CDA as a predictive marker for life-threatening toxicities in patients with AML treated with cytarabine

Blood Advances
Raphaelle FanciullinoRegis Costello

Abstract

Cytarabine (Ara-C) is the backbone of acute myeloid leukemia (AML) chemotherapy. Little is known about possible risk factors predictive for the frequent (ie, up to 16%) life-threatening or lethal toxicities caused by Ara-C. Ara-C is detoxified in the liver by a single enzyme, cytidine deaminase (CDA), coded by a gene known to be highly polymorphic. In this proof-of-concept study, we particularly investigated the role of the CDA poor metabolizer (PM) phenotype in Ara-C toxicities. CDA phenotyping (measurement of CDA residual activity in serum) and genotyping (search for the CDA*2 allelic variant) were performed in 58 adult patients with AML treated with the standard 7+3 (Ara-C + anthracyclines) protocol. Statistically significantly lower CDA activity was observed in patients experiencing severe/lethal toxicities as compared with patients who did not (1.5 ± 0.7 U/mg vs 3.95 ± 3.1 U/mg; Student t test P < .001). Subsequent receiver operating characteristic analysis identified a threshold in CDA activity (ie, 2 U/mg) associated with PM syndrome and increased risk of developing severe toxicities. Five percent of patients experienced lethal toxicities, all displaying CDA PM status (1.3 ± 0.5 U/mg). In terms of efficacy, a trend towar...Continue Reading

References

Feb 1, 1981·The American Journal of Medicine·H M HauptG W Moore
Apr 9, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kan YonemoriJun-Ichi Sawada
Oct 20, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Cédric MercierJoseph Ciccolini
Jul 5, 2008·Nucleosides, Nucleotides & Nucleic Acids·E GiovannettiG J Peters
Sep 25, 2009·The New England Journal of Medicine·Bob LöwenbergUNKNOWN Swiss Group for Clinical Cancer Research (SAKK) Collaborative Group
Nov 26, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Joseph CiccoliniCédric Mercier
Dec 5, 2009·Best Practice & Research. Clinical Haematology·Jacob M Rowe
Mar 6, 2010·Pediatric Blood & Cancer·Emilie MoreauJoseph Ciccolini
Mar 31, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Elisa GiovannettiGodefridus J Peters
Jan 12, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Alan BurnettBob Löwenberg
Jan 12, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Guido MarcucciHartmut Döhner
Feb 10, 2011·Nature Reviews. Clinical Oncology·Joseph CiccoliniNicolas André
Mar 18, 2011·The New England Journal of Medicine·Bob LöwenbergUNKNOWN Dutch-Belgian Cooperative Trial Group for Hemato-Oncology (HOVON) and Swiss Group for Clinical Cancer Research (SAKK) Collab
Jun 10, 2011·Annals of Oncology : Official Journal of the European Society for Medical Oncology·C TibaldiG J Peters
Feb 12, 2013·Pharmacogenomics·Alexandre EvrardJoseph Ciccolini
Jun 19, 2014·Nucleosides, Nucleotides & Nucleic Acids·Godefridus J PetersUNKNOWN EORTC-Pharmacology and Molecular Mechanism Group
Aug 22, 2014·British Journal of Haematology·Kenneth F BradstockUNKNOWN Australasian Leukaemia and Lymphoma Group
Sep 10, 2014·British Journal of Haematology·Walter J F M van der VeldenNicole M A Blijlevens
Dec 17, 2014·Expert Opinion on Drug Metabolism & Toxicology·Cindy SerdjebiJoseph Ciccolini
Nov 26, 2015·The Lancet Oncology·Joseph Ciccolini
May 25, 2016·Expert Opinion on Drug Metabolism & Toxicology·Joseph CiccoliniRaphaelle Fanciullino
Mar 1, 2012·Annals of Oncology : Official Journal of the European Society for Medical Oncology·C TibaldiG J Peters

❮ Previous
Next ❯

Citations

Jun 20, 2020·Clinical Pharmacology and Therapeutics·Florent FerrerJoseph Ciccolini
Feb 3, 2021·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M DonnetteR Fanciullino
Aug 28, 2019·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Melanie DonnetteRaphaëlle Fanciullino
Aug 21, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Mélanie DonnetteRaphaelle Fanciullino
Dec 17, 2021·International Journal of Cancer. Journal International Du Cancer·Nao Yoshida-SakaiShinya Kimura

❮ Previous
Next ❯

Related Concepts

Related Feeds

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.