Adult Acute Leukemia Research Articles

The Association between Single Nucleotide Polymorphisms rs1042522 and rs1642785 in the TP53 gene and Acute Myeloid leukemia in a sample of the Baghdad/ Iraq population

يمثل سرطان الدم النخاعي الحاد (AML) أكثر أنواع سرطان الدم الحاد انتشارًا بين البالغين تصل نسبته 80% من جميع الحالات. الجين المثبط للورم TP53 هو جين تمت دراسته بشكل متكرر في مرض السرطان .والطفرات في هذا الجين تسبب ما يقارب 50% من الامراض السرطانية. هدفت هذه الدراسة إلى تقييم العلاقة بين اثنين من تعدد أشكال النوكليوتيدات المفردة في جين TP53: rs1042522 ، rs1642785 ومجموعة من المرضى العراقيين الذين يعانون من التشخيص الاولي لسرطان الدم النخاعي الحاد. جمعت عينات الدم من ستين مريضاً 26 ذكور و 34 أناث وستين عينة سيطرة 26 ذكور و 34 أناث متوافقين في الجنس والعمر والعرق. تم استخلاص الحمض النووي الجيني من عينات الدم المجمدة بالكامل باستخدامEasy Pure® Blood Genomic Kit . ثم تم قياس النقاوة والتركيز باستخدام مقياس الطيف الضوئي Nano drop NAS-99. حيث تراوحت قراءات التركيز بين (7-55 نانوغرام / ميكرولتر) وتراوحت النقاوة بين 1.78 - 1.9 تم استخدام تقنيةreal time PCR (High resolution melt (HRM للكشف عن تعدد اشكال النيوكليوتيدات المفردة و كانت تكرارات النمط الجيني لجين TP53 متوافقة مع توازن هاردي-واينبرغ مع وجود فروق معنوية ذات دلالة إحصائية p≤0.05 بين الأنماط الجينية لمجموعة السيطرة والمرضى. كان تكرار النمط الجيني rs1042522 مختلفًا بشكل كبير بين المرضى وافراد السيطرة p = 0.0001، وكان المشاركون الذين لديهم النمط الوراثي GA أكثر عرضة للإصابة بسرطان الدم النخاعي الحاد OR=7.8, 95% CI 3.2–18.4, p = 0.0001. بالإضافة الى تكرار النمط الجيني rs1642785 مختلفًا بشكل كبير بين المرضى و افراد السيطرة p=0.002 والذين يحملون النمط الجيني GA أكثر عرضة للإصابة بسرطان الدم النخاعي الحاد OR=3.5, 95% CI 1.5–8.12, p=0.002.

Genomic and global gene expression profiling in pediatric and young adult acute leukemia with PICALM::MLLT10 Fusion.

MLLT10 fusion is a rare but recurrent genetic driver in acute leukemias. To better understand the genomic landscape of PICALM::MLLT10 (PM) positive acute leukemia, we performed genomic profiling and gene expression profiling in twenty PM-positive patients, including AML (n = 10), T-ALL/LLy (n = 8), Mixed-phenotype acute leukemia (MPAL), T/B (n = 1) and acute undifferentiated leukemia (AUL) (n = 1). Besides confirming the known activation of HOXA, differential gene expression analysis compared to hematopoietic stem cells demonstrated the enrichment of genes associated with cell proliferation-related pathways and relatively high expression of XPO1 in PM-AML and PM-T-ALL/LLy. Our study also suggested PHF6 disruption as a key cooperating event in PICALM::MLLT10-positive leukemias. In addition, we demonstrated differences in gene expression profiles as well as remarkably different spectra of co-occurring mutations between PM-AML and PM-T-ALL/LLy. Alterations affecting TP53 and NF1, hallmarks of PM-AML, are strongly associated with disease progression and relapse, whereas EZH2 alterations are highly enriched in PM-T-ALL/LLy. This comprehensive genomic and transcriptomic profiling provides insights into the pathogenesis and development of PICALM::MLLT10 positive acute leukemia.

Increased expression of CD70 in relapsed acute myeloid leukemia after hypomethylating agents.

