Treosulfan-based conditioning for hematopoietic stem cell transplantation in patients with Diamond–Blackfan anemia

Abstract

Busulfan-based conditioning regimens before hematopoietic stem cell transplantation (HSCT) in patients with Diamond–Blackfan anemia (DBA) are the standard therapy for a long time. Unfortunately, the high incidence of toxic complications is the cause of transplant-related mortality (TRM) or low quality of life. Treosulfan-based conditioning is very attractive, however only limited data exists of its administration in DBA patients. In this article, we present the experience of treosulfan usage along with novel approaches to “graft versus host” disease (GVHD) prophylaxis in Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. From 2012 to 2020, 9 patients with DBA underwent HSCT. Matched unrelated donors were used in 7 patients, mismatched related in 1, and HLA-identical sibling in 1 patient. All patients received treosulfan-based conditioning. The sources of HSC were bone marrow (n = 3) and peripheral blood after TCRab+/CD19+ graft depletion (n = 6). Eight patients received various regimens of post-transplant prophylaxis, included calcineurin inhibitors alone or in combinations, 1 patient – mycophenolate mofetil. All transplanted patients engrafted. Median follow-up in survivors (n = 8) was 35.6 months. One patient (Karnofsky-index before HSCT 40%) died on day +58 due to multio rgan failure, caused by toxic and infectious complications. Besides, three patients had clinically signifiant toxic complications: oral mucositis grade 3 in 1 patient, treosulfan skin toxicity in 2, and moderate veno-occlusive-disease in 1 patient. Five patients had acute GVHD grade II with complete response to the 1st line therapy. There was no evidence of acute GVHD grade III–IV as well as chronic GVHD. Our data demonstrate, that treosulfan-based conditioning, alongside new cellular engineering approaches is effctive options for HSCT outcomes in patients with DBA.