Praghakaran K, Wise B, Chen A, Schwarz K, Colombani P
Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
J Pediatr Surg. 1999 Jan;34(1):112-5; discussion 115-6. doi: 10.1016/s0022-3468(99)90239-7.
BACKGROUND/PURPOSE: Posttransplant lymphoproliferative disorder (PTLD) is a potentially lethal complication in the pediatric transplant patient secondary to Epstein-Barr virus (EBV) infection and potent immunosuppression. PTLD may develop in up to 10% of pediatric transplant recipients with mortality rates up to 80%. The authors report their experience with the diagnosis and efficacy of aggressive sequential management of PTLD in five patients under age 5 years.
A review of 75 pediatric liver transplant recipients on FK-506-based immunosuppression identified five biopsy-proven cases of PTLD and one probable case (8%). The probable case was a teenager, 6 months posttransplant in Spain, with mediastinal masses. No treatment or diagnosis was sought, and the patient died. The other five cases were managed with sequential therapy on an "intent-to-treat" basis with initial withdrawal of immunosuppression. If the disease progressed, patients were treated with four courses of intravenous cyclophosphamide, vincristine, Adriamycin, and intrathecal methotrexate and ara-C.
Five children were anti-EBV titer negative at the time of transplant. Three of five received EBV-positive donor organs and two children received EBV-negative livers. Monoclonal PTLD developed between 2 and 31 months posttransplant (mean, 15.7 months). With onset of PTLD (four B cell lymphoma, one B cell leukemia) all patients had tapering or withdrawal of immunosuppression and initiation of highdose acyclovir. Two of five patients had complete remission and resumed immunosuppression. Two patients progressed and required chemotherapy. One patient with initial response relapsed 4 months later with B cell leukemia and required chemotherapy. All five patients are alive 10 to 38 months postdiagnosis (mean, 29 months). Three patients had rejection requiring resumption of FK-506 therapy. Two patients are maintained on low-dose alternate-day prednisone and no FK-506. All patients have normal liver function. Central nervous system lymphoma developed in one child with significant neurological sequelae.
PTLD can develop in pediatric liver transplant recipients. Early withdrawal of immunosuppression and aggressive chemotherapy enabled us to achieve 100% patient and graft survival.
背景/目的：移植后淋巴细胞增生性疾病（PTLD）是小儿移植患者中一种潜在致命的并发症，继发于爱泼斯坦-巴尔病毒（EBV）感染和强效免疫抑制。PTLD在高达10%的小儿移植受者中可能发生，死亡率高达80%。作者报告了他们对5名5岁以下患者进行PTLD积极序贯治疗的诊断及疗效经验。
回顾75例接受基于FK-506免疫抑制治疗的小儿肝移植受者，确定5例经活检证实的PTLD病例和1例可能病例（8%）。可能病例是一名青少年，在西班牙移植后6个月，患有纵隔肿块。未寻求治疗或诊断，患者死亡。其他5例患者在“意向性治疗”基础上接受序贯治疗，最初停用免疫抑制。如果疾病进展，患者接受四个疗程的静脉注射环磷酰胺、长春新碱、阿霉素，以及鞘内注射甲氨蝶呤和阿糖胞苷治疗。
5名儿童在移植时抗EBV滴度为阴性。5名中有3名接受了EBV阳性供体器官，2名儿童接受了EBV阴性肝脏。单克隆PTLD在移植后2至31个月（平均15.7个月）发生。随着PTLD的发生（4例B细胞淋巴瘤，1例B细胞白血病），所有患者均逐渐减少或停用免疫抑制，并开始使用大剂量阿昔洛韦。5名患者中有2名完全缓解并恢复免疫抑制。2名患者病情进展，需要化疗。1例最初有反应的患者4个月后复发B细胞白血病，需要化疗。所有5名患者在诊断后10至38个月（平均29个月）仍存活。3名患者发生排斥反应，需要恢复FK-506治疗。2名患者维持低剂量隔日泼尼松治疗，未使用FK-506。所有患者肝功能正常。1名儿童发生中枢神经系统淋巴瘤，伴有明显的神经后遗症。
PTLD可在小儿肝移植受者中发生。早期停用免疫抑制和积极化疗使我们能够实现100%的患者和移植物存活。
