ALBERT

Description: Introduction: Risk stratification in acute myeloid leukemia (AML) is continually being refined as we learn more about the molecular pathophysiology of this heterogeneous disease. European LeukemiaNet (ELN) 2017 used widely to stratify the 'genetic' risk of AML, but there are considerable challenges in its application, particularly in centres where molecular genetic testing either not available, or not sufficiently timely for clinical decision making. Up to a third of the study subjects cannot be stratified using a full cytogenetic-molecular model in real-time, real-life setting. There are few attempts to combine clinical features and genetic factors aiming to find a scoring system to improve AML survival prediction. There is only one to our knowledge (Sorror ML et al. 2017). This study has generated an Adapted Genetic Risk (AGR) assessment, and used it in combination with clinical risk parameters to create a novel scoring system which has now been validated using two independent cohorts. Methods: A training cohort from São Paulo (FMUSP, n = 167) of intensively treated AML patients (18-65 years) was assessed using ELN2017 genetic criteria. A comparative validation with our AGR which permits missing cytogenetic or molecular data (Figure 1) split these patients into favorable-risk (FR), intermediate-risk (IR), and adverse-risk (AR). This cohort was also used for Cox Proportional-Hazard Model (CPHM) univariate and multivariate analysis to find clinical parameters that would inform a novel Survival AML Score (SAMLS). Variables which are included in SAMLS had to be either significant in both CPHM models or significant in univariate and crucial for multivariate fitness as measured for the Akaike Information Criterion (AIC). We then applied the AGR strategy and SAMLS to 2 independent test cohorts of intensively treated adult AML patients : Riberao Preto (FMRP, n=145) and Oxford (OUH, n=157). The study was approved by the institutional review boards of the 3 participating centers. Informed consent was obtained from all patients according to the Declaration of Helsinki. Results: Table 1 shows the clinical characteristics for all the 3 cohorts. The median follow-up (FUP) was 72.3, 44.4, and 70.5 months for FMUSP, FMRP, and OUH, respectively. The median Overall Survival (OS) was 12.4, 12.5, and 56.4 months and the 5-year OS were 29.6%, 29.7%, and 49.7% respectively. Both ELN2017 and AGR correlated with significant differences in OS (p-value

Description: Introduction: Burkitt lymphoma (BL) has become an AIDS-defining disease by Centers for Disease Control (CDC) definition since 1993, emphasizing the strong relationship between this subtype of non-Hodgkin Lymphoma (NHL) and the Human Immunodeficiency Virus (HIV) infection. Although it is widely recognized that the HIV-associated BL represents a distinct entity and a more difficult-to-treat disease, reported results from developed countries seem to corroborate that these regimens do not need to be tailored to the HIV-positive population. There is no available data on outcomes of this population in developing countries. In this study, we report a real-world cohort of adult HIV-associated BL patients in Brazil. Methods: This is a retrospective multicenter cohort encompassing 4 academic hospitals in Brazil. Ethics approval for the study was obtained in all centers. Patients were treated according to their local protocol, which included Hyper-CVAD, CODOX-M IVAC or CHOP-like regimens, on a clinical judgement basis. Further reductions in the dose could be done at discretion of physician in case of excessive toxicity. For all patients who were not using cART, HIV-directed therapy was promptly started and administered along with chemotherapy. A cytoreductive regimen could be administered prior to the actual regimen to minimize the risk of tumor lysis. Survival analysis was performed using the Kaplan-Meier method and log-rank test for comparison. Cumulative incidence of relapse (CIR) was calculated using death as a competitor. Results: A total of 54 patients with HIV-associated BL were included in this analysis. Median age was 39 years (range, 15 - 64) and the vast majority were male (78%). 41% of patients were using cART prior to the BL diagnosis. Advanced disease was found in 86% of patients. CNS disease was observed in 31%. Regarding the immune status at the presentation, 52% had CD4+ T-cells count lower than 200 cells/mm3 and 19% had undetectable levels of HIV viral load. Other features are summarized in Table 1. Five patients died before starting any regimen due to sepsis. Among the 49 patients, most were treated with a modified Hyper-CVAD (26/49, 53%), CODOX-M IVAC (9/49, 18%) and a CHOP-like regimen (8/49). Only 8/49 (16%) patients received rituximab in upfront therapy. Radiotherapy was used in 4/49 patients (2 cranial irradiation, 1 in initial bulky site and 1 in testicles). A treatment-related mortality of 38.7% (95% confidence interval [CI] 25.5 - 53.7) was found and the complete response (CR) rate was 44.9% (95% CI 30.9 - 59.6). Primary refractory disease was found in 14%. Regarding the patients who achieved a CR at the end of treatment, 3-year CIR was 6.2% (95% CI 1.6 - 15.7%). There was no recommended regimen for salvage, and most patients received an alternate classic regimen for BL if feasible. Only one relapsed patient proceeded to autologous stem-cell transplantation, but eventually died after a second relapse. Median follow-up time was 4.4 years. A 4-year OS of 36.1% (95% CI 25.2 - 51.8) for total cohort and 39.8% (95% CI 28.1 - 56.5) for those patients who received any regimen was calculated (Figure 1). A univariate analysis for CR and OS did not show any statistically significant difference regarding sex, age, staging, CD4+, viral load, prior cART, extranodal infiltration, blood counts, lactate dehydrogenase (LDH), employed regimen or use of rituximab. All relapsed and primary refractory patients eventually died in our cohort. Aside from those patients who died from disease progression per se, remaining patients died from infections (24/34), despite intensive antimicrobial prophylaxis and associated cART. Conclusion: Outcomes of HIV-positive BL population are scarcely reported worldwide. While HIV patients seem to have a higher relapse rate in other studies, our early mortality and overall survival were far worse than those reported in developed countries and with more selected cohorts. In comparison with literature, our patients experienced higher toxicity with classic regimens and higher refractoriness rate. Therefore, these findings warrant further cooperative multicenter studies in developing countries, aiming at improving supportive care and optimizing regimens locally feasible. Disclosures Delamain: Novartis: Honoraria.

