编者按：12月5日，第57届ASH年会开幕式当天，Ham-Wasserman Lecture邀请到严重先天性中性粒细胞症（SCN）的重要奠基人Ivo Touw教授做大会首个主旨报告。该项目的名称为两位已故的血液学领域科学巨匠Thomas Hale Ham教授和Louis R. Wasserman教授的姓氏而命名。会后，本刊非常荣幸地对Touw教授进行了现场独家专访。
《肿瘤瞭望》：严重先天性中性粒细胞症（SCN）患者进展为MDS/AML的比例正逐年增加，尤其是接受rh-GCSF治疗的患者。在这种情况下，造血干细胞移植在治疗SCN的地位如何？
Ivo Touw：当患者出现克隆进化的证据时即是恰当的时机。一旦患者出现粒细胞集落刺激因子受体（G-CSF）的首个突变，我们就应当对其进行长期随访并定期监测。我建议每六个月监测一次，如果某一克隆持续超过6~12个月，应考虑进行异体干细胞移植，而不是继续用G-CSF治疗。当然，这种情况下，有合适的供体很重要，而且异体移植存在治疗相关的死亡风险，所以在停用G-CSF治疗选择移植时我们应权衡利弊。
The proper timing is when the patients are showing evidence of clonal evolution. Once the first clones with mutations in the granulocyte colony-stimulating factor (G-CSF) receptor arise， it is important to follow-up on those patients and to do very regular monitoring. I would recommend monitoring every six months and if there is a persistent clone that remains present over six months to a year or so， then consideration should be given to going for an allotransplant rather than continuing with G-CSF therapy. Of course， it is important to have a suitable donor and there is riskof treatment-related mortality， so it is an important decision when switching from G-CSF treatment to allotransplantation.
《肿瘤瞭望》：如何监测SCN的基因演变、监测频率、和检测基因突变的类型？
Ivo Touw：这是我们仍在努力做的事情。我们现在所知道的是，到目前为止，在中性粒细胞减少时期G-CSF受体突变是最普遍的突变。随着二代测序方法的不断进步，我们希望能找到能够预测白血病进展的新的生物学标志物，从而联合G-CSF受体突变及新的生物学标志物来预测哪些患者可能会进展为白血病。不幸的是，我们还没有寻找到这些生物学标志物，所以现在我们不得不完全依靠G-CSF受体基因突变。这意味着，如果患者存在G-CSF受体突变，它可以在任何时间点向白血病转化。这个时间框架是不可预测的，然而G-CSF受体突变仍是我们目前所能找到的最好的预测指标。未来，我们还需要寻找新的生物学标志物。
This is something we are still working on. What we currently know is that the mutations in the G-CSF receptor are， by far， the most prevailing mutations in the neutropenic phase. With the next generation sequencing methods， we are hoping to find additional biomarkers for leukemic evolution that we could use in combination with the G-CSF receptor mutations to predict which patients would or would not develop leukemia. Unfortunately， we don’t yet have those markers so we have to exclusively rely on the G-CSF receptor mutations at this point in time. What that means is that if you have the mutations present， it can take any length of time for the disease to transform into leukemia. That timeframe is not currently predictable but it is the best that we have available. We need additional biomarkers.
《肿瘤瞭望》：大部份SCN患者对于G-CSF治疗效果良好，哪些基因突变的类型对于G-CSF治疗反应良好？
Ivo Touw：绝大多数患者（＞90%）对G-CSF治疗反应良好。因此，根据遗传学来区分它是很困难的。大多数患者有中性粒细胞弹性蛋白酶的突变，且对治疗反应良好，极少数此类患者对治疗反应欠佳。遗传缺陷影响这些患者对治疗反应的具体机制仍不清楚。
The vast majority of patients (>90%) respond well to G-CSF therapy. If you want to make a distinction based on genetics， it is very difficult. Most patients have the mutation in neutrophil elastase and all of those patients respond well. There are other rarer cases that do not respond as well but there are not many of those. It is not exactly clear how the genetic defect in those patients determines whether the patient will respond to treatment.
专家简介
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Ivo Touw. PhD，荷兰Erasmus大学医学中心血液学教授、分子医学研究院科学委员会主席，荷兰癌症协会成员。主要研究兴趣是急性髓系白血病，1994年他的研究小组发现，造血生长因子受体G-CSF治疗重度先天性中性粒细胞减少易进展为急性髓系白血病，并进一步证实了这些基因突变的功能性后果。担任Blood杂志副主编，欧洲血液学协会（EHA）董事会成员。