Abstract: Introduction: Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare, but life-threatening, hematological disorder characterized by severe thrombocytopenia, hemolytic microangiopathic anemia, and frequent organ damage. The underlying pathophysiology of aTTP is a functional deficiency of plasma ADAMTS13 activity caused by antibodies directed against the ADAMTS13 protease. Despite plasma exchange (PEX) and immunosuppression with corticosteroids, and, more recently, rituximab, which achieve remission in most patients with aTTP, 10-20% of patients are refractory to treatment and die as a result of disease progression. Most of such deaths occur during first episodes of aTTP, as subsequent relapses tend to be milder. These patients would probably benefit from new therapies aimed at temporarily halting the microvascular thrombosis. This study was aimed at identifying predictive factors of mortality during a first episode of aTTP. Methods: We searched the Spanish TTP Registry (REPTT, Registro Español de la Purpura Trombocitopénica Trombótica) for patients with a clinical diagnosis of TTP (n = 345) with ADAMTS13 activity 〈 10%, and anti-ADAMTS13 inhibitors in plasma (n = 143). Among these, we selected 103 patients with complete information on their first episode of aTTP. The patients were diagnosed between 2004 and 2018, and all were treated with daily PEX and corticosteroids. Additional treatments (rituximab, vincristine, etc.) were used at the discretion of the attending hematologist. Clinical and laboratory data of the episodes were analyzed at diagnosis and during the course of the treatment. The impact of refractoriness, exacerbations (as defined by the international consensus; DOI: 10.1111/jth.13571) and platelet transfusions on mortality was also studied. Results: The 103 patients examined suffered a total of 111 episodes of aTTP (103 with a first episode and 8 with a relapse). Eight deaths (7.7%) took place during an initial episode of aTTP and none during relapses. The time elapsed from the diagnosis to the events of death ranged from a few hours to 36 days (Figure). One patient died before starting the treatment. In the multivariate analysis, stupor or coma at diagnosis was the only clinical and biological factor associated with mortality, as 6 out of 18 patients with stupor or coma died vs. 2 out of 85 without these symptoms (OR: 21.95% CI: 4-114; p = 0.001). Persistently low platelet counts during PEX (i.e. refractoriness) were also strong predictors of subsequent mortality, with a platelet count 〈 20 x109/L after 6 PEX procedures yielding the highest positive and negative values (Table). Exacerbation of aTTP while on treatment occurred in 44 of the 95 patients, all of whom eventually achieved remission with no events of death. Patients with exacerbations required a higher number of PEX procedures to achieve clinical remission (23, IQR: 19-31 vs. 12, IQR: 8-16; p 〈 0.001) and were more likely to receive rituximab (39% vs. 9%; p = 0.001). Platelets were transfused into 16 patients, including 2 patients who died a few days later and 14 survivors. Conclusions: Stupor or coma at diagnosis and lack of response to PEX by the 6th-7th day in patients experiencing first episodes of aTTP are strong predictors of mortality. These patients are candidates for new treatments aimed at controlling the microvascular thrombotic phenomena until effective immunosuppression is achieved. Disease exacerbation does not seem to increase mortality but requires a more intensive treatment. Disclosures De La Rubia: Celgene Corporation: Consultancy; AbbVie: Consultancy; AMGEN: Consultancy; Janssen: Consultancy; Takeda: Consultancy. Pascual Izquierdo:Novartis: Consultancy; Sanofi: Consultancy.