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. While induction chemotherapy leads to remission in most patients, a significant number will experience relapse. Therefore, there is a need for novel therapies that can improve remission rates in patients with relapsed and refractory AML. CD70 is the natural ligand for CD27 (a member of the TNF superfamily) and appears to be a promising therapeutic target. Consequently, there is considerable interest in developing chimeric antigen receptor (CAR) T-cell therapy products that can specifically target CD70 in various neoplasms, including AML. In this study, we employed routine diagnostic techniques, such as immunohistochemistry and flow cytometry, to investigate the expression of CD70 in bone marrow samples from treatment-naïve and relapsed AML patients after hypomethylating agents (HMA). Also, we evaluated the impact of HMA on CD70 expression and examined CD70 expression in various leukemic cell subsets and normal hematopoietic progenitors.

Significance of OCT3/4 and SOX2 antigens expression by leukemic blast cells in adult acute leukemia

ObjectiveThis study aimed to address the prognostic impact of SOX2 and OCT3/4 expression on adult acute leukemia patients’ outcomes.MethodsSOX2 and OCT3/4 expression by blast cells were evaluated by flow cytometry in 80 acute leukemia patients and 8 healthy controls.ResultsBaseline SOX2 and OCT3/4 expression were significantly higher in both ALL (P = < 0.001, P = 0.005 respectively) and AML patients (P < 0.001, P = 0.003 respectively) as compared to control, and decline at complete remission (CR) and elevated again at relapse. High SOX2 and OCT3/4 levels were significantly correlated with the presence of adverse risk stratification parameters.ConclusionOur findings indicated that both SOX2 and OCT3/4 could serve as biomarkers that could improve risk stratification of acute leukemia patients. Also, both SOX2 and OCT3/4 might be a therapeutic target, especially in resistant acute leukemia.

Transcriptome Analysis in Mexican Adults with Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) represents around 25% of adult acute leukemias. Despite the increasing improvement in the survival rate of ALL patients during the last decade, the heterogeneous clinical and molecular features of this malignancy still represent a major challenge for treatment and achieving better outcomes. To identify aberrantly expressed genes in bone marrow (BM) samples from adults with ALL, transcriptomic analysis was performed using Affymetrix Human Transcriptome Array 2.0 (HTA 2.0). Differentially expressed genes (DEGs) (±2-fold change, p-value < 0.05, and FDR < 0.05) were detected using the Transcriptome Analysis Console. Gene Ontology (GO), Database for Annotation, Visualization, and Integrated Discovery (DAVID), and Ingenuity Pathway Analysis (IPA) were employed to identify gene function and define the enriched pathways of DEGs. The protein-protein interactions (PPIs) of DEGs were constructed. A total of 871 genes were differentially expressed, and DNTT, MYB, EBF1, SOX4, and ERG were the top five up-regulated genes. Meanwhile, the top five down-regulated genes were PTGS2, PPBP, ADGRE3, LUCAT1, and VCAN. An association between ERG, CDK6, and SOX4 expression levels and the probability of relapse and death was observed. Regulation of the immune system, immune response, cellular response to stimulus, as well as apoptosis signaling, inflammation mediated by chemokines and cytokines, and T cell activation were among the most altered biological processes and pathways, respectively. Transcriptome analysis of ALL in adults reveals a group of genes consistently associated with hematological malignancies and underscores their relevance in the development of ALL in adults.

Discovery of novel selective phosphodiesterase‑1 inhibitors for the treatment of acute myelogenous leukemia

Acute myelogenous leukemia (AML) is the most common form of acute leukemia in adults. PDE1 (Phosphodiesterase 1) is a subfamily of the PDE super-enzyme families that can hydrolyze the second messengers cAMP and cGMP simultaneously. Previous research has shown that suppressing the gene expression of PDE1 can trigger apoptosis of human leukemia cells. However, no selective PDE1 inhibitors have been used to explore whether PDE1 is a potential target for treating AML. Based on our previously reported PDE9/PDE1 dual inhibitor 11a, a series of novel pyrazolopyrimidinone derivatives were designed in this study. The lead compound 6c showed an IC50 of 7.5 nM against PDE1, excellent selectivity over other PDEs and good metabolic stability. In AML cells, compound 6c significantly inhibited the proliferation and induced apoptosis. Further experiments indicated that the apoptosis induced by 6c was through a mitochondria-dependent pathway by decreasing the ratio of Bcl-2/Bax and increasing the cleavage of caspase-3, 7, 9, and PARP. All these results suggested that PDE1 might be a novel target for AML.

