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BACKGROUND: Pneumonia is a common cause of morbidity and mortality, yet a causative pathogen is identified in a minority of cases. Plasma microbial cell-free DNA sequencing may improve diagnostic yield in immunocompromised patients with pneumonia. METHODS: In this prospective, multicenter, observational study of immunocompromised adults undergoing bronchoscopy to establish a pneumonia etiology, plasma microbial cell-free DNA sequencing was compared to standardized usual care testing. Pneumonia etiology was adjudicated by a blinded independent committee. The primary outcome, additive diagnostic value, was assessed in the Per Protocol population (patients with complete testing results and no major protocol deviations) and defined as the percent of patients with an etiology of pneumonia exclusively identified by plasma microbial cell-free DNA sequencing. Clinical additive diagnostic value was assessed in the Per Protocol subgroup with negative usual care testing. RESULTS: Of 257 patients, 173 met Per Protocol criteria. A pneumonia etiology was identified by usual care in 52/173 (30.1%), plasma microbial cell-free DNA sequencing in 49/173 (28.3%) and the combination of both in 73/173 (42.2%) patients. Plasma microbial cell-free DNA sequencing exclusively identified an etiology of pneumonia in 21/173 patients (additive diagnostic value 12.1%, 95% confidence interval [CI], 7.7% to 18.0%, P < .001). In the Per Protocol subgroup with negative usual care testing, plasma microbial cell-free DNA sequencing identified a pneumonia etiology in 21/121 patients (clinical additive diagnostic value 17.4%, 95% CI, 11.1% to 25.3%). CONCLUSIONS: Non-invasive plasma microbial cell-free DNA sequencing significantly increased diagnostic yield in immunocompromised patients with pneumonia undergoing bronchoscopy and extensive microbiologic and molecular testing. CLINICAL TRIALS REGISTRATION: NCT04047719.

Introduction: The discovery of gene editing techniques has opened a new era within the field of biology and enabled scientists to manipulate nucleic acid molecules. CRISPR-Cas9 genome engineering has revolutionized this achievement by successful targeting the DNA molecule and editing its sequence. Since genomic changes are the basis of the birth and growth of many tumors, CRISPR-Cas9 method has been successfully applied to identify and manipulate the genes which are involved in initiating and driving some neoplastic processes. Methods: By review of the existing literature on application of CRISPR-Cas9 in cancer, different databases, such as PubMed and Google Scholar, we started data collection for "CRISPR-Cas9", "Genome Editing", "Cancer", "Solid tumors", "Hematologic malignancy" "Immunotherapy", "Diagnosis", "Drug resistance" phrases. Clinicaltrials.gov, a resource that provides access to information on clinical trials, was also searched in this review. Results: We have defined the basics of this technology and then mentioned some clinical and preclinical studies using this technology in the treatment of a variety of solid tumors as well as hematologic neoplasms. Finally, we described the progress made by this technology in boosting immune-mediated cell therapy in oncology, such as CAR-T cells, CAR-NK cells, and CAR-M cells. Conclusion: CRISPR-Cas9 system revolutionized the therapeutic strategies in some solid malignant tumors and leukemia through targeting the key genes involved in the pathogenesis of these cancers. [ABSTRACT FROM AUTHOR]

Introduction: The United States Advisory Committee on Immunization Practices (ACIP) and the Centers for Disease Control (CDC) recommend COVID-19 vaccines for all immunocompromised individuals. Certain disease groups are at increased risk of comorbidity and death for which disease-specific recommendations should be considered. The objective of the Delphi panel of experts was to summarize expert consensus on COVID-19 vaccinations for patients with rheumatologic disease, renal disease, hematologic malignancy and solid organ transplant (SOT) in the US. Methods: A two-stage Delphi panel method was employed, starting with qualitative interviews with key opinion leaders (KOLs) in the four disease areas (n = 4 KOLs, n = 16 total) followed by three rounds of iterative revision of disease-specific COVID-19 vaccine recommendations. Final consensus was rated after the third round. Statements addressed primary and booster dosing (e.g., number and frequency) and other considerations such as vaccine type or heterologous messenger ribonucleic acid (mRNA) vaccination. Following the Delphi Panel, an online survey was conducted to assess physician agreement within the disease areas (n = 50 each, n = 200 total) with the consensus statements. Results: Moderate to strong consensus was achieved for all primary series vaccination statements across disease groups, except one in hematology. Similarly, moderate to strong consensus was achieved for all booster series statements in all disease areas. However, statements on antibody titer measurements for re-vaccination considerations and higher dosages for immunocompromised patients did not reach agreement. Overall, approximately 62%–96% of physicians strongly agreed with the primary and booster vaccine recommendations. However, low agreement (29%–69%) was found among physicians for time interval between disease-specific treatment and vaccination, recommendations for mRNA vaccines, heterologous mRNA vaccination, antibody titer measurement and higher vaccine dosage for immunocompromised groups. Conclusion: Consensus was achieved for disease-specific COVID-19 vaccine recommendations concerning primary and booster series vaccines and was generally well accepted by practicing physicians. [ABSTRACT FROM AUTHOR]

Background: Recent studies have reported an association between Cytotoxic T-lymphocyte antigen-4 (CTLA-4) polymorphisms and hematologic malignancy susceptibility, while the results remain inconsistent. Hence, we performed a meta-analysis to investigate the association between CTLA-4 polymorphisms with hematologic malignancy susceptibility. Methods: A comprehensive and systematic search of Cochrane Library, PubMed, Embase databases was performed up to Sep. 20, 2024. The pooled odds ratio (OR) and its 95% confidence interval (CI) were used to determine the strength of the association between CTLA-4 polymorphisms and hematologic malignancy susceptibility. Statistical analysis was performed in STATA 12.0. Results: A total of 13 studies concerning the CTLA-4 49A/G, CTLA-4 60A/G, CTLA-4 318T/C, CTLA-4 1661A/G, and CTLA-4 319C/T polymorphisms were included in the meta-analysis. The pooled results suggested the CTLA-4 49A/G polymorphism was significantly associated with an increased hematologic malignancy risk (AA vs. GA+GG: OR = 1.77, 95% CI = 1.56-2.02), especially in NHL, multiple myeloma, and leukemia. Similarly, CTLA-4 319C/T polymorphism was found to be associated with decreased chronic lymphocytic leukemia risk. There was no significant association between the CTLA-4 60A/G, 318T/C, and 1661A/G polymorphism and hematologic malignancy risk. Conclusion: CTLA-4 49A/G and 319C/T polymorphisms were associated with hematologic malignancy susceptibility. [ABSTRACT FROM AUTHOR]

