Comparison of Outcomes of Mismatched Related Stem Cell and Unrelated Cord Blood Transplants in Children with Severe T-Cell Deficiencies.
Authors: Fernandes Juliana Folloni , Rocha Vanderson , Labopin Myriam , Neven Benedicte , Gennery Andrew , Friedrich Wilhelm , Porta Fulvio , de Heredia Cristina Diaz , Wall Donna A. , Bertrand Yves , Veys Paul , Slatter Mary , Schulz Ansgar S , Chan Ka Wah , Grimley Michael , Ayas Mouhab F. , Güngör Tayfun , Ebell Wolfram , Bonfim Carmem , Kalwak Krzysztof , Gaspar H. Bobby , Landais Paul , Fischer Alain , Gluckman Eliane , Cavazzana-Calvo Marina 
Published: October 2019

Abstract
Abstract 664
Severe combined immune deficiency (SCID) diseases, as well as other severe T-cell deficiencies like Omenn syndrome, are considered pediatric emergencies. To date, hematopoietic stem cell transplantation (HSCT) is the only curative therapy for these children. Considering the urgency of these transplants, for patients lacking an identical sibling donor, the use of mismatched related donors (MMRD) and unrelated umbilical cord blood (UCB) are important alternatives. In a retrospective study, we compared the outcomes of 175 children with severe T-cell deficiencies (SCID=152, Omenn syndrome=23) receiving MMRD transplants and 74 (SCID=52, Omenn syndrome=15) receiving UCB transplants, reported to the SCETIDE and Eurocord databases, from 1995 to 2005. MMRD transplants were performed in 12 different centers and UCB transplants were distributed among 30 different centers. Only 5 centers performed the two techniques. The median age at transplant was 6.4 months for the UCB group and 6.5 months for the MMRD group (p=0,87). Median time elapsed between diagnosis and transplant was 47 days for MMRD (range 4-485) and 55 days (range 17-526) for UCB transplants (p=0.06). There were no statistically significant differences between the two groups regarding gender and incidence of failure to thrive, chronic diarrhea or respiratory impairment before transplant. Patients receiving UCB had more often B-negative phenotype (61% UCB vs. 41% MMRD; p=0.009), while patients receiving MMRD had a greater incidence of viral infections prior to transplant (59% MMRD vs. 36% UCB; p=0.004). The year of transplantation also differed between the two groups, as more patients receiving UCB were transplanted between 2000-2005 (65%) compared to MMRD (50%) (p=0.014). Regarding HLA (considering HLA-A,B-low resolution and DRB1-high resolution), in the UCB group, 67% of patients had 0 or 1 disparities while 33% had 2 or 3 disparities. In the MMRD group, 10% had 1 disparity and 90% had 2 or 3 disparities. Seven patients receiving UCB (16%) transplants and 30 patients receiving MMRD (17%) did not receive any preparative regimen prior to graft infusion. Conditioning regimen was non-myeloablative in 45% of MMRD transplants and 30% of UCB transplants. The remaining received myeloablative regimens. Graft-versus-host disease (GVHD) prophylaxis was cyclosporine A-based in the majority of the UCB transplants (n=71). T-cell depletion was used in all transplants with MMRD and 52 patients received immunosuppressants, mostly cyclosporine A. The median follow-up time was 84 months for patients given a MMRD and 59 months for UCB transplants recipients. Sixty-one patients receiving UCB transplants engrafted (82%), all with full donor chimerism in CD3+ cells. On the CD3- compartment 75% had full donor, 5% mixed and 20% had recipient chimerism. In MMRD group, 130 patients engrafted (74%), 98% with full donor chimerism in CD3+ cells. On CD3- cells, 33% had full donor chimerism, 48% were mixed and 19% recipient chimerism. Forty-six patients in the MMRD group and 7 patients in the UCB group needed to receive second transplants. The cumulative incidence of acute GVHD had no statistically significant difference between groups (33% UCB vs. 23% MMRD; p=0.13). However, patients receiving UCB transplants had more chronic GVHD (22% UCB vs. 11% MMRD; p=0.04). In a univariate analysis, 5-year overall survival was 62 ± 4% for MMRD and 58% ± 6% for UCB transplants (p=0.83). In a multivariate analysis adjusting for differences between the two groups, 5-year overall survival was not statistically different (p=0.54). Regarding T-cell reconstitution, we analyzed the total lymphocyte, CD3+ and CD4+ cell numbers and there were no statistically significant differences between the two groups comparing absolute numbers at 6, 12 and 24 months after transplantation. In conclusion, both unrelated cord blood and mismatched related donors are choices for transplants in severe T-cell deficiencies lacking an HLA-identical sibling donor. The choice of donor type will depend on centre's strategy regarding the possibility of efficiently deplete MMRD grafts of T-cells, or find a rapidly available UCB unit.

Disclosures:
No relevant conflicts of interest to declare.