Abstract: Introduction The COVID-19 pandemic has affected the entire world. Health systems have been affected in such a way that patients with diseases other than COVID-19 have suffered serious consequences. In Latin America, the disease has emerged in a fragile system with more disparities, making our patients more vulnerable. Acute leukemia patients have a high risk of severe COVID-19 disease. Various expert recommendations have emerged with the aim of minimizing the risk of COVID-19 without affecting leukemia-related outcomes. However, multiple logistical issues tangentially associated with the pandemic have also appeared, potentially limiting the quality of management of these patients. The objective of this study was to register treatment modifications associated with the COVID-19 pandemic and its short-term consequences in Latin American countries. Methods We included patients older than 14 years, from 14 centers of 4 Latin American countries (Mexico, Peru, Guatemala and Panama), with the diagnosis of acute leukemia, who were on active treatment since the first case of COVID-19 was documented in each country. We documented their baseline characteristics and followed the patients prospectively until July 15, were data-cutoff for this pre-planned analysis was performed. The primary outcome was the incidence of COVID-19 disease and its complications. Secondary outcomes included treatment and consult modifications, and cause of death during the study period. Logistic regression was performed to determine factors associated with COVID-19 and all-cause mortality. Results We recorded the information of 635 patients: 58.1% Ph-negative ALL, 25.7% AML, 9% APL and 7.2% Ph+ALL. The median age was 35 years (14-90 years); 58.8% were consideredf high-risk patients. The majority were on CR (68.3%) receiving consolidation or maintenance therapy, while 14.5% were newly diagnosed and 17.2% with relapsed/refractory disease. The majority (91.8%) were treated in centers that were also receiving COVID-19 patients, 40.2% in centers were patients could not be electively hospitalized for leukemia treatment because of the COVID-19 pandemic. The COVID-pandemic led to treatment-modifications in 40.8% of the cases. Reasons for modifications were associated with logistical issues (22.4%), medical decisions (15.1%) or patient choice (3.3%). The most frequent modification was chemotherapy delay (17.3%) followed by regimen modification (13.4%) and dose-reductions (10.1%). (Figure 1) 83 patients (13.1%) developed COVID-19 disease, the majority mild-moderate disease (54.2%), 27.7% severe disease and 18.1% critically ill; 27.7% required mechanical ventilation and 37.7% died from COVID-19 disease, representing 4.9% of the entire cohort. We identify as risk factors for COVID-19 disease the presence of active leukemia (newly diagnosed or relapsed) (OR 3.46 [95% CI: 2.16-5.5], p & lt;0.001), high-risk leukemia (OR 1.63 [95% CI: 1.54-4.52], p & lt;0.001) and being treated in a center were elective hospitalization was possible (OR 2.17 [95% CI 1.29-3.67], p=0.004). Treatment modifications, appointment prolongations or the use of virtual consultation were not associated with a reduction in the risk of COVID-19. On the other hand, 16.7% of patients died during period analyzed due to leukemia (57.5%), COVID-19 (29.2%) or treatment related-mortality (13.2%). Independent factors associated with mortality were AML vs. ALL (OR 1.89 [95% CI: 1.12-3.18], p= 0.016), relapsed-refractory disease (OR 8.34 [95% CI: 4.83-14.41], p & lt;0.001), induction/consolidation vs. maintenance therapy (OR 2.20 [95% CI: 1.25-3.18], p & lt;0.001) and the use of virtual consultation (OR 0.35 [95% CI: 0.13-0.94] p=0.037). (Table 1) Discussion/Conclusions The COVID-19 pandemic led to significant modifications in the standard of care treatment of patients with acute leukemia. The incidence of COVID-19 disease in acute leukemia patients was considerable and more than a third of the patients with acute leukemia and COVID-19 disease died. Despite a short-follow up, 16.7% of the patients died and leukemia-related deaths were the most frequent. In low- and middle-income countries with fragile health systems, the collateral damage for patients with acute leukemia may be just as important as the direct consequences of COVID-19. Disclosures Alvarado: Roche: Speakers Bureau; Novartis: Speakers Bureau; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Alexion: Speakers Bureau. De la Peña-Celaya:Amgen: Speakers Bureau; Janssen: Speakers Bureau; Novartis: Speakers Bureau. Perez:Roche: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau. Gomez-Almaguer:Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Abstract: Background: Acute Myeloid Leukemia (AML) is the most common acute leukemia in adults in the United States with an incidence of 3 to 5 cases per 100,000 population [Siegel RL, CA Cancer J Clin 2018)]. Even though advances in therapies have increased the survival and improved outcomes in younger population, patients over 65 years of age carry a particularly poor prognosis. Previous results of treatment outcomes in AML have showed significant differences between low- and middle-income countries (LMIC) and high-income countries (HIC). The aim of this study is to assess survival rate for patients with diagnosis of AML in a single center in Colombia, South America. Methods: A retrospective cohort study was conducted at a tertiary referral center in Colombia on patients older than 15 years who were diagnosed with AML between July 2013 and November 2017. All patients were managed based on PETHEMA protocol for AML. Descriptive statistics were used to analyze patient's demographic characteristics. The Kaplan-Meier method was used to assess overall survival (OS) and relapse-free survival (RFS) rates at one and five years. Results: One hundred and seventeen patients were included. Fifty-nine were male (50.42%) and 58 were female (47.6%) with a mean age of 63 years (range 15-95). The most common type of AML based on the French-American-British (FAB) classification was M2 (AML with maturation) in 22.8% of the patients, followed by M1 (AML with no maturation) in 10.5%, and M5 (acute monoblastic leukemia with or without maturation) in 8.8% of the patients; however, classification data was missing in several of the patients (45.6%). OS was 54.6% (CI95% 44.4-63.7) at one year and 19.5% (CI95% 10.3-30.9) at five years. RFS was 91.4% (CI95% 84.0-95.4) at one year and 83.3% (CI95% 73.9-89.5) at five years. Classifying patients by age group, OS was 81.8% (CI95% 68.7-89.7) at one year and 36.5% (CI95%19.6-53.6) at five years for patients younger than 65 years, 22.8% (CI95% 10.8-37.5) at one year and 0% at five years for those between 60 and 80 years, and 19.1% (CI95% 1.4-52.4) at one year and 0% at five years for patients older than 80 years. While median OS for patients who achieved complete response after induction regimen was 35.7 months, it was only 8.9 months for those with either partial response or induction failure (HR 1.03, CI95% 1.01-1.05, P 〈 0.01). Median OS by type of treatment was 32 months for idarubicin + cytarabine (3+7), 7 months for FLUGA - fludarabine + cytarabine, and 1 month for those who only received supportive therapy. Only four patients, all older than 60 years, received treatment with hypomethylating agents, none of them achieving any response. The most common cause of death was disease progression (26%), followed by infection (22%). Conclusions: Patients with diagnosis of AML receiving standard combination chemotherapy with idarubicin and cytarabine had better survival rates than patients receiving semi-intensive chemotherapy schemes. The most common cause of death in AML patients was primary disease, and treatment-related mortality was low. Disclosures Montesinos: Novartis: Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy, Speakers Bureau.