Acute myeloid leukemia: Current understanding and management.

Although relatively rare, acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. AML is associated with poor 5-year overall survival and prompt treatment is critical. Classifying AML based on World Health Organization criteria is important for determining prognosis and applying a risk-adapted treatment approach. Throughout therapy, patients require comprehensive supportive care measures with blood product transfusions, antimicrobial treatment, and frequent monitoring for chemotherapy-related complications. This article provides an overview of AML and its treatments. Clinicians in all specialties must be able to recognize the early signs of AML and ensure their patients seek appropriate expert medical care with a hematologist/oncologist.

Isolation of acute myeloid leukemia blasts from blood using a microfluidic device.

Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and associated with poor prognosis. Unfortunately, most of the patients that achieve clinical complete remission after the treatment will ultimately relapse due to the persistence of minimal residual disease (MRD), that is not measurable using conventional technologies in the clinic. Microfluidics is a potential tool to improve the diagnosis by providing early detection of MRD. Herein, different designs of microfluidic devices were developed to promote lateral and vertical mixing of cells in microchannels to increase the contact area of the cells of interest with the inner surface of the device. Possible interactions between the cells and the surface were studied using fluid simulations. For the isolation of leukemic blasts, a positive selection strategy was used, targeting the cells of interest using a panel of specific biomarkers expressed in immature and aberrant blasts. Finally, once the optimisation was complete, the best conditions were used to process patient samples for downstream analysis and benchmarking, including phenotypic and genetic characterisation. The potential of these microfluidic devices to isolate and detect AML blasts may be exploited for the monitoring of AML patients at different stages of the disease.

Acute Myelomonoblastic Leukemia (My1/De): A Preclinical Rat Model.

Since acute myeloid leukemias still represent the most aggressive type of adult acute leukemias, the profound understanding of disease pathology is of paramount importance for diagnostic and therapeutic purposes. Hence, this study aimed to explore the real-time disease fate with the establishment of an experimental myelomonoblastic leukemia (My1/De) rat model using preclinical positron emission tomography (PET) and whole-body autoradiography. In vitro [18F]F-FDG uptake studies were performed to compare the tracer accumulation in the newly cultured My1/De tumor cell line (blasts) with that in healthy control and My1/De bone marrow suspensions. Post transplantation of My1/De cells under the left renal capsule of Long-Evans rats, primary My1/De tumorigenesis, and metastatic propagation were investigated using [18F]F-FDG PET imaging, whole-body autoradiography and phosphorimage analyses. To assess the organ uptake profile of the tumor-carrying animals we accomplished ex vivo biodistribution studies. The tracer accumulation in the My1/De culture cells exceeded that of both the tumorous and the healthy bone marrow suspensions (p<0.01). Based on in vivo imaging, the subrenally transplanted My1/De cells resulted in the development of leukemia in the abdominal organs, and metastasized to the mesenterial and thoracic parathymic lymph nodes (PTLNs). The lymphatic spread of metastasis was further confirmed by the significantly higher %ID/g values of the metastatic PTLNs (4.25±0.28) compared to the control (0.94±0.34). Cytochemical staining of the peripheral blood, autopsy findings, and wright-Giemsa-stained post-mortem histological sections proved the leukemic involvement of the assessed tissues/organs. The currently established My1/De model appears to be well-suited for further leukemia-related therapeutic and diagnostic investigations.

The Relation of Baseline Serum Albumin with the Duration of Neutropenia after Induction Chemotherapy in Adult Acute Leukaemia

The Relation of Baseline Serum Albumin with the Duration of Neutropenia after Induction Chemotherapy in Adult Acute Leukaemia

DNA Copy Number Alterations and Copy Neutral Loss of Heterozygosity in Adult Ph-Negative Acute B-Lymphoblastic Leukemia: Focus on the Genes Involved.

