Treosulfan-based conditioning regimens for allogeneic HSCT in children with acute lymphoblastic leukaemia

Abstract

Standard myeloablative conditioning regimens for children with acute lymphoblastic leukaemia are based on total body irradiation (TBI). However, TBI causes profound short-term and long-term side effects, provoking the necessity for alternative regimens. Treosulfan combines a potent immunosuppressive and antileukaemic effect with myeloablative activity and low toxicity profile. We retrospectively studied toxicity and outcome of 71 paediatric patients with acute lymphoblastic leukaemia (ALL) undergoing haematopoietic stem cell transplantation (HSCT) following treosulfan-based conditioning aiming to identify risk factors for treatment failure and dose-depending outcome differences. Early regimen-related toxicity was low. No case of veno-occlusive disease was reported. There was no association of toxicity with age or number of HSCT. Event-free survival (EFS) of infants was significantly better compared to older children. Overall survival (OS) at 3 years was 51 % and not significantly influenced by number of HSCT (first HSCT 54 %, ≥second HSCT 44 %, p = 0.71). In multivariate analysis, OS and EFS were significantly worse for patients transplanted without complete remission (p = 0.04 and 0.004). Treatment-related mortality was low at 14 %. We conclude that treosulfan-based conditioning is a safe and efficacious approach for paediatric ALL.

Treosulfan-based conditioning for allogeneic HSCT in children with chronic granulomatous disease: a multicenter experience

“…17 cGVHD developed in 9 patients (13%), 6 of whom are now free of symptoms. GVHD was not associated with use of serotherapy or the donor source.…”

“…[14][15][16][17][18] It has a low-toxicity profile, with the most commonly reported acute toxicities being skin, including nappy rash; diarrhea; mucositis; and hepatic toxicity; however, these are generally mild, and importantly, venoocclusive disease (VOD) is very rare. 19 Long-term effects are not welldocumented because of the relatively recent introduction of the drug for conditioning for HSCT.…”

Treosulfan-based conditioning regimens for allogeneic haematopoietic stem cell transplantation in children with non-malignant diseases

“…It is not clear why this occurred as other patients have tolerated this combination quite well. 11 Toxicity was not associated with an increasing dose of treosulfan. There was more respiratory toxicity in the patients under 1 year of age, which may be due to the large number of primary immunodeficiencies in this group, who may have had respiratory infections.…”

“…Further, a multivariate analysis was performed to study the impact of possible confounding factors on the defined outcomes. Cox regression 11,12 was used to model the time to transplantrelated mortality and OS. The statistical analysis was done with SAS System V9.2 (2008, SAS Institute, Cary, NC, USA).…”

“…Since then, treosulfan has increasingly been used for paediatric patients undergoing HSCT for both malignant and nonmalignant diseases. [5][6][7][8][9][10][11][12] An increasing number of patients with non-malignant disorders are eligible for HSCT and these patients present different challenges compared with those with malignant diseases: children with inherited disorders such as SCID often come to transplant as infants under 1 year of age with organ damage and co-morbidities. GvHD, which may be associated with a beneficial GvL effect in patients with high-risk haematological diseases, is of no added value in controlling the underlying genetic illness and may adversely affect subsequent immune reconstitution and have an unnecessarily negative impact on HSCT-related morbidity and quality of life in the short and long term.…”