Epidemiology of posttransplant lymphoproliferative disorders in adult kidney and kidney pancreas recipients: report of the French registry and analysis of subgroups of lymphomas

A registry of posttransplant lymphoproliferative disorders (PTLD) was set up for the entire population of adult kidney transplant recipients in France. Cases of PTLD were prospectively enrolled between January 1, 1998, and December 31, 2007. Ten-year cumulative incidence was analyzed in patients transplanted after January 1, 1989. PTLD risk factors were analyzed in patients transplanted after January 1, 1998 by Cox analysis. Cumulative incidence was 1% after 5 years, 2.1% after 10 years. Multivariate analysis showed that PTLD was significantly associated with: older age of the recipient 47-60 years and >60 years (vs. 33-46 years, adjusted hazard ratio (AHR) = 1.87, CI = 1.22-2.86 and AHR = 2.80, CI = 1.73-4.55, respectively, p < 0.0001), simultaneous kidney-pancreas transplantation (AHR = 2.52, CI = 1.27-5.01 p = 0.008), year of transplant 1998-1999 and 2000-2001 (vs. 2006-2007, AHR = 3.36, CI = 1.64-6.87 and AHR = 3.08, CI = 1.55-6.15, respectively, p = 0.003), EBV mismatch (HR = 5.31, CI = 3.36-8.39, p < 0.001), 5 or 6 HLA mismatches (vs. 0-4, AHR = 1.54, CI = 1.12-2.12, p = 0.008), and induction therapy (AHR = 1.42, CI = 1-2.02, p = 0.05). Analyses of subgroups of PTLD provided new information about PTLD risk factors for early, late, EBV positive and negative, polymorphic, monomorphic, graft and cerebral lymphomas. This nationwide study highlights the increased risk of PTLD as long as 10 years after transplantation and the role of cofactors in modifying PTLD risk, particularly in specific PTLD subgroups.     

Metabolic Syndrome and Solid-Organ Transplantation

The metabolic syndrome is proposed as a cluster of known cardiovascular risk factors, interrelated by a common pathophysiological defect, that symbolize a heightened metabolic burden. Advocates of the concept argue that it is a predictor for both diabetes and cardiovascular disease, complications of great importance posttransplantation. The abundant medical literature on the topic is now expanding into the field of transplantation with evidence linking the metabolic syndrome to adverse patient and graft outcomes. Although the implications posttransplantation are significant, controversy surrounds the concept and the topic has not previously been reviewed in the context of solid-organ transplantation. The purpose of this review is to update transplant clinicians with our current understanding of the metabolic syndrome, review the transplantation literature and examine the controversies surrounding the concept.     

心脏移植术后发生移植后淋巴组织增生性疾病二例并文献复习

目的探讨心脏移植术后发生移植后淋巴组织增生性疾病（PTLD）的发病原因、临床表现、病理特点及防治措施。方法1997年1月至2013年12月,浙江省人民医院心胸外科共开展心脏移植18例,其中2例发生PTLD。回顾性分析2例患者的临床资料并进行文献复习。结果2例患者心脏原位移植术后使用以环孢素为基础的三联免疫抑制方案。从移植术后到确诊PTLD的时间分别为12年和9年。患者均以颈部淋巴结肿大为临床表现,病理活检均提示“非霍奇金恶性淋巴瘤,B细胞源性,弥漫性大B细胞淋巴瘤”。在调整免疫抑制方案的基础上,给予美罗华＋半剂量CHOP化疗方案。随访至2013年12月,2例患者生活工作均正常。结论对于心脏移植术后确诊为PTLD的患者,半剂量CHOP方案化疗既不影响心脏移植的抗排斥反应,又能有效控制肿瘤的进展;美罗华可增强化疗药物作用。因此,美罗华＋半剂量CHOP化疗方案是治疗PTLD的优选方案。     

CXCL13 as a Novel Marker for Diagnosis and Disease Monitoring in Pediatric PTLD

Posttransplant lymphoproliferative disease (PTLD) is a severe complication of immunosuppressive treatment in organ‐grafted children. Early diagnosis of PTLD is hampered by both unspecific clinical symptoms and lack of easy accessible markers. The homeostatic chemokine CXCL13, which plays a crucial role in B‐cell homing and lymphoid organ development, is expressed in some lymphomatous diseases. This study aims to investigate whether serum CXCL13 (sCXCL13) levels correlate with occurrence and regression of PTLD in pediatric solid‐organ graft recipients. Serum samples from PTLD patients (n = 21), patients with Epstein–Barr virus (EBV) reactivation (n = 18), and healthy age‐matched controls (n = 19) were tested for CXCL13 using a commercially available ELISA kit. sCXCL13 levels were significantly higher in PTLD patients than in healthy children. PTLD patients had also higher sCXCL13 values than pediatric solid‐organ recipients with EBV reactivation. An increase in sCXCL13 levels was observed from EBV reactivation to PTLD diagnosis in most cases. Elevated sCXCL13 levels were detected up to 2 years prior to PTLD diagnosis and correlated well with response to cytoreductive treatment in individual patients. sCXCL13, thus, may be a readily available surrogate marker for the diagnosis of PTLD and for monitoring of response to treatment in patients with initially elevated sCXCL13 levels.     

Hepatitis C virus related lymphoproliferative disorder in a renal transplant recipient

Posttransplant lymphoproliferative disorders (PTLD) are commonly caused by Ebstein-Barr Virus infection. The role of hepatitis C virus (HCV) in the genesis of lymphomas has been recognized recently. We report a HCV infected renal transplant recipient who developed PTLD 11 months after transplantation. Reduction of immunosuppression led to disappearance of viremia and clearance of PTLD. This is the first such report in the world literature.