Cytidine deaminase genotype and toxicity of cytosine arabinoside therapy in children with acute myeloid leukemia.
Cytidine deaminase genotype and toxicity of cytosine arabinoside therapy in children with acute myeloid leukemia.
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DOI：
10.1111/j.1365-2141.2008.07461.x
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发表时间：
2009-02
影响因子：
6.5
通讯作者：
Davies SM
中科院分区：
文献类型：
--
作者：
Bhatla D;Gerbing RB;Alonzo TA;Conner H;Ross JA;Meshinchi S;Zhai X;Zamzow T;Mehta PA;Geiger H;Perentesis J;Davies SM
阿糖胞苷（ara-C）被胞苷脱氨酶（CDD）不可逆地脱氨为无毒代谢产物。CDD中常见的多态性A79 C将赖氨酸残基改变为谷氨酰胺，导致酶活性降低。我们检测了457例接受CCG 2941和2961治疗的AML患儿的CDD A79 C基因型，并分析了CDD基因型对治疗结果的影响。CC基因型儿童的诱导治疗后相关死亡率（TRM）显著升高（5年TRM 17 ± 13% CC vs 7 ± 4% AA，5 ± 4% AC，p= 0.05）。这在接受IDA-FLAG（ara-C= 7590 mg/m2）（5年TRM 24 ± 21% CC vs 6 ± 6% AA，6 ± 7% AC，p=0.07）作为巩固治疗的儿童中比接受IDA-DCTER（ara-C= 800 mg/m2）（5年TRM 15 ± 20% CC vs 8 ± 6% AA，4 ± 6% AC; p=0.29）的儿童中更明显。在接受IDA-FLAG治疗的CC基因型儿童中，无复发生存率无显著增加（76 ± 20%CC vs 59 ± 12%AA和55 ± 14%AC; p= 0.40）。这些数据表明，具有低活性CDD基因型的儿童在基于Ara-C的AML治疗中治疗相关死亡率的风险增加。
Cytosine arabinoside (ara-C) is irreversibly deaminated by cytidine deaminase (CDD) to a nontoxic metabolite. A common polymorphism, A79C, in CDD changes a lysine residue to glutamine resulting in decreased enzyme activity. We determined CDD A79C genotypes for 457 children with AML treated on CCG 2941 and 2961 and analyzed the impact of CDD genotype on therapy outcomes. Post-Induction treatment related mortality (TRM) was significantly elevated in children with the CC genotype (5 year TRM 17 ± 13% CC vs 7 ± 4% AA, 5 ± 4% AC, p= 0.05). This was more notable in children who received IDA-FLAG (ara-C= 7590 mg/m2) (5 year TRM 24 ± 21% CC vs 6 ± 6% AA, 6 ± 7% AC, p=0.07) as consolidation therapy compared to IDA-DCTER (ara-C= 800 mg/m2) (5 year TRM 15 ± 20% CC vs 8 ± 6% AA, 4 ± 6% AC; p=0.29). Relapse-free survival was non-significantly increased in children with the CC genotype treated with IDA-FLAG (76 ± 20% CC vs 59 ± 12% AA and 55 ± 14% AC; p= 0.40). These data indicate that children with a low activity CDD genotype are at increased risk of treatment-related mortality with Ara-C based therapy for AML.
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影响因子：
15.9
作者：
CHABNER, BA;JOHNS, DG;EVANS, WH
通讯作者：
EVANS, WH
影响因子：
20.3
作者：
Lange, Beverly J.;Smith, Franklin O.;Alonzo, Todd A.
通讯作者：
Alonzo, Todd A.
影响因子：
20.3
作者：
ELLISON, RR;HOLLAND, JF;MOON, JH
通讯作者：
MOON, JH
影响因子：
45.3
作者：
Lange, BJ;Dinndorf, P;Alonzo, TA
通讯作者：
Alonzo, TA
影响因子：
6.5
作者：
Galmarini, CM;Thomas, X;Dumontet, C
通讯作者：
Dumontet, C