Mismatched related vs matched unrelated donors in TCRαβ/CD19-depleted HSCT for primary immunodeficiencies

Abstract

Publisher's Note: There is a [Related article:] Blood Commentary on this article in this issue.

Key Points

• There was no difference in outcomes after MMRD and MUD HSCT with TCRαβ ⁺/CD19 ⁺ graft depletion in patients with primary immunodeficiencies.

• HSCT from MMRDs with TCRαβ ⁺⁺/CD19+ graft depletion is a safe and effective alternative for MUD HSCT in patients with PID.

Abstract

TCRαβ ⁺/CD19 ⁺ graft depletion effectively prevents graft-versus-host disease (GVHD). In the current study, we compared the outcomes of hematopoietic stem cell transplantation (HSCT) with TCRαβ ⁺/CD19 ⁺ depletion from matched unrelated donors (MUDs) and mismatched related donors (MMRDs) in patients with primary immunodeficiency (PID). A total of 98 pediatric patients with various PIDs underwent HSCT with TCRαβ ⁺/CD19 ⁺ graft depletion from MUDs (n = 75) and MMRDs (n = 23). All patients received a fludarabine-/treosulfan-based conditioning regimen, with 73 also receiving a second alkylating agent. For GVHD prophylaxis, all but 2 received serotherapy (antithymocyte globulin) before HSCT and a short course of posttransplant immunosuppression. Neutrophil and platelet engraftment in both the MUD and MMRD groups occurred on days 14 and 13, respectively. The incidence of secondary graft failure was 0.16 and 0.17 ( P = .85), respectively. The cumulative incidence of acute GVHD grade 2 to 4 was 0.17 in the MUD group and 0.22 in the MMRD group ( P = .7). The incidence of cytomegalovirus (CMV) viremia was 0.5 in the MUD group and 0.6 in the MMRD group ( P = .35). The frequency of CMV disease was high (17%), and the most common manifestation was retinitis. The kinetics of immune recovery was similar in both groups. The overall survival was 0.86 in the MUD group and 0.87 in the MMRD group ( P = .95). In our experience, there was no difference in the outcomes of HSCT performed from MUD and MMRD. Hence, given the immediate availability of donors, in the absence of HLA-identical siblings, HSCT with TCRαβ ⁺/CD19 ⁺ graft depletion from MMRDs can be considered as the first choice in patients with PID.

Visual Abstract