Reduced Intensity Allogeneic Peripheral Blood Stem Cell Transplantation in Renal Cell Carcinoma: The EIO Experience.

Background. A less toxic approach than conventional allogeneic stem cell transplantation based on the use of a non-myeloablative and potent immunosuppressive regimen has been previously developed. Aim of such procedure is to establish a mixed chimerism engraftment and to get an immunologic effect against the tumor, eventually potentiated by donor lymphocyte infusion. Such effect is well known to occur in hematological malignancies and is under investigations in solid tumors, mainly renal cell carcinoma (RCC).

Patients and methods. From December 2003 to June 2004 we enrolled 8 pts, median age 57 (34–66), affected by metastatic RCC, in progressive disease (PD) after different lines of therapies. Conditioning regimen was the following: Fludarabine, 30 mg/m², from day −4 to −2 followed by 2Gy TBI on day 0, when all pts received HLA matched related grafts. Prophylaxis of aGvHD was performed with administration of Cyclosporine (6.25mg/kg) p.o. bid from day −3 to +36 followed by a rapid tapering to +56 and mycophenolate mofetil (15mg/kg) p.o. bid, given from day 0 to +27.

Results. After transplantation five pts achieved a SD (62%), 2 experienced PD and response was not evaluable for one pt who died at +24. Three showed graft rejection at day +56, +90 and +120, respectively. After a median follow-up of 152 days (24–440), 3/8 (37%) patients are still alive: 2 in SD at +386 and +144, despite loss of graft in +90 and in +56, respectively and 1 in PD; 5 (62%) pts have died, 4 because of PD, 1 for aGvHD. Hematological toxicity was mild with no G4 neutropenia or thrombocytopenia; infections occurred in 2/8 (25%) pts, none was fatal. Incidence of aGvHD was 25%(2/8), one of which was G4 fatal aGVHD. No patient suffered from cGvHD.

Conclusions. Our results confirm this regimen is safe and feasible in patients affected by metastatic RCC, but further studies are necessary to clarify the high rate of graft rejections (3/8, 37%) and the low clinical activity of the regimen.