Epstein–Barr virus load in transplant patients: Early detection of post-transplant lymphoproliferative disorders

Fellner, Marı́a Dolores; Durand, Karina; Solernou, Verónica; Bosaleh, Andrea; Balbarrey, Ziomara; Dávila, María Teresa García de; Rodríguez, Marisa; Irazú, Lucía; Alonio, Lidia Virginia; Picconi, Marı́a Alejandra

doi:10.1016/j.ram.2016.02.006

Cited by 20 publications

(22 citation statements)

References 21 publications

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“…D+/R− were at a significantly higher risk of developing PTLD than the R+ group, which is consistent with previous studies. 5,10,12,13,15,17 However, other risk factors that were commonly seen in the literature such as young age, 6,8,10,14,15,17 Caucasian race, 8,10,13 and type of immunosuppression used 8,10,12 –19 were not significant risk factors in our population ( P > .05). This may be because of the small effective sample size of cases with PTLD and differences in study populations (studies in the literature were primarily conducted in pediatric populations 7,10,14,15,27 ).…”

Section: Discussioncontrasting

confidence: 50%

“…Posttransplant lymphoproliferative disorder consists of tumors that may contain Epstein–Barr virus (EBV), a herpes virus that infects B cells and causes uncontrollable proliferation. 2,18,19 Several risk factors for developing PTLD are related to EBV, such as recipient EBV seropositivity, 8,10 EBV sero-mismatch with a positive donor and a negative recipient (D+/R−), 5,10,12,13,15,17 and primary EBV infections posttransplant. 12,15,16 Epstein–Barr virus–associated PTLD is diagnosed from tumor biopsy specimens.…”

Section: Introductionmentioning

confidence: 99%

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Incidence, Risk Factors, Clinical Management, and Outcomes of Posttransplant Lymphoproliferative Disorder in Kidney Transplant Recipients

et al. 2019

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Background: Posttransplant lymphoproliferative disorder (PTLD) is a severe complication after kidney transplantation. This study examined the incidence, risk factors, clinical management, and outcomes of PTLD in a cohort of kidney transplant recipients. Design: This single-center cohort study included 1642 patients transplanted from January 1, 2000, to December 31, 2012, with follow-up until December 31, 2013. The incidence and risk factors for PTLD were examined using a Cox proportional hazards model. A Cox model was also used to assess the association of PTLD and graft outcomes. Results: Sixteen recipients developed PTLD over follow-up. The incidence rate was 0.18 (95% confidence interval [CI]: 0.11-0.29) cases per 100 person-years. Four were from Epstein-Barr virus (EBV) mismatched (Dþ/RÀ) transplants and 12 from EBV-positive recipients (Rþ). Recipients with Dþ/RÀ matches were at a significantly higher risk of developing PTLD than Rþ (hazard ratio [HR]: 7.52 [95% CI: 2.42-23.32]). Fifteen cases had immunosuppression reduced, 11 cases were supplemented with rituximab or ganciclovir, 6 cases required chemotherapy or radiation, and 6 cases had tumors excised. By the end of follow-up, 6 patients went into remission, 5 returned to chronic dialysis, and 5 patients died. Patients with PTLD were significantly more likely to have total graft failure (return to chronic dialysis, preemptive retransplant, or death with graft function) than patients without PTLD (HR: 3.41 [95% CI: 1.72-6.78). Discussion: Epstein-Barr virus mismatch continues to be a strong risk factor for developing PTLD after kidney transplantation. Recipients with PTLD have a poor prognosis, as the optimal management remains to be elucidated.

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Section: Discussioncontrasting

confidence: 50%

Section: Introductionmentioning

confidence: 99%

Incidence, Risk Factors, Clinical Management, and Outcomes of Posttransplant Lymphoproliferative Disorder in Kidney Transplant Recipients

et al. 2019

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“…Given the high PAF for NHL (4% among children and approximately 2% among adults), this cancer should be a priority. Because high levels of circulating EBV load can be used as a marker of posttransplantation lymphoproliferative disorder, there may be opportunities to use this biomarker to screen for NHL, especially in pediatric recipients . Treating underlying liver disease (eg, with direct‐acting antiviral medications for hepatitis C virus infection) and screening for liver cancers in high‐risk recipients also should be considered, including among liver recipients, among whom liver cancer contributes the most to mortality.…”

Section: Discussionmentioning

confidence: 99%

“…Because high levels of circulating EBV load can be used as a marker of posttransplantation lymphoproliferative disorder, there may be opportunities to use this biomarker to screen for NHL, especially in pediatric recipients. 29 Treating underlying liver disease (eg, with direct-acting antiviral medications for hepatitis C virus infection) and screening for liver cancers in high-risk recipients also should be considered, 28,30 including among liver recipients, among whom liver cancer contributes the most to mortality. Finally, cancer prevention strategies aimed at modifying lifestyle cancer risk factors, especially smoking cessation but also sun protection, 31 should be prioritized to reduce mortality from lung cancer and melanoma.…”

