Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia
Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia
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DOI：
10.1056/nejmoa075290
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发表时间：
2008-08-07
影响因子：
158.5
通讯作者：
Hillmen, Peter
中科院分区：
文献类型：
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作者：
Rawstron, Andy C.;Bennett, Fiona L.;Hillmen, Peter
背景：慢性淋巴细胞白血病（CLL）的诊断需要计数超过5000循环CLL表型细胞每立方毫米。具有较少CLL表型细胞的无症状者具有单克隆B细胞淋巴细胞增多症（MBL）。本研究的目的是探讨MBL和CLL.Methods之间的关系：我们调查了1520例受试者谁是62至80岁的正常血细胞计数和2228例受试者淋巴细胞增多症（>4000淋巴细胞每立方毫米）的存在MBL，使用流式细胞术。单克隆B细胞通过细胞遗传学和分子分析进一步表征。一个有代表性的队列的185例受试者与CLL-表型MBL和淋巴细胞增多症进行了监测，中位数为6.7年（范围，0.2至11.8）。结果：单克隆CLL表型B细胞检测5.1%的受试者（78 1520）与正常的血细胞计数和13.9%（309 2228）与淋巴细胞增多症。CLL-表型MBL的13 q14缺失和12三体的频率与CLL相似，并显示出免疫球蛋白重链可变区（IGHV）基因的偏斜库。在185例淋巴细胞增多的受试者中，51例（28%）发生了进行性淋巴细胞增多，28例（15%）发生了进行性CLL，13例（7%）需要化疗。绝对B细胞计数是与进行性淋巴细胞增多相关的唯一独立预后因素。在平均6.7年的随访期间，34%的受试者（62/185）死亡，但其中只有4例死亡是由于CLL。年龄在68岁以上和血红蛋白水平低于12.5克每分升是唯一的独立预后因素death.Conclusions：CLL-表型细胞中发现的一般人群和淋巴细胞增多症的受试者有共同的特点与CLL细胞。需要治疗的CLL在具有CLL表型MBL和淋巴细胞增多症的受试者中以每年1.1%的速率发展。
Background: A diagnosis of chronic lymphocytic leukemia (CLL) requires a count of over 5000 circulating CLL-phenotype cells per cubic millimeter. Asymptomatic persons with fewer CLL-phenotype cells have monoclonal B-cell lymphocytosis (MBL). The goal of this study was to investigate the relation between MBL and CLL.Methods: We investigated 1520 subjects who were 62 to 80 years of age with a normal blood count and 2228 subjects with lymphocytosis (>4000 lymphocytes per cubic millimeter) for the presence of MBL, using flow cytometry. Monoclonal B cells were further characterized by means of cytogenetic and molecular analyses. A representative cohort of 185 subjects with CLL-phenotype MBL and lymphocytosis were monitored for a median of 6.7 years (range, 0.2 to 11.8).Results: Monoclonal CLL-phenotype B cells were detected in 5.1% of subjects (78 of 1520) with a normal blood count and 13.9% (309 of 2228) with lymphocytosis. CLL-phenotype MBL had a frequency of 13q14 deletion and trisomy 12 similar to that of CLL and showed a skewed repertoire of the immunoglobulin heavy variable group (IGHV) genes. Among 185 subjects presenting with lymphocytosis, progressive lymphocytosis occurred in 51 (28%), progressive CLL developed in 28 (15%), and chemotherapy was required in 13 (7%). The absolute B-cell count was the only independent prognostic factor associated with progressive lymphocytosis. During follow-up over a median of 6.7 years, 34% of subjects (62 of 185) died, but only 4 of these deaths were due to CLL. Age above 68 years and hemoglobin level below 12.5 g per deciliter were the only independent prognostic factors for death.Conclusions: The CLL-phenotype cells found in the general population and in subjects with lymphocytosis have features in common with CLL cells. CLL requiring treatment develops in subjects with CLL-phenotype MBL and with lymphocytosis at the rate of 1.1% per year.