Epperla Narendranath, Fenske Timothy S, Hari Parameswaran N, Hamadani Mehdi
Narendranath Epperla, Timothy S Fenske, Parameswaran N Hari, Mehdi Hamadani, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI 53226,United States.
World J Transplant. 2015 Sep 24;5(3):81-8. doi: 10.5500/wjt.v5.i3.81.
Lymphomas constitute the second most common indication for high dose therapy (HDT) followed by autologous hematopoietic cell transplantation (auto-HCT). The intent of administering HDT in these heterogeneous disorders varies from cure (e.g., in relapsed aggressive lymphomas) to disease control (e.g., most indolent lymphomas). Regardless of the underlying histology or remission status at transplantation, disease relapse remains the number one cause of post auto-HCT therapy failure and mortality. The last decade has seen a proliferation of clinical studies looking at prevention of post auto-HCT therapy failure with various maintenance strategies. The benefit of such therapies is in turn dependent on disease histology and timing of transplantation. In relapsed, chemosensitive diffuse large B-cell lymphoma (DLBCL), although post auto-HCT maintenance rituximab seems to be safe and feasible, it does not provide improved survival outcomes and is not recommended. The preliminary results with anti- programmed death -1 (PD-1) antibody therapy as post auto-HCT maintenance in DLBCL is promising but requires randomized validation. Similarly in follicular lymphoma, maintenance therapies including rituximab following auto-HCT should be considered investigational and offered only on a clinical trial. Rituximab maintenance results in improved progression-free survival but has not yet shown to improve overall survival in mantle cell lymphoma (MCL), but given the poor prognosis with post auto-HCT failure in MCL, maintenance rituximab can be considered on a case-by-case basis. Ongoing trials evaluating the efficacy of post auto-HCT maintenance with novel compounds (e.g., immunomodulators, PD-1 inhibitors, proteasome inhibitors and bruton's tyrosine kinase inhibitors) will likely change the practice landscape in the near future for B cell non-Hodgkin lymphomas patients following HDT and auto-HCT.
淋巴瘤是高剂量疗法(HDT)继自体造血细胞移植(auto-HCT)之后的第二大常见适应症。在这些异质性疾病中进行HDT的目的各不相同,从治愈(如复发的侵袭性淋巴瘤)到疾病控制(如大多数惰性淋巴瘤)。无论移植时的基础组织学类型或缓解状态如何,疾病复发仍然是自体造血干细胞移植后治疗失败和死亡的首要原因。在过去十年中,有大量临床研究着眼于采用各种维持策略预防自体造血干细胞移植后治疗失败。此类疗法的益处反过来又取决于疾病的组织学类型和移植时间。在复发的、对化疗敏感的弥漫性大B细胞淋巴瘤(DLBCL)中,尽管自体造血干细胞移植后维持使用利妥昔单抗似乎是安全可行的,但它并未改善生存结果,因此不被推荐。抗程序性死亡-1(PD-1)抗体疗法作为DLBCL自体造血干细胞移植后的维持治疗,初步结果很有前景,但需要随机对照验证。同样,在滤泡性淋巴瘤中,自体造血干细胞移植后包括利妥昔单抗在内的维持疗法应被视为试验性的,仅在临床试验中提供。利妥昔单抗维持治疗可改善套细胞淋巴瘤(MCL)的无进展生存期,但尚未显示能改善总生存期,不过鉴于MCL自体造血干细胞移植失败后的预后较差,可根据具体情况考虑使用利妥昔单抗维持治疗。正在进行的评估新型化合物(如免疫调节剂、PD-1抑制剂、蛋白酶体抑制剂和布鲁顿酪氨酸激酶抑制剂)作为自体造血干细胞移植后维持治疗疗效的试验,可能在不久的将来改变HDT和自体造血干细胞移植后B细胞非霍奇金淋巴瘤患者的治疗格局。