ALBERT

Description: Introduction: Post-transplant lymphoproliferative disorders are a rare heterogenous group of diseases occurring in the setting of post-transplant immunossupression (IS). Clinically, extranodal involvement is common, and it occurs in the central nervous system (CNS) in approximately 7-15% of cases. Most data on PTLD-CNS are based on case series/reports and due to paucity of data no treatment algorithms have been established. In our series, we retrospectively analyzed 23 consecutively cases of PTLD-CNS in Hospital do Rim, Sao Paulo, Brazil. Methods: We retrospectively reviewed all cases of PTLD-CNS diagnosed between 2001 and 2014 at Hospital do Rim (HRim), a school hospital from the Federal University of São Paulo, Brazil. HRim is considered the leading renal transplant hospital in the world for the past 15 years. For this study, only PTLD patients with tumors whose histology could be confirmed by hemopathologist review, EBV-association established and whose clinical, epidemiological and laboratorial parameters could be retrieved were included in this study. Response was defined as complete (CR) or less than CR (partial response or refractory disease). Event was defined as treatment related mortality, progression (defined as time for initiation of second-line therapy) or relapse. Results: From 2001 to 2014, from a total of 98 PTLD patients, 23 patients (23%) were diagnosed with PTLD-CNS. Median age at time of diagnosis was 36, with a male:female ratio of 0.9:1. Fifteen (65%) patients received anti-thymocyte globulin (ATG) at the time of transplant and 17 (74%) had at least one episode of acute rejection. The most common immunossupressive regimen (IR) consisted of cyclosporine or tacrolimus associated with prednisone and azathioprine (15, 65%). Median time from transplant to PTLD diagnosis was 31 months (ranging from 8.4 to 153). EBV was positive in tumor lymphocytes by in situ hybridization in 21 cases (91%). Monomorphic cases were diagnosed in 21 (91%) patients. All patients had their IR reduced, usually with suspension of azathioprine and calcineurin inhibitors and change from prednisone to dexamethasone, 19 (82%) patients underwent WBRt (from 25 to 40 Gy) together with intra-thecal (IT) chemotherapy with methotrexate (MTX) 12mg and dexamethasone 2mg. Only 1 patient received high dose MTX and died due to treatment-related toxicities 1 month after diagnosis and 2 patients died before starting WBRt due to disease progression and poor performance status (PS). For those patients who received WBRt together with IT chemotherapy, fourteen patients (74%) had CR, 2 patients (10%) had refractory disease and 3 patients (16%) had relapsed disease within 2 years. Overall Survival (OS) for the group treated with WBRt and IT chemotherapy was 62% in 5 years (CI95% 69-82%). In our series, induction therapy with ATG and acute rejection were associated with increased risk of PTLD-CNS. Age and PS at diagnosis were the only 2 factors predictive of survival. No serious cognitive impairment was identified among the survivors. Conclusions: The current study demonstrated that PTLD-CNS is a serious late EBV-induced B-cell lymphoma, mostly monomorphic with an incidence of 23%, higher than previously described in the post renal transplant setting. Treatment with immunossupression reduction, intrathecal chemotherapy and whole-brain radiotherapy showed a high CR rate with favorable survival in many cases. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Post-Transplant Lymphoproliferative Disease (PTLD) is a rarewell-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. Optimal risk stratifications specific to kidney transplantation are still lacking. Patient and Methods: In our series, we retrospectively analyzed 98 consecutively cases of PTLD diagnosed between 2001 and 2014 at Hospital do Rim (HRim), a school hospital from the Federal University of São Paulo, São Paulo, Brazil. HRim is considered the leading renal transplant hospital in the world for the past 15 years. For this study, only PTLD patients with tumors whose histology could be confirmed by hemopathologist review, EBV-association established and whose clinical, epidemiological and laboratorial parameters could be retrieved were included in this study. Response was defined as complete (CR) or less than CR (partial response or refractory disease). Event was defined as treatment related mortality, progression (defined as time for initiation of second-line therapy) or relapse. Patients with conflicted data or loss of follow up were excluded. Results: A total of 98 patients were diagnosed with PTLD from 7665 renal transplants performed in this period, with a incidence of 1,3%. Two patients were excluded from the analysis due to conflicting 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 diagnosis was 56 months (range 1-967). Thirty-six patients (37.5%) received anti-thymocyte globulin (ATG), and the most common immunossupressive regimen (IR) consisted of cyclosporine or tacrolimus associated with prednisone and azathioprine (66, 69%). Monomorphic PTLD was observed in 75 (78%) patients, and two patients presented with HL. EBV positivity was seen in 67 patients (70.5%), being more frequent within PTLD cases diagnosed during the first 3 years of transplantation (90%). All patients had their IR reduced after PTLD diagnosis. The incidence of loss of engraftment following IR reduction was 19% (20 patients). Overall responses were: CR in 67% (n=64) and Partial response/Refractory disease in 33% (n=32); 30 patients died due to treatment-related toxicity and/or disease progression. Overall Survival (OS) for the entire group was 63% in 5 years (CI95% 73-83%), with a progression free survival (PFS) of 58% (CI95% 91-97%). EBV positivity was seen in 67 patients (70.5%). Median number of extra nodal sites involved was 1,2. The median overall survival time was 97 months. Patient survival following diagnosis was 77% at 1 year, 63% at 5 years and 38% at 10 years. The most common extra-nodal sites involved were: Gastro-intestinal Tract (43, 45%) followed by Central Nervous System (23, 24%). Extra nodal involvement was correlated with poorer outcome (p 0.014) as was the loss of engraftment (p

Description: 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. Disclosures No relevant conflicts of interest to declare.