[ASCO2015]急性髓系白血病:老年患者如何管理?——C.A. Schiffer教授访谈

作者:  C.A.Schiffer   日期:2015/6/2 20:02:50


编者按:急性髓系白血病(AML)是最常见的老年急性白血病类型,且其发病率随着年龄的增长而增加。老年AML患者由于对当前的标准化疗药物的原发耐药和(或)不能耐受高强度的诱导化疗及缓解后化疗,且经常并发其他脏器疾病,其早期死亡率较高,预后较差。美国韦恩州立大学Charles Alan Schiffer教授在本届ASCO年会上对于老年AML的管理进行了专题教育讲座,会后《肿瘤瞭望》就此问题对Schiffer教授进行了专访。

美国韦恩州立大学Charles Alan Schiffer教授






  The heterogeneity is really very interesting and very important. It is not just heterogeneity between or amongst patients, but in fact there is enormous heterogeneity in the population of leukemic blasts within a single patient. So for a patient who has the FLT3 mutation, for example, you can find cells that are negative. You can find cells that have two FLT3 mutations.


  We have learned that some of these small clones can eventually go out and be the dominant clone. Secondary AML, which is the focus of your question, really has similar characteristics to what you see in myelodysplastic syndromes (MDS). Those with complex cytogenetics will frequently have p53 mutations which across all cancers represent an almost impossible entity to cure, but there are also mutations is TET2 and 3A - the kinds of things you see in MDS.






  The scoring system is not one I have used formally clinically. They aim to decide what type of therapy a particular patient can tolerate and particularly whether they can tolerate intensive induction therapy and subsequently whether they might be candidates for stem cell transplant.


  In terms of all the markers that are used, you are trying to identify groups that can do well with chemotherapy alone and have a favorable outcome, groups that will have a poor outcome and might be considered for transplantation, and groups that have mutations that might be targeted or addressed directly with specific drugs such as mutated TK. The purpose is to get as much information as possible to direct you in one way or another. Unfortunately, most of the time, you find yourself stuck in the middle. You can identify the really good ones and the really bad ones, but there are a lot of subtleties in the middle.






  That’s right. Older patients are a challenge. And older patients are also the preponderance of patients because disease incidence is highest in the 65-70+ age group. They have more drug-resistant disease. They have more complex cytogenetics. And they have more medical comorbidities. Frankly, we haven’t improved outcomes in those patients in a decade.


  Occasional patients will have favorable cytogenetic characteristics and NPM1 mutations and, if possible, they should be considered for standard, more intensive induction therapy. Some of them (and probably more than we actually think) should be considered for and would tolerate transplantation. Probably the most important potential therapy that has come along are the IDH1 and IDH2 inhibitors. They have shown sometimes striking responses in people who have those genes mutated and many of those are older patients. That may be the most potentially dramatic improvement in this group of patients. Therapy with cytarabine and azacitidine can be helpful in perhaps 20+% of patients, but unfortunately it doesn’t cure anyone and the response is transient.




  Schiffer教授:对于适合参于临床试验的患者(通常指身体状况良好者),其治愈率最高在10%~15%。此类患者必须进行缓解后的巩固治疗,我们通常给予一个疗程的中等剂量的巩固治疗或者给予几个疗程的低剂量Ara-C (100mg/m2)。然而,一些随机试验显示在年轻患者中经常使用的大剂量Ara-C在老年患者中并没有获益,但是要除外小部分较好细胞遗传学或者有NPM1突变者。


  In people eligible for clinical trials (which means they are generally in good health despite their leukemia), there is a cure rate of 10-15% maximum. They have to get some postremission consolidation to accomplish that and we usually give one course of intermediate dose consolidation or sometimes a few courses of lower dose Ara-C (100mg/m2). Unfortunately, a few randomized trials have shown no benefit in older patients for high-dose Ara-C that we would tend to use in younger patients, with the exception of the occasional patient with favorable cytogenetics or possibly a NPM1 mutation.

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