PURPOSE: The purpose of the study was to assess the contribution of age and disease variables to the outcome of untreated patients with acute myeloid leukemia (AML) receiving varying intensive induction chemotherapy. PATIENTS AND METHODS: Patients 16 to 85 years of age with primary AML, known karyotype, and uniform postremission chemotherapy enrolled onto two consecutive trials were eligible and were randomly assigned to induction either with a standard-dose (cytarabine, daunorubicin, and 6-thioguanine) and a high-dose (cytarabine and mitoxantrone) combination, or with two courses of the high-dose combination. Subgroups were defined by karyotype, nucleophosmin and FLT3 mutation, WBC count, serum lactate dehydrogenase, and residual blasts. RESULTS: In 1,284 patients, the overall survival at 4 years in those younger and older than 60 years was 37% versus 16% (P < .001) and the ongoing remission duration was 46% versus 22% (P < .001). Similar age-related differences in outcome were found for all defined subgroups. No difference in outcome according to randomly assigned treatment regimen was observed in any age group or prognostic subset. Regarding prognostic subgroups, molecular factors were also considered. CONCLUSION: Under harmonized conditions, older and younger patients with AML show modest differences in their risk profiles and equally no dose response to intensified chemotherapy. Their observed fundamental difference in outcome across all subgroups remains unexplained. Further molecular investigation may elucidate the age effect in AML and identify new targets.
RCT Entities:
PURPOSE: The purpose of the study was to assess the contribution of age and disease variables to the outcome of untreated patients with acute myeloid leukemia (AML) receiving varying intensive induction chemotherapy. PATIENTS AND METHODS: Patients 16 to 85 years of age with primary AML, known karyotype, and uniform postremission chemotherapy enrolled onto two consecutive trials were eligible and were randomly assigned to induction either with a standard-dose (cytarabine, daunorubicin, and 6-thioguanine) and a high-dose (cytarabine and mitoxantrone) combination, or with two courses of the high-dose combination. Subgroups were defined by karyotype, nucleophosmin and FLT3 mutation, WBC count, serum lactate dehydrogenase, and residual blasts. RESULTS: In 1,284 patients, the overall survival at 4 years in those younger and older than 60 years was 37% versus 16% (P < .001) and the ongoing remission duration was 46% versus 22% (P < .001). Similar age-related differences in outcome were found for all defined subgroups. No difference in outcome according to randomly assigned treatment regimen was observed in any age group or prognostic subset. Regarding prognostic subgroups, molecular factors were also considered. CONCLUSION: Under harmonized conditions, older and younger patients with AML show modest differences in their risk profiles and equally no dose response to intensified chemotherapy. Their observed fundamental difference in outcome across all subgroups remains unexplained. Further molecular investigation may elucidate the age effect in AML and identify new targets.
Authors: Jianping Mao; Wenliang Gao; Lianguo Xue; Lidong Zhao; Lei Miao; Tao Jia; Yuanxin Zhu; Ying Wang; Lijuan Meng; Juan Wang Journal: Am J Blood Res Date: 2020-12-15
Authors: Rüdiger Hehlmann; David Grimwade; Bengt Simonsson; Jane Apperley; Michele Baccarani; Tiziano Barbui; Giovanni Barosi; Renato Bassan; Marie C Béné; Ute Berger; Thomas Büchner; Alan Burnett; Nicolas C P Cross; Theo J M de Witte; Hartmut Döhner; Hervé Dombret; Hermann Einsele; Georg Engelich; Robin Foà; Christa Fonatsch; Nicola Gökbuget; Elaine Gluckman; Alois Gratwohl; Francois Guilhot; Claudia Haferlach; Thorsten Haferlach; Michael Hallek; Jörg Hasford; Andreas Hochhaus; Dieter Hoelzer; Jean-Jaques Kiladjian; Boris Labar; Per Ljungman; Ulrich Mansmann; Dietger Niederwieser; Gert Ossenkoppele; José M Ribera; Harald Rieder; Hubert Serve; Petra Schrotz-King; Miguel A Sanz; Susanne Saussele Journal: Haematologica Date: 2010-11-03 Impact factor: 9.941
Authors: Anthony D Sung; Shekeab Jauhari; Sharareh Siamakpour-Reihani; Arati V Rao; Janet Staats; Cliburn Chan; Everett Meyer; Vijayakrishna K Gadi; Andrew B Nixon; Jing Lyu; Jichun Xie; Lauren Bohannon; Zhiguo Li; Christopher S Hourigan; Laura W Dillon; Hong Yuen Wong; Rebecca Shelby; Louis Diehl; Carlos de Castro; Thomas LeBlanc; Danielle Brander; Harry Erba; Ahmed Galal; Alexandra Stefanovic; Nelson Chao; David A Rizzieri Journal: Am J Hematol Date: 2020-03-30 Impact factor: 10.047
Authors: P Silva; M Neumann; M P Schroeder; S Vosberg; C Schlee; K Isaakidis; J Ortiz-Tanchez; L R Fransecky; T Hartung; S Türkmen; A Graf; S Krebs; H Blum; C Müller-Tidow; C Thiede; G Ehninger; H Serve; J Hecht; W E Berdel; P A Greif; C Röllig; C D Baldus Journal: Leukemia Date: 2017-04-03 Impact factor: 11.528
Authors: A G Dinmohamed; O Visser; Y van Norden; N M A Blijlevens; J J Cornelissen; G A Huls; P C Huijgens; P Sonneveld; A A van de Loosdrecht; G J Ossenkoppele; B Löwenberg; M Jongen-Lavrencic Journal: Leukemia Date: 2015-07-17 Impact factor: 11.528