Treosulfan-Based Conditioning Regimen for Allogeneic Hepatopoietic Stem Cell Transplantation in Children: A Single Center Experience

Abstract

Objective: Treosulfan is an alkylating agent whose use is increasing in HSCT conditioning regimens. Studies have highlighted its efficacy alongside its low toxicity profile. In this single-center study, we retrospectively report our experience and results with treosulfan in pediatric stem cell conditioning regimens. Methods: Fifty-seven patients who underwent stem cell transplantation with a treosulfan-based conditioning regimen between September 2017 and April 2023 at the Istanbul Medipol University Pediatric Bone Marrow Transplantation Unit were included in the study. Treosulfan doses were determined based on age (under 1 year: 10g/m²/day; 1-2 years: 12g/m²/day; over 2 years: 14g/m²/day for 3 days). Results: Of the 57 patients, 27 (47%) experienced acute GVHD and 3 (5.2%) experienced chronic GVHD. Of the 27 patients who had acute GVHD, 20 had grade I-II GVHD, and 7 had grade III-IV GVHD. Among the 3 patients with chronic GVHD, 1 experienced grade III-IV GVHD and 2 had grade I-II acute GVHD. Among the 14 patients with acute skin GVHD, 3 had grade III-IV, and among the 4 patients with acute gastrointestinal (GI) GVHD, 1 had grade III-IV. Of the 8 patients with acute skin +GI GVHD, 2 had grade III-IV. One patient experienced grade IV skin and liver GVHD. Of the 3 patients with chronic GVHD, 2 developed bronchiolitis obliterans and 1 had chronic skin GVHD. VOD developed in 2 patients. One of these patients had leukocyte adhesion deficiency (LAD) type 3 and underwent a transplant from an MUD without defibrotide. The other patient, diagnosed with HLH, received a haploidentical transplant with defibrotide. Two patients experienced secondary engraftment failure. One had thalassemia major, and the other had Chediak-Higashi syndrome. All patients except these two were followed-up with full donor chimerism. Four of the 57 patients died (overall mortality: 7 %). One patient with ALL died from GVHD-sepsis, and another died due to relapsed disease. One patient with AML was lost due to bronchiolitis obliterans during the third year post-transplant, and another patient with AML succumbed to sepsis and toxicity within the first 100 days. There were no deaths among patients with non-malignant diagnoses. The 100-day mortality rate was 1.75 %, with one patient passing away during this period. Conclusions: Treosulfan can be preferred in the conditioning regimens of pediatric patients due to its similar efficacy and lower toxicity profile. Our study, which includes a broad pediatric patient group, provides guidance in this regard.

Keywords

• Pediatric stem cell transplantation
• treosulfan
• treosulfan-based conditioning regimen

References

1. Greystoke B, Bonanomi S, Carr TF,, Gharib M, Khalid T, Coussons M, et al. Treosulfan-containing regimens achieve high rates of engrafment associated with low transplant morbidity and mortality in children with non-malignant disease and significant co-morbidities. Br J Heamatol. 2008;142(2)-257-62. google scholar
2. Dinur-Schejter Y, Krauss AC, Erlich O, Gorelik N, Yahel A, Porat I, et al. Bone marrow transplantation for non-malignant diseases using treosulfan-based conditioning. Peditr Blood Cancer. 2015;62(2):299-304. google scholar
3. Burroughs LM, Shimamura A, Talano JA, Domm JA, Baker KK, Delaney C, et al. Allogeneic hematopoietic cell transplantation using treosulfan-based conditioning for treatment of marrow failure disorders. Biol Blood Marrow Transplant: J Am Soc Blood Marrow Transplant. 2017;23(10):1669-77 google scholar