RIC regimens followed by allogeneic SCT have demonstrated to induce complete donor chimerism and long-term survival with decreased transplant-related mortality in adults with poor-risk hematological malignancies. Pediatric experience of RIC regimens is mostly reported in children with non malignant diseases in whom late long-term complications should be reduced. There are only limited data in children with malignancies, ineligible for conventional SCT. We conducted a retrospective survey of 28 children who underwent a RIC regimen for a malignant hematological disease (18 AL, 2 RAEBt, 1 CML, 3 NHL, 2 HD) or a solid tumor (1 Ewing sarcoma, 1 rhabdomyosarcoma) from 1998 to 2004 in 11 participating hospitals. All children had contraindications against myeloablative regimen. Median age was 14 years. Fourteen patients (pts) had an advanced disease (> CR2, refractory or progressive).Ten pts had already undergone at least one transplantation. Most RIC were fludarabine-based (n= 26). Nineteen children received additional anti-thymocyte globulin and 4 were transplanted with a T-depleted graft. Source of hematopoietic stem cell was marrow (n= 17), peripheral blood (n= 9) or cord blood (n= 2). Donor was matched related (n= 12) or unrelated (n= 8), mismatched related (n= 2) or unrelated (n= 6). Median follow-up after SCT is 142 days (range: 22–2345). Engraftment was observed in all 25 valuable pts. Day-90 chimerism analysis was performed in 18 pts and showed complete donor cells in 12 and autologous reconstitution in 3 pts. Grade II–IV aGVHD and cGVHD developed in 8/25 and 3/16 valuable pts, respectively. The day-100 transplant-related mortality rate was 18%. Disease progression or relapse occurred in 13 pts. Nineteen pts died: 11 from initial disease, 2 from infection, 2 from GVHD, 4 from other toxic complication. Four pts underwent a second transplantation for relapse or autologous reconstitution (3 myeloablative, 1RIC SCT). Five pts are alive in CR 145, 336, 782, 993, 2345 days after a first transplantation, 2 pts 272 and 1062 days after a second transplantation. Only 1 child among the 14 with an advanced disease is alive versus 6 among those with a lower-risk disease. In conclusion, allogeneic SCT with RIC is feasible in heavily pre-treated children. In order to reduce the high incidence of relapse, further prospective studies are needed to determine best pts selection criteria (initial diagnosis, treatment prior to transplant, chemosensitivity of the disease) and the best transplantation strategy (timing, type of the RIC, post-transplant additional treatment).