The landscape of chromosomal aberrations in the tumor cells of the patients with B-ALL is diverse and can influence the outcome of the disease. Molecular karyotyping at the onset of the disease using chromosomal microarray (CMA) is advisable to identify additional molecular factors associated with the prognosis of the disease. Molecular karyotyping data for 36 patients with Ph-negative B-ALL who received therapy according to the ALL-2016 protocol are presented. We analyzed copy number alterations and their prognostic significance for CDKN2A/B, DMRTA, DOCK8, TP53, SMARCA2, PAX5, XPA, FOXE1, HEMGN, USP45, RUNX1, NF1, IGF2BP1, ERG, TMPRSS2, CRLF2, FGFR3, FLNB, IKZF1, RUNX2, ARID1B, CIP2A, PIK3CA, ATM, RB1, BIRC3, MYC, IKZF3, ETV6, ZNF384, PTPRJ, CCL20, PAX3, MTCH2, TCF3, IKZF2, BTG1, BTG2, RAG1, RAG2, ELK3, SH2B3, EP300, MAP2K2, EBI3, MEF2D, MEF2C, CEBPA, and TBLXR1 genes, choosing t(4;11) and t(7;14) as reference events. Of the 36 patients, only 5 (13.8%) had a normal molecular karyotype, and 31 (86.2%) were found to have various molecular karyotype abnormalities-104 deletions, 90 duplications or amplifications, 29 cases of cnLOH and 7 biallelic/homozygous deletions. We found that 11q22-23 duplication involving the BIRC3, ATM and MLL genes was the most adverse prognostic event in the study cohort.

Epidemiological and clinical characteristics of adult acute lymphoblastic leukemia patients in Chile: A single-center analysis

BackgroundAcute lymphoblastic leukemia represents 20% of acute leukemias in adults. Currently, there is limited data in Chile regarding the clinical, cytogenetic, and prognostic characteristics of this condition. MethodsThis is a retrospective, observational, and descriptive study of 67 patients treated for acute lymphoblastic leukemia at the Arturo Lopez Perez Foundation between 2018 and 2021. The main objective is to evaluate epidemiological and clinical characteristics, as well as identifying factors associated with improved overall survival and/or progression-free survival. Results88% of the cases were B-lineage, mainly the common B phenotype. Cytogenetic analysis was performed in less than 50% of the patients, with lower yield than expected according to the literature. Molecular testing was performed in 86.5% of the patients, with the most frequent alteration being BCR-ABL. No study was performed to search for Ph-like abnormalities. The rate of complete response after induction was 83.3%, the majority of patients having negative minimal residual disease. Only 12% of the patients received consolidation with allogenic bone marrow transplant. At 2 years, the overall survival was 69% and the progression-free survival was 59%. ConclusionThe results in terms of overall survival and progression-free survival are similar to those reported in the literature. Important diagnostic gaps prevent adequate prognostic characterization. Allogeneic consolidation transplantation was performed in a lower percentage than expected, highlighting the national deficit in access to this treatment.

Long-term outcome of children with acute promyelocytic leukemia: a randomized study of oral versus intravenous arsenic by SCCLG-APL group

Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine mainly containing Realgar (As4S4), is highly effective in treating adult acute promyelocytic leukemia (APL). However, the treatment efficacy and safety of RIF have not been verified in pediatric patients. SCCLG-APL group conducted a multicenter randomized non-inferiority trial to determine whether intravenous arsenic trioxide (ATO) can be substituted by oral RIF in treating pediatric APL. Of 176 eligible patients enrolled, 91 and 85 were randomized to ATO and RIF groups, respectively. Patients were treated with the risk-adapted protocol. Induction, consolidation, and 96-week maintenance treatment contained all-trans-retinoic acid and low-intensity chemotherapy, and either ATO or RIF. The primary endpoint was 5-year event-free survival (EFS). The secondary endpoints were adverse events and hospital days. After a median 6-year follow-up, the 5-year EFS was 97.6% in both groups. However, the RIF group had significantly shorter hospital stays and lower incidence of infection and tended to have less cardiac toxicity. All 4 relapses occurred within 1.5 years after completion of maintenance therapy. No long-term arsenic retentions were observed in either group. Substituting oral RIF for ATO maintains treatment efficacy while reducing hospitalization and adverse events in treating pediatric APL patients, which may be a future treatment strategy for APL.

Novel chimeric antigen receptor targets and constructs for acute lymphoblastic leukemia: Moving beyond CD19.

Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults with a poor prognosis with relapsed or refractory (R/R) B-cell lineage ALL (B-ALL). Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown excellent response rates in RR B-ALL, but most patients relapse due to poor persistence of CAR T-cell therapy or other tumor-associated escape mechanisms. In addition, anti-CD19 CAR T-cell therapy causes several serious side effects such as cytokine release syndrome and neurotoxicity. In this review, we will discuss novel CAR targets, CAR constructs, and various strategies to boost CARs for the treatment of RR B-ALL. In addition, we discuss a few novel strategies developed to reduce the side effects of CAR.

Frequency and Prognostic Impact of Aberrant Antigens Expression among Egyptian Adult Acute Leukemia.

Aberrant antigen expression was reported to be due to genetic and epigenetic dysregulation. This study aimed to address aberrant antigen expression and its link to poor prognostic genetic markers in acute leukemia patients. This study included 432 newly diagnosed acute leukemia patients (AML, B-ALL). For all included patients blast cells expression for line assignment CD33 CD13 on B-All and CD7 on cytogenetically normal-AML blasts was assessed by flow cytometry in parallel to FLT3 and Philadelphia and philadelphia like chromosome in B-ALL. From the total 432 cases of acute leukemia, the most frequent aberrant antigen expressed in B acute lymphoid leukemia (ALL) was CD33 (23.3%) followed by CD13(16.7%); while the most frequent one in AML was CD7 (16.7%). Aberrant myeloid phenotype in B-ALL was associated with lower mean total leukocytes count (TLC), low platelets count, positive Philadelphia like chromosome, shorter overall survival compared to the B-ALL without. Aberrant lymphoid phenotype (CD7) in AML was associated with a higher platelets count, FLT3 mutation, shorter disease-free and overall survival compared to those patients without. CD7 aberrant antigen expression is frequently detected in patients with CN-AML and frequently associated with FLT3 mutation. While in patients with B-ALL the most frequently detected ones are CD33 and CD13 which are frequently associated with Philadelphia like chromosome.

The Correlation Study between TP53 Gene Expression and Acute Myeloid Leukemia in Iraq

Acute myeloid leukemia represents the most prevalent type of acute leukemia in adults. Mutations in the tumor protein (TP53) gene have been found in more than half of all human cancers. This study was done to investigate the relationship between TP53 gene expression and the appearance and progression of acute myeloid leukemia in Iraq. This study included 100 subjects, divided into 60 patients suffering from pre-diagnostic acute myeloid leukemia and 40 healthy individuals. The difference in TP53 gene expression between acute myeloid leukemia patients and healthy individuals has been investigated, and the gene expression of TP53 has been measured after extraction of total RNA at concentrations (15–83 ng/µl) and purity (1.76-2). Gene expression has involved calculating the double ΔCt value to assess TP53 expression in the presence of the GAPDH gene as a reference gene. Results showed that gene expression folding (2-∆∆Ct) reflects significant differences in TP53 gene expression. There was overexpression (up-regulation) of the TP53 gene in acute myeloid leukemia patients (mean ± SD: 2.29±2.12) compared with controls (1 ± 0.43), with a p=0.04.

Real-World Study in Acute Leukemia: Epidemiology, Treatment Patterns and Outcomes for Newly Diagnosed AML in Adult Patients from Latin America - Loyal Study

