Improved outcomes using unmanipulated haploidentical hematopoietic stem cells combined with third‐party umbilical cord blood transplantation for non‐malignant diseases in children: The experience of a single center

Abstract

Background: Unmanipulated haploid HSCT for SAA has resulted in improved outcomes over recent years. However, studies related to unmanipulated haploid HSCs combined with tp-UCB transplantation for other types of NMD are rare. Accordingly, we present the outcomes of 109 pediatric patients with life-threatening NMD undergoing unmanipulated haploid HSCs combined with tp-UCB transplantation.Procedure: We retrospectively investigated 109 pediatric patients with lifethreatening NMD treated with unmanipulated haploid HSCs combined with tp-UCB transplantation in a single center. Results:The median days of neutrophil and platelet engraftment were +13 and +22 days, respectively. None of the cases experienced PGF. The incidence rates for grade I-II, III-IV aGVHD and cGVHD were 44.9%, 24.8%, and 9.3%, respectively. The incidence rates of CMV and EBV viremia were 46.7% and 39.4%, respectively. The median follow-up duration was 997 days. In total, 106 patients survived, including 104 cases with FFS and 2 cases with SGF. Three patients died. The 5-year TRM, OS, and FFS were 2.8%, 97.2%, and 96.2%, respectively. Conclusion:The results of unmanipulated haploid HSCs combined with tp-UCB in pediatric patients with life-threatening NMD were promising. However, further research is now needed to determine specific factors that might influence the engraftment of HSCs. K E Y W O R D Sbone marrow failure syndromes, children, haploidentical hematopoietic stem cell transplantation, inborn errors of metabolism, non-malignant diseases, primary immunodeficiency disease How to cite this article: Tang X, Yu Z, Ping L, Lu W, Jing Y, Cao X. Improved outcomes using unmanipulated haploidentical hematopoietic stem cells combined with third-party umbilical cord blood transplantation for non-malignant diseases in children: The experience of a single center. Pediatr Transplant.

Comparison of Haploidentical Hematopoietic Stem Cell Transplant With or Without Unrelated Cord Blood Infusion in Severe Aplastic Anemia: Outcomes of a Multicenter Study

“…In patients with a successful engraftment, the incidence of aGVHD and moderate-to-severe cGVHD was similar between the haplo-HSCT and haplo-cord-HSCT groups, while the overall cGVHD in the haplo-cord-HSCT group tended to be lower than that observed in the haplo-HSCT group. These findings are consistent with those reported by an earlier study ( 15 ). This may be because UCB contains MSCs and CD4 + CD25 + Tregs ( 29 , 30 ), which have an immune regulatory role on the hematopoietic microenvironment and prevention of GVHD.…”

“…Several single-arm studies have demonstrated the feasibility and effectiveness of haplo-cord-HSCT in SAA and other nonneoplastic and malignant hematologic disorders (13)(14)(15)17). However, this approach for SAA is currently considered investigational and requires further study before firm recommendations can be made.…”

“…In recent years, some experienced transplant centers have been investigating strategies to optimize the haplo-HSCT model, such as haplo-HSCT combined with mesenchymal stem cells (MSCs), umbilical cord blood (UCB), or a post-transplant cyclophosphamide conditioning regimen (9)(10)(11). It should be noted that the conditioning regimen, the time and count of UCB infusion, and the mechanism of allo-HSCT success in different hematological diseases are sometimes different (12)(13)(14)(15). Until recently, our two studies not only demonstrated that a haplocord-HSCT achieved 97.1% donor myeloid engraftment and 81.4 ± 3.3% four-year OS in SAA patients but also that failure-free survival and a health-related quality of life were both better in SAA patients after first-line haplo-cord-HSCT than that achieved by IST (16,17).…”

The state of the art in the treatment of severe aplastic anemia: immunotherapy and hematopoietic cell transplantation in children and adults

“…Additionally, CB was associated with a higher GF rate and inferior platelet engraftment. In a study from 2021, HCT in 60 pediatric patients with SAA used unmanipulated haploHCT with third-party 1-5/6 HLA antigen-matched umbilical CB after myeloablative conditioning with busulfan, Cy, and Flu (228). The 5-year transplant-related mortality, OS, and FFS were 2.8%, 97.2%, and 96.2%, respectively.…”