relapse after autologous stem cell transplantation (SCT). However, GVT activity, toxicity, and ability to establish mixed chimerism m ay differ in patients who were heavily pretreated prior to SCT compared wit h patients treated earlier in the course of their disease. We have performe d a series of studies of nonmyeloablative allogeneic transplantation and pr esent data on the subset of 14 patients treated for relapse after autologou s SCT: 4 patients received no conditioning and unstimulated donor leukocyte infusions (DLI), 10 patients received conditioning with fludarabine and cy clophosphamide followed by unstimulated or granulocyte-colony-stimulating f actor (G-CSF)-stimulated allogeneic peripheral blood stern cells (PBSCs), 4 patients received no graft-versus-host disease (GVHD) prophylaxis, and 10 patients received cyclosporine GVHD prophylaxis. All but I patient had sust ained donor chimerism at least 30 days after allogeneic cell therapy (ACT), and 8 patients had more than 80% donor chimerism after ACT. Acute GVHD dev eloped in 11 patients (grade III-IV: n = 6). Aplasia was more frequent in t he patients receiving unstimulated PBSCs, despite the development of mixed chimerism. There were 6 complete responses and 4 partial responses; respons e was independent of conditioning and growth-factor stimulation of the dono r graft. Five patients died of treatment-related causes and 4 patients died from progressive disease. Four patients remained alive 27 to 194 weeks (me dian, 66 weeks) after ACT. Prior autologous SCT may define a subset of pati ents at particularly high risk for GVHD and other toxicity after ACT. Howev er, these data show that ACT with either DLI or G-CSF-stimulated blood cell s results in direct GVT activity in some patients with Hodgkin's disease, m yeloma, and non-Hodgkin's lymphoma, even after relapse from autologous SCT. Most patients developed donor chimerism with minimal conditioning Alternat ive prophylactic regimens that control GVHD while maintaining GVT are neede d to improve outcomes in these heavily pretreated patients.