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

Pediatr Blood Cancer. 2019 Jun;66(6):e27681. doi: 10.1002/pbc.27681. Epub 2019 Mar 7.

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.

Keywords: daunorubicin; doxorubicin; glucose-6-phospate dehydrogenase; leukemia; pharmacogenetics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / therapeutic use*
  • Child
  • Cohort Studies
  • Daunorubicin / therapeutic use*
  • Female
  • Follow-Up Studies
  • Glucosephosphate Dehydrogenase / metabolism*
  • Humans
  • Induction Chemotherapy
  • Male
  • Neoadjuvant Therapy
  • Neoplasm, Residual / drug therapy
  • Neoplasm, Residual / enzymology
  • Neoplasm, Residual / pathology*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / enzymology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology*
  • Prognosis
  • Risk Factors
  • Safety

Substances

  • Antibiotics, Antineoplastic
  • G6PD protein, human
  • Glucosephosphate Dehydrogenase
  • Daunorubicin