Abstract
We recently demonstrated that TCRαβ+/CD19+ graft depletion successfully prevents severe acute and chronic graft-versus-host disease (GVHD) in pediatric patients with primary immunodeficiencies (PID) receiving transplants from both matched unrelated and mismatched related donors. However, in all patients, short-term post-hematopoietic stem cell transplantation (HSCT) immunosuppressive therapy (IST) was used. There are limited data on TCRαβ+/CD19+ graft depletion with no post-HSCT IST implementation. In the current study 74 PID patients who underwent first HSCT from matched unrelated (n=51) or mismatched related donors (n=23) with TCRαβ+/CD19+ graft depletion were included. All received as a conditioning regimen a combination of treosulfan with fludarabine and either melphalan or thiotepa. In all, thymoglobulin 5 mg/kg (days −5, −4, −3) and rituximab at day −1 were used. In 48 patients, various approaches to short-term post-transplantation IST were used, and 26 patients received no post-HSCT IST. The rates of engraftment, acute and chronic GVHD, survival, and mortality were similar in those who received and did not receive IST, with a slightly higher incidence of graft rejection in patients not receiving IST: 19% in the non-IST group against 13% in the IST group (P = .41). The incidence of cytomegalovirus reactivation was 50% and 39% (P = .50) and Epstein-Barr virus reactivation 10% and 0 (P = .20) in the IST and non-IST groups, respectively. No grade 4 adverse events were seen in both groups, although in 19 of 40 (47.5%) patients receiving calcineurin inhibitors, the therapy was discontinued before day 45. More robust immune recovery with both T- and B-lymphocytes was observed in the non-IST group. To conclude, TCRαβ+/CD19+ in combination with particular serotherapy effectively prevents severe acute and chronic GVHD in PID. Regarding remaining risks of infectious complications and additional drug-related toxicity, there are no benefits to post-HSCT IST use in these patients.
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