Background: Splenectomy is an effective second line therapy for patients with immune cytopenias. Fifteen percent of patients are going to relapse after splenectomy. These patients are categorized as refractory and their treatment is challenging. The incidence of an accessory spleen diagnosed by gammagraphy is estimated to be 8-20% in this scenario. Current treatment guidelines do not address the issue of searching for an accessory spleen or performing accessory splenectomy as a treatment strategy for these patients. The aim of this study was to identify risk factors for the presence of accessory spleen diagnosed by gammagraphy in patients with refractory immune cytopenias and analyze the response rate of its removal. Methods: It is a case control, single center, retrospective study. We included adult patients with refractory immune cytopenias who underwent gammagraphy to search for an accessory spleen, from 1996 to 2016. Cases were patients with a positive gammagraphy, controls were those with a negative gammagraphy. Patients who failed to have at least one year of follow-up after splenectomy or accessory splenectomy, were excluded. A logistic regression was performed to determine factors associated with the presence of an accessory spleen. Results: We analyzed 71 refractory patients with a gammagraphy performed searching for an accessory spleen, 87.3% with a diagnosis of immune thrombocytopenia (IT), 7% autoimmune hemolytic anemia (AHA) and 5.6% Evans Syndrome. Fourteen percent of the patients had secondary immune cytopenias all of them due to autoimmune diseases. There was a predominance of women with 74.6% of the subjects studied. Patients received a median of 2 (0-4) lines of treatment before the splenectomy. The majority of patients (98.6%) had received, as first line of treatment corticosteroids, with an overall response rate (ORR) of 84% and a complete response (CR) rate of 38.6%. Of the 71 patients, splenectomy achieved an ORR of 83.1% with CR in 80.3%. The incidence of accessory spleen diagnosed by gammagraphy at their relapse was 15.5% (11 patients). In the multivariate analysis, we found two factors associated with positivity of the gammagraphy: CR to corticosteroids pre-splenectomy with an OR of 5.2 (CI 95% 1.24-21.78; p=0.021) and the presence of Howell Jolly bodies (HJb) with an OR of 0.088 (CI95% 0.02-0.37; p=0.001) as a protective factor. We developed a risk score consisting of: 0 risk factors, 1 risk factor (CR to corticosterois pre-splenectomy or abscense of HJb) and 2 risk factors. The percentage of patients who were positive by gammagraphy using this score was 83.3%, 25.6% and 3% for 2, 1 and no risk factors respectively (p<0.001) (Figure1). Eight patients underwent accesory splenectomy, all of them achieved responses with CR of 87.5%, and none experienced complications associated with the procedure. Seven patients acquired the presence of HJb after accesory splenectomy (Table 1). With a median follow-up of 60.2 months (1.54-194.56), 62.5% mantained the response obtained with the accesory splenectomy. One patient didn´t acquire HJb post accesory splenectomy, he relapsed and was diagnosed with a new accesory spleen. He underwent a second accesory splenectomy and is now in CR with the presence of HJb in the blood smear. Conclusions: The search for an accesory spleen in patients with refractory immune cytopenias with risk factors (absence of Howell Jolly bodies and or complete response to steroids as first line therapy) is usefull. Accesory splenectomy is a safe and effective therapeutic strategy in the treatment of these patients. Disclosures No relevant conflicts of interest to declare.

Background Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapy for acute leukemia (AL) with the potential to achieve long-term remission. Nevertheless, relapse remains the main cause of mortality after allo-HSCT. Isolated extramedullary relapse (iEMR) is defined as the presence of clonal blasts in tissues other than the medullary compartment, in the absence of bone marrow relapse (BMR) and with full donor chimerism. Reports on its prevalence and risk factors are rare and its implications on prognosis and treatment continue to be an area of active study. Our aim was to describe the rates, clinical characteristics, and outcomes of patients with iEMR in the post-allo-HSCT setting. Methods Retrospective multicenter study that included patients ≥15-years-old diagnosed with AL who underwent allo-HSCT with chemotherapy-only conditioning regimens between 1999-2019. Patients referred to participating centers after HSCT and those with incomplete medical records were excluded. The Kaplan-Meier method was used to construct survival curves, differences between groups were analyzed using the log-rank test, and a standard Cox-regression was carried out for multivariate analysis. Results One hundred twenty-four patients were included with a median follow-up of 12 months (1-158) after allo-HSCT. The most common AL phenotype was lymphoblastic (ALL) in 66.1% (n=82). High-risk cytogenetics were present in 23.9% (n= 28). Twenty-three patients (18.5%) had a history of extramedullary disease (EMD) prior to allo-HSCT, CNS being the most common site in 52.2% (n=12). Additional baseline characteristics are presented in Table 1. Median overall survival (OS) for the cohort was 15 months (1-158). Factors related to decreased OS on univariate analysis are shown in Table 2. Independent risk factors for mortality were: belonging to the non-AYA group (HR 4.7,95%CI 1.6-13.3; p=0.004), grade III-IV acute GVHD (HR 3.9, 95%CI 1.6-9.8; p=0.003), and absence of chronic GHVD (HR 10.3, 95%CI 3.4-30.9; p<0.001). Sixty-seven patients (54%) relapsed after allo-HSCT with a median time to relapse of 13 months (1-158). Of these, 19 (28.4%) had EM involvement, of which 16 (23.9%) had iEMR. All cases of iEMR occurred in patients with ALL. The most commonly involved EM sites were CNS in 47.3% (n=9), skin in 26.3% (n=5), and breast in 15.8% (n=3). Of patients with post-allo-HSCT CNS relapse, 85.7% (n=6) had prior history of pre-HSCT CNS EMD. Post-relapse therapy was administered to 76.1% (n=51), including a second allo-HSCT in 25.5% (n=13), the remaining patients transitioned to palliative care. Median relapse free survival (RFS) was 13 months (1-124). Factors demonstrating a protective role are described in Table 2. On multivariate analysis, early disease stage at time of HSCT (HR 0.35, 95% CI 0.18-0.71; p=0.003) and the development of chronic GVHD (HR 0.29, 95% CI 0.15-0.54; p<0.001) had a positive impact on RFS. The median OS after relapse was 4 months (2.6-5.3). Factors related to increased survival on univariate analysis are described in Table 2 and in Figure 1. On multivariate analysis, an iEMR (HR 0.13, 95% CI 0.026-0.67; p= 0.015), as compared to a relapse with a medullary component, and a complete remission after post-relapse therapy (HR 0.095, 95%CI 0.039-0.233; p<0.001) positively impacted OS. Conclusion Isolated EMR was highly prevalent in our population as compared to historical cohorts. This reflects differences in Latin American AL epidemiologic distribution, with high representation of ALL, and our limited access to conditioning regimens based on total body irradiation. Patients that had an iEMR and achieved treatment response had improved survival outcomes which may reflect a more indolent biology allowing the clinician time to implement therapy intensification interventions. Additionally, in our setting, escalation of pre-HSTC therapy to achieve deeper responses and tailoring HSCT, in combination with post-HSCT CNS prophylaxis, are potential strategies that should be pursued further. Disclosures No relevant conflicts of interest to declare.