The toxicity of busulphan and cyclophosphamide as the preparative regimen for bone marrow transplantation.
The toxicity of the conditioning regimen of high dose busulphan (Bu) (16 mg/kg) and cyclophosphamide (Cy) (120 mg/kg) has been compared to cyclophosphamide (Cy) (120 mg/kg) and fractionated total body irradiation (TBI) 12-14 Gy. Since 1985, 67 patients have received conditioning of Bu and Cy for HLA-identical sibling bone marrow transplants. 166 patients have received Cy and TBI since 1981. Veno-occlusive disease of the liver occurred in 19% in the Bu-Cy group and was fatal in 1/12 cases, but only in 1.3% of Cy-TBI group (P less than 0.0005) and was fatal in 1/2. 30% of evaluable patients developed haemorrhagic cystitis in the Bu-Cy group and 14% in the Cy-TBI group (P = 0.008). A multiple logistic regression analysis demonstrated the preparative regimen as the only significant risk factor for the development of veno-occlusive disease or haemorrhagic cystitis. Interstitial pneumonia was diagnosed in 12/56 evaluable patients (21%) in the Bu-Cy group and was fatal in 75%. It occurred in 39/137 evaluable patients (28%) in the Cy-TBI group with a 54% case mortality. Within the Bu-Cy group, the incidence of veno-occlusive disease and haemorrhagic cystitis was similar in chronic myeloid leukaemia (CML) and acute leukaemia (AL) groups, but there was a significant (P = 0.003) incidence of interstitial pneumonia in the CML group 36% as compared to 7% in the AL group. Preparative regimen and age were significant risk factors in the development of interstitial pneumonia in patients with CML. A flexural and acral rash ranging from pigmentation to severe erosion was noted in the Bu-Cy group, but not in the Cy-TBI group. Thus, veno-occlusive disease, haemorrhagic cystitis and cutaneous changes were more common in patients receiving Bu-Cy. Interstitial pneumonia was more common in patients receiving Bu-Cy for CML than for AL.
Morgan
M
M
Department of Haematology, St Vincent's Hospital, Sydney, NSW, Australia.
Dodds
A
A
Atkinson
K
K
Szer
J
J
Downs
K
K
Biggs
J
J
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000009:adverse effects*; D003520:Cyclophosphamide / Q000009:adverse effects*; D003556:Cystitis / Q000139:chemically induced; D004359:Drug Therapy, Combination; D005260:Female; D006417:Hematuria / Q000139:chemically induced; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced; D006801:Humans; D007938:Leukemia / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D011300:Preoperative Care / Q000009:adverse effects*; D011658:Pulmonary Fibrosis / Q000139:chemically induced; D014916:Whole-Body Irradiation / Q000009:adverse effects
D003520:Cyclophosphamide; D002066:Busulfan