Pollack Shirley, Plonsky Moran, Tibi Rami, Libinson-Zebegret Irina, Yakobov Renata, Eisenstein Israel, Magen Daniella
Technion Faculty of Medicine, Haifa, Israel.
Pediatric Nephrology Institute, Ruth Children's Hospital, Rambam Health Care Campus, Haifa, Israel.
Pediatr Nephrol. 2025 Mar;40(3):829-834. doi: 10.1007/s00467-024-06522-2. Epub 2024 Oct 7.
Post-transplant lymphoproliferative disorder (PTLD) is a devastating complication of immunosuppressive treatment in both solid organ transplantations (SOT) and hematopoietic stem cell transplantations (HSCT). Epstein-Barr virus (EBV) infection precedes PTLD in 90% of patients. Rituximab, a monoclonal anti-CD20 antibody, depletes B-lymphocytes, which are the ultimate reservoir for EBV. Although rituximab therapy is commonly used as a preventive measure for PTLD in high-risk HSCT, it is not established in SOT.
Pediatric kidney transplant recipients (PKTR) underwent routine EBV-PCR surveillance. Patients with increasing viral loads, despite immunosuppressive dose reduction, were managed with preventive rituximab therapy.
Between 2012 and 2023, we identified eight episodes of asymptomatic EBV-PCR-positive blood tests in seven out of 65 PKTR (11%) under our care. EBV DNAemia emerged 120-720 days post-transplantation. Five of seven patients with EBV DNAemia (71%) were EBV-seronegative prior to transplantation. All five patients did not respond to MMF dose reduction and were therefore treated with preventive rituximab therapy. Following this treatment, EBV PCR clearance was observed in all patients with only minimal complications.
PKTR who are EBV-naïve prior to transplantation are expected to have a higher prevalence of EBV DNAemia. We found that PKTR who were EBV seronegative prior to transplantation were less likely to achieve EBV clearance in response to immunosuppression dose reduction. We suggest that rituximab therapy in PKTR may be safe and effective in EBV clearance and PTLD prevention.
移植后淋巴细胞增殖性疾病（PTLD）是实体器官移植（SOT）和造血干细胞移植（HSCT）中免疫抑制治疗的一种毁灭性并发症。90%的患者在PTLD发生之前存在爱泼斯坦-巴尔病毒（EBV）感染。利妥昔单抗是一种抗CD20单克隆抗体，可消耗作为EBV最终储存库的B淋巴细胞。尽管利妥昔单抗治疗通常用作高危HSCT中PTLD的预防措施，但在SOT中尚未确立。
小儿肾移植受者（PKTR）接受常规EBV-PCR监测。尽管降低了免疫抑制剂量，但病毒载量仍增加的患者接受预防性利妥昔单抗治疗。
在2012年至2023年期间，我们在我们照护的65例PKTR中的7例（占11%）中发现了8次无症状EBV-PCR阳性血液检测事件。EBV血症在移植后120 - 720天出现。7例EBV血症患者中有5例（占71%）在移植前为EBV血清学阴性。所有5例患者对霉酚酸酯剂量降低无反应，因此接受预防性利妥昔单抗治疗。经过该治疗，所有患者的EBV PCR均转阴，且并发症极少。
移植前未感染EBV的PKTR预计EBV血症患病率更高。我们发现，移植前EBV血清学阴性的PKTR对免疫抑制剂量降低反应时实现EBV清除的可能性较小。我们建议，PKTR中利妥昔单抗治疗在清除EBV和预防PTLD方面可能是安全有效的。
