Goy Andre
Hackensack University Medical Center, Hackensack, NJ 07601, USA.
Clin Lymphoma Myeloma. 2006 Oct;7 Suppl 1:S24-32. doi: 10.3816/clm.2006.s.005.
Mantle cell lymphoma (MCL) is one of the most challenging lymphomas to treat. In the first-line setting, high-dose therapy (HDT) and autologous stem cell transplantation or hyperCVAD/rituximab suggest benefit, especially in patients aged < 60 years. Nucleoside analogue-based regimens represent an alternate option in patients ineligible for HDT. Fludarabine in combination with cyclophosphamide or mitoxantrone has shown activity, and the results were superior with the addition of rituximab. Other cytotoxic agents, such as cladribine, clofarabine, or bendamustin, showed promising activity as well. A variety of new monoclonal antibody (MoAb) agents, such as humanized anti-CD20, alemtuzumab, anti-HLA-DR, anti-CD22 (as an immunotoxin carrier), anti-CD40, as well as MoAb-targeting TRAIL-R1 and TRAIL-R2 are being tested. Radioimmunotherapy with Yttrium 90-ibritumomab tiuxetan and Iodine 131 tositumomab have been tested alone or in combination with chemotherapy, including as part of HDT and autologous stem cell transplantation, in which they showed the best results. New vaccine modalities are exploring the use of tumor cell-based vaccines or of agents that block or activate costimulatory pathways/molecules, such as CTLA-4-Ig. Allogenic transplantation represents a potential curative option for MCL, especially nonmyeloablative transplantation, more feasible in that population. A plethora of novel biologic agents have surfaced, such as bortezomib, temsirolimus, thalidomide, lenalidomide, MoAb anti-vascular endothelial growth factor or vascular endothelial growth factor-Trap, and flavopiridol. Other targets include gene transcription through histone regulation; nuclear factor-ķB pathway; protein kinase C inhibitors; small-molecules targeting apoptosis, such as antisense Bcl-2, pan-Bcl-2 family member inhibitors; MoAb agonists of cell death receptors; caspases regulators (inhibitors of apoptosis proteins, survivin); and MDM2 antagonist regulators of p53. A molecular approach to define biomarkers might help identify subgroups of patients and help develop rational therapies.
套细胞淋巴瘤（MCL）是最难治疗的淋巴瘤之一。在一线治疗中，大剂量疗法（HDT）及自体干细胞移植或hyperCVAD/利妥昔单抗显示出益处，尤其是对于年龄<60岁的患者。基于核苷类似物的方案是不适于HDT的患者的另一种选择。氟达拉滨联合环磷酰胺或米托蒽醌已显示出活性，加入利妥昔单抗后结果更佳。其他细胞毒性药物，如克拉屈滨、氯法拉滨或苯达莫司汀，也显示出有前景的活性。多种新型单克隆抗体（MoAb）药物正在进行试验，如人源化抗CD20、阿仑单抗、抗HLA-DR、抗CD22（作为免疫毒素载体）、抗CD40，以及靶向TRAIL-R1和TRAIL-R2的MoAb。钇90-替伊莫单抗和碘131托西莫单抗的放射免疫疗法已单独或与化疗联合进行了试验，包括作为HDT和自体干细胞移植的一部分，在这些试验中它们显示出最佳结果。新的疫苗模式正在探索使用基于肿瘤细胞的疫苗或阻断或激活共刺激途径/分子的药物，如CTLA-4-Ig。异基因移植是MCL的一种潜在治愈选择，尤其是非清髓性移植，在该人群中更可行。大量新型生物制剂已出现，如硼替佐米、替西罗莫司、沙利度胺、来那度胺、抗血管内皮生长因子或血管内皮生长因子-Trap的MoAb，以及黄酮哌啶醇。其他靶点包括通过组蛋白调节的基因转录；核因子-κB途径；蛋白激酶C抑制剂；靶向凋亡的小分子，如反义Bcl-2、泛Bcl-2家族成员抑制剂；细胞死亡受体的MoAb激动剂；半胱天冬酶调节剂（凋亡蛋白抑制剂、生存素）；以及p53的MDM2拮抗剂调节剂。定义生物标志物的分子方法可能有助于识别患者亚组并有助于制定合理的治疗方案。
