Engraftment rates related to busulphan and cyclophosphamide dosages for displacement bone marrow transplants in fifty children
Hobbs, J.R.; Hugh-Jones, K.; Shaw, P.J.; Downie, C.J.; Williamson, S.
Bone Marrow Transplantation 1(2): 201-208
1986
ISSN/ISBN: 0268-3369 PMID: 2971409 Document Number: 270054
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 .times. 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 .times. 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.