Yazarlar : Kawedia JD, Liu C, Pei D, Cheng C, Fernandez CA, Howard SC, Campana D, Panetta JC, Bowman WP, Evans WE, Pui CH, Relling MV.

Yayın : Blood.

Yayın Yılı : 2011

Pubmed Linki : http://www.ncbi.nlm.nih.gov/pubmed/22117041

Konu : Lösemi

Literatür İçeriği :  

Abstract

We have previously hypothesized that higher systemic exposure to asparaginase may cause increased exposure to dexamethasone, both critical chemotherapeutic agents for acute lymphoblastic leukemia (ALL). Whether interpatient pharmacokinetic differences in dexamethasone contribute to relapse risk has never been studied. The impact of plasma clearance of dexamethasone and anti-asparaginase antibody levels on risk of relapse was assessed in 410 children who were treated on a front-line clinical trial for ALL and were evaluable for all pharmacologic measures, using multivariate analyses, adjusting for standard clinical and biologic prognostic factors. Dexamethasone clearance (average ± standard deviation) was higher (p = 3 x 10(-8)) in patients whose sera was positive (17.7 ± 18.6 L/h/m(2)) vs. negative (10.6 ± 5.99 L/h/m(2)) for anti-asparaginase antibodies. In multivariate analyses, higher dexamethasone clearance was associated with a higher risk of any relapse (p = 0.01) and of CNS relapse (p = 0.014). CNS relapse was also more common in patients with anti-asparaginase antibodies (p = 0.019). In conclusion, systemic clearance of dexamethasone is higher in patients with anti-asparaginase antibodies. Lower exposure to both drugs was associated with an increased risk of relapse

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