title: Intensive therapy with cyclophosphamide, carmustine, etoposide +/- cisplatin, and autologous bone marrow transplantation for Hodgkin's disease in first relapse after combination chemotherapy.
abstract: The optimal timing in which to use intensive chemotherapy and autologous bone marrow transplantation (BMT) in Hodgkin's disease (HD) is uncertain. In 1985, we initiated a program in which this modality was used as the initial salvage therapy in patients relapsing after combination chemotherapy. Fifty-eight patients with HD in first relapse after primary chemotherapy received conditioning with high-dose cyclophosphamide, carmustine, etoposide (VP16-213) +/- cisplatin (CBV +/- P) followed by autologous BMT. All but six of these patients were given a median of two cycles of conventional chemotherapy +/- involved field radiation therapy before CBV +/- P and autologous BMT. These measures were not used as a means for patients selection; all patients receiving such therapy ultimately were transplanted. The probability of nonrelapse mortality, progression of HD, and progression-free survival post-BMT were calculated, and prognostic factors for progression-free survival were evaluated using the Cox proportional hazards method. Treatment-related deaths occurred in only three patients. Thirteen patients have relapsed at a median 0.7 years (range 0.1 to 3.5) post-BMT. At a median follow-up of 2.3 years (range 0.4 to 7.2), the actuarial progression-free survival is 64% (95% confidence interval, 46% to 78%). In the statistical analysis, three similarly weighted but independent prognostic factors were identified: "B" symptoms at relapse, extranodal disease at relapse, and initial remission duration of less than 1 year. Patients with no risk factors had a 3-year progression-free survival of 100%, compared with 81% in patients with one factor, 40% in those with two factors, and 0% in patients with all three factors. CBV +/- P and autologous BMT is highly effective salvage therapy for HD patients in a first relapse, particularly in the subset of patients with less than two adverse factors. Therapy must be improved in the future for patients with > or = 2 adverse factors.
authors.affiliation: Leukemia/Bone Marrow Transplantation Program of British Columbia, Vancouver General Hospital, Canada.
authors.forename: D E
authors.initials: DE
authors.lastname: Reece
authors.forename: J M
authors.initials: JM
authors.lastname: Connors
authors.forename: J J
authors.initials: JJ
authors.lastname: Spinelli
authors.forename: M J
authors.initials: MJ
authors.lastname: Barnett
authors.forename: R N
authors.initials: RN
authors.lastname: Fairey
authors.forename: H G
authors.initials: HG
authors.lastname: Klingemann
authors.forename: S H
authors.initials: SH
authors.lastname: Nantel
authors.forename: S
authors.initials: S
authors.lastname: O'Reilly
authors.forename: J D
authors.initials: JD
authors.lastname: Shepherd
authors.forename: H J
authors.initials: HJ
authors.lastname: Sutherland
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D016026:Bone Marrow Transplantation / Q000379:methods*; D002330:Carmustine / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000601:surgery*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: D005047:Etoposide; D003520:Cyclophosphamide; D002945:Cisplatin; D002330:Carmustine