Similar Outcome Using Sibling, Unrelated Donor, and Cord Blood Grafts after Reduced-Intensity Conditioning in Children: A Retrospective Study from the SFGM-TC

Reduced intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) is increasingly used in children, especially in those who have been heavily pre-treated or who have received prior autologous or allo-SCT. Of note, use of cord blood as stem cell source is currently a standard of care in pediatric patients lacking a sibling or an unrelated donor. Currently, comparison between matched siblings (SIB), unrelated donors (URD), or umbilical cord blood (UCB) allo-SCT has not yet been reported in the RIC setting in children.

Here, we compared reduced-intensity conditioning allo-SCT performed between January 1998 and December 2012 in 124 consecutive children (<18 years) with a median age of 12.8 years (males, n=69). Disease included acute leukemia (n=78), myelodysplastic syndrome (MDS)/myeloproliferative disorder (MPD)/chronic myeloid leukemia (CML) (n=22) and lymphoma (n=24). Status at transplant were as follows: complete remission (CR), n=84, (CR1 n=22, CR2 n=35, CR3 n=20, missing n=7); partial response n=6; primary induction failure n=8; relapse or progression n=19, up-front (MDS) n=2, chronic phase (CML) n=2, missing n=3. Twenty-five patients had received a previous auto-SCT and 44 a previous allo-SCT. Clinical data were prospectively collected using ProMISe (Project Manager Internet Server), an internet-based data registry system shared by all SFGM-TC centres. Type of donor included SIB (n = 32), URD (n = 56), or UCB (n = 36, single n=23; double n=13). The three groups were well balanced in terms of gender, diagnosis, status at transplant, median follow-up, previous transplant status, median time interval between disease diagnosis and allo-SCT, period of transplant, patients aged < or >= 10 years at time of transplant. Regarding RIC regimen, fludarabine and iv busulfan was the most commonly used regimen for SIB and URD cases while it was fludarabine + low-dose total body irradiation (Minneapolis approach) for UCB patients. The use of in-vivo T cell depletion (ATG) was significantly less frequent in the UCB group (16.7% vs 53.1% (SIB) vs 66.1% (URD), p<0.0001). Considering the whole cohort, cumulative incidence of engraftment was 81.4%. With a median follow-up of 49 months (range: 7-163), 5-year overall (OS) and disease free (DFS) survival rates were 40% (31-50) and 39% (31-48), respectively. 5-year cumulative incidences of relapse (RI) and non-relapse mortality (NRM) were 43% (34-52) and 17% (11-24), respectively, while 2-year incidence of chronic GVHD was 20% (12-29).

Engraftment rates were similar between the three groups: 93.3% (SIB) vs 86.8% (URD) vs 77.1% (UCB), p=0.10. The 5-year cumulative incidences of NRM were 13%, 18%, and 19% with SIB, URD, and UCB transplantation, respectively (p=0.73). The 5-year DFS rates were 42% (24-59), 36% (23-48), and 43% (27-60) with SIB, URD, and UCB transplantation, respectively (p=0.70). The 5-year OS rates were 40% (22-59), 40% (27-53), and 38% (17-60) with SIB, URD, and UCB transplantation, respectively (p=0.94). Finally, grade 2-4 acute GVHD and 2-year incidence of chronic GVHD were similar between the three groups: 29.6% (SIB) vs 32.1% (URD) vs 38.2% (UCB), p=0.75; and 10% (SIB) vs 23% (URD) vs 24% (UCB), p=0.51.

In multivariate analysis, donor type had no significant impact on overall survival (SIB vs URD, HR: 1.19; 95%CI: 0.61-2.33, p=0.61; SIB vs UCB, HR: 1.28; 95%CI: 0.69-2.37, p=0.43) while a diagnosis of MDS/MPD/CML was independently associated with better OS (HR: 2.49; 95%CI: 1.17-5.29, p=0.02).

In conclusion, despite evident limitations due to the retrospective setting of this study, results from this national survey support the recommendation to consider any stem cell source (SIB donor, URD, or UCB) in children candidate for a RIC allo-SCT.