ALBERT

Description: Introduction: The development of next-generation sequencing has made it feasible to interrogate the entire genome or exome (coding genome) in a single experiment. Accordingly, our knowledge of the somatic mutations that cause cancer has increased exponentially in the last years. MPNs and MDS/MPD are chronic myeloid neoplasms characterized by an increased proliferation of one or more hematopoietic cell lineages, and an increased risk of transformation to acute myeloid leukemia (AML). MPNs and MDS/MPDs are heterogenous disorders, both in clinical presentation and in prognosis. We sought to determine the genetic landscape of Ph-negative MPNs and MDS/MPD through next-generation sequencing. Methods: Paired DNA (sorted CD66b-granulocytes/skin biopsy) from 102 patients with MPNs or MDS/MPD was subjected to whole exome sequencing on a Illumina HiSeq 2000 platform using Agilent SureSelect kit. Diagnosis included primary myelofibrosis (MF; N=42), essential thrombocythemia (ET; N=28), polycythemia vera (PV; N=12), chronic myelomonocytic leukemia (CMML; N=10), systemic mastocytosis (MS; N=6), MDS/MPD-Unclassified (N=2) and post-MPN AML (N=2). Tumor coverage was 150x and germline coverage was 60x. Somatic variants calls were generated by combining the output of Somatic Sniper (Washington University), Mutect (Broad Institute) and Pindel (Washington University). The combined output of these 3 tools was further filtered by in-house criteria in order to reduce false-positive calls (minimum coverage at both tumor/germline ≥8 reads; fraction of reads supporting alternate allele ≥10% in tumor and ≤10% in germline; ratio of allele fraction tumor:germline 〉2; excluding mutations seen in SNP databases). All JAK2 and CALR mutations were validated through Sanger sequencing. Validation of other somatic mutations is currently underway. Analysis of driver mutations was made with the Intogen web-based software, using the Oncodrive-FM and Oncodrive-cluster algorithms (www.intogen.org). Significantly mutated genes were considered as those with a q-value of

Description: Introduction Idiopathic acquired aplastic anemia (AAA) is a rare and life-threatening disease, characterized by pancytopenia. Its immune-mediated physiopathology is not yet fully understood. However, important associations have been reported in AAA, which include the association with certain HLAs, the presence of a PNH clone in 40-50% of cases, occurrence of a hepatitis associated variant in about 5-10% of cases, the occurrence of interferon gamma (IFN-g) and tumor necrosis factor alpha (TNF-a) producing T cells in the peripheral blood and bone marrow cells. Not much is known about cytokine gene polymorphisms in AAA and its relationship with HLA alleles. The IFN-γ +874 A/T gene polymorphism, and specially the +874TT genotype, have been associated with elevated levels of IFN-γ production. The individuals can present 3 different phenotype (TT, TA or AA). Some groups have demonstrated that the TT (the IFN-gamma “hyper-producer type”) is possibly overrepresented in AA patients and correlates with susceptibility to the disease. In order to better understand the relationship between these immune parameters, we investigated the associations between IFN-g gene polymorphism in AAA patients and its relationship with the presence of HLADR15 (identified as of greater importance in our local patients). Materials and methods In this study we analyze the variations of the gene polymorphism at position +874 interferon in 30 consecutive patients with confirmed diagnosis of AAA,in 2012 and 2013, at the Federal University of the State of Bahia Hospital/Brazil. Diagnosis of AAA was confirmed by bone marrow biopsy. Patients also had their HLA typing and were tested for the IFN-gamma gene polymorphism at +874 T/A position using the ARMS methodology described by Pravica. As controls, 116 healthy individuals from the same population (Bahia/Brazil) were tested for these polymorphism. The analysis of the association between the gene polymorphism and the chances of developing AAA, and the polymorphism and the HLA-DR15, were performed using qui-square/exact fisher test. The results were expressed as OR. Results We have found genotypic frequency of the A allele in 65%(n=39/60) in the aplastic patients (control 64.2%, n = 232, OR 1.05, p=0.87). The T allele was found in 35%(n =21/60)of the cases (control 34.6%, OR 0.95, p=0.87). Thus, there was no difference between the genotypic frequency of the alleles among patients with aplasia and the control group. In addition, there was NO difference between the frequency of the phenotype (TT, AT or AA) between patients with AAA and control group, respectively 16,5%, 36,5%, 46% (AAA, n =30) versus 18.1% , 35.3%, 46.6% (n = 116 control) (p=n.s.). The association of the polymorphism was tested and compared to the HLA-DR15. There was NO association between the IFN-gamma gene polymorphisms and the presence of HLADR15 (p =,90). Conclusion In our brazilian cohort, the +874 T/A IFN-gamma gene polymorphism was Not associated with the onset of AAA. Also, there was No association between IFN-gamma gene polymorphism and the antigen HLA-DR15. TT phenotype, possibly the predisposing one for disease, was expressed only in 15% of patients with AAA. These findings corroborate the presence of a much more complex pathogenesis in AAA ,and that, regional differences in genetic and immune mechanisms may co-exist. Disclosures: No relevant conflicts of interest to declare.

