title: Recombinant interleukin-2 in patients aged younger than 60 years with acute myeloid leukemia in first complete remission: results from Cancer and Leukemia Group B 19808.
abstract: BACKGROUND
  Recombinant interleukin-2 (rIL-2) induces cellular cytotoxicity against leukemia blasts. Patients with acute myeloid leukemia (AML) in first complete remission (CR) may harbor minimal residual disease that is susceptible to rIL-2-activated effector cells.
  
  
  METHODS
  In the Cancer and Leukemia Group B (CALGB) 19808 study, patients with AML in first CR were randomly assigned after all planned chemotherapy to receive a 90-day course of subcutaneously administered rIL-2 or no further therapy. The primary objective was to compare disease-free survival (DFS) between the 2 treatment arms. A total of 534 patients achieved a CR, 214 of whom were randomized. Six courses of low-dose daily rIL-2 were given for the expansion of cytotoxic effector cells, each followed by 3-day high-dose boluses given to trigger cytotoxicity against minimal residual disease.
  
  
  RESULTS
  On the protocol-specified intention-to-treat analysis, the hazards ratio for DFS was 0.75 (95% confidence interval, 0.52-1.09; P = .13); the 5-year DFS rate was 42% in the observation arm and 53% in the rIL-2 treatment arm. The hazards ratio for overall survival (OS) was 0.88 (95% confidence interval, 0.54-1.23; P = .34); the 5-year OS rate was 58% for the observation arm and 63% for the rIL-2 treatment arm. Twenty-five of the 107 patients randomized to treatment with rIL-2 either refused or were unable to initiate therapy and 30 patients did not complete their assigned therapy. However, significant toxicities were not commonly observed. The trial design did not anticipate the difficulties patients would encounter with protocol compliance.
  
  
  CONCLUSIONS
  The efficacy of immunotherapy with rIL-2 administered after intensive postremission treatment was not assessed as planned because of unexpected refusals by patients and/or their physicians to comply with protocol-directed therapy. Neither DFS nor OS was found to be significantly improved.
authors.affiliation: Don Monti Division of Oncology/Division of Hematology, Department of Medicine, Hofstra North Shore-Long Island Jewish School of Medicine, Lake Success, New York.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Kolitz
authors.forename: Stephen L
authors.initials: SL
authors.lastname: George
authors.forename: Don M
authors.initials: DM
authors.lastname: Benson
authors.forename: Kati
authors.initials: K
authors.lastname: Maharry
authors.forename: Guido
authors.initials: G
authors.lastname: Marcucci
authors.forename: Ravi
authors.initials: R
authors.lastname: Vij
authors.forename: Bayard L
authors.initials: BL
authors.lastname: Powell
authors.forename: Steven L
authors.initials: SL
authors.lastname: Allen
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Deangelo
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Shea
authors.forename: Wendy
authors.initials: W
authors.lastname: Stock
authors.forename: Courtney E
authors.initials: CE
authors.lastname: Bakan
authors.forename: Vera
authors.initials: V
authors.lastname: Hars
authors.forename: Eva
authors.initials: E
authors.lastname: Hoke
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
authors.forename: Michael A
authors.initials: MA
authors.lastname: Caligiuri
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
mesh_terms: D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003524:Cyclosporins / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D003524:Cyclosporins; D007376:Interleukin-2; D011994:Recombinant Proteins; D003561:Cytarabine; D005047:Etoposide; C070272:valspodar; D003630:Daunorubicin
keywords: acute myeloid leukemia; adjuvant therapy; immunotherapy; phase 3; recombinant interleukin-2