意大利Amedeo Avogadro大学Gianluca Gaidano 教授访谈

　　《肿瘤瞭望》：目前对于慢性淋巴细胞白血病（CLL）的细胞遗传学有哪些新的检测？

　　Gaidano 教授：FISH和p53基因突变检测对于CLL患者极其重要，通过检测我们可以为患者挑选出最适合的治疗。很多国家资源有限，包括我们自己的国家意大利，因此必须为患者选择最适合的治疗。由于实际的原因，流式细胞术我不一定会用于临床实践，但是p53基因突变检测确实是一个选择最适合治疗的指标，我认为应该在所有患者中进行检测。现在我们有新的手段，包括新药来克服p53基因介导的化疗抵抗。

　　I think sequencing for p53 is really very important for patients. FISH and sequencing for p53 mutation is extremely important for choosing the best treatment for our patients. If there are limited resources， as there are in many countries including my own， Italy， we have to choose the best therapy for our patients. Cytometry is not something I would do and we don’t do it in clinical practice for practical reasons， but p53 really is a predictor for choosing the best treatment and I think should be tested in all patients. Nowadays we have new tools including novel drugs that can overcome the p53-mediated chemorefractory effect.

　　《肿瘤瞭望》：几年CLL的新药不断涌现，如ibrutinib， fostamatinib， idelalisib，是否我们有更新的方法去预测哪一类CLL对于某些药物效果更好？

　　Gaidano 教授：目前还不能明确说ibrutinib和idelalisib这两种药物哪种更有效，因为还没有头对头的临床研究数据，不过我们所知道的是这两种药物和美罗华联用均十分有效。关键问题在于我们应该选择一些患者，还是在所有患者中使用这些新药。在欧洲，至少现在大家的观念是在确诊CLL并伴有p53突变的患者中使用这些药物，因为这类患者化疗无效；同时，在复发或难治CLL患者中作为二线治疗。也许以后，所有患者都需要这些药物治疗，但是现在我们并不确定。除了ibrutinib和idelalisib外，还有很多有效的新药出现。

　　Firstly， we cannot really say which of the two drugs you are asking about， ibrutinib and idelalisib， is better because we don’t have head-to-head trial data， but we know that both of them are very effective in combination with rituximab. The question becomes whether we can select patients for these drugs or whether all patients should be treated with these drugs. In Europe， at least for now， the idea is to treat using these drugs， CLL-diagnosed patients with p53 disruption， because they will be chemorefractory， and the patient with relapsed or refractory CLL， so as a second-line treatment. Maybe in the future， all patients may require these drugs but at the moment， we don’t really know. There are also many new drugs becoming available apart from ibrutinib and idelalisib.

　　《肿瘤瞭望》：目前是否有整合的评分系统，将FISH 流式 IGHV突变 TP53等整合起来，可以应用于CLL病人的初始预后评分？

　　Gaidano 教授：我们在为CLL患者制定预后工具的过程中做了很多努力，通常使用CLL国际预后指标，这包括遗传学（尤其是p53基因干扰），其他生物学标记和临床指标。但是，对这些信息我们必须小心谨慎，以期最有效地利用这些资源。对于所有生物学试验来说，这可能不是最好的，但是我们需要注意挑选对治疗选择有确切帮助的。

　　There are efforts to build prognostic tools for CLL in general with the CLL International Prognostic Index (IPI) which is based on genetics (and in particular p53 disruption)， other biologic markers and clinical markers. But obviously， we have to be careful to be using the resources that we have in the best way. It may not be the best approach to all of the biologic tests that are available but focus on the ones that are truly helpful in choosing the best treatment.

　　《肿瘤瞭望》：在新药越来越多、治疗效果越来越好的情况下，对于CLL的预后预测也越来越完善，是否能根据初始的危险评估指导第一次的化疗方案？

　　Gaidano 教授：这些药物的治疗效果非常不错，我们确实获得较高的总体有效率。这些药物使用后，没有完全缓解的患者很少，至少在复发或难治患者中是这样。我们确实看到持续部分缓解者，因而需要为CLL患者制定治疗反应标准，这在新药中已经展开。对于这些新药，临床医生需要注意Richter综合征的发生以及CLL向弥漫大B细胞的转变，这些不良反应可能发生在新药的应用过程中，因此我们需要对患者密切监测，避免患者向Richter综合征转化。

　　The outcomes with these drugs are really excellent， so we do obtain a high proportion of overall response rates. With these drugs we don’t see frequent incomplete remissions at least with relapsed or refractory cases. We do see durable partial remissions where there is a need for response criteria for CLL， which is something that is being done with these new agents. One thing to be aware of for all clinicians using these new drugs is the emergence of Richter’s syndrome and the transformation of CLL to a diffuse large B-cell lymphoma. This is something that happens with these new drugs， so we need to be very careful to monitor patients for transformation to Richter’s syndrome.

编辑：李耀功