Abstract: Background: Survivors of hematopoietic stem cell transplantation (HSCT) are 2 to 4 times more likely to develop cardiovascular diseases, accounting for 2-11% of mortality among long-term survivors. Early diagnosis and treatment of modifiable risk factors, such as arterial hypertension, are imperative in this group of patients. The aim of this study is to evaluate the prevalence and associated factors for arterial hypertension following HSCT in a Colombian population. Methods: A retrospective study was conducted in 220 consecutive adult HSCT recipients who underwent transplantation between 2009 and 2017 at a third level referral center in Colombia. Blood pressure data, from two different measures, were collected at 7 time points: day of mobilization for autologous HSCT (auto-HSCT) and day 0 before infusion for allogeneic HSCT (allo-HSCT), day 7, and months 1, 3, 6 and 12 post-HSCT. Arterial hypertension was defined as a systolic blood pressure 140mmHg and/or a diastolic blood pressure 90 mmHg. Patients with history of arterial hypertension were excluded. Descriptive statistics were used to analyze patient's demographic data. Bivariate and multivariate analyses were performed to assess the association between clinical characteristics and arterial hypertension. Results: One hundred and seventy-one patients were included, with a median age of 45 years (range 18-71). Eighty-nine patients (52.1%) were male. One hundred and fifteen patients (67.3%) underwent auto-HSCT and 56 (32.7%) allo-HSCT. The most common indication for HSCT were lymphomas (39.8%), followed by leukemia (28.6%) and multiple myeloma (23.4%). Thirty-six patients (21.1%) developed arterial hypertension by the end of the first year of follow-up. Prevalence of hypertension at each time point was 2.3% on day 7 post-HSCT, 4.7%, 5.3%, 5.5% and 8.1% at 1, 3, 6 and 12 months respectively. Allo-HSCT (P 〈 0.001), diagnosis of leukemia (P 〈 0.001) or lymphoma (P 〈 0.05), therapy with calcineurin inhibitors (P=0.004), prophylactic treatment for GvHD with mycophenolate (P 〈 0.05) and acute GvHD (P 〈 0.001) were significantly associated with the development of arterial hypertension. After performing multivariate regression analysis to identify arterial hypertension associated factors, patients with allo-HSCT were found to be 3 times more likely to develop arterial hypertension than patients with auto-HSCT (95% CI 1.85-8.60, P=0.000). Conclusions: Screening for arterial hypertension is warranted in HSCT survivors since it is a modifiable cardiovascular risk factor. Similar to previously reported findings, we found an association between post-HSCT arterial hypertension and allo-HSCT, use of calcineurin inhibitors and mycophenolate, and development of acute GvHD. Patients undergoing allo-HSCT are at increased risk of developing hypertension. Disclosures Sandoval-Sus: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

Abstract: Introduction: Myelodysplastic syndromes (MDS) comprise a varied group of clonal myeloid neoplasms characterized by cytopenias and an increased risk of progression to acute myeloid leukemia. Prognosis is variable, but little is known about the clinical features of MDS in the Colombian population. The diverseness of the disease and changes in standardized diagnostic criteria throughout the years have hinder accurate case detection and epidemiologic evaluation of MDS in our population. Objective: The aim of the present study was to determine the clinical characteristics and evaluate the overall survival (OS) of patients with MDS treated at two large referral centers in Colombia. Methods: An observational, retrospective study was conducted at two tertiary care centers in Colombia. Patients diagnosed with MDS at Clinica FOSCAL and Hospital San Jose between June 2013 and June 2019 were selected. Descriptive statistics were used to analyze baseline demographic characteristics and clinical data such as disease classification, risk stratification, and treatment. The Kaplan-Meier method was used to assess overall (OS) at 1, 3 and 5 years. Results: A total of 96 patients were included. Median age at diagnosis was 75 years (range 31-104). Fifty-two (54.2%) patients were male. According to the 2016 World Health Organization classification of MDS, the most commonly diagnosed subtype was MDS with multilineage dysplasia (31.2%), followed by MDS with excess blasts (13.5%); however, 35.4% of patients had an unclassifiable MDS sub-type. Twenty-nine (31.2%) patients were screened for cytogenetic abnormalities, the most common chromosomal abnormalities were deletion in the long arm of chromosome 5 (4.2%) and deletion of 7q (2.1%). Therapy related MDS was diagnosed in 13 (13.5%) patients and secondary MDS associated to pesticides exposure in 2 (2.1%) patients. After stratifying patients by the International Prognostic Scoring System (IPSS), the majority of patients were in the intermediate risk group, with 21 (34.4%) and 16 (26.2%) patients in the intermediate-1 and intermediate-2 categories respectively. Almost 80% of the patients presented one or more comorbidities, the most common was cardiac disease (30.5%). Supportive care with erythropoiesis-stimulating agents was the most common first-line treatment (61.4%), followed by iron chelation therapy (6.2%). Forty-eight (50%) patients were treated with hypomethylating agents (HMA), 43.7% receiving azacytidine and 6.3% decitabine. Among HMA-treated patients, 49.6% were in the intermediate-2 and high-risk IPSS groups. Two patients underwent allogeneic hematopoietic stem cell transplantation. Only patients treated with HMA and cytarabine/idarubicin chemotherapy achieved a complete response (11.5%). OS at one- and five-years post-diagnosis was 73.4% and 40.7% (95%CI 62.4-81.6 and 27.1-53.9) respectively. Patients in the intermediate-2 and high-risk IPSS groups had lower survival rates compared to those in the low and intermediate-1 risk groups. The OS for patients treated with azacytidine was 77.2% (95%CI 60.7-87.5%) at one-year, 43.2% (95%CI 23.9-61.1%) at three-years, and 37.8% (95%CI 19.0-56.5) at five-years after diagnosis. The most common cause of death was infection (51.3%), followed by disease progression (24.3%). Conclusions: The OS of patients with MDS in our study is similar to the reported in the existing literature. Knowing the epidemiology, clinical characteristics, risk stratification, and disease outcomes of MDS patients in our population is crucial to decide the best treatment strategies and improve the clinical outcomes of our patients. Disclosures Sossa: Roche: Honoraria; Astellas: Honoraria; Takeda: Honoraria; Novo: Honoraria. Abello:Dr. Reddy's: Consultancy, Research Funding; Takeda: Honoraria, Research Funding; Amgen: Consultancy, Research Funding; Novartis: Consultancy, Honoraria; Abbvie: Consultancy, Research Funding. Peña:Roche: Honoraria. Salazar:Novartis: Honoraria; Janssen: Honoraria. Sandoval-Sus:Celgene: Speakers Bureau; Massive Bio: Consultancy; Janssen: Consultancy; MorphoSys US: Consultancy.

