Chronic Leukemia Research Articles

Upregulation of SNHG7 and FAIM2 Expression Levels in Chronic Myelogenous Leukemia Patients Compared with Normal Subjects

Background: Chronic myelogenous leukemia (CML), also known as chronic granulocytic leukemia (CGL), is considered a hematological malignancy with a prevalence of 1.9 per 100,000 population. Recent studies have shown the role of SNHGs in proliferation, apoptosis, CML progression, and even drug resistance through interaction with miRNAs. The positive correlation between lncRNA-small nucleus RNA host gene 7 (SNHG7) and Fas apoptosis inhibitory molecule 2 (FAIM2) with different cancers has been proved. Objectives: This study investigated the role of SNHG7 and FAIM2 in CML for the first time and revealed the potential correlation between these genes. Methods: This examine changed was performed with a case-manipulate design. First, the accuracy of persistent myeloid leukemia changed with the aid of using karyotype in addition to molecular and cell methods. After RNA extraction from white blood cells and cDNA synthesis, gene expression changed into measured with the use of real-time PCR. Finally, the facts have been statistically analyzed. Results: The results of this study showed that the expression levels of SNHG7 and FAIM2 were significantly increased in chronic myelogenous leukemia patients compared with normal individuals (P-value < 0.001). This increased expression may indicate a potential role for this molecule in the progression and development of this cancer. Conclusions: The current study demonstrates the effective roles of SNHG7 and FAIM2 in the progression of chronic myeloid leukemia, which can be investigated in future studies as biomarkers and potential therapeutic targets.

Clinicohaematological Study of Leukaemias at a Tertiary Care Centre, Vindhya Region of India: A Cross-sectional Study

Introduction: Leukaemia is characterised by widespread proliferation of leucocytes and their precursors in the body tissues and is usually associated with qualitative and quantitative changes in circulating white blood cells. The global burden of leukaemia is increasing. Aim: To study the morphology of leukaemia from Peripheral Blood Smears (PBS) and/or bone marrow smears and evaluate the clinical and haematological profile of leukaemia patients. Materials and Methods: This prospective observational study was conducted in a Tertiary Care Centre of the Vindhya region, in the Department of Pathology at Shyam Shah Medical College, Rewa, Madhya Pradesh, India. The study was carried out over a period of one year, from June 2019 to June 2020. A total of 90 newly diagnosed cases of all types of leukaemia during the study period. Detailed history, physical examination, complete blood counts, and bone marrow examinations were performed to confirm the diagnosis. Cytochemistry was used for the diagnosis and classification of acute leukaemia according to the French-American-British (FAB) classification. The data was compiled and analysed using appropriate statistical methods, and the mean was described with Standard Deviation (SD). Statistical significance was assessed using Analysis of Variance (ANOVA) test conducted with Statistical Package for Social Sciences (SPSS) version 22.0. Results: The study included 90 cases of all types of leukaemia, with a mean age of 36.5±22.5 years. There was a male preponderance in the study, with 65 (72.2%) males and 25 (27.8%) females, resulting in a male-to-female ratio of 2.6:1. Chronic Myeloid Leukaemia (CML) was the most common malignancy, accounting for total 40 (44.4%) cases. Non specific symptoms such as fever in 50 (55.6%), weight loss 49 (54.4%), and loss of appetite 42 (46.7%) cases were the most common symptoms across all types of leukaemia. Acute leukaemia also presented with leukopenia and normal leucocyte counts, while chronic leukaemia mostly showed markedly elevated Total Leucocyte Count (TLC) with a mean count of 1,30,912±63,792 per mm3. Conclusion: Light microscopic features of peripheral smear and bone marrow examination still play an important role in the diagnosis of leukaemia, especially in resource-poor health centres lacking immunotyping and cytogenetics.

Trends in mortality from infection among patients with hematologic malignancies: differences according to hematologic malignancy subtype.

