Low Progression-Free Survival for High-Risk Patients Treated with Reduced-Intensity Conditioning Regimen Allogeneic Stem Cell Transplantations with Volunteer Unrelated Donors.

Abstract

Reduced-intensity conditioning regimens (RICR) are increasingly used before allogeneic stem cell transplantation (SCT) for patients not eligible for myeloablative conditioning. The relapse and survival rates after RICR allogeneic SCT were studied in 19 high-risk patients treated between February 2002 and December 2004. Ten males and 9 females with a median age of 47 years (15–55) received PBSC transplantation from a 10/10 (n=15) or 9/10 HLA antigen-matched donor (n=4). Acute leukemia was the main diagnoses (n=12; 6 AML and 6 ALL), the other diagnoses were 3 multiple myeloma, 2 CML, 1 NHL, 1 CLL. All patients had high-risk disease: 12 had second or > 2 complete remission, 5 second partial remission and 2 refractory disease. The preparative regimen consisted of cumulative dose of Busulfan 8mg/kg, Fludarabine 150 mg/m2 and ATG 7.5 mg/kg (Thymoglobulin, Genzyme, Lyon, France). Graft-versus-host disease (GVHD) prophylaxis regimen consisted of cyclosporine A and short-course methotrexate. Median follow-up was 14 months (5–39 months). Engraftment was complete in all but 2 patients with refractory disease and 14 patients achieved 100% donor CD3 (median 56 days, range 18–123). Grade 2 to 3 acute GVHD was seen in 3 (16%) patients, no grade 4 acute GVHD was observed. Grade 1 chronic GVHD was seen in 1 patient. Nine pts relapsed at a median time of 9.5 months, 3 pts had never reached a full CD3 donor chimerism. Twelve pts are alive, seven pts in complete remission, 2 pts with relapsed disease. Three pts relapsed and achieved a subsequent complete remission by chemotherapy, one of them received a second SCT, one a DLI and one other developed hepatic cGVHD and didn't receive DLI. Five pts died from recurrent disease, One pt died from cerebral toxoplasmosis and one other from cerebral hemorrhage due to a secondary poor graft function. Survival rate was 73% (95% CI 0.52–0.93) at 6 months and 60% (95% CI 0.38–0.83) at 1 year. PFS rate was 73% (95% CI 0.52–0.93) at 6 months and 33% (95% CI 0.09–0.57) at 1 year. In conclusion, in this cohort of pts, the progression-free survival is unsatisfactory. This can be explained by the advanced stage diseases and the low incidence of cGVHD, probably due to high immunosuppressive treatment. A less intensive immunosuppressive protocol can be tested to improve the results in this particular group of patients. [Display omitted] [Display omitted]