Abstract: Background: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma subtype. Early stage (I/II) disease is seen in up to 30% of all DLBCL cases, and although outcomes in this subgroup have been reported as optimal, relapses can still occur. Prognostic models such as the International Prognostic Index (Miller, NEJM, 1998) continues to be utilized for risk stratification in DLBCL. However, despite its limitations and lack of validation in specific demographic groups such as Latin American patients, no prognostic models exist for the evaluation of limited stage DLBCL. Therefore, we aim to investigate different clinico-epidemiological and laboratory variables and its impact on survival in early stage DLBCL. Methods: We conducted a retrospective study of newly diagnosed patients with early stage DLBCL. Using the Grupo de Estudio Latinoamericano de Linfroproliferativos (GELL) database, we selected patients that had early stage disease, defined as non-bulky stage I or II. The variables analyzed included demographic and clinical variables (e.g., age, ECOG performance status), the International Prognostic Index (IPI), and laboratory variables such as serum albumin, serum lactate dehydrogenase (LDH), serum beta-2-microglobulin, the lymphocyte-monocyte ratio (LMR), the neutrophil-lymphocyte ratio (LNR), and the platelet-lymphocyte ratio (PLR). To determine the variables associated with mortality, univariate and multivariate Cox regression (step-wise type) analysis was performed. Kaplan-Meier and log-rank test were used for survival analysis. Outcomes with a p-value & lt;0.05 were considered statistically significant. Results: We identified 1,375 patients with DLBCL; 503 were identified as early stage DLBCL of whom 498 had sufficient data for analysis. Almost all cases (n=483, 96%) had nodal disease as the primary site, and 15 (4%) extranodal, all within the gastrointestinal tract. There was a slight female predominance (51.8%). The median age at diagnosis was 64 (IQR: 50 -73) with 57.4% older than & gt;65 years. ECOG performance status of & lt;2 was seen in 77.2% of cases; elevated serum LDH in 32.4%; and elevated serum beta-2-microglobulin in 5.6% (n=11/192). Based on previous data, we evaluated and calculated variables that have been suggested as independent negative prognostic factors for overall survival; the proportion of patients with serum albumin & lt;3.5 mg/dL; LMR & lt;2, NLR & gt;4, and PLR & gt;376 was 34.4%, 10.3%, 9.2%, and 4.7% respectively. With a median follow-up of 45 months, the median 5-year overall survival (OS) rate was 72%. The therapy approaches used, response rates and outcomes with these approaches will be presented at the meeting. Results of the univariate and multivariate analysis are summarized in Table 1. We found that age over 65, ECOG performance status, serum albumin level, beta-2-microglobulin level, LDH ratio, LMR, NLR, PLR, and BCL-2 positivity by immunohistochemistry (IHC) were prognostic factors for OS in the univariate analysis. However, in the multivariate analysis, only NLR, serum albumin level and ECOG performance status were independent factor for worse prognosis. Survival rates were significantly shorter in patients with serum albumin & lt;3.5 g/dL (5-year OS of 49% versus 79%, respectively; p & lt;0.0001); NLR & gt;4 (5-year OS of 46% versus 73%, respectively: p=0.0013); and ECOG performance status ≥2 (5-year OS of 51% versus 74%, respectively; p & lt;0.0001) (Figures 1 to 3). Conclusion: In this large cohort of Latin American patients with early stage DLBCL most patients were older than 65, had nodal disease as the primary site, good performance status, with only a third of patients exhibiting elevated LDH. Moreover, we found serum albumin & lt;3.5 g/dL, NLR & gt;4 and ECOG ≥2 as negative prognostic factors for poor survival in early stage DLBCL. We are currently validating our findings in a prospective cohort of Latin American DLBCL patients and to improve clinical decision-making in those deemed at high-risk for early mortality. Figure 1 Figure 1. Disclosures Otero: Astra Zeneca: Current Employment. Oliver: Roche: Other: conference support and fees ; Abbvie: Other: conference support and fees . Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.

