Second allogeneic hematopoietic stem cell transplantation in patients with inborn errors of immunity

Abstract

Graft failure (GF) remains a serious issue of hematopoietic stem cell transplantation (HSCT) in inborn errors of immunity (IEI). Second HSCT is the only salvage therapy for GF. There are no uniform strategies for the second HSCTs and limited data are available on the second HSCT outcomes. 48 patients with various IEI received second allogeneic HSCT from 2013 to 2020. Different conditioning regimens were used, divided into two main groups: containing myeloablative doses of busulfan/treosulfan (n = 19) and lymphoid irradiation 2-6 Gy (n = 22). Irradiation-containing conditioning was predominantly used in suspected immune-mediated rejection of the first graft. Matched unrelated donor was used in 28 patients, mismatched related in 18, and matched related in 1. 35 patients received TCRαβ/CD19 graft depletion. The median follow-up time was 2.4 years post-HSCT. One patient died at conditioning. The OS was 0.63 (95% CI: 0.41-0.85) after busulfan/treosulfan and 0.68 (95% CI: 0.48-0.88) after irradiation-based conditioning, p = 0.66. Active infection at HSCT significantly influenced OS: 0.43 (95% CI: 0.17-0.69) versus 0.73 (95% CI: 0.58-0.88) without infection, p = 0.004. The cumulative incidence of GF was 0.15 (95% CI: 0.08-0.29). To conclude, an individualized approach is required for the second HSCT in IEI. Low-dose lymphoid irradiation in suspected immune-mediated GF may be a feasible option.

Fig. 1. Cumulative incidence of second HSCT graft failure depending on the type of conditioning regimen.

myeloablative conditioning (MAC) with irradiation, n = 10 (dotted curve) versus reduced intensity conditioning (RIC) with irradiation, n = 12 (solid curve) versus busulfan/treosulfan-based, n = 19 (dash curve).

Fig. 2. Overall survival of the patients with IEI after second HSCT.

a Depending on the type of conditioning regimen: irradiation-based, n = 22 (solid curve) versus busulfan/treosulfan-based, n = 19 (dash curve). b Depending on the type of conditioning regimen: myeloablative conditioning (MAC) with irradiation, n = 10 (solid curve) versus reduced intensity conditioning (RIC) with irradiation, n = 12 (dash curve). c Depending on the presence of active infection at HSCT: with infection, n = 14 (dash curve) versus no infection, n = 34 (solid curve).