title: 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: Treosulfan 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 (87.5%) 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.
authors.affiliation: Department of Blood and Marrow Transplant, Royal Manchester Children's Hospital, Manchester, UK.
authors.forename: Brigit
authors.initials: B
authors.lastname: Greystoke
authors.forename: Sonia
authors.initials: S
authors.lastname: Bonanomi
authors.forename: Trevor F
authors.initials: TF
authors.lastname: Carr
authors.forename: Maged
authors.initials: M
authors.lastname: Gharib
authors.forename: Tasneem
authors.initials: T
authors.lastname: Khalid
authors.forename: Mary
authors.initials: M
authors.lastname: Coussons
authors.forename: Mamta
authors.initials: M
authors.lastname: Jagani
authors.forename: Paru
authors.initials: P
authors.lastname: Naik
authors.forename: Kanchana
authors.initials: K
authors.lastname: Rao
authors.forename: Nicholas
authors.initials: N
authors.lastname: Goulden
authors.forename: Persis
authors.initials: P
authors.lastname: Amrolia
authors.forename: Robert F
authors.initials: RF
authors.lastname: Wynn
authors.forename: Paul A
authors.initials: PA
authors.lastname: Veys
mesh_terms: D000293:Adolescent; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000379:methods*; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D033581:Stem Cell Transplantation / Q000379:methods; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007166:Immunosuppressive Agents; C018404:treosulfan; D002066:Busulfan