Publications by authors named "Kebede Begna"

Purpose: Management of locally advanced rectal cancer (LARC) includes neoadjuvant chemoradiotherapy (NACRT) followed by total mesorectal excision. Recently, total neoadjuvant treatment (TNT) has gained attention. In developing countries, patients with rectal cancer often present at advanced stages.

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The anti-apoptotic protein myeloid cell leukemia-1 (Mcl-1) contributes to the pathophysiology of acute myeloid leukemia (AML) and certain B-cell malignancies. Tumor dependence on Mcl-1 is associated with resistance to venetoclax. Voruciclib, an oral cyclin-dependent kinase (CDK) inhibitor targeting CDK9, indirectly decreases Mcl-1 protein expression and synergizes with venetoclax in preclinical models.

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Patients with newly diagnosed acute myeloid leukemia (ND-AML) derive variable survival benefit from venetoclax + hypomethylating agent (Ven-HMA) therapy. The primary objective in the current study was to develop genetic risk models that are predictive of survival and are applicable at the time of diagnosis and after establishing treatment response. Among 400 ND-AML patients treated with Ven-HMA at the Mayo Clinic, 247 (62%) achieved complete remission with (CR) or without (CRi) count recovery.

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SETBP1 mutations (m) have been previously reported in myeloid neoplasms and are associated with poor prognostic co-mutations and cytogenetic abnormalities. We retrospectively analyzed the charts of 113 patients diagnosed with myeloid neoplasms with SETBP1m. The most common diagnosis was MDS (31%).

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Two-hundred pregnancies involving 100 women with essential thrombocythemia (ET) were accessed from Mayo Clinic databases (1990-2023). Median platelet count displayed a decline during pregnancy, nadiring at 48% of baseline, in the third trimester: 704-369 × 10/L. Live birth rate was 72%.

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The revised 4th edition of the World Health Organization (WHO4R) classification lists myelodysplastic syndromes with ring sideroblasts (MDS-RS) as a separate entity with single lineage (MDS-RS-SLD) or multilineage (MDS-RS-MLD) dysplasia. The more recent International Consensus Classification (ICC) distinguishes between MDS with SF3B1 mutation (MDS-SF3B1) and MDS-RS without SF3B1 mutation; the latter is instead included under the category of MDS not otherwise specified. The current study includes 170 Mayo Clinic patients with WHO4R-defined MDS-RS, including MDS-RS-SLD (N=83) and MDS-RSMLD (N=87); a subset of 145 patients were also evaluable for the presence of SF3B1 and other mutations, including 126 with (87%) and 19 (13%) without SF3B1 mutation.

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Article Synopsis
  • - Chronic myeloid leukemia (CML) is identified by the Philadelphia chromosome, resulting from a specific genetic change between chromosomes 9 and 22, leading to a unique fusion gene (BCR::ABL1).
  • - CML has three phases (chronic, accelerated, and blast), with most diagnoses occurring during the chronic phase in developed regions, and treatment mainly involves tyrosine kinase inhibitors (TKIs) to prevent progression.
  • - The manuscript reviews the NCCN Guidelines for diagnosing and managing chronic phase-CML, highlighting that some patients can discontinue TKI therapy under careful supervision.
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Among 301 newly diagnosed patients with acute myeloid leukaemia receiving venetoclax and a hypomethylating agent, 23 (7.6%) experienced major cardiac complications: 15 cardiomyopathy, 5 non-ST elevation myocardial infarction and/or 7 pericarditis/effusions. Four patients had more than one cardiac complication.

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Article Synopsis
  • * In a study of 138 patients with BCOR mutations, a significant portion had AML and MDS, with common co-mutations in RUNX1 and U2AF1 but low frequency of TP53 mutations.
  • * Patients with isolated BCOR mutations had similar survival rates to those with other high-risk mutations, while complex karyotypes decreased survival; however, allogeneic stem cell transplants improved outcomes despite the risk of relapse associated with RUNX1 mutations.
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Article Synopsis
  • The study looked at 1000 patients with a blood disorder called essential thrombocythemia from 1967 to 2023, mostly affecting middle-aged people, with more females than males.
  • Most patients had certain gene mutations (like JAK2 and CALR) that affected their age and health, with older people having different risks of health problems.
  • The researchers found that factors like age, gender, and previous health issues influenced survival chances and risks for other diseases, and aspirin might help reduce the risk of blood clots.
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Overall survival and response rates of 270 patients with newly diagnosed acute myeloid leukemia receiving venetoclax (Ven) plus hypomethylating agent, stratified by Ven dosing schedule (Cycle 1 Ven 14 vs. 21 vs. 28 days).

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Among 210 patients with myelodysplastic syndromes (MDSs) with del(5q), molecular information was available at diagnosis or at least 3 months before leukaemic transformation in 146 cases. Multivariate analysis identified therapy-related setting (p = 0.02; HR 2.

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Venetoclax + hypomethylating agent (Ven-HMA) is currently the standard frontline therapy for older/unfit patients with newly diagnosed acute myeloid leukemia (ND-AML). Our objective in the current retrospective study of 301 adult patients (median age 73 years; 62% de novo) with ND-AML was to identify molecular predictors of treatment response to Ven-HMA and survival; European LeukemiaNet (ELN) genetic risk assignment was favorable 15%, intermediate 16%, and adverse 69%. Complete remission, with (CR) or without (CRi), count recovery, was documented in 182 (60%) patients.

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The World Health Organization (WHO) classification system categorizes advanced systemic mastocytosis (SM-Adv) into aggressive SM (ASM), mast cell leukemia (MCL), and SM with associated hematological neoplasm (SM-AHN). By contrast, the International Consensus Classification (ICC) requires "immature" MC cytomorphology for the diagnosis of MCL and limits SM-AHN to myeloid neoplasms (SM-AMN). The current study includes 329 patients with SM-Adv (median age 65 years, range 18-88; males 58%): WHO subcategories SM-AHN (N = 212; 64%), ASM (N = 99; 30%), and MCL (N = 18; 6%); ICC subcategories SM-AMN (N = 190; 64%), ASM (N = 99; 33%), and MCL (N = 9; 3%); WHO-defined MCL with "mature" MC cytomorphology and SM-AHN associated with lymphoid neoplasms were operationally labeled as "MCL-mature" (N = 9) and SM-ALN (N = 22), respectively, and distinguished from ICC-defined MCL and SM-AMN.

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Cytologic abnormalities of atypical mast cells in mastocytosis. The mature mast cells have oval-shaped nuclei, cytoplasmic hypogranulation and spindle-shaped cytology. or well-differentiated displaying a round nucleus with condensed chromatin, and abundant dense cytoplasmic granulations.

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