Section: Among Solid Organ Transplant Recipients In the Unitedmentioning

confidence: 99%

Cancer‐attributable mortality among solid organ transplant recipients in the United States: 1987 through 2014

Noone

Pfeiffer

Dorgan

et al. 2019

Cancer

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Background Solid organ transplant recipients have an elevated risk of cancer. Quantifying deaths attributable to cancer can inform priorities to reduce cancer burden. Methods Linked transplantation and cancer registry data were used to identify incident cancers and deaths among solid organ transplant recipients in the United States (1987‐2014). Population‐attributable fractions (PAFs) of deaths due to cancer and corresponding cancer‐attributable mortality rates were estimated using Cox models. Results Among 221,962 solid organ transplant recipients, 15,012 developed cancer. Approximately 13% of deaths (PAF, 13.2%) were attributable to cancer, corresponding to a cancer‐attributable mortality rate of 516 per 100,000 person‐years. Lung cancer was the largest contributor to mortality (PAF, 3.1%), followed by non‐Hodgkin lymphoma (NHL; PAF, 1.9%), colorectal cancer (PAF, 0.7%), and kidney cancer (PAF, 0.5%). Cancer‐attributable mortality rates increased with age at transplantation, reaching 1229 per 100,000 person‐years among recipients aged ≥65 years. NHL was the largest contributor among children (PAF, 4.1%) and lung cancer was the largest contributor among recipients aged ≥50 years (PAFs, 3.7%‐4.3%). Heart recipients had the highest PAF (16.4%), but lung recipients had the highest cancer‐attributable mortality rate (1241 per 100,000 person‐years). Overall, mortality attributable to cancer increased steadily with longer time since transplantation, reaching 15.7% of deaths (810 per 100,000 person‐years) at ≥10 years after transplantation. Comparison of cancer‐attributable mortality rates with specified causes of death indicated that some deaths recorded as other causes might instead be caused by cancer or its treatment. Conclusions Cancer is a substantial cause of mortality among solid organ transplant recipients, with major contributions reported from lung cancer and NHL. Cancer‐attributable mortality increases with age and time since transplantation, and therefore cancer deaths will become an increasing burden as recipients live longer.

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“…This allows for early therapeutic intervention, preventing secondary genetic events rendering proliferating tumor cells less treatable; and may permit intervention before organ dysfunction becomes irreversible. Moreover, EBV‐DNA load monitoring could allow for pre‐emptive reduction of immunosuppression, possibly preventing subsequent PTLD onset . Indeed, in the immunocompetent host, the EBV genome is immortalized, forming an episome in latently infected B‐cells.…”

Section: Discussionmentioning

confidence: 99%

Post‐transplant lymphoproliferative disease in lung transplantation: A nested case‐control study

Leyssens

Dierickx

Verbeken

et al. 2017

Clinical Transplantation

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Post-transplant lymphoproliferative disorder (PTLD) may compromise long-term outcome of lung transplant (LTx) recipients. A case-control study was performed, comparing LTx recipients with PTLD (n=31) to matched recipients without PTLD (Controls, n=62). Risk factors for PTLD and post-transplant outcomes were assessed. PTLD prevalence was 3.9%, time to PTLD 323 (166-1132) days; and 54.8% had early-onset PTLD versus 45.2% late-onset PTLD. At LTx, more Epstein-Barr virus (EBV)-seronegative patients were present in PTLD (42%) compared to Controls (5%) (P<.0001); most of whom had undergone EBV seroconversion upon PTLD diagnosis. EBV viral load was higher in PTLD versus Controls (P<.0001). Overall, lower hemoglobin and higher C-reactive protein levels were present in PTLD versus Controls (P<.0001). EBV status at LTx (P=.0073) and EBV viral load at PTLD (P=.0002) were the most important risk determinates for later PTLD. Patients with PTLD demonstrated shorter time to onset of chronic lung allograft dysfunction (CLAD) (P=.0006) and poorer 5-year survival post-LTx (66.6% versus 91.5%), resulting in worse CLAD-free survival (HR 2.127, 95%CI 1.006-4.500; P=.0483) and overall survival (HR 3.297 95%CI 1.473-7.382; P=.0037) compared to Controls. Late-onset PTLD had worse survival compared to early-onset PTLD (P=.021). Primary EBV infection is a risk for PTLD; which is associated with worse long-term outcome post-LTx.

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Epstein–Barr virus load in transplant patients: Early detection of post-transplant lymphoproliferative disorders

Cited by 20 publications

References 21 publications

Incidence, Risk Factors, Clinical Management, and Outcomes of Posttransplant Lymphoproliferative Disorder in Kidney Transplant Recipients

Incidence, Risk Factors, Clinical Management, and Outcomes of Posttransplant Lymphoproliferative Disorder in Kidney Transplant Recipients

Cancer‐attributable mortality among solid organ transplant recipients in the United States: 1987 through 2014

Post‐transplant lymphoproliferative disease in lung transplantation: A nested case‐control study

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