Alexandrescu Doru T, Wiernik Peter H
Comprehensive Cancer Center, Our Lady of Mercy Medical Center, New York Medical College, 600 East 233rd Street, Bronx, NY 10466, USA.
Med Oncol. 2008;25(3):309-14. doi: 10.1007/s12032-007-9037-8. Epub 2008 Jan 5.
An important biological alteration in chronic lymphocytic leukemia (CLL) is the dysregulation of immunoglobulin production, as a consequence of complex and yet incompletely understood interactions between plasma cells and the neoplastic B-cell clone. As a result, most patients develop severe hypogammaglobulinemia during the course of the disease. Fourteen patients were analyzed retrospectively for changes in globulins produced by antineoplastic treatments. During maximum response to fludarabine, chlorambucil, and overall rituximab, the mean levels of globulins were 2.500, 2.752, and 3.018 g/dl. The mean increase in globulins during clinical response to individual treatments compared to pre-treatment values were 0.050 g/dl for fludarabine, 0.302 g/dl for chlorambucil, 0.267 g/dl for low-dose rituximab, and 0.346 g/dl for high-dose rituximab. Overall, treatment with rituximab produced an average increase in globulins at clinical response of 11.6%, which increased further to 17.3% at maximum clinical response. Serum globulins increased significantly compared with pre-treatment values at maximum clinical response to rituximab overall (P=0.001) and high-dose rituximab (P=0.001), but no statistical significance occurred in the cases of fludarabine (P=0.5), chlorambucil/prednisone (P=0.14), and low-dose rituximab (P=0.07). Serum globulins levels correlate with disease status (complete responders versus partial responders and stable disease groups), but not with peripheral neoplastic load. Therefore, although rituximab is efficient in decreasing the tumor burden, additional mechanisms may be involved in relieving suppressive effects on immunoglobulin-producing cells, which especially manifest at high doses of the agent. Use of high doses of rituximab in CLL can avoid T-cell dysfunction and neutropenia, and is associated with humoral immunorestorative effects.
慢性淋巴细胞白血病（CLL）中一个重要的生物学改变是免疫球蛋白产生失调，这是浆细胞与肿瘤性B细胞克隆之间复杂且尚未完全理解的相互作用的结果。因此，大多数患者在疾病过程中会出现严重的低球蛋白血症。对14例患者进行回顾性分析，以观察抗肿瘤治疗后球蛋白的变化。在对氟达拉滨、苯丁酸氮芥以及总体利妥昔单抗的最大反应期，球蛋白的平均水平分别为2.500、2.752和3.018g/dl。与治疗前相比，在对各治疗的临床反应期，氟达拉滨使球蛋白平均增加0.050g/dl，苯丁酸氮芥增加0.302g/dl，低剂量利妥昔单抗增加0.267g/dl，高剂量利妥昔单抗增加0.346g/dl。总体而言，利妥昔单抗治疗在临床反应期使球蛋白平均增加11.6%，在最大临床反应期进一步增至17.3%。与治疗前相比，在对利妥昔单抗总体（P=0.001）和高剂量利妥昔单抗（P=0.001）的最大临床反应期，血清球蛋白显著增加，但氟达拉滨（P=0.5）、苯丁酸氮芥/泼尼松（P=0.14）和低剂量利妥昔单抗（P=0.07）的情况无统计学意义。血清球蛋白水平与疾病状态（完全缓解者与部分缓解者及疾病稳定组）相关，但与外周肿瘤负荷无关。因此，尽管利妥昔单抗在降低肿瘤负荷方面有效，但可能还有其他机制参与缓解对免疫球蛋白产生细胞的抑制作用，这在高剂量药物时尤为明显。在CLL中使用高剂量利妥昔单抗可避免T细胞功能障碍和中性粒细胞减少，并具有体液免疫恢复作用。
