Nademanee Auayporn, Forman Stephen J
Division of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA.
Semin Hematol. 2006 Oct;43(4):240-50. doi: 10.1053/j.seminhematol.2006.07.006.
The prognosis of patients with relapsed or refractory diffuse large cell B-cell lymphoma-B (DLCL-B) is poor with conventional salvage chemotherapy; therefore, high-dose therapy (HDT) combined with autologous stem cell transplant (ASCT) has become the treatment of choice for these patients. The outcomes of transplant are better in patients with chemosensitive relapse: those with a longer duration of first remission (>12 month) and those with an age-adjusted low-risk International Prognostic Index (IPI) at relapse. Several high-dose regimens with or without total body irradiation (TBI) have been used with similar outcomes. Relapse remains the most common cause of treatment failure, and thus the use of radioimmunotherapy (RIT) in the high-dose regimens and incorporation of rituximab in the transplant setting have been explored. Several studies have shown that RIT both at conventional dose and at high dose can be given in combination with high-dose chemotherapy regimens without additional toxicity or delay in hematopoietic recovery after ASCT. Additional studies using RIT in combination with high-dose chemotherapy and ASCT are ongoing, and preliminary results suggest that these approaches may be superior to conventional high-dose regimens. Since rituximab is an effective therapy for B-cell non-Hodgkin's lymphoma and given its limited toxicity, rituximab has been incorporated into HDT and ASCT for DLCL-B as in vivo purging, as part of high-dose regimens, and as maintenance therapy to prevent relapse. Preliminary results suggested that rituximab during ASCT and as maintenance therapy post-transplant reduces the risk of relapse and improves survival; however, these results need to be confirmed in phase III randomized trials. The role of ASCT during first remission as consolidative therapy in patients with DLCL-B remains controversial and should not be performed outside of the clinical trial setting. Allogeneic stem cell transplant (allo-SCT) for patients with relapsed DLCL-B is associated with significant toxicity and should be reserved for patients who relapse after ASCT or those with persistent marrow involvement. Innovative approaches are needed for primary refractory and chemoresistant relapsed DLCL-B since these patients have very poor outcomes after ASCT.
复发或难治性弥漫性大细胞B细胞淋巴瘤（DLCL - B）患者采用传统挽救性化疗预后较差；因此，大剂量治疗（HDT）联合自体干细胞移植（ASCT）已成为这些患者的首选治疗方法。化疗敏感复发患者的移植效果更好：首次缓解期较长（>12个月）以及复发时年龄调整后的国际预后指数（IPI）为低危的患者。几种含或不含全身照射（TBI）的大剂量方案已被使用，疗效相似。复发仍然是治疗失败的最常见原因，因此人们探索了在大剂量方案中使用放射免疫疗法（RIT）以及在移植过程中加入利妥昔单抗。多项研究表明，常规剂量和高剂量的RIT均可与大剂量化疗方案联合使用，且不会增加额外毒性，也不会延迟ASCT后的造血恢复。正在进行更多关于RIT联合大剂量化疗和ASCT的研究，初步结果表明这些方法可能优于传统大剂量方案。由于利妥昔单抗是治疗B细胞非霍奇金淋巴瘤的有效疗法且毒性有限，它已被纳入DLCL - B的HDT和ASCT中，作为体内净化、大剂量方案的一部分以及预防复发的维持治疗。初步结果表明，ASCT期间及移植后作为维持治疗使用利妥昔单抗可降低复发风险并提高生存率；然而，这些结果需要在III期随机试验中得到证实。ASCT在DLCL - B患者首次缓解期作为巩固治疗的作用仍存在争议，不应在临床试验环境之外进行。复发DLCL - B患者的异基因干细胞移植（allo - SCT）毒性显著，应仅用于ASCT后复发或骨髓持续受累的患者。对于原发性难治性和化疗耐药复发的DLCL - B，需要创新方法，因为这些患者在ASCT后的预后非常差。
