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PURPOSE The COVID-19 pandemic is a colossal challenge for global health; nonetheless, specific subgroups face considerably higher risks for infection and mortality. Among patients with malignant diseases, those with hematologic neoplasms are at a higher risk for poor outcomes. The objective of this study was to register treatment modifications associated with the COVID-19 pandemic and their short-term consequences in Latin America. METHODS Multicenter, prospective, observational, cohort study including patients older than 14 years from 14 centers in four countries (Mexico, Peru, Guatemala, and Panama) who had a confirmed diagnosis of acute leukemia, and who were undergoing active treatment since the first COVID-19 case in each country until the cutoff on July 15, 2020. RESULTS We recruited 635 patients. Treatment modifications because of the COVID-19 pandemic were reported in 40.8% of cases. The main reason for such modifications was logistic issues (55.0%) and the most frequent modification was chemotherapy delay (42.0%). A total of 13.1% patients developed COVID-19 disease, with a mortality of 37.7%. Several factors were identified as independently associated with mortality, including a diagnosis of acute myeloid leukemia (odds ratio 2.38 [95% CI, 1.47 to 3.84]; P < .001), while the use of telemedicine was identified as a protective factor (odds ratio 0.36 [95% CI, 0.18 to 0.82]; P = .014). CONCLUSION These results highlight the collateral damage of COVID-19 in oncology patients.

Background: Mexico and Central America have a high incidence of acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYA). Chemotherapy with Hyper-CVAD has been widely used with poor outcomes, with a 3-year overall survival (OS) of 25.7% in this group of age. In low-and middle-income countries (LMIC), limitations in supportive care such as low access to neutrophil stimulant agents, antifungal prophylaxis and limited intensive care access, may increase treatment-related mortality. On the other hand, reports suggest that specific high-risk subgroups may be more frequent in Hispanic patients from Mexico and Central America. We hypothesize that the use of a less-myeloablative regimen, based on L-asparaginase could overcome the bad outcomes previously reported. Methods We modified the original CALGB 10403 based on local drug-access. We include patients with newly diagnosed Philadelphia-negative B- or T-cell ALL between 14-49 years from 4 centers in Mexico and one in Guatemala. We modified the regimen as following: replaced pegaspargase by E. Coli asparaginase, thioguanine by 6-mercapatopurine and incorporate rituximab 375mg/m2 for 6 doses in CD20 positive patients. After the first interim analysis (October 2019), we replaced the prednisone by dexamethasone during induction. Minimal residual disease (MRD) was assessed by flow cytometry after induction and after first consolidation. We considered high-risk karyotype if MLL-rearrangements, complex or hypodiploid and high-white blood cell count (WBC) if &gt;30 x10 3/mcL for B-ALL or &gt;100 x10 3/mcL for T-ALL. The main objective was to evaluate OS and as secondary objectives to evaluate complete response (CR) rate, relapse-free survival (RFS) and to assess the safety of this regimen. Results From January 2017 to December 2020, 95 patients have been enrolled with a median age of 23 years (range 14-49). One third (34.6%) had overweight and 11.7% were obese. The majority (92.6%) had a B-cell ALL and a normal karyotype (81.2%). The median WBC was 18.4 x10 3/mcL (0.2-427.7) and 40.9% had a high-WBC. During induction, adverse events (AE) included grade 3/4 elevated bilirubin (21.1%), transaminases (14.7%), hyperglycemia (14.7%), hypofibrinogenemia (44.2%), thrombosis (10.5%), hypersensitivity (2.2%) and pancreatitis (2.1%). During consolidation, AE included grade 3/4 hepatic toxicity (18.9%), hypertriglyceridemia (14.8%), thrombosis (5.3%) and pancreatitis (2.1%). Neutropenic fever occurred in 55.8% during induction (grade 4: 31.5%), and in 32.9% during consolidation (grade 4/5: 5.3%). A dose adjustment due to AE was required in 22.1% during induction and in 23.2% during consolidation. The induction related-mortality (IRM) rate was 7.4% The CR rate was 87.8%. After-induction, MRD was &lt;0.01% in 39.1%, 0.01-0.1% in 39.1% and &gt; 0.1% in 24.6%. Post-consolidation MRD was only measured in 43 patients and was &lt;0.01% in 37.2%. During follow-up, 26.7% relapsed: 62.5% bone marrow (BM) relapses, 25.0% central nervous system (CNS) relapses and 12.5% CNS + BM relapses. Eight patients (8.4%) received an allogeneic-stem cell transplant (HSCT) as consolidation. The 2-year OS was 72.1%. The post-induction MRD &lt;0.1% was associated with a better OS (figure 1A) (HR: 0.17 (95%CI: 0.06-0.55), p=0.003) and a high-WBC with an inferior OS (figure 1B) (HR: 4.13 (95%CI: 1.68-10.14), p=0.002). The 2-year RFS was 65.2%. The post-induction MRD &lt;0.1% was associate with a better RFS (figure 1C) (HR: 0.19 (95%CI: 0.07-0.50), p=0.001) and a high-WBC and overweight / obesity with an inferior RFS (HR: 4.08 (95%CI: 1.71-9.73), p=0.001 and 2.50 (95%CI: 1.06-5.86), p=0.036 respectively) (figure 1D). Conclusions: The adoption of modified CALGB10403 regimen in Central America based on local resources is feasible. It is associated with a significant improvement in the OS and decrease in IRM when compared with previous reports. Despite a very high-rate of hepatic and metabolic toxicities, these were manageable. As reported by other groups, MRD, high-WBC and overweight/obesity are associated with poor outcomes. Despite being encouraging results, a significant number of patients persist with positive MRD and the main cause of dead is disease progression. Access to cellular therapies, and BiTes is cost restricted in LMIC. Hence, we should generate strategies to intensify treatment in MRD positive patients and expand transplant access to overcome outcomes. Figure 1 Figure 1. Disclosures Rangel-Patiño: Bristol: Consultancy; Abbvie: Speakers Bureau. Ceniceros: Amgen: Speakers Bureau. Espinosa: Amgen: Speakers Bureau; Janssen: Consultancy; Pfizer: Consultancy. Amador: Abbvie: Consultancy, Speakers Bureau; Bristol: Consultancy. Cabrero Garcia: Takeda: Speakers Bureau; Abbvie: Speakers Bureau; Roche: Speakers Bureau; Janssen: Speakers Bureau; Astellas: Consultancy; BD: Speakers Bureau. Inclan-Alarcon: Janssen: Speakers Bureau; Boehringer: Speakers Bureau. Neme Yunes: Janssen: Consultancy, Speakers Bureau; Bristol: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Bristol: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Abbvie: Speakers Bureau. Meillon-García: Amgen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Roche: Speakers Bureau; Astellas: Consultancy. Apodaca: Sanofi: Consultancy; Asofarma: Consultancy, Speakers Bureau; Abbvie: Speakers Bureau. Demichelis: Bristol/Celgene: Consultancy, Speakers Bureau; Astellas: Consultancy; Gilead: Consultancy; ASH: Research Funding; Abbvie: Consultancy, Speakers Bureau; AMGEN: Consultancy, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau; Jazz: Consultancy.