Enhancing the efficacy of CD19 CAR-T cell therapy can significantly improve patient outcomes by reducing relapse rates in CD19 + B cell malignancies. Exogenous or transgenic cytokines are often used to boost the expansion and durability of CAR-T cells but pose risks of severe toxicities. A promising approach to address these limitations is to immobilize cytokines on the surface of CAR-T cells using transmembrane (TM) anchor domains. Given IL-7 can enhance T-cell proliferation and antitumor activity, our study developed membrane-bound IL-7 constructs using different TM anchor domains (CD8, CD28 and B7-1). We primarily found that the CD8 TM provided superior anchoring for IL-7 compared to CD28 and B7-1. Moreover, the IL-7 construct with a CD8 TM (IL7/CD8) enhanced naïve T cell proliferation and effector functions, and improved the in vitro and in vivo antitumor activity of CD19 CAR-T cells. Importantly, although IL7/CD8 could promote T-cell proliferation, it did not sustain long-term autonomous expansion, which could ensure the safety of CD19 CAR-T cells expressing IL7/CD8 in clinical applications. Collectively, the IL7/CD8 construct represents a promising strategy for enhancing the therapeutic potential of CD19 CAR-T cell therapy. [ABSTRACT FROM AUTHOR]

Due to spatial and genomic independence, mitochondria possess a translational mechanism distinct from that of cytoplasmic translation. Several regulators participate in the modulation of mitochondrial translation. Mitochondrial translation is coordinated with cytoplasmic translation through stress responses. Importantly, the inhibition of mitochondrial translation leads to the inhibition of cytoplasmic translation and metabolic disruption. Therefore, defects in mitochondrial translation are closely related to the functions of hematopoietic cells and various immune cells. Finally, the inhibition of mitochondrial translation is a potential therapeutic target for treating multiple hematologic malignancies. Collectively, more in-depth insights into mitochondrial translation not only facilitate our understanding of its functions in hematopoiesis, but also provide a basis for the discovery of new treatments for hematological malignancies and the modulation of immune cell function. [ABSTRACT FROM AUTHOR]

Purpose: The essence of this scholarly work was to carefully outline the key factors intensifying the virulence and protracted contagion of COVID-19, particularly among individuals afflicted with hematologic malignancies (HM), in an epoch predominantly governed by the Omicron variant. Methods: Adults with HM diagnosed with COVID-19 from November 2022 to February 2023 were monitored in this retrospective study. Patient blood samples yielded biochemical data, and COVID-19 was confirmed through RNA or antigen testing. The factors affecting severity and infection duration were examined using both univariate and multivariate logistic regression analyses. For calculating the overall survival probabilities, the Kaplan–Meier product limit approach was employed. Results: In the examined cohort, 133 individuals diagnosed with HM and concomitantly infected with COVID-19 were scrutinized. Of the participants, 29.3% (39 patients) were classified as Severe/Critical, while the other 70.7% (94 patients) were categorized as Non-severe. A significant difference was observed in vaccination status: 61.7% of patients in the Non-severe group had received at least a two-dose vaccine regimen, whereas 61.5% of the Severe/Critical group had either minimal or only one dose of vaccination. The data analysis revealed that elevated C-reactive protein levels (≥ 100 mg/L) significantly raised the risk of severe/critical conditions in HM patients with COVID-19, as determined by advanced multivariate logistic regression. The odds ratio was 3.415 with a 95% confidence interval of 1.294–9.012 (p = 0.013). Patients who continued to have positive nucleic acid tests and ongoing symptoms beyond 30 days were categorized as having a persistent infection, whereas those who achieved infection control within this timeframe were categorized as having infection recovery. Of the HM cohort, 11 did not survive beyond 30 days after diagnosis. The results from a competing risk model revealed that increased interleukin-6 levels (HR: 2.626, 95% CI: 1.361–5.075; p = 0.004) was significantly associated with persistent infection. Conversely, receiving more than two vaccine doses (HR: 0.366, 95% CI: 0.158–0.846; p = 0.019), and having high IgG levels (≥ 1000 mg/dl) (HR: 0.364, 95% CI: 0.167–0.791; p = 0.011), were associated with infection recovery. There was a notable disparity in survival rates between patients with persistent infections and infection recovery, with those in the non-persistent group demonstrating superior survival outcomes (P < 0.001). Conclusions: In conclusion, the study determined that HM patients with COVID-19 and increased C-reactive protein levels had a higher likelihood of severe health outcomes. Persistent infection tended to be more prevalent in those with vaccine dosages (< 2 doses), lower IgG levels, and higher interleukin-6 levels. [ABSTRACT FROM AUTHOR]

Hematological malignancies are a group of cancers that affect the blood, bone marrow, and lymphatic system. Cancer stem cells (CSCs) are believed to be responsible for the initiation, progression, and relapse of hematological malignancies. However, identifying and targeting CSCs presents many challenges. We aimed to develop a stemness index (HSCsi) to identify and guide the therapy targeting CSCs in hematological malignancies. We developed a novel one-class logistic regression (OCLR) algorithm to identify transcriptomic feature sets related to stemness in hematologic malignancies. We used the HSCsi to measure the stemness degree of leukemia stem cells (LSCs) and correlate it with clinical outcomes.We analyze the correlation of HSCsi with genes and pathways involved in drug resistance and immune microenvironment of acute myeloid leukemia (AML). HSCsi revealed stemness-related biological mechanisms in hematologic malignancies and effectively identify LSCs. The index also predicted survival and relapse rates of various hematologic malignancies. We also identified potential drugs and interventions targeting cancer stem cells (CSCs) of hematologic malignancies by the index. Moreover, we found a correlation between stemness and bone marrow immune microenvironment in AML. Our study provides a novel method and tool to assess the stemness degree of hematologic malignancies and its implications for clinical outcomes and therapeutic strategies. Our HSC stemness index can facilitate the precise stratification of hematologic malignancies, suggest possible targeted and immunotherapy options, and guide the selection of patients. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cell transplant (HSCT) is now recognized as a standard treatment option for people with HIV (PWH) who develop high-risk hematologic malignancies. However, the involved polypharmacy can lead to complications from drug interactions and toxicities, affecting the efficacy and safety of chemotherapy and antiretroviral therapy (ART). Managing these patients requires a personalized approach, including the careful selection of ART based on previous therapies and potential interactions, alongside risk assessment for infections. This discussion will address the history of HSCT in PWH and management considerations for this group. [ABSTRACT FROM AUTHOR]

