PURPOSE: To identify effective and less toxic therapy for children with acute myeloid leukemia, we introduced clofarabine into the first course of remission induction to reduce exposure to daunorubicin and etoposide. PATIENTS AND METHODS: From 2008 through 2017, 285 patients were enrolled at eight centers; 262 were randomly assigned to receive clofarabine and cytarabine (Clo+AraC, n = 129) or high-dose cytarabine, daunorubicin, and etoposide (HD-ADE, n = 133) as induction I. Induction II consisted of low-dose ADE given alone or combined with sorafenib or vorinostat. Consolidation therapy comprised two or three additional courses of chemotherapy or hematopoietic cell transplantation. Genetic abnormalities and the level of minimal residual disease (MRD) at day 22 of initial remission induction determined final risk classification. The primary end point was MRD at day 22. RESULTS:Complete remission was induced after two courses of therapy in 263 (92.3%) of the 285 patients; induction failures included four early deaths and 15 cases of resistant leukemia. Day 22 MRD was positive in 57 of 121 randomly assigned evaluable patients (47%) who received Clo+AraC and 42 of 121 patients (35%) who received HD-ADE (odds ratio, 1.86; 95% CI, 1.03 to 3.41; P = .04). Despite this result, the 3-year event-free survival rate (52.9% [44.6% to 62.8%] for Clo+AraC v 52.4% [44.0% to 62.4%] for HD-ADE, P = .94) and overall survival rate (74.8% [67.1% to 83.3%] for Clo+AraC v 64.6% [56.2% to 74.2%] for HD-ADE, P = .1) did not differ significantly across the two arms. CONCLUSION: Our findings suggest that the use of clofarabine with cytarabine during remission induction might reduce the need for anthracycline and etoposide in pediatric patients with acute myeloid leukemia and may reduce rates of cardiomyopathy and treatment-related cancer.
RCT Entities:
PURPOSE: To identify effective and less toxic therapy for children with acute myeloid leukemia, we introduced clofarabine into the first course of remission induction to reduce exposure to daunorubicin and etoposide. PATIENTS AND METHODS: From 2008 through 2017, 285 patients were enrolled at eight centers; 262 were randomly assigned to receive clofarabine and cytarabine (Clo+AraC, n = 129) or high-dose cytarabine, daunorubicin, and etoposide (HD-ADE, n = 133) as induction I. Induction II consisted of low-dose ADE given alone or combined with sorafenib or vorinostat. Consolidation therapy comprised two or three additional courses of chemotherapy or hematopoietic cell transplantation. Genetic abnormalities and the level of minimal residual disease (MRD) at day 22 of initial remission induction determined final risk classification. The primary end point was MRD at day 22. RESULTS: Complete remission was induced after two courses of therapy in 263 (92.3%) of the 285 patients; induction failures included four early deaths and 15 cases of resistant leukemia. Day 22 MRD was positive in 57 of 121 randomly assigned evaluable patients (47%) who received Clo+AraC and 42 of 121 patients (35%) who received HD-ADE (odds ratio, 1.86; 95% CI, 1.03 to 3.41; P = .04). Despite this result, the 3-year event-free survival rate (52.9% [44.6% to 62.8%] for Clo+AraC v 52.4% [44.0% to 62.4%] for HD-ADE, P = .94) and overall survival rate (74.8% [67.1% to 83.3%] for Clo+AraC v 64.6% [56.2% to 74.2%] for HD-ADE, P = .1) did not differ significantly across the two arms. CONCLUSION: Our findings suggest that the use of clofarabine with cytarabine during remission induction might reduce the need for anthracycline and etoposide in pediatric patients with acute myeloid leukemia and may reduce rates of cardiomyopathy and treatment-related cancer.
