title: Dose-dependent effect of etoposide in combination with busulfan plus cyclophosphamide as conditioning for stem cell transplantation in patients with acute myeloid leukemia.
abstract: To evaluate the efficacy and toxicity of two different etoposide (VP-16) dosages (30 or 45 mg/kg) in combination with busulfan/cyclophosphamide as conditioning therapy followed by stem cell transplantation in acute myeloid leukemia (AML), 90 patients with AML received either 30 mg/kg (n = 60) or 45 mg/kg (n = 30) etoposide in combination with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg). The stem cell source was allogeneic related bone marrow (BM) (n = 53), allogeneic unrelated BM (n = 5), allogeneic unrelated peripheral blood (PBSC) (n = 2), syngeneic BM (n = 2), autologous BM purged (n = 9) or unpurged (n = 9), autologous PBSC (n = 10). Fifty-six patients (62%) were in first CR, 26 (29%) were > first CR, and eight (9%) were transplanted in relapse. Principal toxicities in both groups were mucositis and hepatotoxicity. Forty-five mg/kg etoposide resulted in greater hepatic toxicity (P = 0.03), and a higher incidence of VOD (23 vs 12%, P = 0.04) and acute GVHD grade III/IV (13 vs 5%, NS). The treatment-related mortality was 17% in the 30 mg/kg group and 33% in the 45 mg/kg group, mainly due to infections, intestinal pneumonia and GVHD. Hematological recovery of leukocytes 1/nl was comparable in both groups (17 vs 16 days). After a median follow-up of 16 months 19% in the 30 mg/kg group and 23% in the 45 mg/kg group relapsed. In patients who had undergone allogeneic related bone marrow transplantation in first CR no relapses occurred after a median follow-up of 3 years. For all patients the 3-year estimated disease-free survival was 62% in the 30 mg/kg group and 40% in the 45 mg/kg group (P = 0.03). For patients in first CR who underwent allogeneic related stem cell transplantation the 3 year disease-free survivals were 80% and 66%, respectively (P = 0.4). We conclude that etoposide 30 mg/kg or 45 mg/kg in combination with busulfan/cyclophosphamide is a highly active regimen for bone marrow transplantation of patients with AML with a low relapse rate. However, conditioning with 30 mg/kg rather than 45 mg/kg etoposide resulted in less toxicity and a better overall survival due to a lower transplant-related mortality. Bone Marrow Transplantation (2000) 26, 711-716.
authors.affiliation: Bone Marrow Transplantation, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Kröger
authors.forename: T
authors.initials: T
authors.lastname: Zabelina
authors.forename: S
authors.initials: S
authors.lastname: Sonnenberg
authors.forename: W
authors.initials: W
authors.lastname: Krüger
authors.forename: H
authors.initials: H
authors.lastname: Renges
authors.forename: N
authors.initials: N
authors.lastname: Stute
authors.forename: F
authors.initials: F
authors.lastname: Finkenstein
authors.forename: U
authors.initials: U
authors.lastname: Mayer
authors.forename: K
authors.initials: K
authors.lastname: Holstein
authors.forename: W
authors.initials: W
authors.lastname: Fiedler
authors.forename: H
authors.initials: H
authors.lastname: Colberg
authors.forename: R
authors.initials: R
authors.lastname: Sonnen
authors.forename: R
authors.initials: R
authors.lastname: Kuse
authors.forename: D
authors.initials: D
authors.lastname: Braumann
authors.forename: B
authors.initials: B
authors.lastname: Metzner
authors.forename: F
authors.initials: F
authors.lastname: del Valle
authors.forename: R
authors.initials: R
authors.lastname: Erttmann
authors.forename: H
authors.initials: H
authors.lastname: Kabisch
authors.forename: A R
authors.initials: AR
authors.lastname: Zander
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D001792:Blood Platelets / Q000166:cytology; D002066:Busulfan / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005047:Etoposide / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000150:complications / Q000188:drug therapy*; D007962:Leukocytes / Q000166:cytology; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods* / Q000592:standards; D016896:Treatment Outcome
chemical_list: D005047:Etoposide; D003520:Cyclophosphamide; D002066:Busulfan