Abstract: Background The SARS CoV-2 / COVID 19 pandemic has challenged the world's health systems, especially services that treat cancer. The first studies in China showed that cancer patients had a higher risk of becoming infected and dying. Other risk factors for mortality were age over 65 years, male sex, the presence of comorbidity, hypertension, cardiovascular disease, diabetes, and obesity. Data on the specific behavior of patients with multiple myeloma (MM) in the pandemic are scarce. The mechanisms by which MM patients may have a higher mortality are multiple, derived both from the disease itself due to cellular and humoral immunity deficiency as well as from anti-myeloma treatment. The present study aims to establish the behavior of the disease in the pandemic period in Latin America. Methods This is a retrospective case series of in and outpatients with a diagnosis of MM and COVID-19 reported from centers from Latin America between March and July 31, 2020. The analysis of demographic, clinical, laboratory, complications and therapy variables were done using descriptive statistics. A Kaplan Meier survival analysis was performed, with Log Rank statistic. Finally, a Cox regression was performed to identify independent risk factors of worse outcome. Pre-admission characteristics, MM status, and comorbidities constituted the reference model and were used to adjust the association of relevant MM characteristics with mortality. Program used for analysis was SPSS statistics 25. Results Fifty-two patients with COVID-19 and MM from 7 countries were included. Demographic characteristics, comorbidities, infection baseline clinical conditions, treatment, and outcomes are shown in Table 1. The characteristics in terms of MM status are shown in Table 2. When performing the survival analysis, it is evidenced that the survival of the entire cohort at day 49 was 67% Figure 1. When we focus on patients with comorbidities, survival drops to 53.5% +/- 10.6 (CI 95% 53.4 - 99.4 and p value of 0.041) for the same day Figure 2. When performing the obesity analysis, a drop in survival of up to 39% was observed (95% CI 24.448 - 56.76, with p = 0.00001) Figure 3. Adjusted HR for obesity is 5,078 (95% CI 1,389-18,558, α0.014) and mechanical ventilation with a HR of 3,943 (95% CI - 1,296 - 11,998, α0.016) When comparing patients with controlled MM ( & gt; PR) versus uncontrolled, the mortality rate was 84% versus 58% respectively (p = 0.109). Comorbidities (presence of either diabetes, arterial hypertension, cardiovascular disease, or "others"), obesity, need of mechanical ventilation, and & lt;VGPR at the time of infection were independent factors of lower survival Table 3. Conclusions Patients with MM and COVID-19 has an overall mortality of approximately 30% and this is strongly influenced by the presence of comorbidities, uncontrolled disease and need of mechanical ventilation. Survival of patients without comorbidities and controlled disease is good, suggesting that this group of patients would not require modification of MM therapy. The main limitations of our study are its retrospective nature and the low number of patients. It must be highlighted that at the time of the analysis most of Latin American countries were still in the peak of the pandemic. Prospective studies are required to elucidate the behavior of these risk factors in mortality, to optimize the management of patients with MM in this period of the SARS CoV-2 / COVID-19 pandemic. Disclosures Peña: BindingSite: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau. Abello:Novartis: Consultancy, Honoraria; Amgen: Consultancy, Research Funding; Takeda: Honoraria, Research Funding; Dr. Reddy's: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding. Idrobo:Abbvie: Honoraria, Speakers Bureau; Tecnofarma: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Rojas:Novartis: Consultancy; Roche: Honoraria; Sandoz: Honoraria; Abbvie: Honoraria. Remaggi:Takeda: Honoraria; Raffo Argentina: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gador Argentina: Research Funding; Amgen: Honoraria, Research Funding. Alvarado:Celgene: Speakers Bureau; Alexion: Speakers Bureau; Amgen: Speakers Bureau; Novartis: Speakers Bureau; Roche: Speakers Bureau. De la Peña-Celaya:Amgen: Speakers Bureau; Janssen: Speakers Bureau; Novartis: Speakers Bureau. Perez:Novartis: Speakers Bureau; Celgene: Speakers Bureau; Roche: Speakers Bureau.