Infection is the most important cause of non-relapse mortality in hematologic malignancy patients, leading to increased costs and prolonged hospitalization times. However, comprehensive and comparable reports on infection-specific mortality (ISM) trends in hematologic malignancy patients are lacking. We aimed to provide updated ISM trends and factors associated with ISM among hematologic malignancy patients. This is a retrospective study. Patients diagnosed with the five most common hematologic malignancies from 1983 to 2016 from the Surveillance, Epidemiology, and End Results database were included. Joinpoint regression was used to analyze mortality trends. ISM decreased beginning in 1983, 1988, and 1994, with yearly decreases of -2.1% for acute leukemia (AL), -1.3% for Hodgkin lymphoma (HL), and -14.3% for non-Hodgkin lymphoma (NHL). In contrast, ISM in patients with chronic leukemia (CL) and multiple myeloma (MM) increased dramatically beginning in 2000, with yearly increases of 2.8% and 3.3%, respectively. ISM rates were higher in males than in females across all hematologic malignancy subtypes. The mortality trends significantly differed according to race, age, sex, and stage, which could help in further etiological investigations. Moreover, male sex, older age at diagnosis, black race, and unmarried status were poor prognostic factors for ISM across all hematologic malignancy subtypes. A promising downward trend in ISM in recent years occurred in patients with AL, HL, and NHL; however, ISM increased dramatically in patients with CL and MM. Our data suggest that risk assessment and careful infection monitoring are recommended for hematologic malignancy patients, particularly those with CL and MM.

A Tale of Two Hematological Malignancies: CML Followed by CLL in the Same Patient

Studies have reported second malignancies occurring in patients with chronic myeloid leukemia (CML) or chronic lymphoid leukemia (CLL). We discuss the case of a 77-year-old man diagnosed with CLL who later developed CML. The CLL was managed with surveillance after diagnosis for 3 years and later treated with ibrutinib and venetoclax. While on treatment with venetoclax for 4 months, the patient had worsening leukocytosis shown via peripheral flow cytometry and fluorescence in situ hybridization, with the presence of myeloid lineage cells positive for BCR-ABL and complete disappearance of lymphoid cells. This case report highlights the importance of considering a second malignancy in hematologic malignancies with variable disease prognosis.

Chronic neutrophilic leukemia/chronic eosinophilic leukemia

Chronic neutrophilic leukemia (CNL) is a clonal disorder that is characterized by increasing mature neutrophils. Colony stimulating factor 3 receptor (CSF3R) T618I mutation was frequently identified in patients with CNL and is defined as a molecular marker of the disease. Ruxolitinib, a JAK2 inhibitor, provided a promising therapeutic effect in a phase II study. In particular, ruxolitinib was more efficient for patients with CSF3R mutation. Allogeneic stem cell transplantation (Allo-SCT) may be a curative treatment for CNL. On the other hand, further studies are needed to define the optimal method of transplantation, source of donor, conditioning therapy, and timing of transplantation. Chronic eosinophilic leukemia (CEL) is a clonal disorder that is characterized by increasing eosinophils. In the World Health Organization Classification 5th edition, diagnostic criteria for CEL are renewed. Because the new criteria will be more specific for CEL than criteria in the older edition, "not otherwise specified (NOS) " is removed from the name of the disease. Anti-CD52 antibody, alemtuzumab, or anti-IL-5 antibody, mepolizumab, are promising drugs to control symptoms that are associated with hypereosinophilic syndrome. Allo-SCT is anticipated as a curative treatment for CEL, but the evidence of Allo-SCT for CEL is still limited. Further study is required to define the treatment strategy.

