Reduced-Intensity Conditioning (RIC) Prior to Allogeneic Stem Cell Transplantation (allo-SCT) In Pediatric Patients Ineligible for Standard Myeloablative Conditioning.

Abstract 3478

RIC regimens prior to allo-SCT are a well-established conditioning approach in elderly adult patients, or in patients with comorbidities not eligible for standard allo-SCT approach. The development of RIC allo-SCT in pediatric patients has been slower than in the adult population because children generally tolerate more intensive myeloablative regimens. However, an increasing proportion of heavily pre-treated pediatric patients might benefit from a non intensive conditioning approach prior to allo-SCT. Thus far, data regarding the efficacy of RIC approaches to treat pediatric patients is still limited, and the role of this approach in pediatric cancer has yet to be defined.

The aim of this single-centre retrospective study was to assess the outcome of 19 children (Median age: 12.1 (range, 2.6–18.1) years; gender: male/female 10/9) treated with RIC allo-SCT for different hematological malignancies (n=17; ALL: 6; AML: 4; JMML: 2; NHL: 1; MDS: 1; sAML: 1; biphenotypic leukemia: 1; CML: 1), bone marrow failure (n=1) and neuroblastoma (n=1). In this series, all children were ineligible for a conventional myeloablative conditioning regimen because of severe comorbidities (n=9), a previous auto or allo-SCT (n=7) or a history of extensive chemotherapy (n=3). At time of RIC allo-SCT, most of the patients were in complete remission (n=13; 68%), 2 in partial response and 4 in stable or progressive disease. All patients received a fludarabine-based RIC regimen before allo-SCT (Flu-i.v.Bu-ATG: 8; Flu-Cy-low dose TBI: 7; other combinations: 4). The allogeneic graft was obtained from a match-related donor in 5 cases, match-unrelated donor in 6 cases, and unrelated cord blood (UCB) cells in the remaining 8 cases (42%). The median infused number of nucleated cells and CD34+ stem cells were 4.54×10⁸ and 4.94×10⁶ /kg for peripheral blood stem cells or bone marrow, respectively, and 0.462 and 0.155×10⁶/kg for UCB stem cells. Two patients who received UCB failed to engraft and the median time to ANC>500/μL was 18 days. With a median follow up of 25 (range, 12–120) months after allo-SCT, treatment related mortality incidence was 16% (n=3). The principal cause of death was relapse (n=6) which occurred at a median time of 112 (range, 29–406) days after RIC allo-SCT. Only 2 patients experienced grade 3–4 acute GVHD and one patient developed chronic GVHD. At 2 years, the Kaplan-Meier estimates of disease-free (DFS) and overall survival (OS) were 45% (95%CI, 25–67%) and 55% (95%CI, 33–75%).

In all, these data suggest that favorable outcomes can be achieved with RIC allo-SCT in pediatric patients who are ineligible for standard myeloablative conditioning. Larger prospective studies focusing on decreasing relapse by decreasing tumor burden prior to RIC and by using early immunomodulating approaches after allo-SCT are needed because RIC allo-SCT may help cure many very-high-risk pediatric patients.