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Pharmacokinetics and pharmacodynamics
PKP-020 Impact of nadph oxidase functional polymorphisms in acute myeloid leukaemia induction chemotherapy
  1. JE Megías Vericat1,
  2. P Montesinos2,
  3. MJ Herrero3,
  4. V Bosó1,
  5. F Moscardó2,
  6. L Rojas4,
  7. D Martínez-Cuadrón2,
  8. SF Aliño5,
  9. MA Sanz2,
  10. JL Poveda6
  1. 1Hospital Universitario Y Politécnico La Fe, Servicio de Farmacia – Área Del Medicamento. Unidad de Farmacogenética- Instituto Investigación Sanitaria La Fe, Valencia, Spain
  2. 2Hospital Universitario Y Politécnico La Fe, Servicio de Hematología Y Hemoterapia, Valencia, Spain
  3. 3Hospital Universitario Y Politécnico La Fe and Facultad de Medicina – Universidad de Valencia, Unidad de Farmacogenética – Instituto Investigación Sanitaria La Fe and Área Del Medicamento and Departamento Farmacología, Valencia, Spain
  4. 4Hospital Universitario Y Politécnico La Fe and Pontificia Universidad Católica de Chile, Unidad de Farmacogenética- Instituto Investigación Sanitaria La Fe and Área Del Medicamento – And Department of Internal Medicine. Faculty of Medicine, Valencia, Sp
  5. 5Hospital Universitario Y Politécnico La Fe and Universidad de Valencia, Unidad de Farmacogenética and Unidad de Farmacología Clínica – Área Del Medicamento – Instituto Investigación Sanitaria La Fe and Área Del Medicamento – And Departamento Farmacología
  6. 6Hospital Universitario Y Politécnico La Fe, Servicio de Farmacia – Área Del Medicamento, Valencia, Spain

Abstract

Background NADPH oxidase, a key mediator of oxidative cardiac damage and remodelling, modulates anthracycline clinical cardiotoxicity.

Purpose Single nucleotide polymorphisms (SNPs) of NADPH oxidase genes could lead to interindividual differences in treatment outcome in acute myeloid leukaemia (AML) patients.

Material and methods The main three NADPH oxidase polymorphisms (CYBA:rs4673, NCF4:rs1883112 and RAC2:rs13058338) were evaluated in 225 adult patients at the initial diagnosis of AML using a mass spectrometry based multiplex genotyping assay (Sequenom). All patients received induction chemotherapy consisting of idarubicin plus cytarabine (PETHEMA 99, 2007 and 2010 trials).

The efficacy of the first induction cycle was evaluated comparing complete remission (CR) versus partial remission (PR) or  resistance (patients dying during induction were excluded). Based on the WHO grading scale, toxicities were grouped as binary variables (grade 0–1 vs grade 2–4), assigning the maximum grade of all the specific toxicities within that group (evaluated in all patients). Genotypes were studied with the co-dominant model. Association between variables was assessed using linear and logistic regression adjusting for age, gender, ECOG, and leucocyte and platelet count at diagnosis (R v.3.1.2).

Results The median age of patients was 51.1 years (16–78 years). There were higher CR rates among patients harbouring variant alleles of NCF4 and RAC2 genes (see data in table 1). Polymorphisms of these genes were not correlated with cardiotoxicity in our patients. Nevertheless, several associations were obtained with other toxicities (summarised in table 2).

View this table:
Abstract PKP-020 Table 1

Association between SNPs and effectiveness

View this table:
Abstract PKP-020 Table 2

Association between SNPs and different toxicities

Conclusion Although our study did not reproduce the cardiotoxicity previously related with these SNPs in other malignancies, we obtained novel associations with efficacy and safety of anthracyclines in AML induction.

References and/or Acknowledgements

  1. Wojnowski. Circulation 2005;112:3754-62

References and/or AcknowledgementsNo conflict of interest.

https://doi.org/10.1136/ejhpharm-2016-000875.423

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