title: Regimen-related toxicity and non-relapse mortality with high-dose cyclophosphamide, carmustine (BCNU) and etoposide (VP16-213) (CBV) and CBV plus cisplatin (CBVP) followed by autologous stem cell transplantation in patients with Hodgkin's disease.
abstract: This analysis compares the regimen-related toxicity (RRT) and overall non-relapse mortality (NRM) in Hodgkin's disease patients conditioned with either CBV (cyclophosphamide, BCNU (carmustine), and VP16-213 (etoposide)) (26 patients) or CBVP (CBV + cisplatin) (68 patients) followed by autologous stem cell transplantation (ASCT). CBVP included a continuous infusion rather than intermittent doses of etoposide, a lower BCNU dose and the addition of cisplatin. RRT and NRM were determined for each regimen and compared; risk factors for each were examined by multivariate analysis. Grade IV (fatal) RRT occurred in five patients (pulmonary in two, cardiac in two, and central nervous system in one). Eighteen patients experienced grade II-III pulmonary RRT, consistent with BCNU damage in 15. Prior nitrosourea exposure was the main risk factor for pulmonary RRT. Grade II mucosal and hepatic RRT occurred less often after CBVP vs CBV (P = 0.031 and 0.0003, respectively). In addition, three other early and eight late non-relapse deaths were seen. Median follow-up of the entire group is 5.1 (range 2.8-10.2) years. The probability of overall NRM was 26% (95% confidence interval (CI) 13-50%) with CBV vs 23% (95% CI 12-41%) with CBVP (P = 0.40). The progression-free survival and relapse rates were similar. Although the rates of fatal RRT, pulmonary RRT and overall NRM were similar with CBV or CBVP, CBVP produced less mucosal and liver RRT with a comparable antitumor effect. As many autografted patients are cured, future efforts should include measures to decrease NRM.
authors.affiliation: Leukemia/Bone Marrow Transplantation Program of British Columbia: Division of Hematology, Vancouver General Hospital, British Columbia Cancer Agency and the University of British Columbia, Canada.
authors.forename: D E
authors.initials: DE
authors.lastname: Reece
authors.forename: T J
authors.initials: TJ
authors.lastname: Nevill
authors.forename: A
authors.initials: A
authors.lastname: Sayegh
authors.forename: J J
authors.initials: JJ
authors.lastname: Spinelli
authors.forename: D A
authors.initials: DA
authors.lastname: Brockington
authors.forename: M J
authors.initials: MJ
authors.lastname: Barnett
authors.forename: H G
authors.initials: HG
authors.lastname: Klingemann
authors.forename: J M
authors.initials: JM
authors.lastname: Connors
authors.forename: S H
authors.initials: SH
authors.lastname: Nantel
authors.forename: J D
authors.initials: JD
authors.lastname: Shepherd
authors.forename: H J
authors.initials: HJ
authors.lastname: Sutherland
authors.forename: N J
authors.initials: NJ
authors.lastname: Voss
authors.forename: R N
authors.initials: RN
authors.lastname: Fairey
authors.forename: S E
authors.initials: SE
authors.lastname: O'Reilly
authors.forename: G L
authors.initials: GL
authors.lastname: Phillips
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002330:Carmustine / Q000008:administration & dosage / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008297:Male; D019172:Transplantation Conditioning / Q000009:adverse effects*; D014182:Transplantation, Autologous
chemical_list: D005047:Etoposide; D003520:Cyclophosphamide; D002945:Cisplatin; D002330:Carmustine