title: High dose chemotherapy without hematopoietic cell support for the treatment of refractory lymphoma.
abstract: Conventional dose combination chemotherapy for patients with relapsed or refractory lymphoma is rarely curative. High dose chemotherapy followed by hematopoietic progenitor cell transplant (HPCT) has a clearly defined role in patients who have first relapsed after standard CHOP chemotherapy for lymphoma. However, the role of HPCT is less well defined for patients with chemo-resistant, or chemo-refractory disease. Sixteen patients (15 Non-Hodgkin's, 1 Hodgkin's Disease) were entered into a phase II study to determine if a dose intensive induction regimen in heavily pre-treated refractory lymphoma patients could permit further consolidation with HPCT. The primary endpoints were survival, response, toxicity, and resource utilization. The regimen consisted of continuous infusion etoposide 1 or 2 gm/m2/72 hours, idarubicin 12 mg/m2/d for 3 days followed by cytarabine 2 gm/m2/72 hours on days 8, 9, and 10 (VIC). Fifteen patients were evaluable for objective response. The overall response rate was 53% with 7 patients achieving a partial response and 1 patient achieving a complete response. Of the 8 responders, 6 patients subsequently received high dose chemotherapy followed by HPCT (4 autologous, 2 allogeneic). The median survival was 176 days for the non-responders contrasted with 722 days for the responders. The average duration of hospitalization was 38 days. Toxicity was mainfest primarily as mucositis with a median grade of 3 among the first 13 patients, and a median grade of 2 in three subsequent patients who received an etoposide dose of 1 gm/m2/72 hours. All patients had an episode of neutropenic fever and 5 patients developed clinically significant pneumonitis during therapy. The VIC regimen is active in the treatment of chemo-refractory lymphoma with clinically significant differences in survival for patients who respond to therapy. Further modifications to the regimen could include the addition of a topoisomerase I inhibitor for synergy with etoposide, and using VIC as part of a tandem transplant regimen where response to VIC would allow further therapy with a myeloablative induction followed by HPCT.
authors.affiliation: Bone Marrow and Stem Cell Transplant Program, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: S
authors.initials: S
authors.lastname: Lonial
authors.forename: T W
authors.initials: TW
authors.lastname: Jones
authors.forename: S
authors.initials: S
authors.lastname: Devine
authors.forename: E F
authors.initials: EF
authors.lastname: Winton
authors.forename: L T
authors.initials: LT
authors.lastname: Heffner
authors.forename: K J
authors.initials: KJ
authors.lastname: Smith
authors.forename: A M
authors.initials: AM
authors.lastname: Yeager
authors.forename: E K
authors.initials: EK
authors.lastname: Waller
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000628:therapy*; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy*; D016879:Salvage Therapy; D016019:Survival Analysis
chemical_list: D003561:Cytarabine; D005047:Etoposide; D015255:Idarubicin