Thomas B Alexander1,2, Lei Wang3, Hiroto Inaba1,4, Brandon M Triplett5, Stanley Pounds3, Raul C Ribeiro1,4, Ching-Hon Pui1,4, Jeffrey E Rubnitz1,4. 1. Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee. 2. Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina. 3. Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee. 4. Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee. 5. Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee.
Abstract
BACKGROUND: Outcomes for children with acute myeloid leukemia (AML) have improved over the past 20 years even though the medications used for induction therapy have not changed. METHODS: This study analyzed data from patients with AML who were enrolled insuccessive protocols (AML97 and AML02) to determine the contributors to the improved outcomes of the latter clinical trial. RESULTS: There were significant improvements in 5-year overall survival (48.9% vs 71.2%; P < .0001) and event-free survival (43.5% vs 61.8%; P = .002) from AML97 to AML02. The 5-year cumulative incidence of early death (ED)/treatment-related mortality (TRM) was reduced for patients treated in AML02 (18.5% vs 7.9%; P = .007). Although the overall incidence of refractory disease (6.5% vs 5.6%; P = .736) and relapse (29.3% vs 21.0%; P = .12) did not differ between the 2 studies, patients with low-risk AML who were treated in AML02 had a reduced incidence of relapse (27.3% vs 8.8%; P = .036). CONCLUSIONS: The improved outcomes of the AML02 trial resulted from improved disease control for low-risk patients and overall decreased ED/TRM. These results emphasize the importance of supportive-care measures throughout chemotherapy courses and hematopoietic cell transplantation and the value of treatment intensity for patients with low-risk AML while underscoring the need for novel therapy, rather than increased therapy intensity, for children with high-risk AML. Cancer 2017;123:3791-3798.
RCT Entities:
BACKGROUND: Outcomes for children with acute myeloid leukemia (AML) have improved over the past 20 years even though the medications used for induction therapy have not changed. METHODS: This study analyzed data from patients with AML who were enrolled in successive protocols (AML97 and AML02) to determine the contributors to the improved outcomes of the latter clinical trial. RESULTS: There were significant improvements in 5-year overall survival (48.9% vs 71.2%; P < .0001) and event-free survival (43.5% vs 61.8%; P = .002) from AML97 to AML02. The 5-year cumulative incidence of early death (ED)/treatment-related mortality (TRM) was reduced for patients treated in AML02 (18.5% vs 7.9%; P = .007). Although the overall incidence of refractory disease (6.5% vs 5.6%; P = .736) and relapse (29.3% vs 21.0%; P = .12) did not differ between the 2 studies, patients with low-risk AML who were treated in AML02 had a reduced incidence of relapse (27.3% vs 8.8%; P = .036). CONCLUSIONS: The improved outcomes of the AML02 trial resulted from improved disease control for low-risk patients and overall decreased ED/TRM. These results emphasize the importance of supportive-care measures throughout chemotherapy courses and hematopoietic cell transplantation and the value of treatment intensity for patients with low-risk AML while underscoring the need for novel therapy, rather than increased therapy intensity, for children with high-risk AML. Cancer 2017;123:3791-3798.
Authors: Jeffrey E Rubnitz; Hiroto Inaba; Gary Dahl; Raul C Ribeiro; W Paul Bowman; Jeffrey Taub; Stanley Pounds; Bassem I Razzouk; Norman J Lacayo; Xueyuan Cao; Soheil Meshinchi; Barbara Degar; Gladstone Airewele; Susana C Raimondi; Mihaela Onciu; Elaine Coustan-Smith; James R Downing; Wing Leung; Ching-Hon Pui; Dario Campana Journal: Lancet Oncol Date: 2010-05-05 Impact factor: 41.316
