Danish Asma, Mughal Sarah I, Zaidi Uzma, Dildar Shabnam, Samad Shafaq, Jamal Aisha, Sharif Zainab, Shamsi Tahir
Department of Clinical Hematology, National Institute of Blood Disease and Bone Marrow Transplantation, Karachi, PAK.
Department of Research and Development, National Institute of Blood Disease and Bone Marrow Transplantation, Karachi, PAK.
Cureus. 2021 Nov 22;13(11):e19824. doi: 10.7759/cureus.19824. eCollection 2021 Nov.
Background and objective The calcineurin inhibitor cyclosporine A is routinely used for prophylaxis against graft-versus-host-disease (GvHD) in human leukocyte antigen (HLA)-matched allogeneic stem-cell transplant patients and is a major etiological factor for neuropathological symptoms that are reversible in most cases. In this study, we aimed to determine the frequency and risk factors of cyclosporine-induced neurotoxicity (CIN) in HLA-matched allogeneic stem cell transplant patients. Methods The study spanned the period from January 2016 to December 2019. Consecutive HLA-matched allogeneic stem-cell transplant patients of all ages were included in the study. Descriptive and risk factor analyses for the development of CIN with respect to age, sex, primary diagnosis, conditioning regimen, electrolyte abnormalities, and cyclosporine trough levels during the neurological episode were performed. Results A total of 106 HLA-matched patients with a median age of 6.3 years [interquartile range (IQR): 0.5-46 years], of which 37 (35%) were females, were included in the study. The mean cyclosporine trough level was 500 ±286 mg/dl. Neurological symptoms were found in 27 (26%) patients. A total of 14 (13%) patients were diagnosed with CIN. The frequency of other neurological symptoms included headache in 46 (43%), disorientation in 17 (16%), seizures in 12 (11%), visual disturbance in 11 (10%), and aphasia in seven (7%) patients. Posterior reversible encephalopathy syndrome (PRES) was found in six (6%) patients. All patients with CIN had hypertension and none had a fever. Multivariate logistic analysis showed that the presence of seizures [odds ratio (OR): 10.0, p<0.001] and the absence of fever (OR: 0.02, p<0.001) were associated with the diagnosis of CIN. Conclusion The prevalence of CIN is not uncommon (13%) in patients receiving cyclosporine for GvHD prophylaxis. Neurological complications, especially seizures, are common in CIN, and fever might indicate an alternative diagnosis. Prompt recognition of neurological signs and symptoms and early intervention can halt the progression of the disease.
背景与目的 钙调神经磷酸酶抑制剂环孢素A常用于人类白细胞抗原（HLA）匹配的异基因干细胞移植患者预防移植物抗宿主病（GvHD），并且是大多数情况下可逆转的神经病理症状的主要病因。在本研究中，我们旨在确定HLA匹配的异基因干细胞移植患者中环孢素诱导的神经毒性（CIN）的发生率及危险因素。方法 本研究涵盖2016年1月至2019年12月期间。纳入所有年龄的连续HLA匹配的异基因干细胞移植患者。对CIN发生情况进行关于年龄、性别、初始诊断、预处理方案、电解质异常以及神经发作期间环孢素谷浓度的描述性和危险因素分析。结果 共有106例HLA匹配患者，中位年龄6.3岁[四分位间距（IQR）：0.5 - 46岁]，其中37例（35%）为女性纳入研究。环孢素平均谷浓度为500±286mg/dl。27例（26%）患者出现神经症状。共有14例（13%）患者被诊断为CIN。其他神经症状的发生率包括头痛46例（43%）、定向障碍17例（16%）、癫痫发作12例（11%）、视觉障碍11例（10%）以及失语7例（7%）。6例（6%）患者发现有后部可逆性脑病综合征（PRES）。所有CIN患者均有高血压且无发热。多因素logistic分析显示癫痫发作的存在[比值比（OR）：10.0，p<0.001]以及无发热（OR：0.02，p<0.001）与CIN诊断相关。结论 在接受环孢素预防GvHD的患者中，CIN的患病率并不罕见（13%）。神经并发症，尤其是癫痫发作，在CIN中很常见，发热可能提示其他诊断。及时识别神经体征和症状并早期干预可阻止疾病进展。