Abstract: Introduction: The neutrophil-lymphocyte ratio (NLR) is a measure of systemic inflammation that appears prognostic in different cancers. Although the exact mechanism remains to be elucidated, reduced lymphocyte intra tumor infiltration coupled with the formation of neutrophil extracellular traps (or NETosis) have been postulated as endogenous mechanisms for tissue damage and inflammation. Along this line, serum albumin has also been studied as a biomarker of inflammation and has been associated to prognosis in certain cancers. We have previously reported on the prognostic value of the NLR and serum albumin in diffuse large B-cell lymphoma (Villela, ASH meeting, 2019; Castro, ASH meeting, 2019) and peripheral T-cell lymphoma, not otherwise specified (Idrobo, ASH meeting, 2019), but nothing on follicular lymphoma (FL) yet. Therefore, we aim to investigate the role of different biomarkers on the prognosis of patients with FL diagnosed and managed in Latin America. Methods: We analyzed patients with FL diagnosed between 2010 and 2020 from 30 centers in 10 Latin American countries. The study outcomes were overall survival (OS) and progression-free survival (PFS) in relation to different biomarkers. Kaplan-Meier and log-rank test were used for survival analysis. Univariate and multivariate Cox regression analysis were used to estimate hazard ratios (HR) with a 95% confidence interval (CI) and adjusted to the Follicular Lymphoma International Prognostic Index (FLIPI) score. Outcomes with a p-value & lt;0.05 were considered statistically significant. Results: We identified 939 FL patients; 741 were included for the final analysis (median age 58 y, female 52%). There was no significant correlation between the NLR and other clinical factors such as: age, clinical stage, histological FL grading, and chemotherapy regimen used. A cutoff of 2.15 for NLR was defined as the maximum point for sensitivity and specificity based on ROC analysis. Table 1 and 2 summarizes the results from the univariate and multivariate analysis for 2 years OS and PFS, respectively. Both, serum albumin & lt;3.5 g/dL and a NLR & gt;2.15 were independently associated with worse OS (adjusted, aHR 2.48 [1.26-4.91], p=0.009; and 2.55 [1.21-5.37] , p=0.014) and PFS (aHR 1.62 [1.03-2.55], p=0.038; 2.22 [1.45-3.40] , p & lt;0.001), respectively. The lymphocyte:monocyte ratio (LMR) was not found to be prognostic for OS or PFS, although with a trend for worse PFS with a LMR ≤2.5. With a median follow of 43 months, (95% CI: 40-47), the survival rates in patients with FL and albumin & lt;3.5 were OS of 83% (vs. 95%) and PFS of 70% (vs. 83%); whereas in patients with NLR & gt;2.15 the survival rates were OS of 91% (vs. 96%) and PFS of 75% (vs. 88%) (Figures 1 and 2; table 3). Conclusions: In this study, serum albumin and NLR emerge as reliable predictors for survival for FL patients in Latin America. Although these markers have been associated to an increased inflammatory state in cancer patients; other factors such as poor nutritional status, and advanced disease stage due to delayed access to specialized cancer care in our region may have contributed to the observed outcome. Further studies are needed to better understand the role of these biomarkers on lymphoma care and to validate our findings. Lastly, we are currently working on evaluating these biomarkers on existing prognostic models and to improve prognostication for FL patients in Latin America. Figure 1 Figure 1. Disclosures Otero: ASTRA ZENECA: Current Employment. Ramirez-Ibarguen: Asofarma: Consultancy; MSD: Consultancy; Abbvie: Speakers Bureau; Astra Zeneca: Speakers Bureau; Janssen: Speakers Bureau; Roche: Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Perini: Roche: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Janssen: Consultancy, Other: Travel/Accommodations/Expenses, Speakers Bureau; Takeda: Speakers Bureau; Abbvie: Consultancy, Other: Travel/Accommodations/Expenses, Speakers Bureau. Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.

