Graft-versus-tumor effect following reduced-intensity allogeneic stem cell transplantation in prostate cancer

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6551 Background: Allogeneic transplantation has been utilized as adoptive immunotherapy for patients with solid tumors resistant to conventional therapy. Methods: In 2001 we started a pilot study of allogeneic hematopoietic cell transplantation after a reduced-intensity regimen in patients with metastatic, androgen-independent prostate cancer, aged 18–70, ECOG PS 0–1. Planned sample size was 10 patients. Primary endpoint was feasibility of the procedure. The conditioning regimen included thiotepa, fludarabine, and cyclophosphamide. Patients received allogeneic peripheral blood cells from an HLA-identical sibling. A median of 6.9×10e6 CD34+ cells/kg were infused (range 4.8–11.8). Graft-versus-Host Disease (GvHD) prophylaxis consisted of cyclosporine A and short-course methotrexate. All the patients were evaluable for engraftment and chimerism. Results: Six patients have been enrolled. The median age was 61 years (range 51–66). The median time to reach an absolute neutrophil count of 1.0×10e9/l and a platelet count of 20×10e9/l was 11 and 12 days respectively (range 10–14 and 11–16). All patients achieved complete lymphoid- and myeloid-chimerism at day +90 by cytogenetics or by VNTR polymorphism analysis. Median day of cyclosporine A withdrawal was +85. Three patients developed acute GvHD grade ≥2, usually soon after cyclosporine withdrawal. At a median follow-up of 401 days (range 93–682), 2 patients are alive and 4 died, 2 for disease progression (+214 and +275), one for CMV disease (+93) and one for hemorrhagic cystitis (+527). This last patient achieved an almost complete response confirmed on choline-PET scan after cyclosporine withdrawal and limited chronic GvHD. In other 4 patients we observed a PSA reduction, concurrently with cyclosporine withdrawal or development of GvHD. Conclusions: The close association between GvHD and/or cyclosporine withdrawal and tumor responses strongly suggests that tumor regression was associated with an immune-mediated reaction related to allografting. Future strategies will aim at enhancing the anti-tumor effect and at decreasing GvHD and transplant-related mortality. No significant financial relationships to disclose.