title: Postremission therapy with low-dose interleukin 2 with or without intermediate pulse dose interleukin 2 therapy is well tolerated in elderly patients with acute myeloid leukemia: Cancer and Leukemia Group B study 9420.
abstract: OBJECTIVE
  The purpose of the study is to investigate the tolerability of interleukin 2 (IL-2) after intensive chemotherapy in elderly acute myeloid leukemia (AML) patients in first complete remission (CR).
  
  
  METHODS
  AML patients > or =60 years in CR after induction and consolidation chemotherapy on Cancer and Leukemia Group B study 9420 were eligible if they had neutrophils > or =1 x 10(9)/liters and platelets > or =75 x 10(9)/liters. Patients received low-dose IL-2 (1 x 10(6) IU/m(2)/day s.c. for 90 days) or low-dose IL-2 with intermediate pulse doses (6-12 x 10(6) IU/m(2)/day s.c. for 3 days) every 14 days (maximum five pulses). In a subset of patients, we investigated the expression of NKG2D ligands by leukemic cells because they are likely important mediators of natural killer cytotoxicity.
  
  
  RESULTS
  Of 35 CR patients receiving IL-2, 34 were evaluable for toxicity. Median age was 67 (range, 60-76) years. Thirteen of 16 patients receiving low-dose IL-2 completed the planned therapy, and 11 of 18 who also received intermediate pulse dose IL-2 therapy completed all five pulses. The spectrum of toxicity in both groups was similar, with predominantly grade 1-2 fatigue, fever, injection site reactions, nausea, anemia, and thrombocytopenia. Grade 3-4 hematological and nonhematological toxicity were more frequent in patients also receiving intermediate pulse dose IL-2 therapy. Grade 3-4 fatigue and hematological toxicity, although uncommon, were the major causes for discontinuing or attenuating therapy. In 8 cases, mRNA for one or more NKG2D ligands was detected in leukemic cells obtained at diagnosis before treatment.
  
  
  CONCLUSIONS
  Low-dose IL-2, with or without intermediate pulse dose therapy, given immediately after chemotherapy in first CR to elderly AML patients is well tolerated. Expression of NKG2D ligands by leukemic cells was detected in the majority of cases tested and should be assessed for correlation with response to IL-2 in future studies.
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
authors.forename: Sherif S
authors.initials: SS
authors.lastname: Farag
authors.forename: Stephen L
authors.initials: SL
authors.lastname: George
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Lee
authors.forename: Maria
authors.initials: M
authors.lastname: Baer
authors.forename: Richard K
authors.initials: RK
authors.lastname: Dodge
authors.forename: Brian
authors.initials: B
authors.lastname: Becknell
authors.forename: Todd A
authors.initials: TA
authors.lastname: Fehniger
authors.forename: Lewis R
authors.initials: LR
authors.lastname: Silverman
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Crawford
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
authors.forename: Charles A
authors.initials: CA
authors.lastname: Schiffer
authors.forename: Michael A
authors.initials: MA
authors.lastname: Caligiuri
mesh_terms: D000208:Acute Disease; D000367:Age Factors; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003524:Cyclosporins / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D005221:Fatigue / Q000139:chemically induced; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D015993:Life Tables; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K; D009325:Nausea / Q000139:chemically induced; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D011971:Receptors, Immunologic / Q000187:drug effects; D055607:Receptors, Natural Killer Cell; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D003524:Cyclosporins; D007155:Immunologic Factors; D007376:Interleukin-2; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D009363:Neoplasm Proteins; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D011993:Recombinant Fusion Proteins; D003561:Cytarabine; D005047:Etoposide; C070272:valspodar; D003630:Daunorubicin