Outcomes After Reduced-Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) In 163 Pediatric Patients (<18 years old): A Retrospective Study On Behalf Of The SFGM-TC

Outcomes after RIC allo-SCT in children are rarely reported. The largest series published thus far included 47 children with hematologic malignancies (Pulsipher et al, Blood, 2009). There is thus currently no large series describing the results of RIC allo-SCT in children.

163 pediatric patients (<18 years old, median age: 15.8 years (range: 2.9-17.9)) who received RIC allo-SCT for a hematologic malignancy were reported to the SFGM-TC registry between 1998 and 2011. Median year for transplant was 2005. The majority of cases had myeloid malignancies (59.5%) and most of the patients were in complete remission (CR) at transplant (65%, CR1 n=45; CR2 n=39, CR3 n=23, active disease n=40, missing data n=16). Forty-eight (29.5%) and 30 (18.5%) patients had received prior autologous SCT or allo-SCT, respectively. Donors were HLA-matched related in 48 cases; mismatched related n=5; MUD n=59; mismatch unrelated n=10. The source of stem cells was bone marrow, PBSC and cord blood in 44%, 31% and 25% of cases, respectively.

Engraftment was observed in 85.5% of cases with a median time for neutrophils recovery of 20 days (range: 1-79). With a median follow-up of 23 months (range: 1-169), 2-year (2-y) OS, DFS, RI and NRM were 46+-5%, 37.5+-4%, 40+-3% and 22+-3%, respectively. Cumulative incidence (CI) of acute GVHD at day+100 was 36+-4% while 2-y CI of chronic GVHD was 24.5+-3%. In univariate analysis, factors such as disease status (CR vs active), donor type, source of stem cells, TBI or ATG administration were not associated with outcomes. There were a trend for better 2-y DFS in patients allotransplanted after 15.5 months from the diagnosis (42+-6% vs 33+-6%, p=0.09), for higher 2-y RI but a lower 2-y NRM in patients allografted before 10 years old (52+-7% vs 35+-5%, p=0.07; 12+-5% vs 35+-5%, p=0.06, respectively) and finally a trend for better 2-y OS in patients with lymphoid malignancies (54+-7 vs 41+-6%, p=0.09). Patients allografted after 2004 (n=122; median age: 13.2 years (range: 1-17.9); male 60%; myeloid malignancies 59%, CR: 63%) showed significantly higher 2-y OS (52+-5% vs 31+-7%, p=0.006) and DFS (45+-5% vs 18+-6%) due in part to a significantly lower 2-y NRM (17+-4% vs 36+-8%, p=0.01) reflecting probably a better patient’s selection before transplant. In patients allografted since 2004 multivariate analysis revealed that lymphoid malignancy was the only favourable and independent factor for LFS and OS (HR: 0.55, 95%CI: 0.32-0.97, p=0,04; HR: 0.47, 95%CI: 0.25-0.88, p=0.02).

This large series shows that RIC allo-SCT is feasible with acceptable toxicity in pediatric patients, especially in cases of lymphoid malignancy. Prospective studies are needed to confirm the potential role of RIC allo-SCT in the pediatric setting, with a special focus on long-term side effects, which are a matter of concern in children.

Mohty:Novartis: Honoraria, Research Support Other.