Format

Send to

Choose Destination
Blood Adv. 2018 Mar 13;2(5):462-469. doi: 10.1182/bloodadvances.2017014126.

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

Author information

1
SMARTc Unit, Pharmacokinetics Laboratory, Unité Mixte de Recherche (UMR) INSERM U1068 Centre de Recherche en Cancerologie de Marseille, Aix Marseille University, Marseille, France.
2
Hematology and Cellular Therapy Department, La Conception University Hospital of Marseille, Marseille, France.
3
Laboratoire de Biologie Médicale, Assistance Publique-Hôpitaux de Marseille, Marseille, France; and.
4
Service de Transfert d'Oncologie Biologique, Aix Marseille University, Assistance Publique-Hôpitaux de Marseille, INSERM, UMR 911 CRO2, Marseille, France.

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 toward higher response rates and longer progression-free survival and overall survival were observed in patients with low CDA activity. Taken together, the results of this study strongly suggest that CDA is a predictive marker of life-threatening toxicities in patients with AML receiving induction therapy with standard Ara-C.

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center