Department of Medicine III, University Hospital Grosshadern/LMU Munich, Munich, Germany.
Leuk Lymphoma. 2011 Dec;52(12):2226-36. doi: 10.3109/10428194.2011.600488. Epub 2011 Aug 18.
Mantle cell lymphoma (MCL) is a distinct subtype of malignant lymphoma characterized by the chromosomal translocation t(11;14)(q13;q32), resulting in constitutional overexpression of cyclin D1 and cell cycle dysregulation in virtually all cases. Clinically, MCL shows an aggressive clinical course with a continuous relapse pattern and a median survival of only 3-5 years. However, recently a subset of up to 15% long-term survivors has been identified with a rather indolent clinical course. Advanced stage disease is usually apparent already at first clinical manifestation; in general, conventional chemotherapy is only palliative and median duration of remissions is only 1-2 years. In 2000, the European MCL Network ( http://www.european-mcl.net ) was founded, which consists of 15 national lymphoma study groups supplemented by experts in hematopathology, cytogenetics and molecular genetics. During the last decade, the European consortium has successfully initiated the largest phase III trials in MCL worldwide. In the current study generation, the addition of high-dose Ara-C to a rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP)-like regimen followed by myeloablative consolidation achieved a significant improvement of progression-free survival. Similarly, in elderly patients, rituximab maintenance until progression led to a marked prolongation of remission duration. Emerging strategies include proteasome inhibitors, immune modulatory drugs (IMiDs), mammalian target of rapamycin (mTOR) inhibitors and others, all based on the dysregulated control of cell cycle machinery and impairment of several apoptotic pathways. Combination strategies are currently being investigated in numerous trials, but their introduction into clinical practice and current treatment algorithms remains a challenge. Future strategies will apply individualized approaches according to the molecular risk profile of the patient. At the annual conference in Warsaw, recent results of molecular pathogenesis, analyses of current clinical trials and new study concepts were discussed.
套细胞淋巴瘤（MCL）是一种独特的恶性淋巴瘤亚型，其特征是染色体易位 t（11；14）（q13；q32），导致几乎所有病例中环细胞 D1 的组成性过表达和细胞周期失调。临床上，MCL 表现出侵袭性临床过程，具有连续复发模式，中位生存期仅为 3-5 年。然而，最近发现高达 15%的长期幸存者存在相对惰性的临床过程。晚期疾病通常在首次临床表现时就已明显；一般来说，常规化疗只是姑息性的，缓解期的中位持续时间仅为 1-2 年。2000 年，成立了欧洲套细胞淋巴瘤网络（http://www.european-mcl.net），由 15 个国家淋巴瘤研究小组组成，并由血液病理学、细胞遗传学和分子遗传学专家补充。在过去的十年中，欧洲财团已成功在全球范围内发起了最大的 III 期 MCL 试验。在当前的研究中，阿糖胞苷联合利妥昔单抗、环磷酰胺、多柔比星、长春新碱和泼尼松（R-CHOP）样方案，然后进行骨髓清除性巩固，显著改善了无进展生存期。同样，在老年患者中，直到疾病进展时进行利妥昔单抗维持治疗，显著延长了缓解期持续时间。新兴策略包括蛋白酶体抑制剂、免疫调节剂（IMiDs）、雷帕霉素靶蛋白（mTOR）抑制剂等，这些策略都基于细胞周期机制的失调控制和几种凋亡途径的损害。目前正在对多种试验进行联合策略研究，但将其引入临床实践和当前的治疗方案仍然是一个挑战。未来的策略将根据患者的分子风险特征应用个体化方法。在华沙年会上，讨论了分子发病机制的最新结果、当前临床试验的分析以及新的研究概念。