Description: Background: Sickle cell disease (SCD) has a clinical heterogeneity and vasoocclusive events are an important clinical characteristic among patients. The paraoxonase 1 (PON 1) is a serum glycoprotein associated with the high-density lipoproteins cholesterol (HDL-C) and the variability of the PON1 activity has been associated with the PON1 genotypes. We tested a possible relevance of the PON1 in SCD patients in steady and crisis state, studying its activity and genotype, investigating M55L (rs854560) and R192Q (rs662) polymorphisms, and their association with markers of hemolysis, inflammation and organ dysfunction. Methods: The casuistic of the study was compound by 373 individuals, 154 SCD patients in steady state, 23 SCD patients in crisis, and 196 healthy controls. Chemistry, inflammatory and hematological biomarkers were investigated by chemiluminescence, immunoassay and electronic cell counter respectively. Molecular biology analyses were performed by PCR and PCR-RFLP techniques. Results: The allelic frequency of PON1192R among SCD patients group was 0.38 and of PON1192Q was 0.62. The allelic frequency of the control group individuals was 0.45 to the PON1192R and 0.55 to PON1192Q. The allelic frequency of PON1M55L gene polymorphism was 0.91 to the PON155L and 0.09 to the PON155M among the SCD patients group. The allelic frequency of the PON155L was 0.85 and for the PON155M was 0.15 among individuals of the control group. PON1 gene polymorphisms allelic frequencies were in Hardy-Weinberg equilibrium. Patients with genotype RR of PON1192 (p=0.0015) and MM of PON155 (p=0.0013) showed less PON1 activity than others genotypes. PON1 activity was higher among SCD patients in crisis and steady states than in control group individuals (p

Description: Background: In the pivotal Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients (ENESTnd) study, frontline NIL 300 mg and 400 mg twice daily (BID) resulted in higher rates of deep molecular response and lower rates of disease progression than imatinib in pts with CML-CP. In the ENEST-Extending Molecular Responses (ENESTxtnd) study, the kinetics of molecular response to NIL 300 mg BID and novel dose optimization strategies were evaluated. Methods: ENESTxtnd was a 24 months (mo), phase 3b study of de novo pts with CML-CP within 6 mo of diagnosis. Primary endpoint was rate of major molecular response (MMR; BCR-ABL1 ≤ 0.1% on the International Scale [IS]) by 12 mo. Initial dose for all pts was NIL 300 mg BID. Dose escalation to NIL 400 mg BID was permitted for pts with suboptimal response (SoR) or treatment failure. Dose reduction to NIL 450 mg once daily (QD) was performed as required by the protocol; reescalation was permitted following adverse event (AE) improvement. Successful reescalation was defined as ≥ 4 weeks of NIL 300 mg BID with no dose adjustments for any AE. Rates of overall survival (OS; considering all deaths during the study) and progression-free survival (PFS; considering events during study treatment) were estimated by Kaplan-Meier analysis. Results: A total of 421 pts (median age, 48 y; males, 53.7%) were enrolled. Median time on study treatment was 23.7 mo; 328 pts (77.9%) completed 24 mo of treatment, and 93 pts (22.1%) discontinued early due to AEs (n = 43), consent withdrawal (n = 7), disease progression (n = 6), protocol deviation (n = 6), loss to follow-up (n = 5), death (n = 4), pregnancy (n = 2), or other reasons (n = 20). Of the 92 pts (21.9%) dose-escalated, 88 (20.9%) were dose-escalated due to lack of efficacy (SoR, 83, 19.7%; treatment failure, 5, 1.2%) and 4 due to dosing error; 11 pts were dose-escalated at 3 mo. Of the dose-escalated pts, 5 and 9 pts discontinued due to SoR and treatment failure, respectively. A total of 144 pts (34.2%) had dose reductions, dose reduction due to AEs were reported in 74 pts; 106 pts attempted to reescalate to NIL 300 mg BID, and 92 successfully reescalated. Median duration