异基因造血干细胞移植相关中枢神经系统移植后淋巴增殖性疾病诊治分析

Diagnosis and Treatment of Central Nervous System-Posttransplant Lymphoproliferative Disorders After Allogeneic Hematopoietic Stem Cell Transplantation

目的分析中枢神经系统移植后淋巴增殖性疾病(central nervous system-posttransplant lymphoproliferative disorders,CNS-PTLD)患者的临床特征及预后。方法收集2018年—2022年苏州大学附属第一医院移植后病房收治的6例异基因造血干细胞移植(hematopoietic stem cell transplantation,HSCT)后CNS-PTLD患者,分析患者基本资料、临床特征、治疗和随访情况。结果6例患者中位年龄29岁(6~57岁),其中5例为急性髓系白血病,1例为骨髓增生异常综合征。患者均接受亲缘半相合造血干细胞移植,预处理过程均使用抗胸腺细胞球蛋白(antithymocyte globulin,ATG),5例患者合并移植物抗宿主病病史。1例患者既往诊断PTLD,行供体淋巴细胞输注治疗后好转。6例患者通过神经系统症状及体征、头颅影像学检查及脑脊液EBV-DNA定量、脑脊液流式细胞学确诊EBV相关CNS-PTLD。确诊后均减停免疫抑制剂,均接受了系统性利妥昔单抗及鞘注利妥昔单抗治疗,其中3例患者接受系统性甲氨蝶呤治疗,1例患者接受鞘注第三方供体淋巴细胞治疗,2例患者接受泽布替尼治疗。3例患者对治疗有应答,截至统计时间,4例患者死亡,中位生存时间76.5 d(6~1056 d)。结论CNS-PTLD患者病情进展快,对传统治疗效果欠佳,需早期发现、早期干预,可尝试细胞过继疗法、BTK抑制剂等新型治疗方法。

Objective To analyze the clinical characteristics and prognosis of patients with central nervous system-posttransplant lymphoproliferative disorders(CNS-PTLD).Methods 6 patients diagnosed with CNS-PTLD after hematopoietic stem cell transplantation(HSCT)admitted to the First Affiliated Hospital of Soochow University from 2018 to 2022 were enrolled,and their basic information,clinical characteristics,treatment and follow-up were analyzed.Results The median age of the 6 patients was 29 years old(6-57),including 5 cases of acute myeloid leukemia and 1 case of myelodysplastic syndrome.All patients received HLA haploidentical HSCT,and antithymocyte globulin(ATG)was used in the conditioning regimen.5 patients had a history of graft-versus-host disease.1 patient was previously diagnosed with PTLD and improved after donor lymphocyte infusion.6 patients were confirmed by neurological symptoms and signs,cranial imaging,EBV-DNA quantification of cerebrospinal fluid(CSF)and CSF flow cytology.After diagnosis,all patients stopped immunosuppressive therapy and received systemic and intrathecal therapy with rituximab.Among them,3 patients received systemic MTX therapy,1 patient received intrathecal therapy with donar lymphocytes,and 2 patients received Bruton tyrosine kinase(BTK)inhibitor.3 patients responded to treatment,and 4 patients died up to cut-off time,with a median survival time of 76.5 days(6-1056).Conclusion CNS-PTLD does not respond well to traditional treatment.Early detection and early interventions are necessary.Adoptive cellular immunotherapy,BTK inhibitors and other new therapies can be tried.