Description: Introduction: There is no consensus regarding the best salvage regimen for refractory or relapsed acute myeloid leukemia (r/rAML), with classic regimens traditionally based on high-dose cytarabine in a changeable combination with anthracyclines, purine analogs, and etoposide. Outcomes of r/rAML patients in developing countries are underreported, even though the same regimens are widely used. Methods: This is a retrospective single-center study, conducted in an academic center in Brazil. Local research ethics committee approved this analysis. All patients above 16 years of age who received MEC (mitoxantrone, etoposide and cytarabine) or FLAG-IDA (fludarabine, cytarabine, filgrastim and idarubicin) as originally reported (Amadori, S. et al. and Steinmetz, H. T. et al.) for r/rAML between December/2009 and January/2019 were included. Only patients with refractory or relapsed disease following standard upfront therapy ("7+3" regimen) were included in this analysis, being divided among refractory (less than partial response after one cycle of "7+3"), early relapsed (relapse within one year from first complete response [CR]) and late relapsed (relapse after one year of CR). Only the first salvage was considered for this study. Results: Sixty patients were included in the final analysis, with a median age of 45 years (range, 17 - 69). There were no cases of therapy-related AML. Four AML cases (7%) were secondary to myeloproliferative neoplasm (MPN) or myelodysplastic syndrome (MDS). All FLT3-ITD positive cases had an associated NPM1 mutation. Two patients had chronic human immunodeficiency virus infection and received antiretroviral therapy. Baseline characteristics of the whole cohort are summarized in Table 1. Three patients had undergone SCT in first CR and were post-SCT relapses. Twenty-eight patients received MEC and 32 received FLAG-IDA. By comparing the baseline characteristics of both groups, no difference statistically significant was found except for the indication for salvage treatment, in which there were more refractory cases in FLAG-IDA group (56 vs. 28%, p=0.029) (Table 2). Overall, 17/60 achieved CR and 12/60 CRi, with a total CR rate (CR+CRi) of 48.3% (95% confidence interval [CI], 35.4 - 61.5). Sixteen patients (27%) early died before a response assessment. By univariate analysis, only age affected the CR rate (p=0.045). No difference in CR rate was found between the two protocols (MEC 53.5 vs. FLAG-IDA 43.7%, p=0.447). Looking into this data, it can be seen that there were more refractory patients in FLAG-IDA arm (37.5 vs. 4%, p=0.02) but more patients early-died in MEC arm (35.7 vs. 18.7%, p=0.137), even though the latter was not statistically significant. After correcting the initial differences between the two groups regarding indication for salvage through a propensity score calculation, a post-matching cohort with 44 subjects was found. In this cohort, no difference in refractoriness rate could be detected (p=0.077). In the whole cohort, 17 patients proceeded to allogeneic SCT - 15 in CR/CRi and 2 with active disease, with no difference in SCT execution rate between the two groups (p=0.470). 4/17 transplanted patients were alive. Median follow-up was 48 months. Median survival for total cohort was 4 months (95% CI, 2.7 - 9.2), with a 3-year OS of 9.7% (95% CI, 4 - 23.7) and a 3-year EFS of 7.5% (95% CI, 2.5 - 22.4). In the univariate analysis for OS, age (p=0.04), FLT3 status (p

