Moser Elizabeth C, Noordijk Evert M, Carde Patrice, Tirelli Umberto, Baars Joke W, Thomas Jose, Bron Dominique, Meerwaldt Jacobus H, van Glabbeke Martine, Raemaekers John M M, Kluin-Nelemans Hanneke C
European Organisation for the Research and Treatment of Cancer Data Center, Brussels, Belgium.
Clin Lymphoma Myeloma. 2005 Sep;6(2):122-30. doi: 10.3816/CLM.2005.n.038.
A significant proportion of patients with aggressive non-Hodgkin's lymphoma (NHL) become long-term survivors. A European Organisation for Research and Treatment of Cancer database of patients with aggressive NHL, consistently treated with doxorubicin-based chemotherapy since 1980, afforded the possibility to explore late complications in this patient group.
Of 951 randomized patients, complete data on late complications could be collected in 757 patients who were alive > or = 2 years after the start of therapy and were seen at yearly follow-ups (median follow-up, 9.4 years; range, 2.1-20.4 years). We computed cumulative incidences of late events in a competing risk model by Gray (death being the competing event) to avoid bias caused by the high percentage of NHL-related deaths. Risk factors were estimated in a Cox proportional-hazards model and also evaluated with the Gray test.
Late non-neoplastic events were found in 46% of the 757 patients. At 15 years, the cumulative incidences of cardiac disease and infertility were 20% and 29%, respectively. Renal insufficiency (11%), acquired hypertension (8%), and disabling neuropathy (13%) were also frequent. Salvage treatment was a risk factor in most cases. Smoking, age > 50 years during treatment, and preexistent hypertension were the main risk factors for cardiovascular disease. In-field radiation therapy (RT) was related to hypothyroidism, lung fibrosis, hypertension, gastrointestinal toxicity, and renal insufficiency but not to cardiovascular events. Autologous stem cell transplantation and cisplatin- and MOPP (mechlorethamine/vincristine/procarbazine/prednisone)-containing therapies were associated with infertility and renal insufficiency.
Altogether, almost half the patients with aggressive NHL experienced events addressed as late non-neoplastic complications. Salvage therapy, smoking, age > 50 years, and in-field RT are important risk factors.
相当一部分侵袭性非霍奇金淋巴瘤（NHL）患者成为长期幸存者。欧洲癌症研究与治疗组织的一个侵袭性NHL患者数据库，自1980年以来一直采用以阿霉素为基础的化疗进行持续治疗，这使得探索该患者群体的晚期并发症成为可能。
在951例随机分组的患者中，能够收集到757例患者的晚期并发症完整数据，这些患者在治疗开始后存活≥2年，并接受每年一次的随访（中位随访时间为9.4年；范围为2.1 - 20.4年）。我们在一个竞争风险模型中由格雷计算晚期事件的累积发生率（死亡为竞争事件），以避免因NHL相关死亡的高比例所导致的偏差。在Cox比例风险模型中估计风险因素，并也用格雷检验进行评估。
在757例患者中有46%出现晚期非肿瘤性事件。在15年时，心脏病和不孕症的累积发生率分别为20%和29%。肾功能不全（11%）、获得性高血压（8%）和致残性神经病变（13%）也很常见。在大多数情况下，挽救性治疗是一个风险因素。吸烟、治疗期间年龄>50岁以及既往高血压是心血管疾病的主要风险因素。野内放射治疗（RT）与甲状腺功能减退、肺纤维化、高血压、胃肠道毒性和肾功能不全相关，但与心血管事件无关。自体干细胞移植以及含顺铂和MOPP（氮芥/长春新碱/丙卡巴肼/泼尼松）的治疗与不孕症和肾功能不全相关。
总体而言，几乎一半的侵袭性NHL患者经历了被视为晚期非肿瘤性并发症的事件。挽救性治疗、吸烟、年龄>50岁和野内RT是重要的风险因素。
