No evidence that G6PD deficiency affects the efficacy or safety of daunorubicin in acute lymphoblastic leukemia induction therapy

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) de...

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Published in:Pediatric blood & cancer 2019-06, Vol.66 (6), p.e27681-n/a
Main Authors: Robinson, Katherine M., Yang, Wenjian, Karol, Seth E., Kornegay, Nancy, Jay, Dennis, Cheng, Cheng, Choi, John K., Campana, Dario, Pui, Ching‐Hon, Wood, Brent, Borowitz, Michael J., Gastier‐Foster, Julie, Larsen, Eric C., Winick, Naomi, Carroll, William L., Loh, Mignon L., Raetz, Elizabeth A., Hunger, Stephen P., Devidas, Meenakshi, Mardis, Elaine R., Fulton, Robert S., Relling, Mary V., Jeha, Sima
Format: Article
Language:English
Subjects:
Antibiotics, Antineoplastic - therapeutic use
Child
Cohort Studies
daunorubicin
Daunorubicin - therapeutic use
doxorubicin
Female
Follow-Up Studies
Glucosephosphate Dehydrogenase - metabolism
glucose‐6‐phospate dehydrogenase
Humans
Induction Chemotherapy
leukemia
Male
Neoadjuvant Therapy
Neoplasm, Residual - drug therapy
Neoplasm, Residual - enzymology
Neoplasm, Residual - pathology
pharmacogenetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy
Precursor Cell Lymphoblastic Leukemia-Lymphoma - enzymology
Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology
Prognosis
Risk Factors
Safety
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Summary: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.
ISSN:1545-5009
1545-5017
DOI:10.1002/pbc.27681