Authors: Bob Löwenberg; Thomas Pabst; Johan Maertens; Yvette van Norden; Bart J Biemond; Harry C Schouten; Olivier Spertini; Edo Vellenga; Carlos Graux; Violaine Havelange; Georgine E de Greef; Okke de Weerdt; Marie-Cecile J C Legdeur; Juergen Kuball; Marinus van Marwijk Kooy; Bjorn T Gjertsen; Mojca Jongen-Lavrencic; Arjan A van de Loosdrecht; Daniëlle van Lammeren-Venema; Beata Hodossy; Dimitri A Breems; Yves Chalandon; Jakob Passweg; Peter J M Valk; Markus G Manz; Gert J Ossenkoppele Journal: Blood Date: 2017-01-03 Impact factor: 22.113
Authors: Ursula Creutzig; Martin Zimmermann; Jean-Pierre Bourquin; Michael N Dworzak; Gudrun Fleischhack; Norbert Graf; Thomas Klingebiel; Bernhard Kremens; Thomas Lehrnbecher; Christine von Neuhoff; Jörg Ritter; Annette Sander; André Schrauder; Arend von Stackelberg; Jan Starý; Dirk Reinhardt Journal: Blood Date: 2013-05-23 Impact factor: 22.113
Authors: Sima Jeha; Bassem Razzouk; Michael Rytting; Susan Rheingold; Edythe Albano; Richard Kadota; Lori Luchtman-Jones; Lisa Bomgaars; Paul Gaynon; Stewart Goldman; Kim Ritchey; Robert Arceci; Arnold Altman; Kimo Stine; Laurel Steinherz; Peter Steinherz Journal: J Clin Oncol Date: 2009-08-03 Impact factor: 44.544
Authors: Elizabeth A M Feijen; Wendy M Leisenring; Kayla L Stratton; Kirsten K Ness; Helena J H van der Pal; Huib N Caron; Gregory T Armstrong; Daniel M Green; Melissa M Hudson; Kevin C Oeffinger; Leslie L Robison; Marilyn Stovall; Leontien C M Kremer; Eric J Chow Journal: J Clin Oncol Date: 2015-08-24 Impact factor: 44.544
Authors: Courtney D DiNardo; Keith W Pratz; Anthony Letai; Brian A Jonas; Andrew H Wei; Michael Thirman; Martha Arellano; Mark G Frattini; Hagop Kantarjian; Relja Popovic; Brenda Chyla; Tu Xu; Martin Dunbar; Suresh K Agarwal; Rod Humerickhouse; Mack Mabry; Jalaja Potluri; Marina Konopleva; Daniel A Pollyea Journal: Lancet Oncol Date: 2018-01-12 Impact factor: 41.316
Authors: Stefan Faderl; Meir Wetzler; David Rizzieri; Gary Schiller; Madan Jagasia; Robert Stuart; Siddhartha Ganguly; David Avigan; Michael Craig; Robert Collins; Michael Maris; Tibor Kovacsovics; Stuart Goldberg; Karen Seiter; Parameswaran Hari; Jochen Greiner; Norbert Vey; Christian Recher; Farhad Ravandi; Eunice S Wang; Michael Vasconcelles; Dirk Huebner; Hagop M Kantarjian Journal: J Clin Oncol Date: 2012-05-14 Impact factor: 44.544
Authors: R Peto; M C Pike; P Armitage; N E Breslow; D R Cox; S V Howard; N Mantel; K McPherson; J Peto; P G Smith Journal: Br J Cancer Date: 1976-12 Impact factor: 7.640
Authors: Chengzhi Xie; Christina Drenberg; Holly Edwards; J Timothy Caldwell; Wei Chen; Hiroto Inaba; Xuelian Xu; Steven A Buck; Jeffrey W Taub; Sharyn D Baker; Yubin Ge Journal: PLoS One Date: 2013-11-11 Impact factor: 3.240
Authors: Jessica A Pollard; Todd A Alonzo; Robert Gerbing; Patrick Brown; Elizabeth Fox; John Choi; Brian Fisher; Betsy Hirsch; Samir Kahwash; Kelly Getz; John Levine; Lisa Eidenschink Brodersen; Michael R Loken; Susana Raimondi; Katherine Tarlock; Andrew Wood; Lillian Sung; E Anders Kolb; Alan Gamis; Soheil Meshinchi; Richard Aplenc Journal: J Clin Oncol Date: 2022-03-29 Impact factor: 50.717
Authors: Maarten Fornerod; Jing Ma; Sanne Noort; C Michel Zwaan; Tanja A Gruber; Yu Liu; Michael P Walsh; Lei Shi; Stephanie Nance; Yanling Liu; Yuanyuan Wang; Guangchun Song; Tamara Lamprecht; John Easton; Heather L Mulder; Donald Yergeau; Jacquelyn Myers; Jennifer L Kamens; Esther A Obeng; Martina Pigazzi; Marie Jarosova; Charikleia Kelaidi; Sophia Polychronopoulou; Jatinder K Lamba; Sharyn D Baker; Jeffrey E Rubnitz; Dirk Reinhardt; Marry M van den Heuvel-Eibrink; Franco Locatelli; Henrik Hasle; Jeffery M Klco; James R Downing; Jinghui Zhang; Stanley Pounds Journal: Blood Cancer Discov Date: 2021-09-09
Authors: Neel S Bhatt; Malek J Baassiri; Wei Liu; Nickhill Bhakta; Wassim Chemaitilly; Matthew J Ehrhardt; Hiroto Inaba; Kevin Krull; Kirsten K Ness; Jeffrey E Rubnitz; Deokumar Srivastava; Leslie L Robison; Melissa M Hudson; Daniel A Mulrooney Journal: Leukemia Date: 2021-01-25 Impact factor: 11.528
Authors: Mayuko Iijima; Melanie Stall; Lei Wang; John C Panetta; Brandon M Triplett; Ching-Hon Pui; Raul C Ribeiro; Jeffrey E Rubnitz; Stanley B Pounds; Hiroto Inaba Journal: Blood Adv Date: 2022-05-10