Engraftment rates related to busulphan and cyclophosphamide dosages for displacement bone marrow transplants in fifty children.
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.
Hobbs
J R
JR
Westminster Hospital, London, UK.
Hugh-Jones
K
K
Shaw
P J
PJ
Downie
C J
CJ
Williamson
S
S
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
D003520:Cyclophosphamide; D002066:Busulfan