title: Engraftment rates related to busulphan and cyclophosphamide dosages for displacement bone marrow transplants in fifty children.
abstract: The use of busulphan and cyclophosphamide permitted engraftment in 44 of 49 children receiving 'displacement' bone marrow transplants. Three patients who received T-cell-depleted marrow cells from HLA-haploidentical donors failed to engraft and other graft failures were due to inadequate induction dosage. Our standard schedule comprises busulphan 80 mg/m2/day x 4 days (adjusted if necessary to a minimum of 4 mg/kg/day or a maximum of 5 mg/kg/day) followed by cyclophosphamide 2 g/m2/day x 4 days but reduced so as not to exceed 75 mg/kg/day, a maximum dose preferred for patients with full marrows (e.g. those with thalassaemia major). Of 21 recipients of mixed lymphocyte culture (MLC)-negative donor marrow cells with full engraftment at 100 days, there were three late rejections. Of patients transplanted with marrow from MLC-positive donors, one had late rejection after cyclosporin A toxicity had necessitated withdrawal of the drug at day + 146 but six other patients, whose cyclosporin A was stopped routinely 1 year, remain well with full grafts. Ten patients died as a result of graft-versus-host disease. We are therefore exploring new approaches to T-cell depletion and storing autologous marrow for use in the event of graft failure. If necessary, a second transplant with busulphan and cyclophosphamide is best performed at 3 months after full recovery of the host. We conclude that elective transplants can be performed successfully in children with normal immune function without the need for irradiation.
authors.affiliation: Westminster Hospital, London, UK.
authors.forename: J R
authors.initials: JR
authors.lastname: Hobbs
authors.forename: K
authors.initials: K
authors.lastname: Hugh-Jones
authors.forename: P J
authors.initials: PJ
authors.lastname: Shaw
authors.forename: C J
authors.initials: CJ
authors.lastname: Downie
authors.forename: S
authors.initials: S
authors.lastname: Williamson
mesh_terms: D001853:Bone Marrow / Q000187:drug effects; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000627:therapeutic use*; D002648:Child; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D006085:Graft Survival / Q000187:drug effects*; D006239:Haplotypes; D006801:Humans; D007959:Lymphocyte Culture Test, Mixed; D011292:Premedication; D013997:Time Factors; D014019:Tissue Donors
chemical_list: D003520:Cyclophosphamide; D002066:Busulfan