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

Katherine M. Robinson, Wenjian Yang, Seth E. Karol, Nancy Kornegay, Dennis Jay, Cheng Cheng, John K. Choi, Dario Campana, Ching Hon Pui, Brent Wood, Michael J. Borowitz, Julie Gastier-Foster, Eric C. Larsen, Naomi J Winick, William L. Carroll, Mignon L. Loh, Elizabeth A. Raetz, Stephen P. Hunger, Meenakshi Devidas, Elaine R. MardisRobert S. Fulton, Mary V. Relling, Sima Jeha

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere27681
JournalPediatric Blood and Cancer
DOIs
StatePublished - Jan 1 2019

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Glucosephosphate Dehydrogenase Deficiency
Daunorubicin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Residual Neoplasm
Safety
Erythrocyte Transfusion
Pediatrics
Glucosephosphate Dehydrogenase
Anthracyclines
Therapeutics
Clinical Protocols
Oxidative Stress
Research

Keywords

  • daunorubicin
  • doxorubicin
  • glucose-6-phospate dehydrogenase
  • leukemia
  • pharmacogenetics

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

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

In: Pediatric Blood and Cancer, 01.01.2019.

Research output: Contribution to journalArticle

Robinson, KM, Yang, W, Karol, SE, Kornegay, N, Jay, D, Cheng, C, Choi, JK, Campana, D, Pui, CH, Wood, B, Borowitz, MJ, Gastier-Foster, J, Larsen, EC, Winick, NJ, Carroll, WL, Loh, ML, Raetz, EA, Hunger, SP, Devidas, M, Mardis, ER, Fulton, RS, Relling, MV & Jeha, S 2019, 'No evidence that G6PD deficiency affects the efficacy or safety of daunorubicin in acute lymphoblastic leukemia induction therapy', Pediatric Blood and Cancer. https://doi.org/10.1002/pbc.27681
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 J ; 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. / No evidence that G6PD deficiency affects the efficacy or safety of daunorubicin in acute lymphoblastic leukemia induction therapy. In: Pediatric Blood and Cancer. 2019.
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title = "No evidence that G6PD deficiency affects the efficacy or safety of daunorubicin in acute lymphoblastic leukemia induction therapy",
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.",
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author = "Robinson, {Katherine M.} and Wenjian Yang and Karol, {Seth E.} and Nancy Kornegay and Dennis Jay and Cheng Cheng and Choi, {John K.} and Dario Campana and Pui, {Ching Hon} and Brent Wood and Borowitz, {Michael J.} and Julie Gastier-Foster and Larsen, {Eric C.} and Winick, {Naomi J} and Carroll, {William L.} and Loh, {Mignon L.} and Raetz, {Elizabeth A.} and Hunger, {Stephen P.} and Meenakshi Devidas and Mardis, {Elaine R.} and Fulton, {Robert S.} and Relling, {Mary V.} and Sima Jeha",
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T1 - No evidence that G6PD deficiency affects the efficacy or safety of daunorubicin in acute lymphoblastic leukemia induction therapy

AU - Robinson, Katherine M.

AU - Yang, Wenjian

AU - Karol, Seth E.

AU - Kornegay, Nancy

AU - Jay, Dennis

AU - Cheng, Cheng

AU - Choi, John K.

AU - Campana, Dario

AU - Pui, Ching Hon

AU - Wood, Brent

AU - Borowitz, Michael J.

AU - Gastier-Foster, Julie

AU - Larsen, Eric C.

AU - Winick, Naomi J

AU - Carroll, William L.

AU - Loh, Mignon L.

AU - Raetz, Elizabeth A.

AU - Hunger, Stephen P.

AU - Devidas, Meenakshi

AU - Mardis, Elaine R.

AU - Fulton, Robert S.

AU - Relling, Mary V.

AU - Jeha, Sima

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - daunorubicin

KW - doxorubicin

KW - glucose-6-phospate dehydrogenase

KW - leukemia

KW - pharmacogenetics

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