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单株B细胞淋巴球增生在某些病患会演变成白血病
— 单株B细胞球增生（MBL）是个比较新的诊断分类，对某些病患而言，这将可能演变为慢性淋巴球性白血病（CLL），研究者在8月7日的新英格兰医学期刊上报导这项发现。
　　
　　如果病患的循环CLL表现型细胞多於5000/mm3，即合乎诊断CLL的标準；如果一位无症状病患，CLL表现型细胞较少，则诊断为MBL。在这项研究中，研究人员们发现在185位淋巴球增生病患中，51位（28%）淋巴球增生越来越严重，而28位（15%）发展成逐渐恶化的CLL。除此之外，其中13位（17%）发展成CLL的病患需要接受化学治疗。
　　
　　CLL是一种B细胞淋巴增生异常，是西方国家最常发生的白血病，且临床病程不定。高敏感度流式细胞仪的发展使得我们可以侦测有CLL表现型的B细胞，即使数量仅少到10,000个正常白血球中只有1个，正常血球数目病患中，有CLL表现型病患占超过3%。
　　
　　主要作者、英国里兹圣詹姆斯癌症机构主要临床科学家Andy C. Rawstron博士表示，大约每20位一般大眾中，就有1位有CLL型式的MBL，但是通常数量非常少，许多研究中典型地仅低於1500/mm3。我们文献中所提到的问题是，不论这些细胞是否天生就具有癌化趋向，如果是这样的话，何时它们变得临床上显著的？
　　
　　这项研究的结果显示，即使在非常低但侦测得到的量，CLL型式的MBL与CLL的基因变异相同，Rawstron博士向Medscape肿瘤学表示，虽然这一般并不代表不好的预后指标，且以目前可获得的科技并无法与CLL区分。但CLL细胞数目低於1900/ml的个体几乎都是稳定的。演变成需要治疗的CLL，是当B细胞数目低於1900/ml，且每年发生机率约为1%。
　　
　　透过流式细胞仪，Rawstron博士与其同事针对两个不同有MBL的病患族群进行研究，其中一个包括1,520位血球数目正常的人们，另一项包括2,228位有淋巴球增生（淋巴球 >4000/mm3）问题患者；在第一组中，78位病患（5.1%）有CLL表现型MBL，而27位（1.8%）有非CLL表现型的MBL。
　　
　　研究者追踪185位有CLL表现型MBL与淋巴球数目增生的病患，且监测他们平均达6.7年；在这一组中，在后续追踪阶段，51位病患（28%）淋巴球数目增生的现象持续恶化，而其中31位淋巴球数目超过30,000/mm3。
　　
　　在28位（55%）罹患进展性淋巴球数目过多的病患中，研究者们观察到进展性CLL的证据，主要是淋巴结病变，且整体来说，13位病患最终进展到需要进行化学治疗的阶段；治疗在起始诊断后平均4年内开始，进展成需要化学治疗的CLL机率为每年1.1%。
　　
　　Rawstron医师表示，对肿瘤学家的讯息为淋巴球数目过多状况并不明显且CLL细胞数目不高，目前有很清楚的诊断类别及5年预后数据，这在过去是块灰色地带；端看转介习惯，大约10~20%过去被诊断已有初期CLL的病患将会符合MBL的标準。
　　
　　在随后的主编评论中，乌拉圭Pasteur de Montevideo机构的执行主任Guillaume Dighiero医师写道，应该进行确认淋巴球数目过多病患淋巴球表现型与增殖程度。
　　
　　他写道，对这些病患只有持续观察的策略，且每年评估单株族群状态；在没有进展的情况下，对这种潜伏状况的病患，并不需要进行定义IGVH基因与染色体突变资料的检验。
　　
　　这项研究由白血病研究（经费编号0378）以及Ellis family赞助；共同作者Peter Hillmen博士，他来自英国里兹教学医院，他表示接受Alexion药厂、拜耳健康照护、与Genzyme的经费赞助。其他共同作者并没有表示有相关资金上的往来。

Monoclonal B-Cell Lymphocytosis Progresses to Leukemia in Some Patients


— Monoclonal B-cell lymphocytosis (MBL) is a relatively new diagnostic category and, in some patients, it will progress to chronic lymphocytic leukemia (CLL), researchers report the August 7 issue of the New England Journal of Medicine.

