Cacciarelli T V, Green M, Jaffe R, Mazariegos G V, Jain A, Fung J J, Reyes J
Department of Transplant Surgery, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, Pennsylvania 15213, USA.
Transplantation. 1998 Oct 27;66(8):1047-52. doi: 10.1097/00007890-199810270-00014.
Posttransplant lymphoproliferative disease (PTLD) after pediatric liver transplantation has been associated with high mortality rates.
The present study examined 282 consecutive pediatric liver transplant recipients from October 1989 to June 1996 who received primary tacrolimus immunosuppression. The aim was to determine the incidence of PTLD, management strategies, and patient outcome.
The incidence of PTLD was 13% (361282) with a mean age of 5.5+/-0.7 years (range 0.6 to 15) at diagnosis. The average time from transplantation to PTLD was 10.1+/-2.1 months. Initial treatment of PTLD consisted of reduction (3 patients) or discontinuation (33 patients) of tacrolimus and initiation of antiviral therapy (intravenous ganciclovir, 14 patients; intravenous acyclovir, 22 patients; or both, 5 patients). Alpha-interferon was used in four patients (two successfully). One patient also received gamma-interferon, chemotherapy, and radiation for a central nervous system lesion. Chemotherapy was also used in one patient with Burkitt's, whereas one patient with a pulmonary lesion received additional radiation therapy. Three patients received supportive surgery for gastrointestinal involvement, and one patient had a splenectomy for hemolysis. Overall mortality was 22% (8/36) with 5 (14%) PTLD-related deaths (disseminated disease, 4 patients; bowel perforation, 1 patient). Of 31 survivors, 23 had acute rejection at a median time of 24 days after PTLD, with 2 patients developing chronic rejection. One patient required retransplantation. Present immunosuppression consists of tacrolimus monotherapy in 14 patients, tacrolimus/prednisone in 8 patients, and none in 6 patients.
In summary, PTLD can be successfully treated with reduction of immunosuppression and administration of antiviral agents in most patients. The management of rejection after PTLD requires reassessment of disease status and judicious reintroduction of immunosuppression therapy.
小儿肝移植后发生的移植后淋巴细胞增生性疾病（PTLD）与高死亡率相关。
本研究对1989年10月至1996年6月连续接受初次他克莫司免疫抑制治疗的282例小儿肝移植受者进行了检查。目的是确定PTLD的发病率、管理策略和患者结局。
PTLD的发病率为13%（36/282），诊断时的平均年龄为5.5±0.7岁（范围0.6至15岁）。从移植到PTLD的平均时间为10.1±2.1个月。PTLD的初始治疗包括减少（3例患者）或停用（33例患者）他克莫司，并开始抗病毒治疗（静脉注射更昔洛韦，14例患者；静脉注射阿昔洛韦，22例患者；或两者都用，5例患者）。4例患者使用了α干扰素（2例成功）。1例患者还因中枢神经系统病变接受了γ干扰素、化疗和放疗。1例伯基特淋巴瘤患者也接受了化疗，而1例肺部病变患者接受了额外的放疗。3例患者因胃肠道受累接受了支持性手术，1例患者因溶血接受了脾切除术。总死亡率为22%（8/36），5例（14%）与PTLD相关的死亡（播散性疾病，4例患者；肠穿孔，1例患者）。在31名幸存者中，23例在PTLD后中位时间24天发生急性排斥反应，2例发生慢性排斥反应。1例患者需要再次移植。目前的免疫抑制治疗包括14例患者采用他克莫司单药治疗，8例患者采用他克莫司/泼尼松治疗，6例患者未进行免疫抑制治疗。
总之，大多数患者通过降低免疫抑制和给予抗病毒药物可以成功治疗PTLD。PTLD后排斥反应的管理需要重新评估疾病状态并谨慎重新引入免疫抑制治疗。