Demographic status of adult leukemia patients in Sulaymaniyah, the Kurdistan region of Iraq

Leukemia is one of the most common cancer types that affects both adults and children. The purpose of current study was to assess the demographic status of adult leukemic patients among Kurdish population in Iraq. The records of 484 adult patients at Hiwa Cancer Hospital in Sulaymaniyah, Kurdistan region (Iraq) between January 2015 and December 2020 were the subject of this retrospective descriptive analysis. The different types of cancer observed at Hiwa Cancer Hospital were acute lymphatic leukemia (ALL), acute myeloblastic leukemia (AML), chronic lymphatic leukemia (CLL), and chronic myeloid leukemia (CML). There were 307 male and 177 female cancer patients (ratio 1.734:1), with age range between 16 and 98 years and mean age of 54.49 years. It was found that 291 (60.1%) patients were non-educated, while 109 (22.5%), 34 (7.0%), and 50 (10.3%) patients were tertiary, post-basic and basic educated, respectively. Based on the employment status, 276 (57.0%) patients were unemployed, 145 (37.0%) employed, and 63 (13.0%) were retired. It was found that both educational status and employment status were correlated with leukemia incidence at p value equal to 0.0001 and 0.002, respectively.

Professor Daniel Catovsky 19 September 1937-2 December 2022.

Daniel Catovsky was trained in Argentina and graduated in Medicine in 1961. He emigrated to London in 1967 with his wife, Julia Pollack, and their daughter Mina. Subsequently they had two boys, Sebastian and Michael. Daniel joined the Hammersmith Hospital and Royal Postgraduate Medical School as a Research fellow in 1967 and in 1976, he became Honorary Consultant Physician/Senior Staff Member in the Medical Research Council Leukaemia Unit under Professor David Galton. Colleagues at that time included John Goldman and Sandy Spiers. From 1976 onwards he was a member of the French–American–British (FAB) cooperative group, which had a major impact on the diagnosis and classification of haematological neoplasms. In 1987 he was awarded a Personal Chair in Haematological Malignancies at the Royal Postgraduate Medical School, Hammersmith Hospital. The next year he moved to the Royal Marsden Hospital/Institute of Cancer Research where he established an Academic Haemato-Oncology Unit, continuing as Professor of Haematology until his retirement in 2003. Thereafter, he continued to be fully engaged in research at the Institute of Cancer Research as Professor Emeritus and Fellow, impacting all around him. Through all these years Daniel had an extraordinary active life encompassing research, teaching and diagnostic and clinical activities. He served as a member, chairman or leader in many boards such as the Central Institutional Review Board of Cancer Research UK (CRUK) (2003–2005); Leukaemia Research Fund Data Monitoring Committee (Chairman 2004–2006); Scientific Advisory Board of the CLL (chronic lymphocytic leukaemia) Global Research Foundation; Data Monitoring Committee UKCLL2006 trial, Arctic and Admire trials, CLL11 trial, and Parexel independent response review panel; Scientific Advisory Board of the Hairy Cell Leukaemia Consortium; National Cancer Research Institute CLL Trials Steering Committee; Scientific Advisory Committee of the CLL Genome Consortium (Spain); Data Safety Monitoring Board for the German CLL12 trial and CLL13 trial (chairman); and a variety of editorial boards of national and international journals. In addition, he also coordinated the UK CLL 1, 2, 3, 4 and 5 trials. Daniel was President of the British Society of Haematology (1996–1997) and of the European Research Initiative on CLL (ERIC) (2006–2009). He was awarded the BSH Medal for his contributions to British haematology (2000) and the IWCLL Binet–Rai medal for outstanding contributions to CLL research (2005). His work is clearly reflected in more than 850 peer-reviewed publications and he is the eighth most cited researcher in the field of oncology in clinical medical journals. Daniel had unique qualities, being a remarkable scientist and an excellent clinician. Most of his work was devoted to CLL and other chronic lymphoid leukaemias. He was a pioneer of studies of familial CLL and identified and described distinct lymphoid disorders, a relevant issue with implications in the correct diagnosis and management of these patients. His unit had wide appeal to many and was always open to visiting physicians and scientists who came from everywhere in the world, eager to learn from him. His valuable teaching had, and still has, a major impact in many units worldwide. Besides his scientific and medical skills, Daniel was a remarkable and unforgettable man with unique attributes and amazing appeal, full of humanity, well reflected in his empathy towards patients, fellows and colleagues. We have lost Daniel, but his imprint will remain. Life would not have been the same without him, nor will it be the same from now on. A sad loss to his family, to science and to the entire community.

