The experience of hematopoietic stem cells transplantation with TCRαβ+/CD19+ depletion without posttransplantation prophylaxis of GVHD in patients with primary immunodeficiencies (PID)
Estimation of feasibility and safety of allogeneic hematopoietic stem cell transplantation (HSCT) with TCRαβ +/CD19+ cell depletion in patients with primary immunodeficiency (PID) without usage of posttransplant immunosuppressive therapy.
Patients and methods
Ten allogeneic HSCTs were performed from October 2017 to May 2018 to the patients with PID (Nijmegen breakage syndrome, 1; Chronic granulomatous disease, 2; CID with CD40L deficiency, 3; PID with PI3K-delta deficiency, 1; X-linked lymphoproliferative syndrome type I, 1; leukocyte adhesion deficiency; 1; severe congenital neutropenia, 1). We carried out trans plants from unrelated (n=8) or haploidentical donors (n=2) using TCRαβ+/CD19 + depletion. Nine patients were conditioned for HSCT with treosulfan 42 g/m2, fludarabine 150 mg/m2, melphalan 140 mg/m2; one patient (Nijmegen’s syndrome) – treosulfan 30 g/m2, fludarabine 150 mg/m2, cyclophosphamide 40 mg/kg. Antithymocyte immunoglobulin – Thymoglobulin® (“Genzyme Europe B.V.”, The Netherlands) was used as a serotherapy at the doses of 5 to 7.5 mg/kg in all cases. Posttransplant GVHD prophylaxis was not performed.
Transplant engraftment was recorded in all the patients. Acute GVHD was verified in 3 out of 10 cases, in 2 of which GVHD of 2nd degree was limited to skin. Only one patient (with Nijmegen syndrome) had acute liver GVHD stage 3 and combined immunosuppressive therapy was required. All the patients are alive at 2 to 10 months after HSCT, with good functional characteristics of the transplants.
Exclusion of posttransplant immunosuppressive therapy after HSCT with TCRαβ+/CD19+ depletion in patients with PID has demonstrated safety in relation to the risk of GVHD development. Severe visceral form of GVHD was recorded only in a patient being at high risk of developing this complication, due to characteristics of the disease (Nijmegen syndrome). Currently, the recruitment of patients is underway, and estimation of immune reconstitution rates reactivation of viral infections, and other factors should be evaluated later.
Hematopoietic stem cell transplantation, TCRαβ+/CD19+ depletion, graft-versus-host disease, posttransplant immunosuppressive therapy, primary immunodeficiency.