title: A randomized controlled multicenter study comparing recombinant interleukin 2 (rIL-2) in conjunction with recombinant interferon alpha (IFN-alpha) versus no immunotherapy for patients with malignant lymphoma postautologous stem cell transplantation.
abstract: We have earlier shown an advantage in overall survival for malignant lymphoma (ML) patients who received combined Interleukin-2 (rIL-2) and interferon alpha (IFN-alpha) immunotherapy after autologous stem cell transplantation (AutoSCT) in comparison with historic controls. On the basis of these results, we initiated a control prospective randomized multicenter 2-arm study, comparing the same combined immunotherapy treatment versus control for patients with malignant lymphoma after AutoSCT. One hundred nine patients were included in this study. After AutoSCT, patients were randomized either to the treatment group or to the control group. Patients in the treatment group received daily subcutaneous injections of rIL-2 6x10 IU/m/d for 5 consecutive days followed by 2-weeks rest period. Subsequently, they were treated daily with rIL-2 6x10 IU/m/d combined with INF-alpha 3x10 U/d for 5 consecutive days per week for 4 consecutive weeks. After 4 weeks of rest, IFN-alpha 3x10 U was administered for the next 6 months 3 times per week. Patients in the control group were followed up at the outpatient clinic. There was a significant enhancement of survival (P=0.05) and a clear trend in disease-free survival in favor of NHL patients receiving post-AutoSCT immunotherapy, in comparison with the control group. Eighty-nine percent of patients with NHL treated with immunotherapy were alive and 64% were disease free. In the control group, 66% of patients survived and 46% were disease free. Among the HL patients no significant differences were observed regarding survival, disease-free survival, and relapse rate. No serious toxicity events were observed. These results suggest that outpatient administered immunotherapy with IFN-alpha and rIL-2 is relatively well tolerated and may intensify remission in NHL patients, but not HL patients after AutoSCT.
authors.affiliation: Institute of Hematology, Tel Hashomer, Israel. arnon.nagler@sheba.health.gov.il
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.forename: Raanan
authors.initials: R
authors.lastname: Berger
authors.forename: Aliza
authors.initials: A
authors.lastname: Ackerstein
authors.forename: Jaroslaw A
authors.initials: JA
authors.lastname: Czyz
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Diez-Martin
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Naparstek
authors.forename: Reuven
authors.initials: R
authors.lastname: Or
authors.forename: Shlomit
authors.initials: S
authors.lastname: Gan
authors.forename: Avichai
authors.initials: A
authors.lastname: Shimoni
authors.forename: Shimon
authors.initials: S
authors.lastname: Slavin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D005334:Fever / Q000139:chemically induced; D006689:Hodgkin Disease / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D007370:Interferon Type I / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009325:Nausea / Q000139:chemically induced; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D033581:Stem Cell Transplantation / Q000379:methods*; D016019:Survival Analysis; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced; D055815:Young Adult
chemical_list: D007370:Interferon Type I; D007376:Interleukin-2; D011994:Recombinant Proteins