Bishnoi Rohit, Minish Jordan, Franke Aaron J, Skelton William P, Shah Chintan P, Wang Yu, Dang Nam H
Hematology and Oncology, University of Florida, Gainesville, USA.
Internal Medicine, University of Florida, Gainesville, USA.
Cureus. 2020 Feb 7;12(2):e6912. doi: 10.7759/cureus.6912.
Background Post-transplant lymphoproliferative disorder (PTLD) is a rare complication following transplant (solid organ or allogeneic) due to the proliferation of lymphoid cells in the immunosuppressed state. The incidence of PTLD follows a bimodal distribution, with high incidence immediately after transplant (early-onset PTLD), followed by a decline and then a high-incidence again five years after transplantation (late-onset PTLD). This study exclusively aims to identify prognostic factors for the subgroup of PTLD, described as very late-onset PTLD, occurring after 10 years of transplant. Methods This study was conducted at the University of Florida, with the requisite study population identified through the cancer registry. Data were collected by individual chart review and analyzed. Survival estimates and univariate and multivariate analyses were performed to measure the effects of each variable on overall survival. Results A total of 33 patients were identified, with a median age at transplant of 42.3 years, while the median age at PTLD diagnosis was 54.7 years. Median time from transplant to PTLD diagnosis was 13.3 years. Kidney (30.3%), liver (27.3%), and heart (24.2%) transplants were the most common allografts associated with very late PTLD development. The most common pathology was diffuse large B-cell lymphoma (DLBCL) in 45.5% of patients. CHOP+/-R (cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin), prednisone, rituximab) was the most common chemo regimen used as the initial choice in 36.4% of patients. Median survival was 5.4 years. Univariate analysis showed that age at diagnosis over 65, male gender, bone marrow involvement, past medical history (PMH) of malignancy, immunosuppression regimen at PTLD diagnosis, and initial and final best response to treatment were statistically significant (p <0.05) factors associated with survival. On multivariate analysis, bone marrow involvement was significantly associated with poor survival (p=0.008). Surprisingly, performance status, Epstein-Barr virus (EBV) status, pathology type, Ann-Arbor stage, and chemotherapy regimen were not significantly associated with survival. At the end of the study, 48.5% of patients achieved complete remission and the allograft survived in 84.8%. Conclusions In this retrospective study of very-late onset PTLD, we identified factors associated with survival different from early and late PTLD. These factors should be considered during the treatment of this subgroup of PTLD patients.
移植后淋巴细胞增生性疾病（PTLD）是移植（实体器官或同种异体移植）后一种罕见的并发症，由于免疫抑制状态下淋巴细胞的增殖所致。PTLD的发病率呈双峰分布，移植后立即发病率较高（早发型PTLD），随后下降，然后在移植后五年再次出现高发病率（晚发型PTLD）。本研究专门旨在确定PTLD亚组（称为极晚发型PTLD，发生在移植10年后）的预后因素。方法：本研究在佛罗里达大学进行，通过癌症登记处确定所需的研究人群。通过个体病历审查收集数据并进行分析。进行生存估计以及单因素和多因素分析，以衡量每个变量对总生存的影响。结果：共确定33例患者，移植时的中位年龄为42.3岁，而PTLD诊断时的中位年龄为54.7岁。从移植到PTLD诊断的中位时间为13.3年。肾脏移植（30.3%）、肝脏移植（27.3%）和心脏移植（24.2%）是与极晚发型PTLD发生相关最常见的同种异体移植。最常见的病理类型是弥漫性大B细胞淋巴瘤（DLBCL），占患者的45.5%。CHOP+/-R（环磷酰胺、盐酸多柔比星（羟基柔红霉素）、硫酸长春新碱（安可平）、泼尼松、利妥昔单抗）是36.4%患者最初选择的最常见化疗方案。中位生存期为5.4年。单因素分析显示，诊断时年龄超过65岁、男性、骨髓受累、既往恶性肿瘤病史（PMH）、PTLD诊断时的免疫抑制方案以及对治疗的初始和最终最佳反应是与生存相关的具有统计学意义（p<0.05）的因素。多因素分析显示，骨髓受累与生存不良显著相关（p=0.008）。令人惊讶的是，体能状态、爱泼斯坦-巴尔病毒（EBV）状态、病理类型、Ann-Arbor分期和化疗方案与生存无显著相关性。在研究结束时，48.5%的患者实现完全缓解，同种异体移植在84.8%的患者中存活。结论：在这项关于极晚发型PTLD的回顾性研究中，我们确定了与早发型和晚发型PTLD不同的与生存相关的因素。在治疗这一亚组PTLD患者时应考虑这些因素。