of exposure of all pts was 23.2 mo and median actual dose intensity was 598.8 mg/d (range, 150-760 mg/d). At 12 mo, 306, 33, 16, and 7 pts were on NIL 300 mg BID, 400 mg BID, 450 mg QD, and other doses respectively; 59 pts had discontinued prior to 12 mo. Of the 306 pts on NIL 300 mg BID at 12 mo, 136 did not have any dose modification (interruption/reduction/escalation) prior to 12 mo and 170 had ≥1 dose modification. Of the 170 pts, 88 had ≥ 1 dose reduction followed by reescalation to 300 mg BID. Among the 16 pts on a reduced dose at 12 mo, 4 later re-escalated to NIL 300 mg BID. The cumulative MMR rate (95% CI) was 70.8% (66.2%-75.1%) by 12 mo and 81.0% (76.9%-84.6%) by 24 mo (figure). Of the 88 pts with dose escalation due to lack of efficacy, 63.6% achieved MMR by 24 mo (Table 1). Of the 144 pts with dose reduction, 75.7% achieved MMR by 24 mo, including 78 of 92 pts (85%) who successfully reescalated to NIL 300 mg BID (Table 2). The cumulative rate of complete cytogenetic response by 24 mo was 74.1 %. Ten pts had PFS events on treatment (progression, n = 6; death, n = 4), and 9 deaths were reported at any time on study and during follow-up 2 due to CML; 1 each due to cardiorespiratory arrest, intestinal infarction, acute leukemia, increased intracranial pressure, accident, suicide, and unknown). The estimated rates (95% CI) of PFS and OS at 24 mo were 97.0% (95.1%-98.8%) and 97.6% (96.1%-99.2%), respectively. The most common nonhematologic drug-related AEs of any grade were rash (15.4%), headache (10.5%), and nausea (10.2%), and new or worsening grade 3/4 laboratory abnormalities were lipase abnormalities (14.5%), neutropenia (11.9%), and thrombocytopenia (10.5%). Cardiovascular events were observed in 19 pts (4.5%), including ischemic heart disease (n = 14), ischemic cerebrovascular events (n = 1), and peripheral artery disease (n = 5). Conclusion: Dose-optimized frontline NIL resulted in rapid reductions in BCR-ABL1IS levels andvery few progressions or deaths. Most pts achieved MMR by 24 mo, including 〉 60% of pts who were dose-escalated due to lack of efficacy and 〉 80% of pts who were successfully reescalated after dose reduction. The safety profile of NIL was consistent with previous studies. These results support the use of NIL 300 mg BID, with dose optimization as necessary, in pts with newly diagnosed CML-CP. Disclosures Hughes: ARIAD: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Off Label Use: The indicated label for newly diagnosed CML chronic phase patients is 300 mg twice daily. This abstract discusses modifications of this dose.. Salvino:Novartis: Research Funding. Shortt:Novartis, Bristol Meyers Squibb: Honoraria, Other: Sponsorship to attend conferences, Speakers Bureau. Quach:Celgene Corp, ONYX, Janssen, Takeda, Novartis, BMS: Honoraria, Research Funding. Pavlovsky:Novartis - Bristol: Speakers Bureau. Louw:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Unrestricted educational grant, Research Funding, Speakers Bureau. Shih:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Turkina:Novartis International AG: Consultancy; Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy. Meillon:Novartis, Bayer, BMS, Pfizer, AMGEN: Honoraria, Speakers Bureau. Jin:Novartis: Employment. Khanna:Novartis: Employment. Dalal:Novartis: Employment, Equity Ownership. Lipton:Ariad: Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Description: Sickle cell disease (SCD) has heterogeneous clinical picture and there are several pathway involved in SCD pathogenesis, and chronic inflammation and hemolysis are important hallmarks of the disease. Based on such points, there is a search for prognostic markers to establish possible sub-genotypes of the disease. The present study investigated the alpha-1 antitrypsin (AAT) levels, a serum glycoprotein inhibitor of proteases responsible for trigger inflammatory reactions, describing its associations with SERPINA1 gene polymorphisms, hematological