A Case of Cerebral Aspergillosis in a Patient with Chronic Lymphoid Leukemia

A Case of Cerebral Aspergillosis in a Patient with Chronic Lymphoid Leukemia

Study of Discriminating Markers for the Diagnosis of Chronic Lymphoid Leukemia and Evaluation of Matutes Scores

The study of the expression level by lymphoma cells (MFI: mean fluorescence intensity) completed by ROC curve for diagnostic markers is a valuable aid for the daily interpretation of lymphocyte immunophenotyping as well as the differential diagnosis with other chronic lymphoproliferative B syndromes. The aim is to provide diagnostic guidance, increase the power of the diagnostic test based on the discriminating capacity of each marker and validate the value of the Matutes score adapted to our study population. Materials and Methods: This is a technical validation study with retrospective recruitment of 91 patients diagnosed with B-CLL according to clinical, cytological and biological results. Statistical analysis is performed by the SPSS software. Results: The ROC curve shows the discriminative power of each diagnostic marker. The combination of discriminatory markers (CD23, CD5, CD43) either in double or triple marking did not increase the power of the test; The diagnosis of B-CLL according to our threshold values is changed to a score value greater than or equal to 3. Conclusion: The analysis of each marker, using the ROC curve allows us to identify the most discriminating markers useful to orient the diagnosis by elaborating a diagnostic score

PLATELET INDICES IN LEUKEMIAS: - A CROSS SECTIONAL STUDY

Objective: To evaluate the pattern of changes in the platelet indices in different Leukemias. Material and method: This descriptive cross-sectional study was conducted in the Pathology Department of Khyber Teaching Hospital from January 2021 to December 2021 (1-year duration). Diagnosed acute and chronic leukemia cases were included while those receiving therapeutic chemotherapy were excluded. The platelet count was analyzed as a part of complete blood counts by the Sysmex Hematology analyzer in the Hematology section of the Pathology department. The changes observed in the platelet counts in different types of leukemia were recorded in a proforma. Mean, standard deviation, frequency and percentages were used to compute variables. Results: The age range of the 100 included cases of leukemia was 01 - 50 years. The mean age of the study population was 30 ± 10 SD years. Platelet count was low in acute Leukemias and chronic lymphocytic leukemia. Only in chronic myeloid leukemia, raised platelet count was seen (in 62% of cases). Mean platelet volume and platelet distribution width were decreased in all leukemias. Conclusion: Platelet indices are decreased in Leukemias, with the exception of chronic myeloid leukemia where platelet count is raised. Keywords: Platelet count, Acute lymphoid leukemia, Acute myelogenous leukemia, Chronic lymphocytic leukemia, Chronic myelogenous leukemia.

Chronic hematologic manifestations of benzene exposure in fuel dispatchers

Introduction: benzene is an aromatic hydrocarbon considered carcinogenic due to its high toxicity, although in recent years its exposure has decreased, however, it has not been sufficient to prevent complications. Chronic exposure in concentrations greater than or equal to 1 ppm for a period of more than 8 hours a day for 10 constant years or when exposure exceeds 10 ppm for 1 year, there is a risk of developing hematological disorders.Objective: identify chronic hematological manifestations due to exposure to benzene in fuel dispatchers.Methods: a narrative review was carried out, compiling information from January 2000 to November 2022 in scientific databases such as Pubmed, Environmental Pollution, Dialnet, SAGE, Taylor and Francis, Springerlink, Science Direct, Scielo; using key words. Results: hematological manifestations that develop after chronic exposure to benzene at any concentration include lymphoid leukemia, non-Hodgkin's lymphoma, acute myeloid leukemia, myelodysplastic syndrome, chronic myeloid leukemia, multiple myeloma, chronic myeloid leukemia and aplastic anemia.Conclusions: there are various manifestations of chronic exposure to benzene, including chronic lymphatic leukemia, non-Hodgkin's lymphoma, acute or chronic myeloid leukemia, myelodysplastic syndrome and multiple myeloma; therefore, annual medical check-ups and the application of strategies to reduce the time of occupational exposure are recommended in order to diagnose and prevent hematological diseases, since there are currently no prevention regulations to guarantee the wellbeing of dispatchers

Emerging roles of circRNAs in leukemia and the clinical prospects: An update.

