Clinicopathologic Characteristics, Treatment, and Outcomes of Post-transplant Lymphoproliferative Disorders: A Single-institution Experience Using 2017 WHO Diagnostic Criteria

Abstract

The World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues (WHO 2017) included updated criteria for diagnosis and classification of post-transplant lymphoproliferative disorders (PTLDs). This study evaluated the clinicopathologic spectrum using WHO 2017 criteria and adult PTLD patients’ outcomes over 30 years between 1987 and 2017 at Mayo Clinic (Rochester, MN). Patients were retrospectively reviewed for clinical features, outcomes, and diagnostic pathology material and classified based on WHO 2017 criteria. A total of 227 patients were diagnosed with PTLD, with a median time from transplant to PTLD of 45 months. PTLD occurred >1 year after transplant in 149 (66%) patients. Monomorphic PTLD was the most common subtype (173, 76%), with diffuse large B cell lymphoma as the commonest morphology (n = 137). Epstein-Barr virus was positive in 61% of total cases and 90% of PTLD that developed within 1 year from transplant. The median event-free survival (EFS) and overall survival for the entire cohort were 21 months (95% confidence interval [CI]: 9–35) and 82 months (95% CI: 39–115), respectively. The EFS or overall survival was not impacted by Epstein-Barr virus status but differed based on WHO subtypes and year of diagnosis. Management changed over time with increased use of rituximab or chemotherapy + immunosuppression reduction as initial therapy. When compared to the matched general population and de novo diffuse large B cell lymphoma, patients not achieving EFS 24 status (no progression/treatment or death within 24 mo of diagnosis) had a worse standardized mortality ratio 16.75 (95% CI: 13.91–20) versus SMR 1.72 (95% CI: 1.26–2.28) in those who achieved EFS24. Cause of death was mostly attributed to non-lymphoma–related causes in those achieving EFS 24.

New concepts in EBV-associated B, T, and NK cell lymphoproliferative disorders

“…In a recent large single-institution study, CHL PTLD had the best prognosis of all the destructive type PTLD with a 2-year point estimate overall survival of 1.00 versus monomorphic B cell PTLD (0.62) and polymorphic PTLD (0.69). [68] This is in contrast to what has been reported in OIIA-LPD in patients with rheumatic diseases where overall survival of Hodgkin-type LPD was similar to DLBCL-type, but PFS was worse for the Hodgkin cases. [74]…”

“…The published literature is not consistent in terms of whether patients with polymorphic PTLD have a better prognosis than those with monomorphic PTLD with a recent large study reporting similar overall survivals (see below). [68]…”

Characteristics and Outcome of Post-Transplant Lymphoproliferative Disorders After Solid Organ Transplantation: A Single Center Experience of 196 Patients Over 30 Years

“…11 cases (5.6%) of polymorphic PTLD, which is less than previously reported (3,26,37,42). A more recent report noted a similar rate, with 5.7% polymorphic PTLD in a single center analysis of 227 adult PTLD after SOT (14). Tsai et al also reported that PTLD morphology has changed over the past 3 decades, with a gradual increase in the number of monomorphic PTLD and a steady number of polymorphic PTLD (38).…”

“…However, we observed a significant relation between EBV status and OS in PT-DLBCL, with clinically meaningful improved survival in EBV(-) PT-DLBCL compared to EBV(+) PT-DLBCL (8.8 years versus 2.5 years, respectively). Previous reports have shown conflicting results on the relation between EBV status and OS (13,14,18,25,50,57,58).…”

“…Several single-and multicenter reports have previously been published (11)(12)(13)(14). However, they are often hampered by their heterogenous population and limited numbers of patients.…”