Purpose: To assess the self-reported oral health and oral health-related quality of life of patients diagnosed with hemato-oncological disease. Patients and methods: Data was collected through a digital questionnaire in collaboration with the Dutch patient organization Hematon. The questionnaires EORTC-QLQ-C30, EORTC-QLQ-OH15, shortened Xerostomia Inventory (XI), and the OHIP-14 were used. Results: Seven hundred five patients were included (52.5% female, mean age 63.2 ± 10.1). The majority was diagnosed more than 2 years ago (86%) and had received treatment (81%) for their disease. Lymphoma, leukemia, and multiple myeloma were the most frequent malignancies. Chemotherapy alone, chemotherapy in combination with targeted therapy or immunotherapy, and myeloablative chemotherapy followed by autologous stem cell transplantation were the most common treatment modalities. The XI identified that 40.5% met the criteria for xerostomia. Other complaints included mouth soreness and sensitivity, gingival pain and bleeding, problems with teeth or with an ill-fitting denture. Despite reporting oral complaints, most patients experienced a rather good OH-QoL. A high xerostomia score led to a significantly lower OH-QoL. Female gender, history of stem cell transplantation, radiation to head and neck, and multiple daily medication use were significant predictors of xerostomia. Conclusion: Patients with hematologic malignancies frequently reported a dry mouth and other oral complaints including mouth soreness and sensitivity, gingival pain and bleeding, and problems with teeth. Despite these oral complaints, most patients experienced a relatively good OH-QoL. Future longitudinal studies are needed, and health professionals should have an active role in providing oral supportive care based on patients’ individual needs. [ABSTRACT FROM AUTHOR]

Background: Early reports suggest that hematological malignancy (HM) is a relevant risk factor for morbidity and mortality in COVID-19. We investigated the characteristics, outcomes, and risk factors for mortality in patients hospitalized with HM and COVID-19. Methods: We conducted a retrospective, nationwide study using data from hospitalized patients that were provided by the Spanish Ministry of Health including all patients admitted to a Spanish hospital from 2020 to 2022 with a COVID-19 diagnosis. A descriptive analysis and correlational analyses were conducted. Logistic regression was used to assess mortality in these patients and to calculate odds ratios (ORs). Results: We collected data on 1.2 million patients with COVID-19, including 34,962 patients with HMs. The incidence of hospitalization for patients with HMs was 5.8%, and the overall mortality rate was higher than for patients without HMs (19.8% versus 12.7%, p = 0.001). Mortality rates were higher for patients with lymphomas, multiple myelomas, and leukemias than for those with myeloproliferative disorders. Having HMs was a risk factor for mortality, with OR = 1.7 (95% CI 1.66–1.75, p = 0.001). By subtype, non-Hodgkin lymphomas were the highest risk factor for mortality (OR = 1.7), followed by leukemias (OR = 1.6), Hodgkin lymphomas (OR = 1.58), and plasma cell dyscrasias (OR = 1.24). Conclusions: This study identifies the different clinical profiles of patients with HMs who are at a high risk for mortality when hospitalized with COVID-19. As members of a vulnerable population, these patients deserve special prophylactic and therapeutic measures to minimize the effects of SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Introduction Materials and Methods Results Conclusion Patients with hematologic malignancy have a higher risk of developing red blood cell (RBC) alloimmunization which can delay blood transfusion. Information on the risk factors for alloimmunization in this group is still limited. This study aimed to determine the prevalence and predictors of RBC alloimmunization among these patients.Electronic medical records of the patients with acute myeloid leukaemia (AML), acute lymphoid leukaemia (ALL), multiple myeloma (MM) and lymphoma from a tertiary care hospital between January 2018 and December 2022 were retrospectively reviewed. Clinical, demographic and transfusion history data of the included patients were analysed.Of the 983 patients with hematologic malignancy, 798 were included in the study. The prevalence of RBC alloantibodies in this population was 4.8% (38 patients). The alloimmunization rate of each subgroup was as followed: AML 9.1%, ALL 2.9%, MM 3.8% and lymphoma 2.5%. The most common alloantibodies were anti‐Mia, anti‐E and anti‐Lea. The majority (29/38, 76.3%) of alloimmunization had a single alloantibody. RBC autoantibody was detected in 10 patients. The detection of autoantibodies and having AML were independently associated with RBC alloimmunization (adjusted odds ratio [aOR] 13.41, 95% confidence interval [CI] 2.00–89.72, p = 0.007 and aOR 11.44, 95% CI 2.02–64.72, p = 0.006, respectively).The prevalence of RBC alloimmunization in the patients with hematologic malignancy was 4.8%. The alloimmunization rate of the AML subgroup was higher than those of other hematologic malignancies. The detection of autoantibodies and the AML diagnosis were identified as potential risk factors for RBC alloimmunization. [ABSTRACT FROM AUTHOR]

AbstractWe report the outcomes of patients with haematological malignancies admitted to ICUs and define pre-ICU prognostic factors for in-hospital mortality. In a retrospective, single-center study, we included all patients with haematologic malignancies admitted to ICUs between 2009 and 2019. The primary outcome was in-hospital mortality. One hundred and forty-four patients with hematologic malignancies were admitted to ICUs during the study period. Fifteen (10.4%) were in remission, 36 (25.0%) were in remission after hematopoietic stem cell transplantation. Acute Leukemias and aggressive lymphomas were the most common diagnoses, occurring in 34.7%. The in-hospital mortality was 49%. The main predictors for in-hospital mortality were age >65 years, post allogeneic hematopoietic stem cell transplantation, non-remission, respiratory rate >22 bpm, bilirubin >2 mg/dl, PH< 7.35, and time from hospital admission to ICU transfer ≥3 days. In-hospital mortality of patients with hematologic malignancies admitted to ICU was 49%. We identified pre-ICU parameters that predict in-hospital mortality. [ABSTRACT FROM AUTHOR]

