Hematology and Cell Therapy, A.O. Mauriziano, Nuclear Medicine and Hematology, A.O.U.S. Giovanni B., Clinica Medica, A.O.U.S. Luigi-Orbassano, University of TorinoTorino, Italy.
J Clin Oncol. 2011 Mar 1;29(7):814-24. doi: 10.1200/JCO.2010.28.9777. Epub 2010 Dec 28.
High-dose chemotherapy with peripheral blood progenitor cell (PBPC) autograft is effective in high-risk lymphoma, particularly with the addition of rituximab; however, it is associated with risk of secondary malignancy. These issues have been addressed in a series of 1,347 patients with lymphoma treated with a high-dose sequential (HDS) program.
A total of 1,024 patients with B-cell lymphoma, 234 patients with Hodgkin's lymphoma, and 89 patients with T-cell lymphoma were treated with HDS between 1985 and 2005 at 11 Gruppo Italiano Terapie Innovative Linfomi centers. HDS was given as salvage treatment to 707 patients (52%); 655 patients (49%) received a modified HDS, with high-dose cytarabine and two consecutive PBPC harvests. Rituximab-supplemented HDS was given to 523 patients (39%).
At a median follow-up of 7 years, the median overall survival (OS) was 16.2 years; in B-cell lymphoma the OS was significantly superior with rituximab HDS compared to HDS alone. The cumulative incidence at 5 and 10 years of secondary myelodysplasia/acute leukemia (sMDS/AL) were 3.09% and 4.52%, respectively, that of solid tumors were 2.54% and 6.79%, respectively. Factors associated with sMDS/AL were male sex and use of the second harvest PBPC for the graft; factors found to be associated with solid tumor were advanced age, post-HDS radiotherapy, and rituximab addition to HDS. Despite the increased risk of solid tumors, rituximab addition to HDS was still associated with survival advantages.
This analysis has relevant implications for the design and use of intensive chemoimmunotherapy with autograft. In addition, it offers useful insights toward the understanding and prevention of tumor development.
含外周血造血祖细胞（PBPC）自体移植的大剂量化疗联合利妥昔单抗治疗高危淋巴瘤，尤其有效；然而，其与继发性恶性肿瘤的风险相关。这些问题已经在一系列接受大剂量序贯（HDS）方案治疗的 1347 例淋巴瘤患者中得到解决。
1985 年至 2005 年期间，在 11 个意大利肿瘤治疗创新小组中心，1024 例 B 细胞淋巴瘤患者、234 例霍奇金淋巴瘤患者和 89 例 T 细胞淋巴瘤患者接受了 HDS 治疗。707 例患者（52%）接受了 HDS 挽救治疗；655 例患者（49%）接受了改良 HDS，包括大剂量阿糖胞苷和两次连续的 PBPC 采集。523 例患者（39%）接受了利妥昔单抗联合 HDS。
中位随访 7 年后，中位总生存（OS）为 16.2 年；B 细胞淋巴瘤中，与单独 HDS 相比，利妥昔单抗 HDS 的 OS 显著提高。5 年和 10 年的继发性骨髓增生异常/急性白血病（sMDS/AL）累积发生率分别为 3.09%和 4.52%，实体瘤分别为 2.54%和 6.79%。sMDS/AL 的相关因素为男性和使用第二份 PBPC 进行移植；与实体瘤相关的因素为年龄较大、HDS 后放疗和利妥昔单抗联合 HDS。尽管实体瘤的风险增加，但利妥昔单抗联合 HDS 仍与生存优势相关。
该分析对强化化疗联合自体移植的设计和应用具有重要意义。此外，它还为理解和预防肿瘤发展提供了有用的见解。
