Centre for Lymphoid Cancer, Department of Medical Oncology, British Columbia Cancer Agency and Division of Medical Oncology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
Blood. 2015 Jul 2;126(1):17-25. doi: 10.1182/blood-2014-10-567461. Epub 2015 Apr 13.
Systemic anaplastic large cell lymphoma (ALCL) is an aggressive CD30(+) non-Hodgkin lymphoma. Anaplastic lymphoma kinase-positive (ALK+) ALCL is associated with the NPM-ALK t(2;5) translocation, which is highly correlated with the identification of the ALK protein by immunohistochemistry. ALK+ ALCL typically occurs in younger patients and has a more favorable prognosis with 5-year survival rates of 70% to 90% in comparison with 40% to 60% for ALK-negative (ALK-) ALCL. Studies support young age as a strong component of the favorable prognosis of ALK+ ALCL. Until recently, no recurrent translocations were identified in ALK- ALCL. However, emerging data now highlight that ALK- ALCL is genetically and clinically heterogeneous with a subset having either a DUSP22 translocation and a survival rate similar to ALK+ ALCL or a less common P63 translocation, the latter associated with an aggressive course. Anthracycline-based regimens such as cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) remain the standard first-line treatment choice for systemic ALCL, but in many patients with ALK- ALCL, it is ineffective, and thus it is often followed by consolidative autologous stem cell transplantation. However, selection of appropriate patients for intensified therapy remains challenging, particularly in light of genetic and clinical heterogeneity in addition to the emergence of new, effective therapies. The antibody drug conjugate brentuximab vedotin is associated with a high response rate (86%) and durable remissions in relapsed/refractory ALCL and is under investigation in the first-line setting. In the future, combining clinical and genetic biomarkers may aid in risk stratification and help guide initial patient management.
系统性间变大细胞淋巴瘤（ALCL）是一种侵袭性 CD30（+）非霍奇金淋巴瘤。间变性淋巴瘤激酶阳性（ALK+）ALCL 与 NPM-ALK t（2；5）易位相关，该易位与免疫组织化学检测 ALK 蛋白高度相关。ALK+ALCL 通常发生在年轻患者中，预后较好，5 年生存率为 70%至 90%，而 ALK-（ALK-）ALCL 的 5 年生存率为 40%至 60%。研究表明，年轻是 ALK+ALCL 预后良好的重要因素。直到最近，ALK-ALCL 中并未发现复发易位。然而，新出现的数据表明，ALK-ALCL 在遗传和临床方面具有异质性，一部分患者存在 DUSP22 易位，其生存率与 ALK+ALCL 相似，或存在较少见的 P63 易位，后者与侵袭性病程相关。以蒽环类药物为基础的方案，如环磷酰胺、多柔比星、长春新碱和泼尼松（CHOP）仍然是系统性 ALCL 的标准一线治疗选择，但在许多 ALK-ALCL 患者中，其效果不佳，因此常随后进行巩固性自体干细胞移植。然而，选择合适的患者进行强化治疗仍然具有挑战性，特别是考虑到遗传和临床异质性，以及新的有效治疗方法的出现。抗体药物偶联物 Brentuximab vedotin 与高缓解率（86%）和复发/难治性 ALCL 的持久缓解相关，正在一线治疗中进行研究。在未来，结合临床和遗传生物标志物可能有助于进行风险分层，并有助于指导初始患者管理。
