获得性纯红细胞再生障碍患者的临床特点与诊疗及难治病因临床分析

Clinical analysis of patients with acquired pure red cell aplasia among their clinical characteristics,diagnosis and treatment,and refractory etiology

目的探讨获得性纯红细胞再生障碍(aPRCA)患者的临床特点、诊疗和难治病因。方法选择2017年9月至2022年9月四川大学华西医院血液内科收治的90例aPRCA患者为研究对象。采用回顾性研究方法,收集患者一般临床资料、纯红细胞再生障碍(PRCA)相关实验室检查、诊疗方案及预后等临床资料,并对患者的临床特点、治疗与转归及难治病因进行分析。本研究遵循的程序符合四川大学华西医院伦理委员会制定的标准,经过该伦理委员会批准[批准文号:2023年审(413)号]。结果①本组90例aPRCA患者的中位发病年龄为56岁(41,65岁);男性患者为37例,女性为53例。继发性aPRCA为44例(48.9%,44/90),其中24例(26.7%,24/90)继发于大颗粒淋巴细胞白血病(LGLL),6例(6.7%,6/90)继发于胸腺瘤,5例(5.6%,5/90)与M蛋白相关,2例(2.2%,2/90)为骨髓增生异常肿瘤(MDS)样aPRCA,其余继发因素包括实体肿瘤、脾边缘带淋巴瘤、促红细胞生成素(EPO)水平低下等。②本组90例aPRCA患者中,73例患者接受环孢素A(CsA)初始治疗后,总缓解率(ORR)为79.5%(58/73),29例患者接受西罗莫司二线治疗后,ORR为62.1%(18/29)。根据病因,对患者采取的后线治疗方案包括氟达拉滨,抗胸腺细胞球蛋白(ATG),硼替佐米+来那度胺,海曲泊帕等。7例接受氟达拉滨治疗患者中,5例获得治疗反应。19例难治性aPRCA患者中,10例原发病为LGLL(1例伴胸腺瘤),2例为M蛋白相关,2例为MDS,2例为EPO抗体相关。19例难治性aPRCA患者接受针对病因的后线治疗后,ORR为47.4%(9/19);3例为多重病因继发,对治疗无反应。结论aPRCA是一种可继发于多种疾病的临床综合征,多数与机体免疫功能异常相关,CsA和西罗莫司对该病患者的治疗有效率较高。对难治性aPRCA患者进行病因诊断时,应特别注意浆细胞疾病相关和MDS样aPRCA。对于继发于LGLL的难治性aPRCA患者,可尝试采用氟达拉滨治疗。

Objective To explore clinical characteristics,diagnosis and treatment,and refractory etiology of patients with acquired pure red cell aplasia(aPRCA).Methods From September 2017 to September 2022,a total of 90 patients with aPRCA admitted to the Department of Hematology of West China Hospital of Sichuan University were selected as study subjects.A retrospective study method was used to collect clinical data of patients′general clinical data,laboratory tests related to pure red cell aplasia(PRCA),diagnosis and treatment protocols,and prognosis,as well as to analyze the clinical characteristics,treatment and outcomes,and refractory etiology of these patients.The procedures followed in this study conformed to the standards set by the Ethics Committee of West China Hospital of Sichuan University and were approved by this Ethics Committee[Approval No.2023(413)].Results①The median age of onset among the 90 patients with aPRCA in this study was 56 years(41,65 years).There were 37 male and 53 female patients.Forty-four cases(48.9%,44/90)were secondary aPRCA,including 24 cases(26.7%,24/90)were secondary to large granular lymphocytic leukemia(LGLL),6 cases(6.7%,6/90)were secondary to thymoma,5 cases(5.6%,5/90)associated with M protein,2 cases(2.2%,2/90)were myelodysplastic neoplasia(MDS)-like PRCA,and the rest of secondary factors included solid tumors,splenic marginal zone lymphomas,and low erythropoietin(EPO)levels.②Among 90 patients with aPRCA in this study,the overall remission rate(ORR)was 79.5%(58/73)of 73 patients who received initial treatment with cyclosporine A(CsA),and was 62.1%(18/29)of 29 patients who received the second-line treatment with sirolimus.Depending on etiology,the backline treatment regimens for patients included fludarabine,anti-thymocyte globulin(ATG),bortezomib+lenalidomide,and herombopag.Among 7 patients receiving fludarabine,5 cases obtained a therapeutic response.Among 19 patients with refractory aPRCA,10 cases were secondary to LGLL(1 case with a thymoma),2 cases were M protein-related,2 cases were secondary to MDS,and 2 cases were EPO antibody-associated.The 19 patients with refractory aPRCA had an ORR of 47.4%(9/19)after receiving cause-specific backline therapy,and the remaining 3 cases were secondary to multiple etiologies and did not respond to treatment.Conclusions APRCA is a clinical syndrome that can be secondary to a variety of diseases,most of which are associated with immune dysfunction.CsA and sirolimus are highly effective in treatment of patients with aPRCA.Special attention should be paid to plasma cell disease-associated and MDS-like aPRCA,when making the etiologic diagnosis of patients with refractory aPRCA.Fludarabine may be attempted for treat patients with refractory aPRCA secondary to LGLL.