title: Pilot study of tandem high-dose chemotherapy and autologous stem cell transplantation with a novel combination of regimens in patients with poor risk lymphoma.
abstract: In an effort to improve the outcome of poor-risk lymphoma patients, we evaluated a novel regimen of tandem high-dose chemotherapy (THDC) with autologous stem cell transplantation. A total of 41 patients (median age 40 years, range 15-68 years) with poor-risk non-Hodgkin's lymphoma and Hodgkin's disease were enrolled. THDC consisted of melphalan (180 mg/m2) and escalating dose mitoxantrone (30-50 mg/m2) (MMt) for the first conditioning regimen, and thiotepa (500 mg/m2), carboplatin (800 mg/m2), and escalating dose etoposide phosphate (400-850 mg/m2), (ETCb) as the second regimen. In all, 31 patients (76%) completed both transplants, with a median time between transplants of 55 days (range 26-120). The maximum tolerated dose was determined as 40 mg/m2 for mitoxantrone and 550 mg/m2 for etoposide phosphate. The overall toxic death rate was 12%. Following high-dose chemotherapy, 10 of 24 evaluable patients (42%) were in CR. The two-year overall survival and event-free survival is 67% (95% CI, 52-81%) and 45%, (95% CI, 29-61%) for the 41 patients enrolled; and 69% (95% CI, 525-586%) and 48% (95% CI, 30-67%) for the 31 patients completing both transplants. This THDC regimen is feasible but with notable toxicity in heavily pretreated patients; its role in the current treatment of high-risk lymphoma remains to be determined.
authors.affiliation: Institute for Drug Development, San Antonio, TX, USA.
authors.forename: K P
authors.initials: KP
authors.lastname: Papadopoulos
authors.forename: W
authors.initials: W
authors.lastname: Noguera-Irizarry
authors.forename: L
authors.initials: L
authors.lastname: Wiebe
authors.forename: C S
authors.initials: CS
authors.lastname: Hesdorffer
authors.forename: J
authors.initials: J
authors.lastname: Garvin
authors.forename: G L
authors.initials: GL
authors.lastname: Nichols
authors.forename: L H
authors.initials: LH
authors.lastname: Vahdat
authors.forename: K M S
authors.initials: KM
authors.lastname: Lo
authors.forename: D
authors.initials: D
authors.lastname: Skerrett
authors.forename: D
authors.initials: D
authors.lastname: Bernstein
authors.forename: E
authors.initials: E
authors.lastname: Sharpe
authors.forename: D G
authors.initials: DG
authors.lastname: Savage
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000633:toxicity; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D008223:Lymphoma / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D010865:Pilot Projects; D012306:Risk; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods; D014182:Transplantation, Autologous
chemical_list: D008942:Mitoxantrone; D008558:Melphalan