Abstract: FLT3, PIM1, PIM2 and CXCR4 are proteins implicated in the signal transduction of the regulation of proliferation, differentiation and survival of hematopoietic stem cells, at different levels. The impairing of these three processes, regulated by these molecules, constitutes the main hallmark of Acute Myeloid Leukemia (AML). The objectives of this work were to evaluate the expression level of the genes that codify such proteins in patients with AML; as well as correlate this level of expression with biological variables at diagnosis and survival. Methods peripheral blood or bone marrow samples from 31 healthy subject (HS) and 92 AML patients at diagnosis between 2004 and 2012 were studied. The median follow up was 14 months (69% of patients had died). We quantified the expression of FLT3, PIM1 and 2, and CXCR4 by real time PCR, employing primer pairs designed in our laboratory to amplify all known protein-coding transcripts; highlighting the presence of a 30.4% FLT3 ITD, 5.4% of other FLT3 mutations and 26% of NMP1 mutations. Results were then analyzed with the statistical package IBM“ SPSS” Statistics, v20 (IBM“, Nueva York). Results FLT3 was overexpressed in AML patients (FLT3 expression: controls 0.99 vs patients 36.97; p 〈 0.001). Table 1 summarizes gene expression level according to presence of FLT3-ITD and other FLT3 and NPM1 mutations. It was noted that NPM1 mutations were associated with lower expression of PIM1 (NPM1+: Log PIM1 1.09 vs NPM1-: Log PIM1 1.38; p=0.046) and PIM2 (NPM1+: PIM2 10.09 vs NPM1-: PIM2 24.48; p 〈 0.01). No significant differences in gene expression level were seen in relation to the presence of FLT3-ITD, with the exception of lower expression of PIM2 (FLT3-ITD: PIM2 10.71 vs No FLT3-ITD: PIM2 24.47; p=0.001). But in the case of other FLT3 mutations, FLT3 expression was higher (FLT3 mutations: FLT3 expression 88.33 vs No FLT3 mutations: FLT3 expression 34.02; p=0.006) and PIM1 was lower (FLT3 mutations: LogPim1 0.79 vs No FLT3 mutations: LogPIM1 1.34; p=0.049). PIM1 was expressed as controls (90.25 controls vs 55.73 patients; p=0.26); however PIM2 and CXCR4 were underexpressed (PIM2 controls 110.19 vs patients 20.73; p 〈 0.01), (CXCR4 controls 1251.54 vs. patients 99.03; p 〈 0.01). We found a correlation between PIM2 and CXCR4(r=0.9; p 〈 0.01) and the LogPIM1 and PIM2 (r=0.775; p 〈 0.01). We observed a higher expression of PIM2 in secondary AML (PIM2 35.17 vs. 17.8; p=0.01) and lower PIM2 expression in the intermediate genetic risk group (low risk 25.51, intermediate risk 14.7 and high risk 33.28; p=0.015). CXCR4 had lower expression in the intermediate cytogenetic risk group (low risk 113.31, intermediate risk 65.2, high risk 146.94; p=0.041) (Table 2). No differences in gene expression were noted in relation to chemotherapy response level. We studied differences in gene expression between granulocytes and blast cells from 19 samples, finding a marked tendency to higher FLT3 expression (FLT3 blasts 35.26 vs FLT3 granulocytes 17.98; p=0.062) and lower PIM1 (PIM1 blasts 69.14 vs PIM1 granulocytes 206.88; p=0.130), PIM2 (PIM2 blasts 26.25 vs PIM2 granulocytes 107.39; p=0.182) and CXCR4 (CXCR4 blasts 188.96 vs CXCR4 granulocytes 420.28; p=0.186) expression in blast cells. The gene expression was clearly different, but not statistically significant, probably due to the limited number of samples studied. Gene expression variable was categorized as high expression above median and low expression below median. High expression of FLT3 was associated with a tendency to reach higher survival (p=0.146). Patients with CXCR4 low expression level had a lower survival (p= 0.045) (Fig.1). Also PIM2 overexpression –defined as a expression level over 75 percentile- was associated with a slightly lower survival. Summary/Conclusion The deregulated expression of FLT3, PIM1, PIM2 and CXCR4 relates to differential characteristics of certain AML groups and has prognostic implications. It is noteworthy that CXCR4 overexpression seems to be associated with higher survival in AML patients. All these results must be confirmed with future studies including a greater number of samples. Disclosures: No relevant conflicts of interest to declare.

