Lymphocyte/Monocyte Ratio (LMR) at Diagnosis Is Predictive of Survival with Post Transplant Lymphoproliferative Disease (PTLD) after Renal Transplant: An Analysis of 96 Patients of a Brazilian Cohort

Introduction: Post-Transplant Lymphoproliferative Disease (PTLD) is a well-recognized group of lymphoid and or plasmacytic proliferations that occur following both solid organ (SOT) and allogenic hematopoietic stem cell transplantation (HSCT) as a result of immunossupression. A continuum of disease has been described, including early lesions, polymorphic PTLD and monomorphic PTLD. Epstein-bar virus (EBV) is considered the most important causative factor, with EBV positivity observed within up 90% of tumor lymphocytes. There is paucity of prognostic factors in PTLD, but studies have shown that IPI, Performance status and number of disease sites are related to mortality. LMR has shown to be prognostic in different lymphomas, including Hodgkin's Lymphoma (HL), Diffuse Large B-cell lymphomas among others.

Objectives: To assess the role of lymphocyte/monocyte ratio at diagnosis in predicting outcome and survival in PTLD patients.

Patient and Methods: This is a retrospective study conducted by the Universidade Federal de São Paulo, São Paulo, Brazil. Only confirmed cases of PTLD, diagnosed from 2001 to 2015, with clinical, epidemiological and laboratorial parameters available were included in this study. Event was defined as treatment related mortality, progression (defined as time for initiation of salvage therapy) or relapse. Patients with conflicted data or loss of follow up were excluded from the analysis.

Results: A total of 98 patients were diagnosed with PTLD in the study period. Two patients were excluded from the analysis due to conflict clinical data. Median age at diagnosis was 41.4 years (range from 4-74), with a 0,6:1 Female:Male ratio. Median time of transplant to PTLD was 56 months (range 0-967). Twenty-six patients (27%) received anti-thymocyte globulin (ATG), and the most common immunossupressive regimens consisted of cyclosporine or tacrolimus associated with prednisone and azathioprine (68,7%). Monomorphic PTLD was observed in 78% of patients, and two patients presented with HL. With a median follow up of 33.3 months, 35% of patients died. In a univariate analysis, the number of extranodal sites and LMR were associated with worst survival (p=0.026 and p=0.004).

Conclusions: PTLD is a known complication of immunossupresion, usually related to EBV. In our cohort of 96 kidney recipients with PTLD, LMR and number of extranodal sites was associated with inferior outcome.