Introduction. Acute myeloid leukemia (AML) is the most frequent leukemia among adults and representing 90% of all cases of acute leukemia in adults. Differences in incidence and burden of AML among regions of the world have been reported. When compared with registries from the US, UK and Sweden, Latin-America (LA) AML has a younger age at diagnosis (median age of 40-47 versus 64 -67 years old). Furthermore, single center studies have suggested poor treatment outcomes in LA. For example, Silveira et al reported a median age at diagnosis of 46 y, frequency of favorable cytogenetics of 26% and median overall survival (mOS) of 12 months in the Brazilian cohort of patients with newly diagnosed AML (nAML) whereas the respective values at Oxford University were 51.5y, 11% and 48 months in British patients. However, wider studies across the region are scarce and there is a need to further explore AML patient characteristics and treatment outcomes in LA. Methods. This is a non-interventional, retrospective multicenter study that aims to describe the epidemiology, clinical and demographic characteristics, treatment patterns, survival outcomes and healthcare resource use of adult patients with nAML in Argentina, Brazil, Chile, and Colombia. Data from medical records of eligible patients that met the inclusion criteria (≥ 18 years old at diagnosis, confirmed diagnosis of nAML between 01 January 2015 and 31 December 2019, and receiving at least one line of treatment) in these LA countries were considered for the analysis, which was descriptive in nature as no hypothesis has been tested. Results: A total of 518 nAML patients were included in the study, 166 from Argentina, 205 from Brazil, 63 from Chile, and 84 from Colombia. Table 1 shows the demographics and clinical characteristics. At treatment initiation, an evaluation of fitness (eligibility) for intensive chemotherapy was available for 94% of the patients (n=489). The majority were considered fit (75.5%; n=391) and received standard 7+3 therapy. About 11% of patients (n=9) were refractory to induction therapy. Median OS for fit patients was 11.9 months, whereas for unfit patients was 5.8 months. Mutational status of genes listed by the European LeukemiaNet (ELN) Classification of 2017 was not available for the majority of cases; risk categories were assigned based on cytogenetics. Patients in the favorable-risk category had a mOS of 30.5 months, whereas those in the intermediate- and unfavorable-risk had 11.1 and 9.1 months, respectively (Figure 1). The probability of 5year OS rates for favorable, intermediate- and unfavorable-risk groups were of 38.8%, 16.6% and 20.9%, respectively. Eighty-six patients (17%) discontinued treatment with reasons being adverse event/toxicity (33%; n=28), death (32%; n=27), and disease progression (17%; n=14). Only 24% of patients (n=125) underwent a subsequent stem cell transplantation (SCT), mainly allogenic (98%; n=121). For SCTs, identical (matched) related (50%; n= 59) and haploidentical donor (35%; n=41) were the most common. Patients not eligible to intensive chemotherapy were treated with HMA (9%; n=47) and LDAC (5%; n=25), with 10% of the patients receiving palliative/supportive care. The most common treatment protocols used in relapsed or refractory (R/R) patients were high-dose cytarabine (HDAC) (31%; n=85), followed by FLAG-IDA (24%; n=66). Conclusions: This study of newly diagnosed acute leukemia characterizes real-world treatment patterns and outcomes in LA clinical practices. Prior to this study, there has been limited published data on the epidemiology and treatment patterns across LA. This study highlights that for nAML patients, the most common treatment in LA is 7+3 and most patients are classified as fit. The vast majority of patients had their risk accessed by cytogenetics analysis only, reflecting the limited access to molecular tests. Fewer patients underwent stem cell transplantation as part of the treatment compared to that reported in US and Europe, probably due to restricted availability of hospital beds dedicated to bone marrow transplantation. When evaluating the overall survival, the study shows higher mOS for favorable risk. In addition, mOS for intermediate and poor cytogenetic risk were similar. A broader access in the region to molecular tests, transplant and new therapies are needed in order to reduce the gap in outcome, especially for patients with intermediate-risk.

Disparities in Genetic Profiles, Risk Stratification and Outcomes in Adults with Acute Myeloid Leukemia Comparing Patients of Hispanic and Non-Hispanic Ethnicity in Central California