Circular RNAs (circRNAs) are a new category of endogenous non-protein coding RNAs (ncRNAs), and show the characteristics of high conservation, stability, and tissue specificity. Due to rapid advances in next-generation sequencing and transcriptome profiling technologies, circRNAs have been widely discovered in many organisms and participated in the development and progress of a variety of diseases. As a type of molecular sponge, circRNAs mainly absorb micro RNAs competitively and interplay with RNA-binding proteins to modulate the splicing as well as transcription of target genes. This review is based on a literature search using the Medline database. Search terms used were "circular RNAs and leukemia," "circRNAs and leukemia," "circRNAs and acute lymphoblastic leukemia," "circRNAs and chronic lymphoblastic leukemia," "circRNAs and acute myeloid leukemia," "circRNAs and chronic myeloid leukemia," and "circRNAs, biomarker, and hematological system." CircRNAs have been proven as potential biomarkers and therapeutic targets in a variety of tumors. Recent research has found that circRNAs aberrantly exist in hematological cancers, especially leukemia, and are significantly associated with the incidence, progress, and metastasis of diseases as well as the prognosis of patients. The current work summarizes the latest findings on circRNAs in various types of leukemia, aiming to propose prospective therapies and new drug screening methods for the treatment of leukemia.

Electrochemical Biosensors in the Diagnosis of Acute and Chronic Leukemias.

Until now, morphological assessment with an optical or electronic microscope, fluorescence in situ hybridization, DNA sequencing, flow cytometry, polymerase chain reactions, and immunohistochemistry have been employed for leukemia identification. Nevertheless, despite their numerous different vantages, it is difficult to recognize leukemic cells correctly. Recently, the electrochemical evaluation with a nano-sensing interface seems an attractive alternative. Electrochemical biosensors measure the modification in the electrical characteristics of the nano-sensing interface, which is modified by the contact between a biological recognition element and the analyte objective. The implementation of nanosensors is founded not on single nanomaterials but rather on compilating these components efficiently. Biosensors able to identify the molecules of deoxyribonucleic acid are defined as DNA biosensors. Our review aimed to evaluate the literature on the possible use of electrochemical biosensors for identifying hematological neoplasms such as acute promyelocytic leukemia, acute lymphoblastic leukemia, and chronic myeloid leukemia. In particular, we focus our attention on using DNA electrochemical biosensors to evaluate leukemias.

Detection of Thrombocytopenia, Anemia and Leukocytosis by Using Ensemble Learning

Blood disorders are conditions that impact the blood’s ability to function correctly. There is a range of different symptoms depending on the type. There are several different types of blood disorders such as Leukemia, chronic myelocytic leukemia, lymphoma, myelofibrosis, polycythemia, Thrombocytopenia, anemia and Leukocytosis. Some resolve completely with therapy, or do not cause symptoms and do not affect overall lifespan Some are chronic and lifelong but do not affect how long you live. Other blood disorders, like sickle cell disease and blood cancers, can be fatal. Thereneeds to capture of hidden information in the medical data for detecting diseases in the early stage. In this study, we apply the Ensemble Learning technique for classification. We compared our result with other classification methods. The results show that Ensemble Learning methods can predict the Tumor of blood disease better than the other classifiers.

A survival prediction model and nomogram based on immune-related gene expression in chronic lymphocytic leukemia cells.