Background Splenectomy is a therapy for patients with treatment‐refractory autoimmune cytopenias. Antiphospholipid antibodies (aPL) can be identified in 25%–85% of these patients. In this study, we sought to identify whether the presence of aPL was associated with worse outcomes in autoimmune cytopenia's patients who had undergone splenectomy. Methods We conducted a retrospective cohort study of patients who underwent splenectomy from 2000 to 2018. We describe clinical characteristics and outcomes in patients with autoimmune cytopenia's diagnosis with positive determinations of aPL. Additionally, we performed a case–control sub‐analysis 1:1 of the cases with autoimmune cytopenia's matched control patients with negative aPL determination. Results A splenectomy was performed in 707 patients, of which we included 34 for the analysis. The median age at the time of splenectomy was 37 years (range 19–61), 53% corresponded to immune thrombocytopenia (ITP) and 47% to autoimmune hemolytic anemia (AIHA). Compared with controls (n = 34), patients had more treatment lines in addition to steroids (p = .02). There were no differences in complete response rate, 65% in cases and 80% in controls (p = .17). However, there was numerically a higher incidence of early infections (21% of cases vs. 3% controls, p = .05). During the entire follow‐up, 15% of aPL patients compared with 9% of control patients had a thrombotic event (p = .70). Discussion Splenectomy for treatment‐refractory autoimmune cytopenia's patients with persistent aPL is an effective treatment despite some safety concerns related to early infections. These results suggest that the presence of aPL should not impact the decision to undergo splenectomy.

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&lt;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.