Albusoul Linda, Abu-Hashyeh Ahmad, Donthireddy Vijayalakshmi
Internal Medicine, Henry Ford Health System, Detroit, USA.
Hematology and Oncology, Henry Ford Health System, Detroit, USA.
Cureus. 2022 Dec 15;14(12):e32567. doi: 10.7759/cureus.32567. eCollection 2022 Dec.
Post-transplant lymphoproliferative disease (PTLD) is a complication of solid organ and hematopoietic stem cell transplantation that occurs as a result of immunosuppression. PTLD isolated to the central nervous system (CNS) is a rare disease and it presents with nonspecific signs and symptoms. Optimal therapy guidelines have not yet been established for CNS PTLD. Here, we report a case of successful treatment of CNS PTLD in an adult female following two subsequent kidney transplants. Initial management was with immunosuppression reduction and a trial of rituximab. There were concerns regarding using methotrexate (MTX) given the patient's fragile transplant status. Magnetic resonance imaging of the brain following four cycles of rituximab revealed the progression of the disease. Subsequently, high-dose MTX (HD-MTX) was considered within the constraints of potential kidney toxicities given her transplant status and chronic kidney disease. Potential toxicities from other therapies, such as brain radiation, also factored into the final decision. The patient was treated with one cycle of a combination of rituximab and HD-MTX 1 g/m. The patient tolerated HD-MTX and did not have evidence of renal toxicity in laboratory studies. Following that, she was started on a reduced dose of HD-MTX at 2 g/m every two weeks instead of the higher MTX dose range of 3.5 to 8 g/m, which was a shared decision with the patient and nephrology after weighing the risk of kidney dysfunction with the possibility of a less than optimal response with regards to her lymphoma. She was followed with a magnetic resonance imaging of the brain, which demonstrated a complete response after four cycles. Further consolidation treatments with HD-MTX 2 g/m every four weeks were administered to complete one year of treatment. Following the completion of chemotherapy, the patient was able to achieve and maintain a complete response without affecting her kidney function. She continues to do well one year following treatment. This case highlights the significance of tailoring therapy to each individual based on their comorbidities and clinical response, as well as the possible merit in exploring the use of a reduced dose of HD-MTX in the treatment of CNS PTLD in patients at high risk for renal toxicity.
移植后淋巴细胞增生性疾病（PTLD）是实体器官和造血干细胞移植的一种并发症，由免疫抑制引起。孤立于中枢神经系统（CNS）的PTLD是一种罕见疾病，表现为非特异性体征和症状。目前尚未建立针对CNS PTLD的最佳治疗指南。在此，我们报告一例成年女性在接受两次肾移植后成功治疗CNS PTLD的病例。初始治疗是减少免疫抑制并试用利妥昔单抗。考虑到患者脆弱的移植状态，对使用甲氨蝶呤（MTX）存在担忧。利妥昔单抗四个周期治疗后进行的脑部磁共振成像显示疾病进展。随后，鉴于她的移植状态和慢性肾脏病，在考虑潜在肾脏毒性的情况下，考虑使用大剂量MTX（HD-MTX）。其他治疗方法（如脑部放疗）的潜在毒性也在最终决策中予以考虑。患者接受了一个周期的利妥昔单抗与1 g/m的HD-MTX联合治疗。患者耐受HD-MTX，实验室检查未发现肾毒性证据。此后，她开始每两周接受一次剂量降低至2 g/m的HD-MTX治疗，而非更高的3.5至8 g/m的MTX剂量范围，这是在与患者及肾脏病学专家权衡肾功能障碍风险与淋巴瘤反应欠佳可能性后共同做出的决定。对她进行脑部磁共振成像随访，结果显示四个周期后完全缓解。之后每四周给予2 g/m的HD-MTX进行进一步巩固治疗，以完成一年的治疗。化疗完成后，患者能够实现并维持完全缓解，且未影响其肾功能。治疗一年后她情况仍然良好。该病例强调了根据患者合并症和临床反应制定个体化治疗方案的重要性，以及在肾毒性高危患者中探索使用降低剂量的HD-MTX治疗CNS PTLD可能具有的价值。
