Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA.
Center for Oncology Hematology Outcomes Research and Training (COHORT) and Division of Hematology and Oncology, University of California Davis School of Medicine, Sacramento, CA.
J Clin Oncol. 2020 May 20;38(15):1664-1675. doi: 10.1200/JCO.19.01937. Epub 2020 Feb 21.
Therapeutic advances for diffuse large B-cell lymphoma (DLBCL) have led to an increasing number of survivors. Both DLBCL and its treatments perturb the immune system, yet little is known about immune health during extended survivorship.
In this retrospective cohort study, we compared 21,690 survivors of DLBCL from the California Cancer Registry (CCR) to survivors of breast, prostate, head and neck, and melanoma cancers. We linked their CCR records to a statewide database documenting hospital, emergency room, and ambulatory surgery visits and investigated the incidence of autoimmune conditions, immune deficiencies, and infections 1-10 years after cancer diagnosis.
We found elevated incidence rate ratios (IRRs) for many immune-related conditions in survivors of DLBCL compared with other cancer survivors, including significantly and consistently elevated IRRs for viral and fungal pneumonias (up to 10.8-fold), meningitis (up to 5.3-fold), as well as humoral deficiency (up to 17.6-fold) and autoimmune cytopenias (up to 12-fold). IRRs for most conditions remained high even in the late survivorship period (5-10 years after cancer diagnosis). The elevated risks could not be explained by exposure to chemotherapy, stem-cell transplantation, or rituximab, except for IRRs for humoral deficiency, which were consistently higher after the incorporation of rituximab into DLBCL treatments.
To our knowledge, this is the largest cohort study with extended follow-up to demonstrate impaired immune health in survivors of DLBCL. The observed persistent, elevated risks for autoimmune diseases, immune deficiencies, and infectious conditions may reflect persistent immune dysregulation caused by lymphoma or treatment and may lead to excess morbidity and mortality during survivorship. Improved understanding of these risks could meaningfully improve long-term care of patients with DLBCL.
弥漫性大 B 细胞淋巴瘤（DLBCL）的治疗进展导致越来越多的幸存者。DLBCL 及其治疗都会扰乱免疫系统，但对于延长生存期后的免疫健康状况知之甚少。
在这项回顾性队列研究中，我们将加利福尼亚癌症登记处（CCR）中 21690 例 DLBCL 幸存者与乳腺癌、前列腺癌、头颈部癌和黑色素瘤幸存者进行了比较。我们将他们的 CCR 记录与全州数据库相链接，该数据库记录了医院、急诊室和门诊手术就诊情况，并调查了癌症诊断后 1-10 年内自身免疫性疾病、免疫缺陷和感染的发病率。
与其他癌症幸存者相比，我们发现 DLBCL 幸存者许多与免疫相关的疾病的发病率比值（IRR）升高，包括病毒性和真菌性肺炎（高达 10.8 倍）、脑膜炎（高达 5.3 倍）、体液缺陷（高达 17.6 倍）和自身免疫性细胞减少症（高达 12 倍）的发病率比值明显且持续升高。即使在晚期生存期间（癌症诊断后 5-10 年），大多数情况下的风险仍然很高。除了在将利妥昔单抗纳入 DLBCL 治疗后，体液缺陷的发病率比值一直较高之外，这些升高的风险不能用化疗、干细胞移植或利妥昔单抗的暴露来解释。
据我们所知，这是最大的队列研究，具有延长随访时间，以证明 DLBCL 幸存者的免疫健康受损。观察到的持续存在的自身免疫性疾病、免疫缺陷和感染性疾病的风险升高可能反映了淋巴瘤或治疗引起的持续免疫失调，并且可能导致生存期间的发病率和死亡率增加。对这些风险的更好理解可以显著改善 DLBCL 患者的长期护理。
