Single-institution Retrospective Analysis of Prognostic Factors Influencing Very Late-onset Post-transplant Lymphoproliferative Disorder

Abstract

BackgroundPost-transplant lymphoproliferative disorder (PTLD) is a rare complication following transplant (solid organ or allogeneic) due to the proliferation of lymphoid cells in the immunosuppressed state. The incidence of PTLD follows a bimodal distribution, with high incidence immediately after transplant (early-onset PTLD), followed by a decline and then a high-incidence again five years after transplantation (late-onset PTLD). This study exclusively aims to identify prognostic factors for the subgroup of PTLD, described as very late-onset PTLD, occurring after 10 years of transplant. MethodsThis study was conducted at the University of Florida, with the requisite study population identified through the cancer registry. Data were collected by individual chart review and analyzed. Survival estimates and univariate and multivariate analyses were performed to measure the effects of each variable on overall survival. ResultsA total of 33 patients were identified, with a median age at transplant of 42.3 years, while the median age at PTLD diagnosis was 54.7 years. Median time from transplant to PTLD diagnosis was 13.3 years. Kidney (30.3%), liver (27.3%), and heart (24.2%) transplants were the most common allografts associated with very late PTLD development. The most common pathology was diffuse large B-cell lymphoma (DLBCL) in 45.5% of patients. CHOP+/-R (cyclophosphamide, doxorubicin hydrochloride (hydroxydaunorubicin), vincristine sulfate (Oncovin), prednisone, rituximab) was the most common chemo regimen used as the initial choice in 36.4% of patients.Median survival was 5.4 years. Univariate analysis showed that age at diagnosis over 65, male gender, bone marrow involvement, past medical history (PMH) of malignancy, immunosuppression regimen at PTLD diagnosis, and initial and final best response to treatment were statistically significant (p <0.05) factors associated with survival. On multivariate analysis, bone marrow involvement was significantly associated with poor survival (p=0.008). Surprisingly, performance status, Epstein-Barr virus (EBV) status, pathology type, 1 2 3 3 1 4 5

Characteristics, management, and outcome of pediatric patients with post‐transplant lymphoproliferative disease—A 20 years' experience from Austria

“…The incidence of LPD following transplantations shows a biphasic distribution, with a first peak occurring within 12 months, and another either at 3 to 5 or at 7 to 10 years after transplantation. 11 , 25 , 49 , 50 , 51 , 52 Our study showed that half of the patients presented with early‐onset disease at a median time of 0.44 years and half with late‐onset disease at a median time of 5.61 years after transplantation. In accordance with the literature, all four patients with PTLD after HSCT were diagnosed within the first year after transplantation.…”

Extremely delayed-onset post-transplant lymphoproliferative disorder in a renal transplant patient

“…About 80%–85% of PTLD cases occur within the first year of transplantation 1 3. PTLD tends to follow a bimodal distribution in which there is high incidence in the first year after transplant (early onset), and around 5 years after transplant (late onset) 5. Rarely, PTLD can occur more than 10 years after transplant (very late onset).…”

“…Rarely, PTLD can occur more than 10 years after transplant (very late onset). One retrospective analysis compared patients with very late-onset PTLD compared with those with early and late-onset PTLD 5. The analysis showed that known prognostic factors for early and late-onset PTLD were not statistically significant in very late-onset PTLD, with bone marrow involvement being the only statistically significantly prognostic factor on multivariate analysis 5.…”

“…Other risk factors include older age and Caucasian ethnicity 3. Diffuse large B cell lymphoma (DLBCL) is the most common appearing cancer in PTLD 4 5…”

Natural Killer Cells in Post-Transplant Lymphoproliferative Disorders

“…EBV-negative PTLDs have historically represented a small minority of PTLDs, but their proportion has constantly increased in recent years [ 21 ], currently representing 30–50% of PTLDs depending on different cohorts [ 20 , 21 , 61 , 62 , 63 ]. As EBV-negative PTLDs develop late after transplantation, 5–10 years or more [ 64 ], the identification of predictive biomarkers, and therefore prevention, is difficult. EBV-negative PTLDs generally present as aggressive monomorphic lymphomas ( Table 1 ).…”