Paul J. Bröckelmann, Helen Goergen, Charlotte Kohnhorst, Bastian von Tresckow, Michael Fuchs, Peter Borchmann, and Andreas Engert, University Hospital of Cologne, Cologne; Julia Meissner, University of Heidelberg, Heidelberg; Andrea Kerkhoff, University Hospital of Münster, Münster; Wolf-Dieter Ludwig, Helios Kinikum Berlin-Buch, Berlin, Germany; Alden Moccia, Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland; and Jana Markova, University Hospital Kralovske Vinohrady, Prague, Czech Republic.
J Clin Oncol. 2017 May 1;35(13):1444-1450. doi: 10.1200/JCO.2016.71.3289. Epub 2017 Feb 27.
Purpose Clinical characteristics, therapeutic approaches, and prognosis of late relapse (LR) in patients with classic Hodgkin lymphoma (cHL) are poorly understood. We performed a comprehensive analysis of LR of Hodgkin lymphoma (LR-HL). Methods To estimate the incidence of LR-HL, we retrospectively analyzed 6,840 patients with cHL included in the German Hodgkin Study Group trials HD7 to HD12. Patients who experienced a relapse > 5 years into remission were compared with patients in continued remission for > 5 years and with those who experienced a relapse ≤ 5 years after first diagnosis. Results With a median observation time of 10.3 years, 141 incidences of LR-HL were observed. Cumulative incidences at 10, 15, and 20 years rose linearly and were 2.5%, 4.3%, and 6.9%, respectively. The standardized incidence ratio for HL with respect to age- and sex-matched German reference data was 84.5 (95% CI, 71.2 to 99.7). LR-HL was more frequently observed in patients with early-stage favorable than unfavorable or advanced stage at first diagnosis (15-year cumulative incidence, 5.3% v 3.9% and 3.9%, respectively; P = .01). Overall survival from first diagnosis was worse after LR compared with nonrelapse survivors (10-year estimate, 95.8% v 86.1%; hazard ratio, 2.5; 95% CI, 1.7 to 3.5; P < .001). In patients with LR-HL, survival was better compared with 466 patients with earlier relapse (hazard ratio, 0.6; 95% CI, 0.4 to 0.9, P = .01). Forty-four percent and 49% of patients with LR-HL and earlier relapse, respectively, received stem cell transplantations. Conclusion Apart from treatment-associated adverse effects, survivors after initially successful therapy for cHL are at an 85-fold risk for recurrence of disease compared with the general German population. After risk-adapted treatment strategies, especially in early-stage favorable HL, regular clinical follow-up is recommended for timely detection of LR-HL. With adequate treatment, prognosis of LR-HL is better compared with early relapses.
目的 经典型霍奇金淋巴瘤（cHL）患者的晚期复发（LR）的临床特征、治疗方法和预后尚不清楚。我们对霍奇金淋巴瘤的 LR（LR-HL）进行了全面分析。
方法 为了估计 LR-HL 的发生率，我们回顾性分析了德国霍奇金研究组试验 HD7 至 HD12 中纳入的 6840 例 cHL 患者。将缓解 > 5 年的复发患者与缓解 > 5 年的患者和首次诊断后复发 ≤ 5 年的患者进行比较。
结果 中位观察时间为 10.3 年，观察到 141 例 LR-HL 发病。10、15 和 20 年时的累积发生率呈线性上升，分别为 2.5%、4.3%和 6.9%。HL 的标准化发病比（SIR）与年龄和性别匹配的德国参考数据相比为 84.5（95%CI，71.2 至 99.7）。首次诊断时处于早期良好分期的患者比不良分期或晚期的患者更常发生 LR-HL（15 年累积发生率分别为 5.3%、3.9%和 3.9%；P =.01）。与非复发幸存者相比，LR 后首次诊断的总生存更差（10 年估计值分别为 95.8%和 86.1%；危险比为 2.5；95%CI，1.7 至 3.5；P <.001）。在 LR-HL 患者中，与 466 例较早复发的患者相比，生存情况更好（危险比为 0.6；95%CI，0.4 至 0.9，P =.01）。LR-HL 和早期复发的患者中分别有 44%和 49%的患者接受了干细胞移植。
结论 除了与治疗相关的不良反应外，与普通德国人群相比，最初成功治疗 cHL 后的幸存者发生疾病复发的风险高 85 倍。在风险适应治疗策略后，特别是在早期良好的 HL 中，建议进行定期临床随访，以及时发现 LR-HL。通过充分的治疗，LR-HL 的预后优于早期复发。
