Long-term outcomes of αβ T-cell/CD19 B-cell-depleted peripheral blood stem cell transplantation from unrelated donors in pediatric and adolescent patients with severe aplastic anemia: a single-center study.

Abstract

Hematopoietic stem cell transplantation (HSCT) from matched unrelated donor (MUD) is a curative option for severe aplastic anemia (SAA) patients, refractory to horse anti-thymocyte globulin (ATG) and cyclosporin A (CsA) mmunosuppression. Although the results of MUD HSCT in SAA have improved significantly, graft-versus host disease (GVHD) remains a serious problem, associated with significant morbidity and mortality. We investigated the role of alpha/beta T cell depletion of the graft as a way to improve the results of MUD HSCT in SAA. Forty-seven patients with SAA were treated since September 2012 till February 2022. Median age at HSCT was 12.4 (3-22.7) years, 26 males/21 females. All patients were either refractory or relapsed (35:12) after combined immune suppression therapy, 5 pts had concurrent severe hemolytic paroxysmal nocturnal hemoglobinuria (PNH). The median time from diagnosis to transplant was 1.2 years (0.5-11.8 years). Preparative regimen included cyclophosphamide 100 mg/kg, fludarabine 150 mg/kg, ATGAM at 100 mg/kg (27pts) or thymoglobulin 5 mg/kg (15 pts) and 6 Gy thoraco-abdominal irradiation. Thiotepa at 10 mg/kg and rituximab at 200 mg/m² were used in a proportion of cases. Patients with PNH (n = 5) received eculizumab 600 mg once every 7 days from -7 to +14 days. Post-transplant GVHD prophylaxis included tacrolimus till day 180. Peripheral blood stem cell (PBSC) grafts were depleted of T cell receptor (TCR) alpha/beta cells and CD19 cells with CliniMACS device, as recommended by the manufacturer. Patients received a median of 9.2 (2.7-18.30) х10⁶ CD34 per kg, 21.8 (0.85-316)x10³ αβ T cells per kg. Forty-six patients (cumulative incidence (CI) 0.96 (95% 0.9-1)) engrafted with a median of 14 (7-24) days for white blood cells (WBC) and 12 (9-18) days for platelets. In 8 patients after MUD transplantation secondary graft failure (rejection) developed, cumulative incidence was 0.15 (95% 0.08-0.3), three of them was successfully retransplanted. CI of acute graft-versus host disease (aGVHD) grade II-IV was 0.15 (95% 0.08-0.29). No cases of grade III-IV aGVHD were registered. CI of chronic graft versus host disease (cGVHD) was 0.11 (95% 0.05-0.25). All were mild and off-IST at last follow-up. A median follow-up is 9 years. Ten patients died. At a median follow-up of 9 years, the overall survival was 79% (67-90). Failure-free survival was 72% (60-85) and the GRFS was 72% (60-85). TCR alpha/beta depletion is a robust platform for allogeneic HSCT from MUD in severe aplastic anemia. Results should be further improved by additional measures to control viral infections and prevent rejection.