and chemistry biomarkers, and clinical history in a group of SCD children in steady-state. The study was approved at FIOCRUZ research board and followed the principle of Declaration of Helsinki. A total of 356 steady state unrelated SCD patients were included at the present study and a control group (CG) compound by 100 unrelated healthy individuals sex and age matched with the patients group, which were from the same geographical origin. Patients age ranging 13.96+9.91 years of age, the AAT levels higher than the 50th percentile (158.0 mg/mL) had significantly lower red blood cells (RBC) count (p=0.003), hemoglobin (Hb) (p=0.0002) and hematocrit (Hct) (0.0002) concentration, and higher white blood cells (WBC) (p=0.004) and neutrophils (p=0.0001) counts, and higher C-reactive protein (CRP) levels (p

Description: Introduction Aplastic anemia (AA) is perceived as an immune mediated disease where T-lymphocytes recognize and destroy bone marrow elements leading to varying degrees of failure of hematopoiesis. Many autoimmune diseases have been linked to certain HLA alleles and such a relationship has been also been reported in AA. Expansion of CD8+ oligoclones has been reported in AA and likely contributes to pathogenesis. However, the interaction of CD4+ and CD8+ T cells and their targets mediated by human leukocyte antigen (HLA) class I and II peptides remain elusive. Thus, it has been speculated that polymorphic loci of these genes could be implicated in the susceptibility to the disease. Various alleles and haplotypes of HLA molecules have been implicated in the predisposition of AA development. The influence of HLA has been studied in North America, European and Asian countries. Data from Latin America, where there is a large mixture of Hispanic, European, and African descendants, is still lacking. This study focuses on the association between HLA alleles in AA patients in different regions of Brazil with particular ethnic groups. Patients and methods From 2000 to 2013, all patients with a diagnosis of acquired AA in the Brazilian state of Bahia (BA) followed at the Federal University of Bahia Hospital/ Foundation Hemoba who tested the HLA typing were included, totaling 215 patients. In this northeast region there is a predominance of African descendant (25% white, 75% brown/black). The genes in the analysis included HLA A, B, DR and DQ. SPSS was used to statistical calculations. Qui-square test/Fisher test were using the p-value correction of Bonferroni (p significant

Description: Introduction: Mutations that activate the RAS-RAF-MEK-ERK pathway have long been known to occur in patients with solid tumors and hematological malignancies. The most common mutations occur in the Ras family of GTPases (HRAS, NRAS, KRAS) and the Raf family of serine-threonine kinases (ARAF, BRAF, CRAF). In myeloid malignancies, RAS mutations have mainly been described in patients with acute myeloid leukemia, chronic myelomonocytic leukemia (CMML) and myelodysplastic syndrome. There are few studies describing the incidence of mutations of the RAS-RAF-MEK-ERK pathway in patients with MPNs other than CMML. Objective: To describe the incidence, clinical features and prognostic impact of Ras and Raf mutations in patients with Ph-negative MPNs and MPN/MDS-U Methods: Paired DNA (sorted CD66b-granulocytes/skin biopsy) from patients with MPNs or MPN/MDS was subjected to whole exome sequencing on a Illumina HiSeq 2000 platform using Agilent SureSelect kit (see our abstract “Whole Exome Sequencing of Myeloproliferative Neoplasms and Myelodysplastic/Myeloproliferative Disorders”). Tumor coverage was 150x and germline coverage was 60x. Somatic variants calls were generated by combining the output of Somatic Sniper (Washington University), Mutect (Broad Institute) and Pindel (Washington University), followed by in-house filters to reduce false positive calls. Statistical calculations were done in Stata, v11.0. Results: We found clonal