There are many different chronic lymphoblastic leukemia (CLL) survival prediction models and scores. But none provide information on expression of immune-related genes in the CLL cells. We interrogated data from the Gene Expression Omnibus database (GEO, GSE22762; Number = 151; training) and International Cancer Genome Consortium database (ICGC, CLLE-ES; Number = 491; validation) to develop an immune risk score (IRS) using Least absolute shrinkage and selection operator (LASSO) Cox regression analyses based on expression of immune-related genes in CLL cells. The accuracy of the predicted nomogram we developed using the IRS, Binet stage, and del(17p) cytogenetic data was subsequently assessed using calibration curves. A survival model based on expression of 5 immune-related genes was constructed. Areas under the curve (AUC) for 1-year survivals were 0.90 (95% confidence interval, 0.78, 0.99) and 0.75 (0.54, 0.87) in the training and validation datasets, respectively. 5-year survivals of low- and high-risk subjects were 89% (83, 95%) vs. 6% (0, 17%; p < 0.001) and 98% (95, 100%) vs. 92% (88, 96%; p < 0.001) in two datasets. The IRS was an independent survival predictor of both datasets. A calibration curve showed good performance of the nomogram. In vitro, the high expression of CDKN2A and SREBF2 in the bone marrow of patients with CLL was verified by immunohistochemistry analysis (IHC), which were associated with poor prognosis and may play an important role in the complex bone marrow immune environment. The IRS is an accurate independent survival predictor with a high C-statistic. A combined nomogram had good survival prediction accuracy in calibration curves. These data demonstrate the potential impact of immune related genes on survival in CLL.

The role of bone marrow biopsy in patients with pyrexia of unknown origin

Background: Pyrexia of unknown origin (PUO) is a major complication which remains undiagnosed. Different diagnostic test were used to arrive at final investigation. Bone marrow biopsy (BMB) plays a vital role in diagnosis of PUO. The objective of current study was to determine the role of bone biopsy in diagnosing various types of causes of pyrexia of unknown origin.&#x0D; Patients and methods: A prospective cross-sectional study was conducted from 1st September 2018 to 28th February 2019 at Department of Hematology, Combined Military Hospital Lahore, Pakistan. The data of 120 patients who were remained undiagnosed for at least 1 week were enrolled. Standard procedures were used to obtain the biopsy specimens and bone marrow aspiration was sent for microbiological examination. All the demographic information was kept on a structured self-designed proforma. Data was entered and analyzed using SPSS v.24.&#x0D; Results: Out of 120 patients recruited in the study there were 67 (55.8%) were from age group 16 to 35 years, were males (65.8%) and 65.0% patients were suffering from fever for more than 3 days. The majority of the participants (30%) were diagnosed with infections, fever due to reactive changes (10.0%), acute leukemia (14.2%), lymphoma (11.7%), chronic leukemia (10.0%), aplastic anemia (4.2%), multiple myeloma (2.5%) and 11.7% patients were undiagnosed&#x0D; Conclusion: In the diagnosis of pyrexia of unknown origin, morphological and histological investigation of bone marrow plays a vital role. However, if it is combined with other diagnostic modalities such as radiological, microbiological, and serological examinations, the efficiency of diagnosis can be improved.

Low-Dose Radiation Risks of Lymphohematopoietic Cancer Mortality in U.S. Shipyard Workers.

