PURPOSE: 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). EXPERIMENTAL DESIGN: 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.
PURPOSE: 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). EXPERIMENTAL DESIGN:AMLpatients > 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 AMLpatients 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: Marc Buyse; Pierre Squifflet; Beverly J Lange; Todd A Alonzo; Richard A Larson; Jonathan E Kolitz; Stephen L George; Clara D Bloomfield; Sylvie Castaigne; Sylvie Chevret; Didier Blaise; Dominique Maraninchi; Kathryn J Lucchesi; Tomasz Burzykowski Journal: Blood Date: 2011-04-25 Impact factor: 22.113
Authors: Jonathan E Kolitz; Stephen L George; Guido Marcucci; Ravi Vij; Bayard L Powell; Steven L Allen; Daniel J DeAngelo; Thomas C Shea; Wendy Stock; Maria R Baer; Vera Hars; Kati Maharry; Eva Hoke; James W Vardiman; Clara D Bloomfield; Richard A Larson Journal: Blood Date: 2010-06-03 Impact factor: 22.113
Authors: Maria R Baer; Stephen L George; Michael A Caligiuri; Ben L Sanford; Sandra M Bothun; Krzysztof Mrózek; Jonathan E Kolitz; Bayard L Powell; Joseph O Moore; Richard M Stone; John Anastasi; Clara D Bloomfield; Richard A Larson Journal: J Clin Oncol Date: 2008-06-30 Impact factor: 44.544
Authors: Nadia Guerra; Ying Xim Tan; Nathalie T Joncker; Augustine Choy; Fermin Gallardo; Na Xiong; Susan Knoblaugh; Dragana Cado; Norman M Greenberg; Norman R Greenberg; David H Raulet Journal: Immunity Date: 2008-04 Impact factor: 31.745