activating mutations of the RAS-RAF-MEK-ERK pathway in 8 patients (6.7% of cases). Diagnosis included primary myelofibrosis (PMF; N=5), MDS/MPD-U (N=2) and essential thrombocythemia (ET; N=1). Their clinical features are summarized in Table 1 (three of these patients [UPIs #11, #13, #99] are also described in the abstract “Genomic Profile of Patients with Triple Negative (JAK2, CALR and MPL) Essential Thrombocythemia and Primary Myelofibrosis”). There were 7 NRAS mutations and 1 BRAF mutation. In 5 cases the variant allele fraction (VAF) of reads in the tumor sample indicated that the mutation was present in a subclone at the time of sequencing. We next compared the clinical features of these 8 patients with 79 patients (MF=43, ET=35, MDS/MPD=1) who did not harbor these mutations. Patients with NRAS/BRAF mutations had lower hemoglobin (8.3 vs. 11.8 g/dL, p=0.001), higher white blood cell counts (28.37 vs. 7.7 x109/L, p=0.008) and had higher lactate dehydrogenase (1041 vs. 685 IU/L, p=0.02). They also had worse overall survival compared to unmutated cases (Hazard ratio [HR]=11.57; p=0.001). Most patients with NRAS/BRAF mutations had a high number of concomitant driver mutatons (median 5 vs. 1; p

Description: Introduction: Autologous Hematopoietic Stem Cell Transplant (AHCT) is an integral part of the treatment for many hematological and immunological diseases. However, the AHCT is associated with several complications, including liver diseases, such as sinusoidal obstruction syndrome (SOS), viral hepatitis, and sepsis-associated cholestasis. Drug-induced liver injury (DILI) is one of the most common and serious adverse drug side effects. This issue is particularly important in the context of high dose chemotherapy but it is still understudied. This study aims to determine the incidence of SOS and DILI among patients who underwent the autologous stem cell transplant. Methods: A retrospective cohort study was conducted among all patients who had undergone an autologous stem cell transplant at the hospital of Universidade Federal da Bahia (UFBA), Brazil, from July 2010 to July 2017. Daily weight and clinical and laboratory data ̶ aminotransferases, alkaline phosphatase (ALP), gamaGT (GGT), and total bilirubin (TB) levels ̶ were collected from beginning of the conditioning regimen to D+21 post-transplant. SOS diagnosis was based on modified Seattle Criteria (2 of 3 of the following items during the first 21 days post-transplant: TB ≥ 2mg/dl, hepatomegaly or upper right quadrant abdominal pain, and weight gain above 2% of pre-transplant weight). SOS severity was based on EBMT criteria. The International Serious Adverse Events Consortium 2011 criteria was used for DILI diagnosis, considering any of the following: (1) hepatocellular DILI: ALT ≥ 5 x upper limit normal (ULN); (2) cholestatic DILI: ALP ≥ 2 x ULN, especially in patients with elevated GGT, and without bone-disease-related ALP elevation; (3) mixed DILI: ALT ≥ 3 x ULN and total bilirubin (TB) ≥ 2 x ULN. All patients with SOS were excluded for the DILI diagnosis. All statistics were calculated using SPSS v 20.0 (SPSS Inc). Descriptive analysis and chi-square were applied, and the alpha error was 5%. The study protocol was approved by the institutional review board. Results: One hundred and seventy-five patients were included in the study. The mean age was 44.2 ± 15.4 years old, and 56.6% of patients (n= 99) were male. The main transplant indications were the following: multiple myeloma (55.4%, n= 97), lymphoma (36.0%, n= 63), acute myeloid leukemia (3.4%, n= 6), and germ cell tumor (3.4%, n= 6). Most patients presented aminotransferases (73.1%, n= 128) or ALP (44.0%, n= 77) elevations, but DILI incidence was 12% (n= 21). Hepatic, cholestatic, and mixed DILI were found in 3 (1.7%), 15 (8.6%), and 3 (1.7%) patients respectively. Five of six patients who developed hepatocellular or mixed DILI were exposed to etoposide (p=0.006). Cholestatic DILI