The prognostic significance of a positive direct antiglobulin test in chronic lymphocytic leukemia: a beneficial effect of the combination of fludarabine and cyclophosphamide on the incidence of hemolytic anemia
The prognostic significance of a positive direct antiglobulin test in chronic lymphocytic leukemia: a beneficial effect of the combination of fludarabine and cyclophosphamide on the incidence of hemolytic anemia
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DOI：
10.1182/blood-2007-07-101303
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发表时间：
2008-02-15
期刊：
影响因子：
20.3
通讯作者：
Catovsky, Daniel
中科院分区：
文献类型：
--
作者：
Dearden, Claire;Wade, Rachel;Catovsky, Daniel
自身免疫性溶血性贫血（AHA）是慢性淋巴细胞白血病（CLL）的常见并发症.英国LRF CLL4试验是CLL中最大的前瞻性试验，旨在检查阳性直接抗球蛋白试验（DAT）和AHA的预后影响。777例患者随机接受苯丁酸氮芥或氟达拉滨，单独或与环磷酰胺（FC）。治疗前阳性DAT的发生率为14%。10%的人发展了AHA。在83%的病例中，DAT正确预测了治疗后AHA的发生或未发生，但只有28%的DAT阳性患者发生了AHA。在299例治疗前后均进行检测的患者中，接受单药氟达拉滨治疗的患者最有可能保持DAT阳性，并从阴性变为阳性。接受苯丁酸氮芥或氟达拉滨治疗的患者发生AHA的可能性是接受FC治疗的患者的两倍多。在多变量分析中，C期疾病和高β 2微球蛋白是阳性DAT结果的独立预测因素。AHA或阳性DAT（伴或不伴AHA）可独立预测总生存期（OS）降低。4例死亡（均接受氟达拉滨单药治疗）归因于AHA。总之，DAT状态在治疗开始时提供了一个新的预后指标，虽然FC可能保护AHA。该试验在http://isrctn.org上注册为58585610。
Autoimmune hemolytic anemia (AHA) is a common complication in chronic lymphocytic leukemia (CLL). The UK LRF CLL4 trial is the largest prospective trial in CLL to examine the prognostic impact of both a positive direct antiglobulin test (DAT) and AHA. Seven-hundred seventy-seven patients were randomized to receive chlorambucil or fludarabine, alone or with cyclophosphamide (FC). The incidence pretreatment of a positive DAT was 14%. Ten percent developed AHA. The DAT correctly predicted the development, or not, of AHA after therapy in 83% of cases, however only 28% of DAT-positive patients developed AHA. Of 299 patients tested both before and after treatment, those treated with single-agent fludarabine were most likely to remain DAT positive and to change from negative to positive. Patients treated with chlorambucil or fludarabine were more than twice as likely to develop AHA as those receiving FC. In a multivariate analysis, stage C disease and high beta 2 microglobulin were independent predictors of a positive DAT result. AHA, or a positive DAT, with or without AHA, independently predicted for reduced overall survival (OS). Four deaths, all on fludarabine monotherapy, were attributed to AHA. In conclusion, DAT status at the time of initiation of therapy provides a new prognostic indicator, although FC may protect against AHA. This trial was registered at http://isrctn.org as no.58585610.