Abstract: Introduction Acute lymphoblastic leukemia (ALL) is a clonal hematopoietic disorder that originates from B or T lymphoid progenitors and has well validated prognostic and predictive factors that influence outcomes. One of the strongest prognostic factors is the detection of minimal residual disease (MRD) which measures residual cell population after treatment when a morphologic complete response has been achieved. MRD positivity is associated with a higher risk of relapse and poor response to chemo or radiotherapy Objectives The aim of the study was to assess the prognostic impact of post-induction MRD status in a cohort of ALL Colombian patients in terms of relapse-free survival (RFS) and overall survival (OS). Methods This is a retrospective observational study conducted at a Colombian university hospital and included a cohort of ALL patients diagnosed between 2013 and 2020 treatment according to protocol PETHEMA (Spanish Program for Hematology Treatments). MRD was measured with 8-color flow cytometry evaluate on bone marrow. MRD status was classified as negative MRD (NMRD) or positive MRD (PMRD) based on a sensitivity threshold of & lt;0,01% or ≥0,01% leukemic cells, respectively, following to international guides. Demographic and clinical characteristics were analyzed using descriptive statistics. Kaplan-Meier method was used to assess overall RFS and OS. Results A total 128 patients were included. The median age at diagnosis was 34 years (range 0-89 years), 54% were men, 26% were overweight, 22% obese, 6.2% had type 2 DM (T2DM), and most had a ECOG PS of £2 (94%). Most patients (80.5%) had high risk according PETHEMA, B-ALL and were classified as ALL-2 (58%) according to FAB classification with Pre-B cell ALL being the most common phenotype (54.7%). Ph+ ALL was diagnosed in 12% of patients. Most used treatments protocols were PETHEMA-AR and PETHEMA-RI in 43.8% and 11.6% of patients, respectively. Post-induction MRD measurement was available in 98 patients, 36 (36.7%) had NMRD and 62 (63.3%) PMRD. From the 36 patients with NMRD, eight patients (22.2%) received Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT): two of them, were transplanted in first complete remission, one because of high risk and the other one for BCR-ABL positivity. The other six patients received alloHSCT in second remission and all of them relapsed after late consolidations. Finally, alloHSCT was done in 28 patients with PMRD (45.2%). The 12-month OS for patients with NMRD was 68.7% (95%CI 50.5-81.2) compared to 63.7% (95%CI 50.3-74.4) in the ones with PMRD, p=0.375. 12-month RFS was 83.3% (95%CI 61.5-93.4) in patients with NMRD and 90.0% (95%CI 72.1-96.7) in patients with PMRD, p=0.436. (Figure 1). OS was significantly higher for the PMRD patients who underwent AlloHSCT 96.4% (95%CI 77.2-99.4) versus not underwent 36.8% (95%CI 20.6-53.2), HR: 0.39 (95%CI 0.005-0.29) p=0.002 (Figure 2). Conclusion MRD assessment is a strong prognostic in ALL, however it was not associated with significant differences in RFS or OS in this single institution cohort of Colombian patients. Patients with PMRD taken to AlloHSCT had superior OS compared to NMRD that underwent transplant. A small sample size and short follow-up could explain our results. Larger cohorts with extended follow up and with different MRD methods are needed to better understand the role of MRD assessment in minority ALL populations, such as Colombian patients. Figure 1 Figure 1. Disclosures Peña: Amgen: Research Funding. Salazar: Amgen: Research Funding. Sandoval-Sus: BMS: Other: Advisory Board, Speakers Bureau; SeaGen, Janssen, MassiveBio, TG: Other: Advisory Board. Sossa: Amgen: Research Funding.