title: Soluble interleukin-2 receptor α activation in a Children's Oncology Group randomized trial of interleukin-2 therapy for pediatric acute myeloid leukemia.
abstract: OBJECTIVE
  To assess associations of soluble IL-2 receptor alpha (sIL-2rα) concentration with outcomes in pediatric acute myeloid leukemia (AML) in a phase 3 trial of IL-2 therapy.
  
  
  METHODS
  We randomized 289 children with AML in first remission after intensive chemotherapy to receive IL-2 infused on days 0-3 and 8-17 (IL-2 group) or no further therapy (AML control group). We measured sequential serum sIL-2rα concentrations in both groups before, during and after therapy in both groups and in reference controls without AML.
  
  
  RESULTS
  Before treatment, mean sIL-2rα concentrations were similar in the IL-2 group and AML controls, but significantly higher than in reference controls. Both AML groups experienced reduction in sIL-2rα concentration after chemotherapy. Thereafter in the IL-2 group, mean sIL-2rα concentration increased from 2,669 pg/ml before IL-2 to 15,534 pg/ml on day 4 (P < 0.001) and 10,585 pg/ml on day 18 (P < 0.001). In the control group sIL-2rα concentration did not change after 28 days of follow-up. Five-year disease-free survival (DFS) was 51% in the IL-2 group and 58% in the controls (P = 0.489) and overall survival was 70% and 73%, respectively (P = 0.727).
  
  
  CONCLUSIONS
  SIL-2rα concentration was elevated in AML at diagnosis and tended to normalize after chemotherapy. IL-2 infusion significantly increased sIL-2rα concentration, but did not improve DFS or survival in pediatric AML. Furthermore, sIL-2rα concentration was not predictive of outcome before, during or after treatment for AML.
authors.affiliation: The Children's Hospital of Philadelphia, Philadelphia, PA, USA. lange@email.chop.edu
authors.forename: Beverly J
authors.initials: BJ
authors.lastname: Lange
authors.forename: Richard K
authors.initials: RK
authors.lastname: Yang
authors.forename: Jacek
authors.initials: J
authors.lastname: Gan
authors.forename: Jaquelyn A
authors.initials: JA
authors.lastname: Hank
authors.forename: Eric L
authors.initials: EL
authors.lastname: Sievers
authors.forename: Todd A
authors.initials: TA
authors.lastname: Alonzo
authors.forename: Robert B
authors.initials: RB
authors.lastname: Gerbing
authors.forename: Paul M
authors.initials: PM
authors.lastname: Sondel
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007223:Infant; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000627:therapeutic use; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood* / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D011379:Prognosis; D012995:Solubility; D016019:Survival Analysis
chemical_list: C508017:IL2RA protein, human; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit