Preliminary results of high-dose busulfan and cyclophosphamide with syngeneic or autologous bone marrow rescue.
The toxic effects of high-dose busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg) with autologous or syngeneic bone marrow rescue were evaluated in 19 patients (11 with acute myelocytic leukemia, one with acute lymphocytic leukemia, one with acute myelofibrosis, two with chronic myelocytic leukemia, one with Hodgkin's disease, and three with non-Hodgkin's lymphoma). Their mean age was 26 years (range, 6-50); nine patients had syngeneic and ten had autologous bone marrow rescue (six of whom had in vitro bone marrow incubation with 4-hydroperoxycyclophosphamide). Severe myelosuppression was expected and was seen in all patients; leukocyte and platelet count recovery occurred at a median of 19 days (range, 11-59) and 30 days (range, 20-89), respectively. Nausea, vomiting, and diarrhea were frequent but readily managed with vigorous medical therapy. Stomatitis was severe in 14 patients. Skin, renal, cardiac, pulmonary, and CNS complications directly attributable to drug-related toxic effects were transient and non-life-threatening. Hepatic function abnormalities were common but tended to be transient. Most patients tolerated high-dose busulfan and cyclophosphamide with manageable side effects. Hepatic veno-occlusive disease was fatal in two patients, while diffuse interstitial pneumonitis with disseminated herpes virus infection was fatal in three patients with lymphoma. All patients treated in relapse or without previous therapy had a complete tumor response. Further studies with this regimen should be pursued.
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use*; D004341:Drug Evaluation; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007239:Infections / Q000139:chemically induced / Q000188:drug therapy; D007938:Leukemia / Q000628:therapy; D007951:Leukemia, Myeloid / Q000628:therapy; D008223:Lymphoma / Q000628:therapy; D008297:Male; D008875:Middle Aged; D014182:Transplantation, Autologous; D014185:Transplantation, Isogeneic
D003520:Cyclophosphamide; D002066:Busulfan