Malignant tumors of the hematologic system have a high degree of malignancy and high mortality rates. Chimeric antigen receptor T cell (CAR-T) therapy has become an important option for patients with relapsed/refractory tumors, showing astonishing therapeutic effects and thus, it has brought new hope to the treatment of malignant tumors of the hematologic system. Despite the significant therapeutic effects of CAR-T, its toxic reactions, such as Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), cannot be ignored since they can cause damage to multiple systems, including the cardiovascular system. We summarize biomarkers related to prediction, diagnosis, therapeutic efficacy, and prognosis, further exploring potential monitoring indicators for toxicity prevention. This review aims to summarize the effects of CAR-T therapy on the cardiovascular, hematologic, and nervous systems, as well as potential biomarkers, and to explore potential monitoring indicators for preventing toxicity, thereby providing references for clinical regulation and assessment of therapeutic effects. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Blastic plasmacytoid dendritic cell neoplasm is a rare hematologic malignancy and appropriate diagnosis encounters difficulties in both clinical and pathologic aspects. This case report aims to present a clinical case to help familiar clinicians and pathologists with this rare entity. Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an uncommon hematologic malignancy. Because of the rarity of the disease and aggressive behavior, we present this case. A 71‐year‐old man presented with a forehead ulcerated skin lesion. On histopathologic examination, pan‐dermal atypical mononuclear infiltrate, consisting of small‐medium sized cells with fine chromatin pattern was seen without epidermotropism which were immunoreactive for CD123, CD56, TdT and CD4, while negative for CD3, CD20, and MPO that confirmed the diagnosis of BPDCN. BPDCN is a highly aggressive hematologic malignancy derived from plasmacytoid dendritic cells. Male‐to‐female ratio is 3.3:1. Skin involvement can present as either an isolated purplish nodule or disseminated purplish nodules or papules or macules. On microscopic examination, skin involvement is characterized by monomorphic infiltrates of immature neoplastic cells with blastoid morphology, involving the superficial and deep dermis, often with extension into the subcutis with epidermal spare. Immunophenotyping shows usually positive reactions for CD123, CD45, CD4, CD56, TCL1, CD2AP, CD43, BCL2, TdT, Granzyme B, and TCF4, whereas tumor cells are negative for CD3, CD19, CD20, MPO, CD13 and Lysozyme. Differential diagnoses of BPDCN include myeloid sarcoma, myelomonocytic leukemia, mature plasmacytoid dendritic cell proliferation (MPDCP) and Merkel cell carcinoma. Pathologists ought to be familiar with this WHO entity for early disease diagnosis, because of disease rarity and diagnosis difficulties. [ABSTRACT FROM AUTHOR]

The treatment landscape for acute myeloid leukemia (AML) is rapidly changing. Many new agents and lower-intensity regimens have been approved and can be safely used by hematologists and oncologists in both academic and community settings. The US Food and Drug Administration (FDA) held a virtual symposium on AML treatment in the community in November 2022. Several members of the FDA, along with practicing hematologists and oncologists in both academic and community settings, participated in the symposium. The goal of the symposium was to discuss challenges and opportunities in the treatment of patients with AML in community oncology settings. A summary of these discussions and key considerations are presented here. [ABSTRACT FROM AUTHOR]

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a clinically aggressive hematologic malignancy derived from plasmacytoid dendritic cells. It commonly presents as cutaneous lesions. To date, no standard treatment protocol for BPDCN exists. Traditionally treated similarly to acute leukemia or lymphoma, its prognosis remains poor. Radiation therapy is employed for isolated skin lesions, for patients that are ineligible for chemotherapy due to age or comorbidities and for post-chemotherapy recurrence. However, very limited reports are available on radiotherapy for BPDCN. We present a case involving a 94-year-old BPDCN patient treated with radiation therapy, highlighting an atypical situation of two separate radiotherapy sessions with different dosages for isolated skin lesions. Initially, 45 Gy was administered in 15 fractions (45 Gy/15 Fr), followed by a second session of 30 Gy in 10 fractions (30 Gy/10 Fr) after disease recurrence. This case is unique in detailing radiation therapy for the exceedingly rare BPDCN, particularly dose fractionation. The findings indicate that 45 Gy/15 Fr can provide adequate local control, while even a lower dose of 30 Gy/10 Fr may be effective. This case report contributes to the limited literature by proposing potential therapeutic approaches and dosage guidelines to refine future BPDCN treatment protocols.

Abstract Enhancing the efficacy of CD19 CAR-T cell therapy can significantly improve patient outcomes by reducing relapse rates in CD19 + B cell malignancies. Exogenous or transgenic cytokines are often used to boost the expansion and durability of CAR-T cells but pose risks of severe toxicities. A promising approach to address these limitations is to immobilize cytokines on the surface of CAR-T cells using transmembrane (TM) anchor domains. Given IL-7 can enhance T-cell proliferation and antitumor activity, our study developed membrane-bound IL-7 constructs using different TM anchor domains (CD8, CD28 and B7-1). We primarily found that the CD8 TM provided superior anchoring for IL-7 compared to CD28 and B7-1. Moreover, the IL-7 construct with a CD8 TM (IL7/CD8) enhanced naïve T cell proliferation and effector functions, and improved the in vitro and in vivo antitumor activity of CD19 CAR-T cells. Importantly, although IL7/CD8 could promote T-cell proliferation, it did not sustain long-term autonomous expansion, which could ensure the safety of CD19 CAR-T cells expressing IL7/CD8 in clinical applications. Collectively, the IL7/CD8 construct represents a promising strategy for enhancing the therapeutic potential of CD19 CAR-T cell therapy.

Abstract Purpose The essence of this scholarly work was to carefully outline the key factors intensifying the virulence and protracted contagion of COVID-19, particularly among individuals afflicted with hematologic malignancies (HM), in an epoch predominantly governed by the Omicron variant. Methods Adults with HM diagnosed with COVID-19 from November 2022 to February 2023 were monitored in this retrospective study. Patient blood samples yielded biochemical data, and COVID-19 was confirmed through RNA or antigen testing. The factors affecting severity and infection duration were examined using both univariate and multivariate logistic regression analyses. For calculating the overall survival probabilities, the Kaplan–Meier product limit approach was employed. Results In the examined cohort, 133 individuals diagnosed with HM and concomitantly infected with COVID-19 were scrutinized. Of the participants, 29.3% (39 patients) were classified as Severe/Critical, while the other 70.7% (94 patients) were categorized as Non-severe. A significant difference was observed in vaccination status: 61.7% of patients in the Non-severe group had received at least a two-dose vaccine regimen, whereas 61.5% of the Severe/Critical group had either minimal or only one dose of vaccination. The data analysis revealed that elevated C-reactive protein levels (≥ 100 mg/L) significantly raised the risk of severe/critical conditions in HM patients with COVID-19, as determined by advanced multivariate logistic regression. The odds ratio was 3.415 with a 95% confidence interval of 1.294–9.012 (p = 0.013). Patients who continued to have positive nucleic acid tests and ongoing symptoms beyond 30 days were categorized as having a persistent infection, whereas those who achieved infection control within this timeframe were categorized as having infection recovery. Of the HM cohort, 11 did not survive beyond 30 days after diagnosis. The results from a competing risk model revealed that increased interleukin-6 levels (HR: 2.626, 95% CI: 1.361–5.075; p = 0.004) was significantly associated with persistent infection. Conversely, receiving more than two vaccine doses (HR: 0.366, 95% CI: 0.158–0.846; p = 0.019), and having high IgG levels (≥ 1000 mg/dl) (HR: 0.364, 95% CI: 0.167–0.791; p = 0.011), were associated with infection recovery. There was a notable disparity in survival rates between patients with persistent infections and infection recovery, with those in the non-persistent group demonstrating superior survival outcomes (P