Acute myeloid Leukemia (AML) is the most common type of acute leukemia in adults. Ethnic disparities due to distinct biology and socioeconomic status have been described in AML. Prior studies indicated Hispanic AML patients had a younger age at presentation, more frequent high-risk mutations, and worse survival compared with non-Hispanics. We conducted a retrospective study to investigate the differences in AML risk stratification, mutational profiles and outcomes between Hispanic and non-Hispanic AML patients treated at Community Medical Centers (CMC) in Central California. Methods: We retrospectively analyzed patients ≥ 18 years diagnosed with AML between January 2016-December 2022 and treated at CMC in Fresno, CA. Patients with Acute promyelocytic leukemia and patients without complete cytogenetic and molecular data were excluded. The clinical data including age, sex, ethnicity, race, zip code, WBC on diagnosis, cytogenetics, molecular data and treatment regimens were reviewed. Molecular profiling was performed by next generation sequencing using established myeloid panels by NeoGenomics (NeoTYPE comprising of 63 genes) or Foundation One Heme laboratory (406 genes). Risk groups were identified based on the European Leukemia Network (ELN) 2022 criteria. RedCap data collection tool was used for data collection. A comparison of patient characteristics and rate of genetic alterations between Hispanic and Non-Hispanic patients was done using the Fisher exact test or Chi-square test. Kaplan-Meier Curve with log-rank test was used for evaluation of overall survival (OS) and progression-free survival (PFS). Results: 201 patients met the study criteria, 30 of them did not receive treatment and were included for their diagnostic data only but excluded from the survival analysis. The mean age at diagnosis was 65.6. 58.5% were males and 30% were Hispanic. Hispanic patients were younger than non-Hispanics (57.6 vs 64.6 years, p=0.01). Hispanic patients were also more likely to live in the relatively low Socioeconomic status (SES) neighborhoods (i.e., living in zip codes with the 1st or 2nd quartile of median income level) p=0. 007. More Hispanic patients needed interpreter P&amp;lt;0.001. However, Hispanics were more likely to experience favorable risk AML (8.4 % vs 0.7%, p=0.012), while non-Hispanics had higher rate of poor risk disease (63.8 Vs 55.9%, p=0.012).). There was no significant difference between Hispanics and non-Hispanics in terms of sex, de novo versus secondary AML, WBC at time of diagnosis, Extramedullary or Central nervous system (CNS) involvement, type of induction regimen or rate of consolidative or subsequent allogeneic stem cell transplant. Median OS in Hispanics was 17.3 months compared to 10.28 months for non-Hispanics, p=0.117.and median PFS for Hispanics was 9.17months compared to non-Hispanics at 6.04 months P=0.034 (Figure 1). In univariate analysis PFS and OS were better in patients with normal cytogenetics compared to those with abnormal cytogenetics (15.3 vs 3.52 months and 20.4 vs 7.69 months respectively, p &amp;lt; 0.001) and in patients with favorable compared to intermediate risk and poor risk groups (84.5 vs 11.4 vs 4.1 months for PFS and Non reached vs 18.1 vs 7.8 months for OS, p&amp;lt; 0.001). There was no significant effect of income level in terms of OS or PFS. The most common genetic mutations in our patients were NPM1, FLT3-ITD, DNMT3A, TET2 and TP53. However, there were differences in the rates between Hispanics and non-Hispanics. 5q deletion and STAG2 were more common in non-Hispanics while KMT2C was detected more in Hispanics (table 1). Conclusion: Our study identified biologic differences between Hispanic and non-Hispanic AML patients with heterogeneity in genetic mutations. While Hispanic patients had lower income, they were younger at diagnosis and more likely to have favorable risk AML. Hispanic patients had better PFS and a trend towards improvement in OS. Further studies on larger patient population are warranted to evaluate the effect of ethnicity and SES on outcomes of AML patients.

A Systematic Review of Venetoclax and Azacitidine: Effectiveness and Safety for Newly Diagnosed and Relapsed Acute Myeloid Leukemia Patients

Introduction: Acute Myeloid Leukemia (AML) remains the most prevalent acute leukemia in adults, often associated with a bleak prognosis. Current treatment recommendations for elderly AML patients incorporate a combination of venetoclax (Ven) and azacitidine (AZA) following trials that underscored Ven's efficacy. This review seeks to analyze and summarize the literature concerning the effectiveness and safety of the Ven + AZA regimen for adult patients with newly diagnosed (ND) and relapsed/refractory (R/R) AML, and those unsuitable for intensive chemotherapy. Materials and Methods: Following PRISMA guidelines, a comprehensive electronic literature search was conducted across PubMed, Embase, Clinicaltrials.gov, Cochrane Library, and Web of Science from inception to 2023. MeSH terms and relevant keywords for (Leukemia, Myeloid, Acute) AND (Venetoclax) AND (Azacitidine) were used. From 327 initially identified articles, 12 studies were selected for inclusion, and citation searching further added 2 studies, summing up to 14. We analyzed data from a combined patient pool of 1256. Results: The review encompassed 13 non-randomized and 1 randomized clinical trials. The median patient age was 75.2 years. Primary outcomes comprised complete remission (CR) and complete remission with incomplete count recovery (CRi), yielding a pooled CR/CRi of 57.8%. Secondary outcomes included an overall response rate (ORR) of 61.1%, and a median overall survival (mOS) of 8.94 months with a median follow-up duration of 13.25 months (Table 1). Notably, high-grade adverse effects were predominantly hematological (anemia, neutropenia, thrombocytopenia, febrile neutropenia) while low-grade effects primarily involved gastrointestinal symptoms (nausea, vomiting, diarrhea, constipation, decreased appetite, etc). Conclusion: The current data suggest that the Ven + AZA regimen is both efficacious and well-tolerated for treating newly diagnosed and relapsed/refractory AML. Cytopenias across all three cell lines emerged as the most reported adverse effects of Ven + AZA therapy. Ongoing Phase III clinical trials are expected to enhance our understanding of this regimen's efficacy and safety profile, solidifying its role in standard AML therapy.