occurred in 12 melphalan-based and 3 busulfan-based patients. The prophylactic use of ursodeoxycholic acid (UDCA) was associated with lower incidence of DILI (incidence among UDCA users: 1/43; incidence among non-users of UDCA: 20/132; p= 0,028). Mortality among DILI patients was 12% (n=2). SOS incidence was 6.9% (n= 12); 4 (33.3%) patients with mild, 4 (33.3%) with moderate, 2 (16.7%) with severe, and 2 (16.7%) with severe SOS. A higher incidence of SOS was found among recipients who was transplanted for germ cell tumors (p= 0.004); those previously submitted to abdominal irradiation (p= 0.068) and iron overload (p= 0.068); only one patient died from this syndrome. Almost all (83.3%; n=5) patients submitted to AHCT for germ cell tumors (using carboplatin + etoposide as conditioning regimen) developed liver injury (3 patients developed SOS and 2 developed DILI). Conclusion: Liver injury associated with the autologous hematopoietic stem cell transplant, represented mainly by DILI and SOS, had a high incidence (18.9%) among the subjects in the study and was associated with an elevated mortality rate. Drug induced liver injury has been underestimated and deserves further studies. Disclosures No relevant conflicts of interest to declare.

Description: Background: CD38-targeting antibody Daratumumab (Dara) has been demonstrating significant improvement in (MM) patient's survival. Cyclophosphamide (C), thalidomide (T) and dexamethasone (D) - (CTd) is one of the most used induction protocols worldwide and the MAX-Dara study was the first that combine Dara-CTd as induction for (NDMM) (TE) patients. We hypothesized that this new combo + autologous stem cell transplantation (ASCT) could affect the quantitative recovery of distinct lymphocytes subsets. Objective: Primary endpoint was to quantify lymphocytes subpopulations in (NDMM) (TE) patients at different treatment phases. Secondary endpoint was to evaluate B cells subsets at same times. Methods: Peripheral blood of 10 NDMM TE patients was collected at three different moments: at diagnose, after 4 induction cycles and after two consolidation cycles post- (ASCT). Dara-CTd protocol was for up to four 28-day induction cycles: C-500mg per oral (PO) d 1,8 and 15, T at 100-200mg PO d 1 to 28, Dex at 40mg PO d 1,8,15 and 22 and Dara 16mg/Kg/dose IV on d 1,8,15 and 22 during cycles 1 - 2 and every other week in cycles 3 - 4, followed by ASCT. Consolidation was started at D+30 after ASCT and all patients received up to four 28-day consolidation cycles: Dara 16mg/Kg and (D) at 40mg every other week, associated with T at 100mg PO d 1 - 28. Dara 16mg/Kg was used monthly as maintenance until progression or limiting toxicity. Flow cytometry was used to detect lymphocyte surface by CD3, CD4, CD5, CD8, CD16, CD19, CD20, CD38, CD45 and CD56 in the scatter plot. B cells were isolated and subpopulations (naïve B cells, class and non-class switched memory B cells, , IgD-CD27- memory B cells and plasma blasts) were detected by CD20, CD24, CD27, CD38, CD45 and IgD. Statistical analysis was performed using the SPSS® v25.0. Results: The median number of lymphocytes subsets at diagnosis were 1139 x 10³/μL for T cells, 155 x 10³/μL for B cells and 284 x 10³/μL for NK cells. After four cycles of Dara-CTD the median number of T, B and NK cells had dropped to 834, 7.5 and 8.0 x 10³/μL respectively (p

Description: Introduction Acute myeloid leukemia (AML) is the most prevalent acute leukemia in adults and originates from hematopoietic precursor cells that suffers genetics and epigenetics alterations leading to a clone able to proliferate with survival advantages. The last years have been of great advances in AML because of more profound knowledge of its pathogenic mechanisms. This lead to a better stratification of the patients based on cytogenetics and molecular criteria and development of targeted therapy that changed its natural course. Unfortunately, the tests and new drugs are expensive and not easily available worldwide, especially in low and middle-income countries (LMIC) with distinct realities between private and public care. Methods To determine the profile and outcomes of patients in a public health center in Brazil, we did a retrospective analysis of all the cases of non-promyelocytic AML diagnosed between 2007 and 2017 in the University Hospital Professor Edgar Santos of Federal University of Bahia. 