title: Phase I/II trial of GN-BVC, a gemcitabine and vinorelbine-containing conditioning regimen for autologous hematopoietic cell transplantation in recurrent and refractory hodgkin lymphoma.
abstract: Autologous hematopoietic cell transplantation with augmented BCNU regimens is effective treatment for recurrent or refractory Hodgkin lymphoma (HL); however, BCNU-related toxicity and disease recurrence remain challenges. We designed a conditioning regimen with gemcitabine in combination with vinorelbine in an effort to reduce the BCNU dose and toxicity without compromising efficacy. In this phase I/II dose escalation study, the gemcitabine maximum tolerated dose (MTD) was determined at 1250 mg/m(2), and a total of 92 patients were treated at this dose to establish safety and efficacy. The primary endpoint was the incidence of BCNU-related toxicity. Secondary endpoints included 2-year freedom from progression (FFP), event-free survival (EFS), and overall survival (OS). Sixty-eight patients (74%) had 1 or more previously defined adverse risk factors for transplant (stage IV at relapse, B symptoms at relapse, greater than minimal disease pretransplant). The incidence of BCNU-related toxicity was 15% (95% confidence interval, 9%-24%). Only 2% of patients had a documented reduction in diffusing capacity of 20% or greater. With a median follow-up of 29 months, the FFP at 2 years was 71% and the OS at 2 years was 83%. Two-year FFP was 96%, 72%, 67%, and 14% for patients with 0 (n = 24), 1 (n = 37), 2 (n = 23), or 3 (n = 8) risk factors, respectively. Regression analysis identified PET status pretransplant and B symptoms at relapse as significant prognostic factors for FFP. This new transplant regimen for HL resulted in decreased BCNU toxicity with encouraging FFP and OS. A prospective, risk-modeled comparison of this new combination with other conditioning regimens is warranted.
authors.affiliation: Department of Medicine, Blood and Marrow Transplantation, Stanford University Medical Center, Stanford, California 94305, USA. sarai1@stanford.edu
authors.forename: Sally
authors.initials: S
authors.lastname: Arai
authors.forename: Renee
authors.initials: R
authors.lastname: Letsinger
authors.forename: Ruby M
authors.initials: RM
authors.lastname: Wong
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Johnston
authors.forename: Ginna G
authors.initials: GG
authors.lastname: Laport
authors.forename: Robert
authors.initials: R
authors.lastname: Lowsky
authors.forename: David B
authors.initials: DB
authors.lastname: Miklos
authors.forename: Judith A
authors.initials: JA
authors.lastname: Shizuru
authors.forename: Wen-Kai
authors.initials: WK
authors.lastname: Weng
authors.forename: Philip W
authors.initials: PW
authors.lastname: Lavori
authors.forename: Karl G
authors.initials: KG
authors.lastname: Blume
authors.forename: Robert S
authors.initials: RS
authors.lastname: Negrin
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Horning
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002330:Carmustine / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006689:Hodgkin Disease / Q000188:drug therapy / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000628:therapy; D011446:Prospective Studies; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014182:Transplantation, Autologous; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077235:Vinorelbine; D055815:Young Adult; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D014747:Vinblastine; D000077235:Vinorelbine; D002330:Carmustine; D000093542:Gemcitabine