Distinct Clinical and Genetic Features of Acute Myeloid Leukemia (AML) in Obese Vs. Non-Obese Patients: A Comparative Study

Aims: Acute myeloid leukemia (AML) represents 80% of the cases of acute leukemia in adults, and obesity has been found to be associated with an increased risk of developing AML. However, there is no data regarding the presenting clinical, cytogenetic, and molecular features of AML in obese patients. Methods: We retrospectively evaluated adult patients with newly diagnosed AML treated at our institution from January 2017 to January 2021. Patients with acute promyelocytic leukemia (APL), as well as those with secondary and therapy-related AML, were excluded. Patients with an available genetic profile obtained from next-generation sequencing (NGS) were included. Demographic, clinical, laboratory, and pathologic data were obtained from clinical records. Obesity was defined as a BMI &amp;gt; 30. A 97-gene panel was used for NGS analysis. Cytogenetic and molecular data, along with responses to treatments, were classified according to the European LeukemiaNet2022 (ELN) guidelines. Statistical analysis included the Mann-Whitney test for continuous variables, Fisher's exact test for categorical variables, and Kaplan-Meier survival curves for overall survival and relapse-free survival. Results: We identified 185 newly diagnosed de novo AML cases for analysis, of which 90 (49%) were classified as obese (Table). The median age at diagnosis was 60 (range, 20-91), and 84 (46%) were male. The most commonly mutated gene was DNMT3A (n=42, 23%), followed by IDH2 (n=36, 19%), and FLT3-ITD (n=33, 18%). Approximately 47% (n=79) of patients had adverse risk based on ELN2022 risk classification by genetics, and 40% (n=23) had adverse cytogenetic risk. The majority of patients were treated with intermediate or high-dose cytarabine-based regimens (n=128, 73%), and the rest with HMA plus venetoclax (n=29, 16%) and HMA alone (n=19, 11%). The median follow-up was 22 months (range, 1-71 months), and the estimated median overall survival (OS) was 21 months for the entire patient population. Within the follow-up, approximately half of the patients (n=90, 47%) died. Compared to non-obese patients, obese patients were younger at presentation (55 vs. 63, p=0.04) and consisted of more females (n=48 (55%) vs. n=36 (38%), p=0.02). Obese patients had a significantly lower number of mutations (p=0.01), particularly in spliceosome (n=12 (13%) vs. n=29 (31%), p=0.007) and transcription factor genes (n=17 (19%) vs. n=31 (33%), p=0.04). Obese patients were noted to have more NPM1 mutations (n=21 (23) vs. n=11 (11%), p=0.05) (Figure). According to ELN2022, obese patients were classified more favorably than non-obese patients (p=0.002). Patients were treated with similar regimens across the study populations, and obese patients' estimated OS was significantly longer than that of non-obese patients (44 vs. 13 months, p=0.02). The median follow-up was comparable in obese vs. non-obese patients, and within the follow-up, fewer obese patients died (n=36 (40%) vs. n=54 (57%), p=0.02). Conclusions: AML in obese patients appears to have distinct clinical and genetic characteristics compared to non-obese patients. This suggests that different underlying mechanisms may contribute to leukemogenesis in these two patient groups. Future studies should focus on elucidating the specific molecular pathways and mechanisms through which obesity influences AML development, which could pave the way for novel treatment approaches tailored to obese patients.