Abstract Hematological malignancies are a group of cancers that affect the blood, bone marrow, and lymphatic system. Cancer stem cells (CSCs) are believed to be responsible for the initiation, progression, and relapse of hematological malignancies. However, identifying and targeting CSCs presents many challenges. We aimed to develop a stemness index (HSCsi) to identify and guide the therapy targeting CSCs in hematological malignancies. We developed a novel one-class logistic regression (OCLR) algorithm to identify transcriptomic feature sets related to stemness in hematologic malignancies. We used the HSCsi to measure the stemness degree of leukemia stem cells (LSCs) and correlate it with clinical outcomes.We analyze the correlation of HSCsi with genes and pathways involved in drug resistance and immune microenvironment of acute myeloid leukemia (AML). HSCsi revealed stemness-related biological mechanisms in hematologic malignancies and effectively identify LSCs. The index also predicted survival and relapse rates of various hematologic malignancies. We also identified potential drugs and interventions targeting cancer stem cells (CSCs) of hematologic malignancies by the index. Moreover, we found a correlation between stemness and bone marrow immune microenvironment in AML. Our study provides a novel method and tool to assess the stemness degree of hematologic malignancies and its implications for clinical outcomes and therapeutic strategies. Our HSC stemness index can facilitate the precise stratification of hematologic malignancies, suggest possible targeted and immunotherapy options, and guide the selection of patients.

Abstract Due to spatial and genomic independence, mitochondria possess a translational mechanism distinct from that of cytoplasmic translation. Several regulators participate in the modulation of mitochondrial translation. Mitochondrial translation is coordinated with cytoplasmic translation through stress responses. Importantly, the inhibition of mitochondrial translation leads to the inhibition of cytoplasmic translation and metabolic disruption. Therefore, defects in mitochondrial translation are closely related to the functions of hematopoietic cells and various immune cells. Finally, the inhibition of mitochondrial translation is a potential therapeutic target for treating multiple hematologic malignancies. Collectively, more in-depth insights into mitochondrial translation not only facilitate our understanding of its functions in hematopoiesis, but also provide a basis for the discovery of new treatments for hematological malignancies and the modulation of immune cell function.

Objective: This cross-sectional study aimed to assess the frequency of potential drug–drug interactions (DDIs) and demographic correlates of moderate and major DDIs among patients with hematologic cancer at a referral hematology hospital in Iran. Methods: In this study, for 6 months, all patients suffering from hematologic cancers admitted to the tertiary oncology hospital, Omid, Isfahan, were considered. Data from all medications prescribed to patients during hospitalization were analyzed using the online Lexicomp® drug interaction checker, recording all interactions classified by risk level: C, D, or X. Findings: A total of 674 DDIs were detected in 109 patients. The prevalence of treatments with at least one clinically relevant interaction was 95%, being 57.9% for those at level C and 31.5% for levels D and X. According to the frequency, the main interaction was between aprepitant and corticosteroids, followed by the interaction between aprepitant and vincristine. The most common interaction between antineoplastic agents was between doxorubicin and cyclophosphamide. In terms of mechanism, most of DDIs (54.9%) were pharmacodynamics. Only the number of administered medications was associated with DDI occurrence. Conclusion: Potential DDIs of moderate to major severity are common among patients with hematologic malignancies. This underscores the importance of implementing different strategies to mitigate this clinically significant risk.

Abstract Background The Hemoglobin, Albumin, Lymphocyte, Platelet Score (HALP) is a novel predictive biomarker that has surfaced in the literature in recent years. It has been applied to the prediction of many clinical outcomes related to different neoplasms. Each of these inflammatory and nutritional markers is taken into account by the HALP score, which provides an overall prognosis for patients with cancer. Methods Retrospective data was collected on the demographics of patients hospitalized to our hospital's intensive care unit (ICU) for hematologic malignancies between January 2014 and March 2021. To measure the prognostic value of the HALP score, it was retrospectively calculated for patients with hematologic malignancies on the first day of ICU admission. This study looked into the link between the HALP score and general prognostic characteristics because it has been suggested that the HALP score is a relevant prognostic marker. Results Patients with an HALP score

Background Patients who undergo treatment for hematologic malignancies may experience a decline in sexual health, alterations in sexual functioning, and reproductive capacity during survivorship. Aim This study investigated the prevalence of sexual dysfunction and factors influencing sexual activity and functioning in patients with hematologic malignancies, to identify potential targets for interventions in clinical practice. Methods This nationwide cross-sectional study included adult patients diagnosed with a hematologic malignant disease in Denmark in the period from January 20, 2013, to August 20, 2022. Eligible participants received electronic questionnaires through their officially assigned digital mailbox. Outcomes Outcomes included the Female Sexual Function Index, International Index of Erectile Function, Female Sexual Distress Scale–Revised, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Sexual Health, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Results A total of 362 patients, on average 5.7 ± 3.4 years postdiagnosis, completed the questionnaires. Of these, 52.5% women and 73.2% men reported sexual dysfunction, with more women (40.9%) than men (34.1%) being sexually inactive. Across gender, this was significantly more prevalent in patients >65 years of age and in those with a low quality of life. In addition, for women a significant association with fatigue and sleep difficulties was observed. In total, 40.3% reported sexual-related personal distress, with the highest proportion among patients 40 to 65 years of age. Most patients (98.7%) with sexual dysfunction had not discussed sexual issues with their healthcare professional. Clinical implications It is hoped that knowledge from this study will help healthcare professionals in clinical practice and encourage them to proactively address and discuss sexual health issues with their patients, irrespective of age. Strengths and Limitations Sexually inactive participants may reduce the overall score of sexual function in the scoring of both the Female Sexual Function Index and International Index of Erectile Function. We therefore analyzed sexual function in a subgroup analysis in only those being sexually active to emphasize that level of dysfunction persists in sexually active participants. Conclusion Patients report a high prevalence of sexual dysfunction, sexual distress, and gender-specific sexual symptoms following diagnosis and treatment of a malignant hematologic disease, impacting their quality of life. Sexual Health in Patients With Hematologic Malignancies; NCT05222282; https://clinicaltrials.gov/study/NCT05222282. [ABSTRACT FROM AUTHOR]

