Katherine M Robinson1, Wenjian Yang1, Seth E Karol2, Nancy Kornegay1, Dennis Jay3, Cheng Cheng4, John K Choi3, Dario Campana5, Ching-Hon Pui2, Brent Wood6, Michael J Borowitz7, Julie Gastier-Foster8, Eric C Larsen9, Naomi Winick10, William L Carroll11, Mignon L Loh12, Elizabeth A Raetz11, Stephen P Hunger13, Meenakshi Devidas14, Elaine R Mardis8, Robert S Fulton15, Mary V Relling1, Sima Jeha2. 1. Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee. 2. Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee. 3. Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee. 4. Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee. 5. Department of Paediatrics, National University of Singapore, Singapore. 6. Department of Laboratory Medicine, Seattle Children's Hospital, Seattle, Washington. 7. Department of Hematologic Pathology, John's Hopkins University, Baltimore, Maryland. 8. Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio. 9. Department of Pediatric Hematology-Oncology, Maine Medical Center, Scarborough, Maine. 10. Department of Pediatrics, UT Southwestern Medical Center, Dallas, Texas. 11. Perlmutter Cancer Center, Department of Pediatrics, NYU Langone Medical Center, New York City, New York. 12. Department of Pediatrics, Benioff Children's Hospital and the Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California. 13. Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 14. Department of Biostatistics, University of Florida, Gainesville, Florida. 15. Department of Genetics, Washington University School of Medicine, St. Louis, Missouri.
Abstract
BACKGROUND/ OBJECTIVES: Anthracyclines are used in induction therapy of pediatric acute lymphoblastic leukemia (ALL) and are known to generate oxidative stress; whether this translates into enhanced antileukemic activity or hemolytic effects in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency is unknown. DESIGN/ METHODS: Among 726 pediatric patients with newly diagnosed ALL treated at St. Jude Children's Research Hospital, 22 had deficient G6PD activity. We compared the prevalence of positive minimal residual disease (MRD) ≥1% at Day 15/Day 19 of induction or ≥0.01% at Day 42/Day 46 (end of induction) and the number of red blood cell (RBC) transfusions after daunorubicin in induction between patients with or without G6PD deficiency, adjusting for ALL risk group, treatment protocol, age, and gender. RESULTS: There was no difference in Day 15/19 (P = 1) or end of induction MRD (P = 0.76) nor in the number of RBC transfusions (P = 0.73); the lack of association with MRD was confirmed in a dataset of 1192 newly diagnosed male patients enrolled in a Children's Oncology Group trial (P = 0.78). CONCLUSION: We found no evidence that G6PD deficiency affects daunorubicin activity during induction treatment for ALL.
BACKGROUND/ OBJECTIVES:Anthracyclines are used in induction therapy of pediatric acute lymphoblastic leukemia (ALL) and are known to generate oxidative stress; whether this translates into enhanced antileukemic activity or hemolytic effects in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency is unknown. DESIGN/ METHODS: Among 726 pediatric patients with newly diagnosed ALL treated at St. Jude Children's Research Hospital, 22 had deficient G6PD activity. We compared the prevalence of positive minimal residual disease (MRD) ≥1% at Day 15/Day 19 of induction or ≥0.01% at Day 42/Day 46 (end of induction) and the number of red blood cell (RBC) transfusions after daunorubicin in induction between patients with or without G6PD deficiency, adjusting for ALL risk group, treatment protocol, age, and gender. RESULTS: There was no difference in Day 15/19 (P = 1) or end of induction MRD (P = 0.76) nor in the number of RBC transfusions (P = 0.73); the lack of association with MRD was confirmed in a dataset of 1192 newly diagnosed male patients enrolled in a Children's Oncology Group trial (P = 0.78). CONCLUSION: We found no evidence that G6PD deficiency affects daunorubicin activity during induction treatment for ALL.
Authors: M V Relling; E M McDonagh; T Chang; K E Caudle; H L McLeod; C E Haidar; T Klein; L Luzzatto Journal: Clin Pharmacol Ther Date: 2014-05-02 Impact factor: 6.875
Authors: Y Liu; C A Fernandez; C Smith; W Yang; C Cheng; J C Panetta; N Kornegay; C Liu; L B Ramsey; S E Karol; L J Janke; E C Larsen; N Winick; W L Carroll; M L Loh; E A Raetz; S P Hunger; M Devidas; J J Yang; C G Mullighan; J Zhang; W E Evans; S Jeha; C-H Pui; M V Relling Journal: Clin Pharmacol Ther Date: 2017-04-04 Impact factor: 6.875
Authors: Ellen M McDonagh; Caroline F Thorn; José M Bautista; Ilan Youngster; Russ B Altman; Teri E Klein Journal: Pharmacogenet Genomics Date: 2012-03 Impact factor: 2.089
Authors: Ching-Hon Pui; Dario Campana; Deqing Pei; W Paul Bowman; John T Sandlund; Sue C Kaste; Raul C Ribeiro; Jeffrey E Rubnitz; Susana C Raimondi; Mihaela Onciu; Elaine Coustan-Smith; Larry E Kun; Sima Jeha; Cheng Cheng; Scott C Howard; Vickey Simmons; Amy Bayles; Monika L Metzger; James M Boyett; Wing Leung; Rupert Handgretinger; James R Downing; William E Evans; Mary V Relling Journal: N Engl J Med Date: 2009-06-25 Impact factor: 91.245
Authors: Katherine M Robinson; Wenjian Yang; Cyrine E Haidar; Jane S Hankins; Dennis W Jay; Nancy Kornegay; Jeffrey E Rubnitz; Ulrich Broeckel; Cheng Cheng; Ching-Hon Pui; Sima Jeha; Mary V Relling Journal: Pharmacogenomics J Date: 2018-09-12 Impact factor: 3.550
Authors: Sarah A Morris; Kristine R Crews; Randall T Hayden; Clifford M Takemoto; Wenjian Yang; Donald K Baker; Ulrich Broeckel; Mary V Relling; Cyrine E Haidar Journal: Pharmacogenet Genomics Date: 2022-04-01 Impact factor: 2.089