The linear, non-threshold (LNT) hypothesis of cancer induction derived from studies of populations exposed to moderate-to-high acute radiation doses may not be indicative of cancer risks associated with lifetime radiation exposures less than 100 mSv. The objective of this study was to examine risks and dose-response patterns of lymphohematopoietic cancer (LHC) and its types associated with low radiation exposure while adjusting for possible confounding factors. A retrospective cohort of 437,937 U.S. nuclear shipyard workers (153,930 radiation and 284,007 non-radiation workers) was followed from 1957 to 2011, with 3,699 LHC deaths observed. The risk of LHC in radiation workers was initially compared to the risk in non-radiation workers. Time dependent accumulated radiation dose, lagged 2 years, was used in categorical and continuous dose analysis among radiation workers to examine the LHC risks and possible dose-response relationships based on Poisson regression models. These analyses controlled for sex, race, time dependent age, calendar time, socioeconomic status, solvent-related last job, and age at first hire. The median lifetime radiation dose for the radiation worker population was 0.82 mSv and the 95th percentile dose was 83.63 mSv. The study shows: 1. LHC mortality for radiation workers was significantly lower than non-radiation workers relative risk: 0.927; 95% confidence intervals (95% CI): 0.865, 0.992; P = 0.030]. Among LHC types, the risks for lymphoid leukemia and lymphomas in radiation workers were lower than the risk in non-radiation workers with statistical significance, while the risk for the rest of LHC types did not show any statistically significant difference. 2. In categorical dose analysis among radiation workers, sample size weighted linear trend of relative risk (RRs) for LHC and its types in five dose categories (>0-<25, 25-<50, 50-<100, 100-<200, and > = 200 mSv) vs. 0 mSv were not statistically significant, although there was an elevation of RR for chronic myeloid leukemia only in the 50-<100 mSv category (RR: 2.746; 95% CI: 1.002, 7.521; P = 0.049) vs. 0 mSv. 3. The Poisson regression analyses among radiation workers using the time dependent radiation dose as a continuous variable showed an excess relative risk (ERR) for LHC at 100 mSv of 0.094 (95% CI: -0.037, 0.225; P = 0.158) and leukemia less chronic lymphoid leukemia, of 0.178 (95% CI: -0.085, 0.440; P = 0.440) vs. 0 mSv. The ERRs and their linear trend for all other types were not statistically significant.

1992. Risk of Infective Endocarditis in Streptococcal mitis Bloodstream Infections Among Patients with Neutropenia from Hematologic Malignancies

Abstract Background Streptococcus mitis is a common colonizer of the human oral and gastrointestinal tract. Patients with neutropenia due to hematologic malignancy (HM), particularly those prescribed fluoroquinolone prophylaxis are at increased risk of a S. mitis bloodstream infection (BSI). Risk of infective endocarditis (IE) in this patient population remains unclear. Methods This was a multicenter, retrospective study of neutropenic (ANC &amp;lt; 500 K/uL) patients with HM from November 2016 - February 2022. Patients were included if they had S. mitis isolated in at least 1 blood culture bottle. The primary outcome was number of patients who developed IE based on cardiac imaging. Secondary outcomes included number of patients who underwent IE workup via cardiac imaging and BSI recurrence within 12 weeks. Results Among 171 patients who met the inclusion criteria, 101 (59%) were male and median age was 60 years old (range 19-86). Patient demographics, microbiologic information and outcomes are shown in Table 1. All patients in the cohort had native cardiac valves. Acute leukemia/myelodysplastic syndrome was the most common HM (n=129, 75%), followed by lymphoma (n=27, 16%), multiple myeloma (n=10, 6%) and chronic leukemia (n=5, 3%). Most patients had a transthoracic echocardiogram (TTE) (n=97, 56.7%) within 7 days of BSI. Of these patients, 1 had suspected valvular vegetations on TTE, but transesophageal echocardiogram (TEE) was negative. Two patients had negative TTEs, but there was a high clinical suspicion, so cardiac computed tomography was performed and showed no valvular vegetations. Despite negative cardiac imaging, 1 patient completed 6 weeks of empiric treatment for IE based on radiographic findings in the torso suggesting visceral infarcts. One patient had S. mitis BSI recurrence within 12 weeks of first positive culture. Median duration of antimicrobial therapy for BSI was 15 days (range 8-43). Conclusion IE is uncommon in neutropenic HM patients with native cardiac valves and S. mitis BSI. In this cohort where approximately half had a TTE after bacteremia and median duration of BSI therapy was 15 days, recurrent BSI was rare, suggesting that IE cases were not underdiagnosed in those without cardiac imaging. Cardiac imaging such as TTE to rule out IE may not be necessary for all patients in this population. Disclosures Ramy H. Elshaboury, PharmD, Eli Lilly: Honoraria|Gilead Sciences: Grant/Research Support David W. Kubiak, PharmD, BCPS, BCIDP, FIDSA, Astellas Pharma, Inc.: Advisor/Consultant|AVIR Pharma Inc: Advisor/Consultant|Cidara Therapeutics: Advisor/Consultant Sarah P. Hammond, MD, F2G: Advisor/Consultant|F2G: Grant/Research Support|GSK: Grant/Research Support|Scynexis: Grant/Research Support.

