Treosulfan‐containing regimens achieve high rates of engraftment associated with low transplant morbidity and mortality in children with non‐malignant disease and significant co‐morbidities

Abstract

SummaryTreosulfan is an immuno-suppressive and myeloablative alkylating agent that has been introduced as a conditioning agent in stem cell transplantation (SCT). Most studies have been performed in adult patients with malignancy where a low incidence of regimen-related toxicity has been reported. We report the use of treosulfan in 32 consecutive children undergoing SCT for non-malignant disease. Patients received a total treosulfan dose of 36 or 42 g/m 2 /patient given in three daily, divided doses. A range of other conditioning agents and serotherapy was administered to patients who underwent family donor SCT (n = 11), or unrelated donor SCT (n = 21). One patient (3%) died early. Transplant morbidity was limited and mucositis was only mild. Dermatological toxicity was frequent but mild. Twenty-eight patients (87AE5%) established donor cell engraftment. In 25 patients (78%) there was adequate, stable donor engraftment. Four patients have required additional transplant procedures to maintain adequate donor-derived haemopoiesis. Twenty-seven patients (84%) survive with a median follow up of 417 d. There were four late deaths due to progression of the underlying disease, graft-versus-host disease or infection. Treosulfan-based conditioning regimens achieve excellent engraftment with reduced regimen-related toxicity in children with non-malignant disease at high risk for both regimen-related toxicity and graft failure.

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

“…5,6,9,14,20,21 In this retrospective EBMT study, we evaluated the toxicity profile and outcome of 316 patients with non-malignant diseases undergoing HSCT, following treosulfan-based conditioning. To our knowledge, this is the largest such study to date.…”

“…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.…”

Reduced Intensity Transplantation for Primary Immunodeficiency Disorders

“…13 Two centers in the UK have recently examined the outcome in 70 children with PID undergoing HCT with treosulfan based regimens. 14 Children received 42 g/m 2 or 36 g/m 2 of treosulfan with cyclophosphamide 200 mg/kg (30) or fludarabine 150 mg/m 2 (40), with alemtuzumab in most.…”

Treosulfan-based conditioning before hematopoietic SCT: more than a BU look-alike

“…Greystoke et al 75 studied 32 children with non-malignant diseases, including primary immunodeficiency, metabolic disorders and malignant infantile osteopetrosis, following SCT with treosulfan-based conditioning. Toxicity included only mild mucositis and dermatologic toxicity, and no VOD.…”