62 patients were included and we used a modified model of European LeukemiaNet 2017 classification to risk stratification, with cases of secondary AML (sAML) included in the high risk group. Results A total of 62 patients were analyzed, 1 died prior treatment and was excluded. Median age at diagnosis was 44 years (range, 16-83 years) with 58% females. 68% werede novoAML. 11% of patients were classified as favorable risk, 8% as intermediate and 42% as high risk. 39% had unknown risk because of absence of cytogenetic and/or molecular tests. The chemotherapy protocol in patients eligible to intensive treatment was 7+3 in 87%. 20% of the patients died during induction and 65% achieved response (53% complete + 12% partial remission). Analyzing only sAML, 35% were considered fit for intensive treatment and most of less intensive regimens were based in low-dose cytarabine (64%). The overall response rate of sAML after induction was 20%. During the treatment, 31% relapsed with a median time to relapse of 8 months. 43% of the relapses happened in patients classified as unknown risk. 37% of patients that survived induction were submitted to allogeneic bone marrow transplant (alloBMT) and had survival advantage (hazard ratio, HR: 2,52, 95% CI: 1.103 - 5,795;P= 0.028; Figure 1), with superior median overall survival (mOS) (49 months) when compared with the chemotherapy group (11 months) (P= 0.021). During the follow-up, 77% of the patients died and most of the deaths (61%) occurred in the first year of diagnosis. The primary cause of death was infection (52%) followed by leukemia progression (31%). The mOS was 7 months and 5-year OS was 27%. Stratifying by the risk, the mOS was shorter in patients with unknown and high risk (5 and 4 months, respectively) than in low and intermediate risk (not reached,P= 0.01; Figure 2). The median relapse free survival (RFS) was 15 months, reached only in the high risk group (14 months;P= 0.31; Figure 3). The patients with sAML had mOS of 3 months versus 11 months ofde novoAML(P =0.024; Figure 4). Discussion In summary, we found statistical difference in better OS among patients that received BMT, AMLde novoand favorable/intermediate risk. Our findings were similar to those reported by other groups of university hospitals in Brazil. An alarming data is the high proportion of patients who were not adequately stratified. Our data are from real life and this subgroup still exists because cytogenetic and molecular tests are not universally available in the brazilian public health system. Those patients had similar outcomes to high risk ones suggesting that a proportion of them were undertreated. It is important for every center to be aware of their survival curves to better individualize their approaches. We suggest that patients with inadequate risk assessment should undergo alloBMT as this remains the primary curative intervention and the main outcome changer in real-world setting of LMIC. Our high mortality rate, in comparison with data from developed countries, reflects the absence of more effective therapies, especially for high risk cases, and an inferior hospital infrastructure contributing to a higher incidence of infections. Considering the discovery of new powerful drugs, the tendency of discrepant outcomes between centers from LMIC and developed countries is considerably high. Therefore, the improvement of access to diagnostic techniques and treatment is still an unmet need in AML scenario. Disclosures No relevant conflicts of interest to declare.