Risk of primary haematologic cancers following incident non-metastatic breast cancer: A Danish population-based cohort study

BackgroundBreast cancer survivors may have increased risk of subsequent haematologic cancer. We compared their risk of haematologic cancers with the general population during 38 years of follow-up. MethodsUsing population-based Danish medical registries, we assembled a nationwide cohort of women diagnosed with incident non-metastatic breast cancer during 1980–2017, with follow-up through 2018. We compared breast cancer survivors with the general population by computing standardised incidence ratios (SIR) and 95% confidence intervals (CI). ResultsAmong 101,117 breast cancer survivors, we observed 815 incident haematologic cancers (median follow-up: 7.9 years). We observed excess risk of acute myeloid leukaemia (AML) (SIR: 1.65, 95%CI: 1.33–2.01), particularly in women who received chemotherapy (SIR: 3.33, 95%CI: 2.24–4.75) and premenopausal women (SIR: 3.23, 95%CI: 2.41–4.25). The risk of acute lymphoid leukaemia (ALL) was increased (SIR: 2.25, 95%CI: 1.29–3.66), whereas the risk of chronic lymphoid leukaemia (CLL) was decreased (SIR: 0.66, 95%CI: 0.53–0.82). An additional analysis showed elevated risk of CLL 0–6 months after breast cancer diagnosis (SIR: 3.00 95%CI: 1.75–4.80). ConclusionCompared to the general population, breast cancer survivors had elevated risk of AML, particularly when treated with chemotherapy. The risk of ALL was elevated, whereas the risk of CLL was lower. The higher risk of CLL in the first six months after diagnosis likely reflects surveillance bias—due to intensified diagnostic efforts at breast cancer diagnosis and treatment—prompting earlier detection. This has likely reduced the long-term risk of CLL in breast cancer survivors.

Using natural killer cell-derived exosomes as a cell-free therapy for leukemia.

Natural killer (NK) cells are components of the innate immune system which play a pivotal role in cancer cell surveillance. Despite promising results in clinical trials, the use of NK-based therapies is limited due to unsatisfactory efficiencies and safety issues. In recent years, exosomes have emerged as a powerful, natural therapeutic tool. Since exosomes are known to carry cargos that reflect the cellular makeup of their cell of origin, we were prompted to test whether NK-derived exosomes (NKexo) maintain the anti-leukemia capacity of NK-cells. We found NK92MI-cells to secrete large amounts of 100-200nm cap-shaped particles expressing exosomal and NK biomarkers (CD63, CD81, CD56). We demonstrated that NKexo exert a potent, selective, anti-leukemia effect on all leukemia cell-lines tested. Furthermore, NKexo eliminated leukemia cells isolated from patients with acute and chronic leukemia and inhibited hematopoietic colony growth. While leukemia cells were targeted and severely affected by NKexo, healthy B-cells remained unaffected, indicating a selective effect. This selectivity was further confirmed by demonstrating that NKexo were specifically taken up by leukemic cells but not by healthy B-cells. Our in vivo data support our in vitro and ex vivo findings and demonstrate improved human-CD45+ leukemia blast counts and overall survival in NKexo treated humanized acute myeloid leukemia (HL-60) xenograft mice thus supporting the assumption that NKexo possess an anti-leukemia effect. Pending further analyses, our findings provide the pre-clinical evidence needed to test the NKexo approach in future pre-clinical and clinical studies to ultimately develop an acellular "off-the-shelf" product to treat leukemia.