Robak Tadeusz
Department of Hematology, Medical University of Lodz, 93-513 Lodz, Pabianicka 62, Poland.
Curr Treat Options Oncol. 2006 May;7(3):200-12. doi: 10.1007/s11864-006-0013-x.
For many years, alkylating agents, especially chlorambucil, have been considered the drugs of choice for first-line treatment of progressive and symptomatic chronic lymphocytic leukemia (CLL). More recently, treatment approaches have included purine nucleoside analogs (PNAs), fludarabine or cladribine (2-CdA), and monoclonal antibodies (MoAbs). PNAs are highly active in patients with CLL, previously treated and untreated. Significantly higher overall response and complete response in patients treated initially with fludarabine or 2-CdA than in those treated with chlorambucil- or cyclophosphamide-based combination regimens have been recently confirmed in prospective, randomized trials. However, the median survival times do not differ among the patients treated with PNA and alkylating agents. The MoAbs directed against CD52 antigen (alemtuzumab) and CD20 antigen (rituximab) also demonstrate significant activity in CLL and should be used in patients with disease that is refractory to PNAs. Combination therapies with PNAs and cyclophosphamide, and especially with rituximab, are more active than monotherapy with PNAs in regard to response rate and possible survival. Because most patients are older and there is no survival time advantage for alkylating agents or PNA therapies, we recommend chlorambucil as the first-line treatment, with PNAs for consideration as the second-line therapy. PNAs alone or in combination with cyclophosphamide and rituximab as first-line treatment are an option in younger patients, who may be candidates for consolidation therapy with alemtuzumab and/or stem cell transplantation. Alemtuzumab may be an effective treatment for patients refractory to PNAs. Several biological parameters have been gaining increasing importance to evaluate the prognosis of patients with CLL and define optimal therapeutic strategy. Moreover, novel therapies are being evaluated, especially in patients refractory to PNAs, including those targeting the antiapoptotic bcl-2 family of proteins and receptors, vaccines, and allogenic stem cell transplantation, especially after nonmyeloablative chemotherapy.
多年来，烷化剂，尤其是苯丁酸氮芥，一直被视为进行性和有症状的慢性淋巴细胞白血病（CLL）一线治疗的首选药物。最近，治疗方法包括嘌呤核苷类似物（PNA）、氟达拉滨或克拉屈滨（2-CdA）以及单克隆抗体（MoAb）。PNA在初治和未治的CLL患者中具有高度活性。最近在前瞻性随机试验中证实，初始接受氟达拉滨或2-CdA治疗的患者的总体缓解率和完全缓解率显著高于接受基于苯丁酸氮芥或环磷酰胺的联合方案治疗的患者。然而，接受PNA和烷化剂治疗的患者的中位生存时间并无差异。针对CD52抗原（阿仑单抗）和CD20抗原（利妥昔单抗）的MoAb在CLL中也显示出显著活性，应用于对PNA难治的疾病患者。就缓解率和可能的生存期而言，PNA与环磷酰胺，尤其是与利妥昔单抗的联合疗法比PNA单药治疗更具活性。由于大多数患者年龄较大，且烷化剂或PNA疗法在生存时间上并无优势，我们推荐苯丁酸氮芥作为一线治疗，PNA可作为二线治疗的考虑药物。PNA单独或与环磷酰胺和利妥昔单抗联合作为一线治疗是年轻患者的一种选择，这些患者可能是阿仑单抗和/或干细胞移植巩固治疗的候选者。阿仑单抗可能是对PNA难治的患者的一种有效治疗方法。几个生物学参数在评估CLL患者的预后和确定最佳治疗策略方面越来越重要。此外，正在评估新的治疗方法，尤其是在对PNA难治的患者中，包括针对抗凋亡bcl-2蛋白家族和受体的疗法、疫苗以及异基因干细胞移植，尤其是在非清髓性化疗后。
