title: Phase II study of autologous transplantation with interleukin-2-incubated peripheral blood stem cells and posttransplantation interleukin-2 in relapsed or refractory non-Hodgkin lymphoma.
abstract: Previous work suggested that interleukin (IL)-2 can be used for eradicating residual disease in autologous grafts and for preventing recurrence. We report a phase II study of autologous peripheral blood stem cell transplantation with in vitro IL-2 incubation of peripheral blood stem cells and posttransplantation IL-2 in patients with recurrent or refractory non-Hodgkin lymphoma. Salvage chemotherapy consisted of ifosfamide and etoposide. Responding patients underwent autologous peripheral blood stem cell transplantation. IL-2-incubated stem cells were infused on day 0. IL-2 1 mIU/m2 was given from day 1 until day 28. Four monthly maintenance cycles of IL-2 4 mIU/m2 subcutaneously twice daily days 1 to 5 and days 8 to 11 were administered thereafter. Eighty-four evaluable patients were enrolled, and 60 proceeded to transplantation, of which 56 received IL-2-incubated stem cells. The average received dose of posttransplantation IL-2 was 30% to 50% of planned. Only 42 patients received maintenance IL-2. The average received maintenance dose of IL-2 was also approximately 30% of planned. Most dose reductions were due to toxicity or patient refusal. Three-year survival and progression-free survival for all registered patients were 43% (95% confidence interval [CI], 33%-53%) and 31% (95% CI, 21%-41%), respectively. For the 60 patients undergoing transplantation, they were 59% (95% CI, 46%-72%) and 44% (95% CI, 31%-57%), respectively. There was no relation between the dose of IL-2 received and outcome. Survival and disease-free survival of the study group were similar to those of a previous study cohort that received unmanipulated stem cells and no systemic IL-2. Administration of IL-2-incubated peripheral blood stem cells and intensive posttransplantation IL-2 was associated with considerable but rapidly reversible toxicity. No effect on long-term outcome was observed.
authors.affiliation: Section of Hematology/Oncology, University of Illinois Chicago, 60637, USA. Kvbesien@uchicago.edu
authors.forename: Koen
authors.initials: K
authors.lastname: Van Besien
authors.forename: Rakesh
authors.initials: R
authors.lastname: Mehra
authors.forename: Navin
authors.initials: N
authors.lastname: Wadehra
authors.forename: Wendy
authors.initials: W
authors.lastname: Stock
authors.forename: Issa
authors.initials: I
authors.lastname: Khouri
authors.forename: Sergio
authors.initials: S
authors.lastname: Giralt
authors.forename: Steve
authors.initials: S
authors.lastname: Devine
authors.forename: Amittha
authors.initials: A
authors.lastname: Wickrema
authors.forename: David
authors.initials: D
authors.lastname: Peace
authors.forename: Jeff
authors.initials: J
authors.lastname: Sosman
authors.forename: Jim
authors.initials: J
authors.lastname: Gajewski
authors.forename: Richard
authors.initials: R
authors.lastname: Champlin
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D018929:Cell Culture Techniques; D005047:Etoposide / Q000627:therapeutic use; D006801:Humans; D007069:Ifosfamide / Q000627:therapeutic use; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D008228:Lymphoma, Non-Hodgkin / Q000401:mortality / Q000628:therapy*; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D016879:Salvage Therapy / Q000379:methods*; D016019:Survival Analysis; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D007376:Interleukin-2; D005047:Etoposide; D007069:Ifosfamide