Relationship of Post-Transplant Lymphoproliferative Disorders (PTLD) Subtypes and Clinical Outcome in Pediatric Heart Transplant Recipients: A Retrospective Single Institutional Analysis/Experience of 558 Patients

Abstract

Post-transplant lymphoproliferative disorders (PTLD) are heterogenous lymphoproliferative disorders that develop as a consequence of immunosuppression in transplant recipients. We sought to determine if subtypes of PTLD correlated with different outcomes. We performed a retrospective review of PTLD occurring in pediatric heart transplant recipients. A total of 558 children and infants underwent cardiac transplantation at our institution between 1985 and 2019 and were followed until March 2021. Forty-nine of 558 patients developed PTLD (8.8%). As compared to older children (>one year of age), infant recipients (<three months of age) were less likely to develop PTLD. Monomorphic PTLDs (M-PTLD, 61%) was the most common subtype at initial diagnosis, followed by non-destructive (21%), polymorphic (14%), and classic Hodgkin lymphoma (cHL, 4%). Patients who underwent transplantation at a young age (<three months) had significantly lower rates of M-PTLD or cHL and a longer time from transplant to PTLD diagnosis as compared to children older than one year at transplant (p = 0.04). Although not reaching statistical significance, patients with a shorter time to PTLD diagnosis showed a trend toward higher rates of M-PTLD or cHL. As expected, the overall survival (OS) of patients with M-PTLD or cHL was significantly lower than patients with non-destructive or polymorphic PTLD.

Post-transplant Lymphoproliferative Disorder (PTLD) in the US Population With Demographics, Treatment Characteristics, and Survival Analysis

“…In line with previous studies, polymorphic PTLD was found to be the predominant subtype in children [6], although some report that the monomorphic subtype is the most common [10]. In a study of pediatric heart transplants, non-destructive and polymorphic PTLD showed higher survival rates than the monomorphic and classical Hodgkin lymphoma subtypes [11]. However, a recent study of adult PTLD patients found no differences in survival between subtypes [16].…”

“…Non-destructive PTLD is characterized by preserved lymph node architecture and can have benign polyclonal plasmacytic hyperplasia, infectious mononucleosis-like features, or florid follicular hyperplasia. Polymorphic PTLD makes up around 14% of PTLD [11]. Polymorphic PTLD effaces tissue architecture by a pleomorphic lymphoid infiltrate comprised of cells along the spectrum of B cell maturation.…”

Successful Treatment of Refractory Post-Transplant Lymphoproliferative Disorder With Chimeric Antigen Receptor T-Cell Therapy in a Heart Transplant Recipient

“…When PTLD develops, the treatment strategy depends on pathological categorization as well as transplant type. PTLD can be classified using the 2017 World Health Organization (WHO) criteria and 2022 International Consensus classification (ICC) into four categories: non-destructive, polymorphic, monomorphic (B-cell, T-cell, natural killer (NK)-cell types), and classic Hodgkin lymphoma [9]. Since PTLD is associated with increased immunosuppression, the first-line treatment for most categories includes decreasing immunosuppressive therapy [10].…”

The pathobiology of select adolescent young adult lymphomas

“…Factors such as younger age and lesions located in the head and neck are usually associated with a better prognosis. However, outcome correlations with other factors such as EBV tumor status are not as reliable [25–28, 38, 39]. Thus, further investigations into PTLD pathogenesis, particularly those lesions arising in young patients, is needed.…”

“…The location of disease is also somewhat different. Although both adults and younger patients tend to develop disease in extranodal sites, particularly the gastrointestinal tract, there is a predilection for disease to present in the head and neck region, particularly in the tonsils, adenoids and/or cervical lymph nodes in younger patients [11,12,[25][26][27][28][29][30][31][32][33][34][35][36], a pattern of disease that is suggestive of a primary EBV infection [11,12,25,26,28,29,[31][32][33][34]36]. In contrast, PTLDs occurring in adults are more often EBV negative and tend to be more often negative the farther out from transplantation they occur [32][33][34].…”