The use of thiotepa in reduced toxicity conditioning regimens before hematopoietic stem cell transplantation in primary immunodeficiencies

Abstract

The use of reduced toxicity conditioning regimens in patients with primary immunodeficiencies (PID) leads to the reduction of toxic effects of hematopoietic stem cell transplantation (HSCT). Currently, HSCT should result not only in disease control, but also in the improvement of the quality of life. We report the experience of HSCT in PID with TCRab+/CD19+ graft depletion after conditioning regimen containing treosulfan in combination with thiotepa as a second alkylating agent. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. A group of 79 PID patients aged 0.5–17.6 years (the median age was 3.1 years) received HSCT from HLA matched related (n = 5), unrelated (n = 34) and haploidentical (n = 40) donors. The incidence of acute graft-versus-host disease (GVHD) ≥ grade II was 21%, grade III GVHD was observed in 3.8%, and none of the patients had GVHD grade IV. There were no cases of severe toxicity, including venoocclusive disease and thrombotic microangiopathy. The incidence of primary and secondary graft failure was 15.4%. The overall survival was 82.3%. There was no statistical difference between overall survival rates of patients who underwent transplantation from different types of donors (p = 0.164). All deaths were transplant-related and were due to infections. The use of thiotepa in reduced toxicity conditioning regimen is effective and safe, and can be considered as an option for HSCT in PID.