Patients with hematologic malignancies still face a significant risk of severe coronavirus disease 2019 (COVID-19). The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-neutralizing monoclonal antibody combination tixagevimab/cilgavimab (TIX/CGB) could be administered to immunocompromised patients for pre-exposure prophylaxis (PrEP) before the emergence of TIX/CGB-resistant COVID-19 Omicron variants. TIX/CGB application could be carried out regardless of the host's immune response to previous active SARS-CoV-2 vaccinations or infections. Because the efficacy of COVID-19 PrEP remains unclear, especially in SARS-CoV-2-seropositive patients, German national guidelines recommended TIX/CGB PrEP only for SARS-CoV-2-seronegative patients in addition to an intensified active vaccination schedule. Having followed these guidelines, we now report the characteristics and outcomes of 54 recipients of TIX/CGB PrEP in SARS-CoV-2-seronegative patients with hematological disease from a German tertiary medical center and compare them to 125 seropositive patients who did not receive any PrEP. While the number of patients with B-cell lymphomas was significantly higher in the seronegative cohort (33 (61%) vs. 18 (14%) cases, p < 0.01), patients with myeloid diseases were significantly more frequent in the seropositive cohort (51 (41%) vs. 5 (9%) cases, p < 0.01). Strikingly, patients who had undergone allogeneic hematopoietic stem cell transplantation were significantly more likely (forty-nine (39%) vs. six (11%) cases, p < 0.01) to be SARS-CoV-2 seropositive. We observed that prophylactic application of TIX/CGB PrEP to a highly vulnerable group of SARS-CoV-2-seronegative patients resulted in a similar number of COVID-19 breakthrough infections compared to the untreated seropositive control group (16 (32%) vs. 39 (36%), p = 0.62) and comparable COVID-19-related outcomes like hospitalization and oxygen requirement throughout an extended follow-up period of 12 months. In conclusion, our results support the tailored approach of administering TIX/CGB PrEP only to SARS-CoV-2-seronegative patients during the COVID-19 pandemic and might provide a rationale for similar strategies during future outbreaks/diseases, especially in times of initial limited availability and/or financial constraints. [ABSTRACT FROM AUTHOR]

Background: The Hemoglobin, Albumin, Lymphocyte, Platelet Score (HALP) is a novel predictive biomarker that has surfaced in the literature in recent years. It has been applied to the prediction of many clinical outcomes related to different neoplasms. Each of these inflammatory and nutritional markers is taken into account by the HALP score, which provides an overall prognosis for patients with cancer. Methods: Retrospective data was collected on the demographics of patients hospitalized to our hospital's intensive care unit (ICU) for hematologic malignancies between January 2014 and March 2021. To measure the prognostic value of the HALP score, it was retrospectively calculated for patients with hematologic malignancies on the first day of ICU admission. This study looked into the link between the HALP score and general prognostic characteristics because it has been suggested that the HALP score is a relevant prognostic marker. Results: Patients with an HALP score <37.10 had significantly higher APACHE II scores (p < 0.001). They also had significantly higher rates of qSOFA score ≥2 (89.3%), as well as statistically significantly higher rates of intubation (96%) and death (96.1%) (p < 0.001). Our study found that a HALP score <37.1 was associated with a 47.04-fold increase in mortality risk. Conclusion: In patients with hematologic malignancies, the prognosis is strongly correlated with the HALP score. When validated in large cohorts, the HALP score, APACHE II, and q SOFA scores, either individually or collectively, can be used to guide prognostic evaluation of patients and act as a reliable predictor of unfavorable clinical outcomes in patients with hematologic malignancies. [ABSTRACT FROM AUTHOR]

Purpose: Older adults with hematologic malignancies (HM) have unique challenges due to age and fitness. The primary aim of this pilot study was to benchmark the ability of multiple biomarkers of aging (p16, epigenetic clocks, T cell gene expression profiles, and T cell receptor excision circles (TREC) to identify frailty as measured by a clinical impairment index (I2) in patients with HM. Methods: 70 patients newly diagnosed with HM had peripheral blood T lymphocytes (PBTL) analyzed for p16INK4a expression using the OSU_Senescence Nanostring CodeSet. PBTL epigenetic age was measured using 7 epigenetic clocks, and TREC were quantified by qRT-PCR. A composite clinical impairment index (I2) was generated by combining values from 11 geriatric metrics (Independent Activities of Daily Living (iADL), physical health score, Short Physical Performance Battery (SPPB), Body Mass Index (BMI), Eastern Cooperative Oncology Group (ECOG) performance status, self-reported KPS, Blessed Orientation Memory Concentration (BOMC), polypharmacy, Mental Health Inventory (MHI)-17, Medical Outcomes Study (MOS) subscales). Clinical frailty was defined as a score of 7 or greater on the I2. Results: Age-adjusted p16INK4a was similar in newly diagnosed patients and healthy controls (p > 0.1). PBTL p16INK4a levels correlated positively with the Hannum [r = 0.35, 95% CI (0.09–0.75); p adj. = 0.04] and PhenoAge [r = 0.37, 95% CI (0.11–0.59); p adj. = 0.04] epigenetic clocks. The discrimination ability of the I2 model was calculated using the area under the receiver operating characteristic curve (AUC). After adjusting for chronologic age and disease group, baseline p16INK4a [AUC = 0.76, 95% CI (0.56–0.98); p = 0.01], Hannum [AUC = 0.70, 95% CI (0.54–0.85); p = 0.01], PhenoAge [AUC = 0.71, 95% CI (0.55–0.86); p = 0.01], and DunedinPACE [AUC = 0.73, 95% CI (0.57–0.88); p = < 0.01] measures showed the greatest potential to identify clinical frailty using the I2. Conclusions: Our pilot data suggest that multiple blood-based aging biomarkers have potential to identify frailty in older adults with HM. Implications for Cancer Survivors: We developed the I2 index to quantify impairments across geriatric domains and discovered that PBTL p16, Hannum, PhenoAge, and DunedinPACE are promising indicators of frailty in HM. [ABSTRACT FROM AUTHOR]

