title: Treosulfan-based conditioning regimens for hematopoietic stem cell transplantation in children with primary immunodeficiency: United Kingdom experience.
abstract: Children with primary immunodeficiency diseases, particularly those less than 1 year of age, experience significant toxicity after hematopoietic stem cell transplantation, with busulfan- or melphalan-based conditioning. Treosulfan causes less veno-occlusive disease than busulfan and does not require pharmacokinetic monitoring. We report its use in 70 children. Children received 42 g/m(2) or 36 g/m(2) with cyclophosphamide 200 mg/kg (n = 30) or fludarabine 150 mg/m(2) (n = 40), with alemtuzumab in most. Median age at transplantation was 8.5 months (range, 1.2-175 months); 46 (66%) patients were 12 months of age or younger. Donors were as follows: matched sibling donor, 8; matched family donor, 13; haploidentical, 4; and unrelated, 45. Median follow-up was 19 months (range, 1-47 months). Overall survival was 81%, equivalent in those age less or greater than 1 year. Skin toxicity was common. Veno-occlusive disease occurred twice with cyclophosphamide. Eighteen patients (26%) had graft-versus-host disease, and only 7 (10%) greater than grade 2. Two patients rejected; 24 of 42 more than 1 year after transplantation had 100% donor chimerism. The remainder had stable mixed chimerism. T-cell chimerism was significantly better with fludarabine. Long-term follow-up is required, but in combination with fludarabine, treosulfan is a good choice of conditioning for hematopoietic stem cell transplantation in primary immunodeficiency disease.
authors.affiliation: Department of Paediatric Immunology, Newcastle upon Tyne Hospital National Health Servcie Foundation Trust, Newcastle upon Tyne, United Kingdom. mary.slatter@nuth.nhs.uk
authors.forename: Mary A
authors.initials: MA
authors.lastname: Slatter
authors.forename: Kanchan
authors.initials: K
authors.lastname: Rao
authors.forename: Persis
authors.initials: P
authors.lastname: Amrolia
authors.forename: Terry
authors.initials: T
authors.lastname: Flood
authors.forename: Mario
authors.initials: M
authors.lastname: Abinun
authors.forename: Sophie
authors.initials: S
authors.lastname: Hambleton
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Nademi
authors.forename: Nick
authors.initials: N
authors.lastname: Goulden
authors.forename: Graham
authors.initials: G
authors.lastname: Davies
authors.forename: Waseem
authors.initials: W
authors.lastname: Qasim
authors.forename: Hubert B
authors.initials: HB
authors.lastname: Gaspar
authors.forename: Andrew
authors.initials: A
authors.lastname: Cant
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Gennery
authors.forename: Paul
authors.initials: P
authors.lastname: Veys
mesh_terms: D000293:Adolescent; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D002066:Busulfan / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D046528:Chimerism; D015331:Cohort Studies; D006086:Graft vs Host Disease / Q000453:epidemiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000601:surgery*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D006113:United Kingdom
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007166:Immunosuppressive Agents; C018404:treosulfan; D002066:Busulfan