title: Preparative regimens for marrow transplantation containing busulphan are associated with haemorrhagic cystitis and hepatic veno-occlusive disease but a short duration of leucopenia and little oro-pharyngeal mucositis.
abstract: One-hundred-and-forty-three patients with haematological malignancy or severe aplastic anaemia received HLA-identical sibling bone marrow transplants. In 111 of these patients who had haematological malignancy and who were prepared for transplant with cyclophosphamide 120 mg/kg and fractionated total body irradiation 12-14 Gy, the incidence of haemorrhagic cystitis and hepatic veno-occlusive disease was 13% and 3%, respectively. In contrast, the incidence in 15 leukaemic patients prepared for transplant with chemotherapy regimens containing high-dose busulphan was 47% and 20%, respectively (p less than 0.001). Two patients in this latter group who developed fatal veno-occlusive disease had chronic myeloid leukaemia and had received long-term low-dose busulphan pre-transplant. Neither complication occurred in 26 patients prepared by cyclophosphamide alone (20 patients with severe aplastic anaemia) or with cyclophosphamide and melphalan (six patients with leukaemia). The regimen of busulphan 16 mg/kg in combination with cyclophosphamide 120 mg/kg was associated with a short duration of total leucopenia with a significantly higher leucocyte count on the day of marrow transplant compared to other regimens. Furthermore, oro-pharyngeal mucositis was not severe even when methotrexate was utilised as post-transplant prophylaxis for graft-versus-host disease. Thus, while the busulphan-cyclophosphamide regimen appeared useful, we suggest that (1) high-dose busulphan should not be used as a preparative regimen for patients previously exposed to busulphan, and (2) bladder irrigation (as well as intravenous hydration) is necessary to minimise haemorrhagic cystitis in patients given regimens that incorporate high-dose busulphan.
authors.affiliation: Department of Haematology, St Vincent's Hospital, Sydney, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Atkinson
authors.forename: J
authors.initials: J
authors.lastname: Biggs
authors.forename: G
authors.initials: G
authors.lastname: Noble
authors.forename: M
authors.initials: M
authors.lastname: Ashby
authors.forename: A
authors.initials: A
authors.lastname: Concannon
authors.forename: A
authors.initials: A
authors.lastname: Dodds
mesh_terms: D000741:Anemia, Aplastic / Q000628:therapy; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000009:adverse effects*; D003556:Cystitis / Q000139:chemically induced*; D006470:Hemorrhage; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced*; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects; D007938:Leukemia / Q000628:therapy; D007970:Leukopenia / Q000139:chemically induced*; D009092:Mucous Membrane; D010608:Pharyngeal Diseases / Q000139:chemically induced*; D013997:Time Factors
chemical_list: D002066:Busulfan