Description: Background It is possible that physical education professionals, especially those who participate in aerobic activities, have predisposing factors, signs and symptoms of overreaching (OVR) and overtraining (OVT) due to a high load and volume of exercise followed by suboptimal recovery time. The present study aimed to identify the predisposing factors, signs and symptoms of OVR and OVT in physical education professionals. Methods A questionnaire consisting of 42 questions (10 questions group) about predisposing factors and signs/symptoms was answered by 132 physical education professionals from both sexes (83 men and 49 women) who were allocated into a resistance training group (RG, n = 74), aerobic training group (AG, n = 20) and resistance and aerobic training group (RAG, n = 38). A mean score was calculated ranging from 1 (completely absent) to 5 (severe) for each question group. A low occurrence of predisposing factors and signs and symptoms of OVR and OVT was considered to be a question group score 4 or lower. Profile of Mood State Questionnaire (POMS) was also applied. Results A mean score of 2.5 ± 0.7, 2.7 ± 0.7 and 2.7 ± 0.8 was found for all question groups for RG, AG and RAG, respectively. Of the total sample, 40.6% trained at least five times/week. The POMS revealed that 67.5% of the RG (n = 50), 80% of the AG (n = 16) and 60.5% of the RAG (n = 23) were classified as having no mood disorders and a standard graphic iceberg was presented. There were no statistical differences (p 〉 0.05) in the total mood disorders among RG (13.9 ± 24.5), AG (10.3 ± 25.1) and RAG (14.6 ± 27.9) groups. Conclusion Despite the volume of training/body working performed by the physical education professionals surveyed being greater than the recommended to achieve improvements on physical fitness, they did not show predisposing factors, signs or symptoms of OVR and OVT.

Description: Background: Early death (ED) during first-line therapy for acute myeloid leukemia (AML) is acknowledged as a pending issue worldwide. Few pivotal studies from developed countries have identified baseline characteristics related to poor outcome. Retrospective reports from Brazil and Mexico indicate alarming ED rates from real-world data, raising the question of which factors contribute towards this finding in low-income centers. In this study, we aimed to identify risk factors for ED in AML to increase the prediction power of previously known tools such as Charlson's Comorbidity Index (CCI) as well as to examine the role of anti-infective prophylaxis in our cohort. Methods: This is a retrospective cohort study involving adult patients (pts) newly diagnosed with AML treated at Instituto do Cancer do Estado de Sao Paulo, Brazil between June 2011 and June 2020. Only pts receiving the classic "7+3" regimen were included. We used a slight modification of European LeukemiaNet 2010 classification previously published by our group - Adapted Genetic Risk (AGR) (Silveira et al., 2020). The primary endpoint was ED rate, calculated by the Kaplan-Meier method. A Cox regression model selected by a stepwise method was used to find risk factors. Post-chemotherapy events (secondary endpoints) constituted any documented infection, bleeding, thrombosis, and acute kidney injury (AKI) during the first 30 days. Results: Overall, 206 out of 337 pts (61%) entered in the analysis. The median age was 54 years (range,17-74) and 50.5% were male. The median time between symptoms' onset and hospital admission was 7 weeks (0-48). Thirteen pts (6.3%) presented with leukostasis, of which 9 proceeded leukapheresis. At the presentation, clinical tumor lysis syndrome was seen in 12% of patients (associated with extramedullary disease [p

Description: Introduction: Chronic lymphocytic leukemia (CLL) typically occurs in elderly patients and has a highly variable clinical course. It is important to understand the aspects that affect the outcomes of CLL in a real-world setting. Besides biological factors, other socioeconomic and health system factors may influence the clinical course of CLL. Hence, data from the Brazilian Registry of CLL was analyzed to compare clinical and treatment-related characteristics in patients with CLL treated in public or in private institutions in Brazil. Objective: To describe the outcomes of a series of CLL patients followed in public or in private hospitals in Brazil. Methods: The Brazilian Registry of CLL was started in 2004 as a prospective non-interventional data collection tool. Inclusion criteria for enrollment followed the IWCLL guidelines. For this analysis, we included all patients with minimum available data for analysis of patient and disease characteristics and survival. Results/discussion: From January 2004 to July 2020, 2927 patients from 37 centers met eligibility criteria for this analysis: 2324 (79%) were followed at public hospitals and 603 (21%) at private hospitals. The majority were male (57%), with median age of 65 years (ranging from 23 to 106). Binet stage was A in 1618 (58%) patients, B in 628 (23%) and C in 525 (19%). FISH for del(17p) was performed in only 479 patients (16%), while FISH for the most common aberrations [del(13q), +12, del(11q), and del(17p)] was performed in only 445 patients (15%). IGVH mutational status was performed in only 211 patients (7%), and karyotype in only 140 patients (5%). Comparing public and private hospitals, we observed that patients in public hospital are slightly older (median age 66 years vs. 64 years for private hospitals, P=0.04), had more advanced diseases at diagnosis (frequency of Binet B or C was 44% in public vs. 32% in private hospital, P