Bartonella species are gram-negative coccobacilli that are globally recognized as significant pathogens causing zoonotic infections. Among Bartonella species, B. henselae, B. quintana, and B. bacilliformis are prominent pathogens causing infections in humans, often manifesting as infective endocarditis. Bartonella endocarditis can pose diagnostic challenges due to its indolent presentation and limitations of standard microbiological culture techniques to identify the organism. We report a case of a 23-year-old male, who initially presented with the manifestations of hepatosplenic T-cell lymphoma, later diagnosed with blood culture–negative endocarditis caused by B. henselae. The patient had a complicated clinical course including pancytopenia, hepatosplenomegaly, and severe aortic valve regurgitation. Despite negative blood cultures, diagnostic clues included persistent fevers and bicuspid aortic valve with abscess. High Bartonella IgG titers (>1:800) supported the diagnosis. This case underscores the importance of considering Bartonella species in patients with suspected endocarditis, particularly in those with predisposing factors and negative blood cultures. Diagnosis relies heavily on serologic assays due to low sensitivity of conventional culture methods. Treatment involves a multidisciplinary approach with antibiotics and surgical intervention for optimal outcomes. Timely recognition and management are crucial to mitigate the high mortality associated with Bartonella endocarditis, and we hope this article offers insight for clinicians. [ABSTRACT FROM AUTHOR]

Background/Aim: Acute myeloid leukemia (AML) is a myeloproliferative neoplasm marked by abnormal clonal expansion of hematopoietic progenitor cells, displaying karyotypic aberrations and genetic mutations as prognostic indicators. The World Health Organization (WHO) and the European LeukemiaNet guidelines categorize BCR::ABL1 p190+ AML as high risk. This study explored the identification of the increased incidence of BCR::ABL1 p190+ in our AML population. Patients and Methods: This study included 96 AML patients stratified according to WHO guidelines. Subsequently, patients were screened for genetic abnormalities, such as BCR::ABL1 p 190+, PML::RARA, RUNX1::RUNX1T1, and CBFB::MYH11 by quantitative reverse transcription polymerase chain reaction (RT-qPCR) analysis. Results: Among 96 AML patients, 36 displayed BCR::ABL1 p190+, overcoming the expected global incidence. Age variations (19 to 78 years) showed no significant laboratory differences between BCR::ABL1 p190+ and non-BCR::ABL p190+ cases. The overall survival analysis revealed no statistically significant differences among the patients (p=0.786). Conclusion: The analyzed population presented a higher frequency of BCR::ABL1 p190+ detection in adult AML patients when compared to what is described in the worldwide literature. Therefore, more studies are needed to establish the reason why this incidence is higher and what the best treatment approach should be in these cases. [ABSTRACT FROM AUTHOR]

Introduction: Neutrophilic dermatoses (NDs) often occur secondary to inflammatory conditions, medication exposure, and hematologic malignancy. While malignancy-associated NDs (MA-NDs) have been well reported among those with hematologic cancers, little is known about drug-induced NDs (DI-NDs) within this population. The objective of this study was to compare the presentations and outcomes of patients with hematologic malignancies who developed MA-NDs and DI-NDs. Methods: Cases of ND occurring between 2013 and 2023 among those with hematologic malignancies were identified from the electronic medical records of our institution. Patient characteristics, recent medication exposures, cancer mutations, and disease outcomes were reviewed. Patients were categorized with DI-ND if they were recently exposed to one of four medications known to be commonly associated with ND or were otherwise categorized with MA-ND. We report a descriptive analysis of cases of DI-ND and MA-ND. Results: We identified 52 patients with ND and co-occurring hematologic malignancy including 16 cases of DI-ND (30.8%) and 36 cases of MA-ND (69.2%). The most common ND in both groups was Sweet's syndrome. Chronic underlying conditions including solid tumors, inflammatory disorders, chronic viral infection, and tobacco use were more common among those with MA-ND. Among those with DI-ND, tyrosine kinase inhibitors were the most commonly associated drugs (43.8%). The most common cancer mutation among those with DI-ND was FLT3 (43.8%), while the most common mutation among those with MA-ND was TP-53 (19.4%). Among those who had died at the time of data collection, 90.0% of those with DI-ND and 66.7% of those with MA-ND died within 1 year of ND diagnosis. Conclusion: Most cases of ND occurring with hematologic malignancies develop secondary to cancer rather than drug exposure. Different cancer mutations may predispose to DI-ND and MA-ND. Further research is needed to establish diagnostic criteria for DI-ND and to determine the pathogenic role of specific cancer mutations, particularly FLT3, in the development of ND. [ABSTRACT FROM AUTHOR]

The development of invasive fungal infections (IFIs) is a serious complication in acute myeloid leukemia (AML) patients who undergo an induction to remission chemotherapy. Given the increased mortality in AML patients with IFI despite prophylaxis, we need to address this problem. Statins have traditionally been employed in clinical settings as agents for reducing lipid levels. Nonetheless, recent investigations have brought to light their antifungal properties in animals, as well as in vitro studies. The objective of this study was to assess the effectiveness of atorvastatin when added to the routine IFI prophylaxis regimen in patients diagnosed with AML. A randomized, multicenter, triple-blind study was conducted on 76 AML patients aged 18–70, who received either placebo or atorvastatin in addition to fluconazole. Patients were followed for 30 days in case of developing IFIs, patient survival, and atorvastatin- related adverse drug reactions. Data were analyzed with SPSS version 26.0. A level of significance of 0.05 was utilized as the threshold for all statistical tests. The data were analyzed by adjusting for the effect of age, regarding that there was a significant difference between the two groups, and showed that atorvastatin reduced the development of both probable and proven IFI (based on EORTC/MSGERC criteria) compared to placebo. IFI-free survival was also significantly better in the atorvastatin group. The incidence of developing aspergillosis did not differ between the two groups. No serious adverse events related to atorvastatin were observed. The present investigation has substantiated the antecedent in vitro and animal research on the fungicidal impact of statins and has suggested the need for additional research involving larger sample sizes and an extended duration of follow-up. Trial registration: This study was registered on the Iranian registry of clinical trials as IRCT20210503051166N1 (Date of confirmation 2021.05.03). [ABSTRACT FROM AUTHOR]

