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Published on: May 10, 2017
Risk factors for post-transplant lymphoproliferative disorder in pediatric patients: a case-control study
Upton D Allen1, Gabrielle Farkas, Diane Hébert
1Division of Infectious Diseases, The Department of Pediatrics, Hospital for Sick Children, University of Toronto, Ontario, Canada. upton.allen@sickkids.ca
Insights
Post-transplant lymphoproliferative disorder (PTLD) is a risk after pediatric transplants. Higher Epstein-Barr Virus (EBV) loads increase PTLD likelihood, even in EBV-seropositive recipients, indicating broader risk factors beyond initial serostatus.
Area of Science:
- Pediatric Transplantation
- Virology
- Immunology
Background:
- Post-transplant lymphoproliferative disorder (PTLD) is a significant complication following pediatric organ transplantation.
- Epstein-Barr Virus (EBV) is a primary driver of PTLD, with EBV-seronegative recipients of EBV-seropositive organs being at highest risk.
- However, risk factors among EBV-seropositive recipients remain less defined.
Purpose of the Study:
- To investigate risk factors for PTLD in pediatric transplant recipients.
- To compare clinical, virologic, and immunosuppressive profiles of PTLD cases and controls.
- To identify specific patient groups, including EBV-seropositive recipients, at risk for PTLD.
Main Methods:
- A case-control study design was employed, matching PTLD cases with two controls based on organ type and transplant period.
- Biopsy-proven PTLD cases were identified over a four-year period (1997-2000).
- Clinical, virologic (including EBV viral load), and immunosuppressive data were compared between cases and controls.
Main Results:
- Twenty-two PTLD cases were diagnosed, occurring at a median of 22.8 months post-transplantation.
- PTLD cases exhibited significantly higher mean baseline EBV loads compared to controls (3.1 log(10) vs. 1.6 log(10)/10^6 PBMCs).
- Each log increase in EBV viral load correlated with a threefold increase in PTLD risk. Approximately 25% of PTLD cases occurred in EBV-seropositive recipients, who tended to be older and had a worse prognosis.
Conclusions:
- Elevated Epstein-Barr Virus (EBV) viral load is a critical risk factor for PTLD in pediatric transplant recipients.
- PTLD occurs not only in EBV-seronegative recipients of EBV-seropositive organs but also in a significant proportion of EBV-seropositive recipients, suggesting broader risk factors.
- Further research is needed to fully elucidate the factors contributing to PTLD development in EBV-seropositive pediatric transplant patients.
Abstract:
Post-transplant Lymphoproliferative Disorder (PTLD) because of the Epstein-Barr Virus (EBV) is a major concern after pediatric transplantation. The group at greatest risk is EBV-seronegative recipients who receive EBV-seropositive organs. Additional risk factors remain to be determined, including those among EBV-seropositive recipients. In this case-control study, PTLD cases were biopsy-proven over a period of 4 yr (1997-2000, inclusive). Each case was matched with 2 controls, based on the type of organ transplanted and the period of transplantation (+/-1 yr). Variables compared between cases and controls included those relating to the clinical and virologic profiles and immunosuppressive therapy. Twenty-two cases of PTLD were diagnosed during the study period. PTLD cases occurred at a median of 22.8 months post-transplantation (range 1-131). The median age of cases was 26.2 months (range 6.1-194) compared with 47.4 months (range 0.8-202.2) for controls (p = 0.93). Cases had a higher mean baseline EBV load compared with controls (3.1 log(10) (s.d. +/- 1.0) vs. 1.6 log(10)/10(6) PBMCs (s.d. +/- 1.4), with every 1 log increase in viral load resulting in a three times increase in the likelihood of PTLD (p < 0.007). Close to one in four cases of PTLD were EBV-seropositive pretransplantation. These seropositive recipients tended to be older patients with a trend to a worse outcome compared with their seronegative counterparts. The occurrence of PTLD was not associated with the use of any specific immunosuppressants. A significant proportion of PTLD cases occurred among EBV-seropositive transplant recipients, with a tendency towards an unfavorable outcome. Besides EBV-seronegative recipients who receive seropositive organs, some EBV-seropositive pediatric patients are at risk of PTLD. Additional studies are warranted to further define the factors associated with PTLD in EBV-seropositive transplant recipients.
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