Risk factors for post‐transplant lymphoproliferative disorder in pediatric patients: A case‐control study

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.

Improved Survival with Recent Post-Transplant Lymphoproliferative Disorder (PTLD) in Children with Kidney Transplants

“…Boyle et al reported a 43% survival among pediatric heart transplant recipients (23) and Newell et al reported 60% survival among pediatric liver transplant recipients (24), both studies published in the 1990s. Allen et al found a 2-year mortality of 36% in children with PTLD in a group of diverse organ transplants (14). More recent studies suggest improved survival after PTLD in this decade even in nonkidney organ transplants (80% in the series by Younes et al, only 18% early mortality in series of Fernandez et al; [22,25]).…”

Early onset, EBV− PTLD in pediatric liver-small bowel transplantation recipients: a spectrum of plasma cell neoplasms with favorable prognosis

“…1,5,6 Polyclonal plasma cell hyperplasia is a relatively common presentation of early PTLD, whereas frank plasmacytomas and multiple myelomas are rarely described in pediatric SOT recipients. 1 We describe a unique group of pediatric patients with EBV Ϫ plasma cell PTLDs with morphology ranging from atypical plasma cell hyperplasia to plasmacytoma-like lesions.…”

“…1 EBV seronegativity at the time of transplantation is one of the main risk factors for PTLD development, and a large number of children undergoing transplantation are EBV naive. 6 Although most PTLDs are EBV ϩ , reports of EBV Ϫ cases are increasing. 1 EBV Ϫ PTLD is more common in adults than children, tends to occur late after transplantation, and is more commonly monomorphic.…”

Using Epstein-Barr Viral Load Assays To Diagnose, Monitor, and Prevent Posttransplant Lymphoproliferative Disorder

“…A higher mean baseline EBV load correlates with heightened risk of PTLD or recurrent PTLD (7,19). Other investigators propose combining EBV DNA measurement with a complementary test, such as EBV-specific T cell enumeration as measured by a peptide tetramer or enzyme-linked immunosorbent spot, EBV serology, reverse transcription-PCR (RT-PCR) targeting EBV transcripts, cytokine gene polymorphism, ATP release, gammopathy by serum protein electrophoresis, microarray-based expression profiles, and CD20 or CD4/CD8/NK cell counts (6,10,17,25,53,107,112,117,123,151,158,166,173,177,192,207,211,213).…”

“…EBV is capable of driving B cell proliferation in vitro to form immortalized cell lines and also in vivo when immune surveillance is inadequate (119,179). In the setting of allogeneic transplantation when iatrogenic immunosuppression is used to prevent graft rejection, an unintended consequence is failure to suppress active EBV infection, which is accompanied by a heightened risk of developing PTLD (7,61,154,167,185,198). PTLD is a potentially life-threatening neoplasm exhibiting a spectrum of histopathologies ranging from reactive-appearing, polyclonal lymphoid infiltrates to sheets of undifferentiated cells that are morphologically indistinguishable from malignant lymphoma or plasma cell myeloma.…”