A diagnosis of CLL is made if a person has more than 5000 circulating CLL-phenotype cells per cubic millimeter; if an asymptomatic person has fewer CLL-phenotype cells, the diagnosis is MBL. In this study, researchers found that among 185 patients with lymphocytosis, progressive lymphocytosis developed in 51 (28%) and progressive CLL developed in 28 (15%). In addition, chemotherapy was required in 13 (7%) of the patients who developed CLL.

CLL, a lymphoproliferative disorder of B?cells, is the most common form of leukemia in Western nations and has a variable clinical course. The development of high-sensitivity flow cytometry has allowed for the detection of B?cells with a CLL phenotype in numbers as low as 1 per 10,000 normal leukocytes; using this method, CLL-phenotype cells have been identified in more than 3% of adults who have otherwise normal blood counts.

\"About 1 in 20 adults in the general population has CLL-type MBL, but usually the count is very low, typically less than 1500 per microliter in various studies,\" said lead author Andy C. Rawstron, PhD, principal clinical scientist at St. James\'s Institute of Oncology, in Leeds, United Kingdom. \"The question addressed in our paper is whether these cells are genuinely neoplastic and, if so, at what level do they become clinically relevant.\"

The results of the study indicate that even at the very lowest detectable levels, CLL-type MBL has the same genetic abnormalities as CLL, although generally not with poor prognosis markers, and are not distinguishable from CLL using currently available technology, Dr. Rawstron explained to Medscape Oncology. \"Individuals with CLL cell counts below 1900 per microliter virtually all had a stable disorder. Progression to CLL requiring treatment was seen in individuals with a B?cell count above 1900 per microliter at the rate of about 1% per year.\"

Using flow cytometry, Dr. Rawstron and colleagues studied 2 separate cohorts for the presence of MBL. One consisted of 1520 people with a normal blood count and the other consisted of 2228 people with lymphocytosis (>4000 lymphocytes/mm3). In the first group, CLL-phenotype MBL was detected in 78 people (5.1%) and non-CLL-phenotype MBL was detected in 27 (1.8%).

The researchers followed 185 participants with CLL-phenotype MBL and lymphocytosis, and monitored them for a median of 6.7 years. Of this group, progressive lymphocytosis was observed in 51 people (28%) during the follow-up period, with 31 of them demonstrating a lymphocyte count above 30,000 per cubic millimeter.

In 28 (55%) of the patients with progressive lymphocytosis, the researchers observed further evidence of progressive CLL, primarily lymphadenopathy, and overall, 13 patients eventually progressed to the point of requiring chemotherapy. Treatment was begun at a median of 4 years after the initial diagnosis, and the estimated rate of progression to CLL that required chemotherapy was 1.1% per year.

\"The take-home message for oncologists is that for cases with a borderline lymphocytosis with low levels of CLL cells, there is now a clear-cut diagnostic category with known 5-year outcome data in what was previously a very grey area,\" said Dr. Rawstron. \"Depending on referral practice, approximately 10% to 20% of patients who would previously have been diagnosed with early-stage CLL will meet the criteria for MBL instead.\"

In an accompanying editorial, Guillaume Dighiero, MD, PhD, executive director of the Institut Pasteur de Montevideo, in Uruguay, writes that studies should be performed to determine the phenotype of the lymphocytes and the degree of clonality in patients presenting with lymphocytosis.

\"Only a watch-and-wait approach is justified for these patients, with annual assessment of the status of the monoclonal population,\" he writes. \"In the absence of progression, studies to define the mutational profile of IGVH genes and of chromosomes are not justified for patients with this indolent condition.\"

The study was supported by Leukaemia Research (grant 0378) and the Ellis family. Coauthor Peter Hillmen, PhD, from Leeds Teaching Hospitals in the United Kingdom, reports receiving grant support from Alexion Pharmaceuticals, Bayer HealthCare, and Genzyme. None of the other authors have disclosed any relevant financial relationships.

发布时间：2008年08月18日
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