Authors: Ursula Creutzig; Martin Zimmermann; Jean-Pierre Bourquin; Michael N Dworzak; Christine von Neuhoff; Annette Sander; André Schrauder; Andrea Teigler-Schlegel; Jan Stary; Selim Corbacioglu; Dirk Reinhardt Journal: Blood Date: 2011-09-26 Impact factor: 22.113
Authors: Christine J Harrison; Robert K Hills; Anthony V Moorman; David J Grimwade; Ian Hann; David K H Webb; Keith Wheatley; Siebold S N de Graaf; Eva van den Berg; Alan K Burnett; Brenda E S Gibson Journal: J Clin Oncol Date: 2010-05-03 Impact factor: 44.544
Authors: William A Wood; Stephanie J Lee; Ruta Brazauskas; Zhiwei Wang; Mahmoud D Aljurf; Karen K Ballen; David K Buchbinder; Jason Dehn; Cesar O Freytes; Hillard M Lazarus; Charles F Lemaistre; Paulette Mehta; David Szwajcer; Steven Joffe; Navneet S Majhail Journal: Biol Blood Marrow Transplant Date: 2014-03-07 Impact factor: 5.742
Authors: Carol O'Hear; Hiroto Inaba; Stanley Pounds; Lei Shi; Gary Dahl; W Paul Bowman; Jeffrey W Taub; Ching-Hon Pui; Raul C Ribeiro; Elaine Coustan-Smith; Dario Campana; Jeffrey E Rubnitz Journal: Cancer Date: 2013-09-04 Impact factor: 6.860
Authors: Michael J Kelly; John T Horan; Todd A Alonzo; Mary Eapen; Robert B Gerbing; Wensheng He; Beverly J Lange; Susan K Parsons; William G Woods Journal: Pediatr Blood Cancer Date: 2013-08-19 Impact factor: 3.167
Authors: Kim Klein; Gertjan Kaspers; Christine J Harrison; H Berna Beverloo; Ardine Reedijk; Mathilda Bongers; Jacqueline Cloos; Andrea Pession; Dirk Reinhardt; Martin Zimmerman; Ursula Creutzig; Michael Dworzak; Todd Alonzo; Donna Johnston; Betsy Hirsch; Michal Zapotocky; Barbara De Moerloose; Alcira Fynn; Vincent Lee; Takashi Taga; Akio Tawa; Anne Auvrignon; Bernward Zeller; Erik Forestier; Carmen Salgado; Walentyna Balwierz; Alexander Popa; Jeffrey Rubnitz; Susana Raimondi; Brenda Gibson Journal: J Clin Oncol Date: 2015-11-16 Impact factor: 44.544
Authors: C Michel Zwaan; Edward A Kolb; Dirk Reinhardt; Jonas Abrahamsson; Souichi Adachi; Richard Aplenc; Eveline S J M De Bont; Barbara De Moerloose; Michael Dworzak; Brenda E S Gibson; Henrik Hasle; Guy Leverger; Franco Locatelli; Christine Ragu; Raul C Ribeiro; Carmelo Rizzari; Jeffrey E Rubnitz; Owen P Smith; Lillian Sung; Daisuke Tomizawa; Marry M van den Heuvel-Eibrink; Ursula Creutzig; Gertjan J L Kaspers Journal: J Clin Oncol Date: 2015-08-24 Impact factor: 44.544
Authors: Sanne Noort; Martin Zimmermann; Dirk Reinhardt; Wendy Cuccuini; Martina Pigazzi; Jenny Smith; Rhonda E Ries; Todd A Alonzo; Betsy Hirsch; Daisuke Tomizawa; Franco Locatelli; Tanja A Gruber; Susana Raimondi; Edwin Sonneveld; Daniel K Cheuk; Michael Dworzak; Jan Stary; Jonas Abrahamsson; Nira Arad-Cohen; Malgorzata Czogala; Barbara De Moerloose; Henrik Hasle; Soheil Meshinchi; Marry van den Heuvel-Eibrink; C Michel Zwaan Journal: Blood Date: 2018-08-27 Impact factor: 22.113
Authors: Laura Hinze; Maren Pfirrmann; Salmaan Karim; James Degar; Connor McGuckin; Divya Vinjamur; Joshua Sacher; Kristen E Stevenson; Donna S Neuberg; Esteban Orellana; Martin Stanulla; Richard I Gregory; Daniel E Bauer; Florence F Wagner; Kimberly Stegmaier; Alejandro Gutierrez Journal: Cancer Cell Date: 2019-04-15 Impact factor: 31.743
Authors: Lane H Miller; Frank Keller; Ann Mertens; Mitchel Klein; Kristen Allen; Sharon Castellino; William G Woods Journal: Pediatr Blood Cancer Date: 2019-09-10 Impact factor: 3.167
Authors: Scott Sauer; Damon R Reed; Michael Ihnat; Robert E Hurst; David Warshawsky; Dalit Barkan Journal: Front Oncol Date: 2021-04-27 Impact factor: 6.244
Authors: Elizabeth A M Feijen; Wendy M Leisenring; Kayla L Stratton; Kirsten K Ness; Helena J H van der Pal; Elvira C van Dalen; Gregory T Armstrong; Gregory J Aune; Daniel M Green; Melissa M Hudson; Jacqueline Loonen; Kevin C Oeffinger; Leslie L Robison; Yutaka Yasui; Leontien C M Kremer; Eric J Chow Journal: JAMA Oncol Date: 2019-06-01 Impact factor: 31.777