儿童异基因造血干细胞移植后淋巴细胞增殖性疾病的临床研究

目的探讨儿童异基因造血干细胞移植（allo-HSCT）后淋巴细胞增殖性疾病（PTLD）的诊治及预后。方法回顾性分析4例allo-HSCT后EBV相关性PTLD（EBV．PTLD）患儿的临床资料。其中，急性淋巴细胞白血病（高危）（ALL—HR）2例，重型再生障碍性贫血（SAA）2例。异基因外周血造血干细胞移植（allo-PBSCT）3例，异基因脐血造血干细胞移植（allo-UCBSCT）1例。结果4例患儿分别于allo．HSCT后第53、101、22、42d发生PTLD。临床表现为发热、鼻塞、扁桃体肿大、淋巴结肿大和肝脾肿大，移植前均EBNA-1-IgG（＋）、VCA．IgG（＋）；移植后EBV．DNA1．69×10^4～8．62×10^8 copies／mL。经淋巴结病理活检确诊为EBV-PTLD，其中1例为T细胞来源，3例为B细胞来源。例1予减停免疫抑制剂、使用利妥昔单抗、联合COP方案化疗及供者淋巴细胞输注（DU）治疗，PTLD反复且发生严重皮肤GVHD、肺部感染，移植后第193d死亡。余3例予减停免疫抑制剂及利妥昔单抗治疗，临床表现消失且EBV．DNA转阴，分别随访17、12、7个月均无病存活。结论动态监测EBV—DNA对PTLD早期发现具有重要意义。减停免疫抑制剂联合利妥昔单抗治疗EBV-PTLD疗效明显。化疗可导致严重感染，DLI治疗存在严重GVHD危险，不宜作为一线治疗。

Clinical study of post-transplantation lymphoproliferative disorder in children after allogeneic hematopoietic stem cell transplantation

Objective To explore the diagnosis, treatment and prognosis of post-transplantation lymphoproliferative disorder （PFLD） in children after allogeneic hematopoietic stem cell transplantation （allo-HSCT）. Methods The clinical data of four cases of PTLD in children after allo-HSCT were analyzed retrospectively. There were two children with acute lymphoblastic leukemia of high risk （ALL-HR）, and two with severe aplastic anemia （SAA）. Three children received allogeneic peripheral blood stem cell transplantation （allo-PBSCT） and one children received allogeneic umbilical cord blood stem cell transplantation （allo-UCBSCT）. Results PTLD of four patients respectively occurred on day 53 th, day 101 th, day 22 th, day 42 th after allo-HSCT. The patients were presented with fever, snuffy nose, antiadoncus, lymphadenectasis and enlargement of liver and spleen. They were presented EBNA-1- IgG（ ＋ ） ,VCA-IgG（ ＋ ） before HSCT and EBV-DNA 1.69 × 10^4 - 8.62 ×10 Scopies/mL after HSCT. ALL were diagnosed by biopsy, one is T cell PTLD and three are B cell PTLD. One patient received treatment of reduction or withdrawal of immunosuppression, rituximab, COP chemotherapy and donor lymphocyte infusion （DLI）. The clinical symptoms of PTLD relapsed and skin sever GVI-ID and pulmonary infection occurred. This patient died in the day 193th after allo-HSCT. The remaining three patients received treatment of reduction or withdrawal of immunosuppression and rituximab. All clinical symptoms disappeared and EBV-DNA turned negative, follow-up of 17 months, 12 months and 7 months, they are all disease-free survived. Conclusions Dynamic monitoring of EBV-DNA is important for early detection of PTLD. Treatment of reduction or withdrawal of immunosuppression combination with rituximab is effective. Chemotherapy can cause serious infections and DLI probably causes serious GVHD, are not be used as the first-line treatment.