Diagnosis and treatment of human parvovirus B19 infection after allogeneic hematopoietic stem cell transplantation and literature review
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摘要: 目的 探讨异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation，allo-HSCT)后细小病毒B19(parvovirus B19，PVB19)感染的临床表现、早期识别和诊断，为治疗提供临床经验。方法 回顾性分析2012年1月—2020年12月在我院血液肿瘤科造血干细胞移植中心行allo-HSCT的446例重型地中海贫血患者的临床资料，其中2例患者移植后感染PVB19(发病率0.45%)，总结这2例患者的临床特征、实验室资料、治疗及预后。2例患者均采用清髓性预处理方案，应用宏基因组测序技术检测外周血病原微生物，通过定量PCR监测治疗前后体内病毒载量变化，结合临床评估治疗效果，并分别以PVB19感染和(或)骨髓移植和(或)干细胞移植和(或)造血干细胞移植、PVB19 infection and/or bone marrow transplantation and/or stem cell transplantation and/or hematopoietic stem cell transplantation为关键词检索国内外相关文献并进行复习，总结分析该病的临床特点。结果 共获取18篇文献44例患者(包括我中心2例)纳入研究，其中男30例，女13例，另外1例文献未提及性别；中位年龄32.5(1~59)岁；起病时PVB19-IgG阳性7例，PVB19-IgM阳性2例，PVB19-DNA PCR病毒载量阳性42例。PVB19感染多为移植后0.03~96.00个月，最主要的临床表现为皮疹和血细胞减少，其他症状包括发热、关节痛、不适、头痛、肌痛和瘙痒。35例患者经静脉注射免疫球蛋白(intravenous immunoglobulin，IVIG)或IVIG联合减量免疫抑制剂治疗，24例患者初始治疗有效。44例患者中7例死亡，其中4例合并心脏、肺或肾脏器官衰竭。我中心2例患者均为重型地中海贫血造血干细胞移植后感染PVB19，移植前均采用清髓性预处理方案，临床表现均为贫血、网织红细胞下降，伴皮疹，其中1例表现为三系减少，PVB19血清学均阴性，其中1例宏基因组测序提示PVB19感染，2例IVIG治疗均有效。结论 及时准确的诊断和IVIG治疗可治愈allo-HSCT后PVB19感染，宏基因组测序有助于血清学阴性PVB19感染的早期诊断，小剂量持续IVIG治疗可能更适宜于造血干细胞移植后感染PVB19的患者。Abstract: Objective To retrospectively analyze the clinical features and early identification and diagnosis of parvovirus B19(PVB19) infection after allogeneic hematopoietic stem cell transplantation(allo-HSCT), and to provide clinical experience for treatment.Methods The clinical data of 446 patients with thalassemia major who received allo-HSCT in the hematopoietic stem cell transplantation center of the hematology and oncology department of our hospital from January 2012 to December 2020 were retrospectively analyzed. Two patients of them infected with PVB19 after transplantation, with an incidence of 0.45%. The clinical features, laboratory data, treatment, and prognosis of these 2 patients were summarized. Both children were treated with a myeloablative conditioning regimen, and metagenomics next-generation sequencing was used to detect pathogenic microorganisms in peripheral blood. Quantitative PCR was used to monitor the changes in viral load in the body before and after treatment, and the treatment effect was evaluated clinically. Related domestic and foreign literature searched respectively with key words PVB19 infection and/or bone marrow transplantation and/or stem cell transplantation and/or hematopoietic stem cell transplantation was reviewed, and the clinical characteristics of the disease were summarized and analyzed.Results A total of 18 articles were obtained and 44 patients(including 2 cases in our center) were included in the study, there were 30 males and 13 females, with a median age was 32.5 years(1-59 years old). Seven cases were PVB19-IgG positive at the onset of PVB19 infection, 2 cases were PVB19-IgM positive and 42 cases were PVB19-DNA PCR viral load positive. PVB19 infection occurred mostly 0.03-96.00 months after transplantation, and the main clinical manifestations were rash and cytopenia, with other symptoms including fever, arthralgia, malaise, headache, myalgia, and pruritus. Thirty-five patients received intravenous immunoglobulin(IVIG) or IVIG combined with reduced-dose immunosuppressive therapy, and 24 patients responded well to the initial treatment. Seven of 44 patients died, including 4 cases complicated with organ failure of the heart, lungs, or kidneys. The 2 patients in our center were infected with PVB19 after thalassemia major hematopoietic stem cell transplantation, and a myeloablative conditioning regimen was used before transplantation. The clinical manifestations in both patients were anemia, reticulocytopenia, and rash, and 1 case showed pancytopenia. Both patients were PVB19-seronegative, and 1 patient was suggested to have PVB19 infection by metagenomics next-generation sequencing. IVIG treatment was effective in both cases.Conclusion Our study shows that timely and accurate diagnosis and IVIG treatment can cure PVB19 infection after allo-HSCT. Metagenomic sequencing is helpful for the early diagnosis of seronegative PVB19 infection, and low-dose continuous IVIG treatment may be more suitable for patients infected with PVB19 after hematopoietic stem cell transplantation.
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