A Multicenter Survey on Post-Transplant Lymphoproliferative Disorders in Pediatric Heart Transplant Recipients: A Case for Development of Consensus Guidelines for Screening, Surveillance and Treatment?

Abstract

Post-transplant lymphoproliferative disorders (PTLD) are a significant cause of morbidity and mortality following pediatric orthotopic heart transplant (OHT), with a reported incidence of 5-20%. In the absence of accepted guidelines, we sought to identify the overall trends in North American pediatric transplant centers in the screening, diagnosis, treatment, and follow-up of PTLD. All 56 Pediatric Heart Transplant Society (PHTS) institutions were asked to complete an anonymous survey in March 2019. No identifiable patient information was shared. From 56 PHTS centers, 22 responses were received (39.3%). 100% indicated that PTLD cannot be diagnosed solely based on elevated EBV load. All respondents routinely screen for Epstein Barr virus (EBV) by qualitative or quantitative EBV PCR, but the frequency of screening varies widely - some screen each visit, others once annually. Twelve of 19 (63.2%) obtain CT and/or PET evaluation for PTLD when EBV load is substantially or persistently elevated, whereas 5 of 19 (26.3%) also require clinical suspicion that PTLD is developing before obtaining imaging. Most centers require a positive biopsy to establish a diagnosis of PTLD (14 of 18, 77.8%), but many will reduce immune suppression in response to a persistently elevated EBV load without pathologic evidence of PTLD (16 of 22, 72.7%). Beyond reduction in immune suppression, rituximab is the most commonly used treatment agent used (9 of 13, 69.2%). Subspecialty consultation with pediatric oncology (17 of 17, 100%) and infectious disease (ID, 8 of 17, 47.1%) are common, but the timing of such consultation varies widely, some triggered by the diagnosis of EBV viremia (2 oncology, 5 ID), others only in rituximab-refractory PTLD (1 oncology). Our survey highlights significant practice variation amongst PHTS institutions in screening, diagnosing and treating PTLD in pediatric OHT patients. Reduction in immune suppression prior to pathologic diagnosis of PTLD is common but not universal. Treatment with rituximab is most often reserved until after establishing the PTLD diagnosis. This study highlights the need for multi-center collaboration to develop evidence-based guidelines for screening, treatment and surveillance of pediatric PTLD.