Key Clinical Message Blastic plasmacytoid dendritic cell neoplasm is a rare hematologic malignancy and appropriate diagnosis encounters difficulties in both clinical and pathologic aspects. This case report aims to present a clinical case to help familiar clinicians and pathologists with this rare entity. Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an uncommon hematologic malignancy. Because of the rarity of the disease and aggressive behavior, we present this case. A 71‐year‐old man presented with a forehead ulcerated skin lesion. On histopathologic examination, pan‐dermal atypical mononuclear infiltrate, consisting of small‐medium sized cells with fine chromatin pattern was seen without epidermotropism which were immunoreactive for CD123, CD56, TdT and CD4, while negative for CD3, CD20, and MPO that confirmed the diagnosis of BPDCN. BPDCN is a highly aggressive hematologic malignancy derived from plasmacytoid dendritic cells. Male‐to‐female ratio is 3.3:1. Skin involvement can present as either an isolated purplish nodule or disseminated purplish nodules or papules or macules. On microscopic examination, skin involvement is characterized by monomorphic infiltrates of immature neoplastic cells with blastoid morphology, involving the superficial and deep dermis, often with extension into the subcutis with epidermal spare. Immunophenotyping shows usually positive reactions for CD123, CD45, CD4, CD56, TCL1, CD2AP, CD43, BCL2, TdT, Granzyme B, and TCF4, whereas tumor cells are negative for CD3, CD19, CD20, MPO, CD13 and Lysozyme. Differential diagnoses of BPDCN include myeloid sarcoma, myelomonocytic leukemia, mature plasmacytoid dendritic cell proliferation (MPDCP) and Merkel cell carcinoma. Pathologists ought to be familiar with this WHO entity for early disease diagnosis, because of disease rarity and diagnosis difficulties.

Major epigenetic changes are associated with carcinogenesis, including aberrant DNA methylations and post-translational modifications of histone. Indeed evidence accumulated in recent years indicates that inactivating DNA hypermethylation preferentially targets the subset of polycomb group (PcG) genes that are regulators of developmental processes. Conversely, activating DNA hypomethylation targets oncogenic signaling pathway genes, but outcomes of both events lead in the overexpression of oncogenic signaling pathways that contribute to the stem-like state of cancer cells. On the basis of recent evidence from population-basedclinical and experimental studies, we hypothesize that factors associated with risk for developing a hematologic malignancy (HM), such as metabolic syndrome and chronic inflammation, may trigger epigenetic mechanisms to increase the transcriptional expression of oncogenes and activate oncogenic signaling pathways. Signaling pathways associated with such risk factors include but are not limited to pro-inflammatory nuclear factor κB (NF-κB) and mitogenic, growth, and survival Janus kinase (JAK) intracellular non-receptor tyrosine kinase-triggered pathways. The latter includes signaling pathways such as transducer and activator of transcription (STAT), Ras GTPases/mitogen-activated protein kinases (MAPKs)/extracellular signal-related kinases (ERKs), phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), and β-catenin pathways. Recent findings on epigenetic mechanisms at work in the biology of cancer and in HMs and their importance in the etiology and pathogenesis of these diseases are herein summarized and discussed. Furthermore, the role of epigenetic processes in the determination of biological identity, the consequences for interindividual variability in disease clinical profile, and the potential of epigenetic drugs in HMs are also considered.

Abstract Background Patients with hematological malignancies often require multidrug therapy using a variety of antineoplastic agents and supportive care medications. This increases the risk of drug-related problems (DRPs). Determining DRPs in patients hospitalized in hematology services is important for patients to achieve their drug treatment goals and prevent adverse effects. This study aims to identify DRPs by the clinical pharmacist in the multidisciplinary team in patients hospitalized in the hematology service of a university hospital in Turkey. Methods This study was conducted prospectively between December 2022 and May 2023 in the hematology service of Suleyman Demirel University Research and Application Hospital in Isparta, Turkey. DRPs were determined using the Pharmaceutical Care Network Europe (PCNE) 9.1 Turkish version. Results This study included 140 patients. Older age, longer hospital stay, presence of acute lymphoblastic leukemia, presence of comorbidities, higher number of medications used, and polypharmacy rate were statistically significantly higher in the DRP group than in the non-DRP group (p

Abstract Background Episil® is a nonabsorbable liquid medical material used to coat and protect the mucosa in patients with oral mucositis. A few studies have reported its efficacy in patients with head and neck cancer. However, reports on its use in patients with hematologic malignancies are scarce. Thus, we aimed to evaluate the efficacy of Episil for the treatment of oral mucositis in patients with acute myelogenous leukemia, malignant lymphoma, acute lymphocytic leukemia, multiple myeloma, and myelodysplastic syndrome. Methods Between May 2018 and March 2019, a total of thirty-seven patients with acute myelogenous leukemia, malignant lymphoma, acute lymphocytic leukemia, multiple myeloma, and myelodysplastic syndrome who received Episil® for the treatment of oral mucositis were included in this study. All patients were treated at the Hiroshima Red Cross and Atomic-bomb Surgery Hospital. To determine the severity of oral mucositis, 22 out of the 37 patients were interviewed and compared objectively using the Common Terminology Criteria for Adverse Events, version 3.0. In addition, subjective measures of the effects of oral mucositis were assessed using an original evaluation protocol (a unique evaluation chart specific to the Department of Oral Surgery, Hiroshima Red Cross & Atomic-bomb Survivors Hospital). Results Out of 37 participants recruited in the study, 31 (84%) described the sensation of Episil® as very good or good. Moreover, the severity of mucositis was found to decrease after the use of Episil® in seven patients out of 22 (19%), particularly in those with mucositis at multiple sites. Participants' evaluations revealed pain relief and improvement in speech and feeding functions. Participants with grade 3 mucositis reported a greater improvement in pain relief, speech, and feeding functions than those with grade 2 mucositis. Conclusions This study suggests the efficacy of Episil® in treating oral mucositis in patients with hematologic malignancies, particularly in those with oral mucositis at multiple sites. In addition to pain relief, Episil® may improve speech and feeding functions.

Objective: The human cluster of differentiation (CD)300A, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, was investigated as a potential immune checkpoint for human natural killer (NK) cells targeting hematologic malignancies (HMs). Methods: We implemented a stimulation system involving the CD300A ligand, phosphatidylserine (PS), exposed to the outer surface of malignant cells. Additionally, we utilized CD300A overexpression, a CD300A blocking system, and a xenotransplantation model to evaluate the impact of CD300A on NK cell efficacy against HMs in in vitro and in vivo settings. Furthermore, we explored the association between CD300A and HM progression in patients. Results: Our findings indicated that PS hampers the function of NK cells. Increased CD300A expression inhibited HM lysis by NK cells. CD300A overexpression shortened the survival of HM-xenografted mice by impairing transplanted NK cells. Blocking PS–CD300A signals with antibodies significantly amplified the expression of lysis function-related proteins and effector cytokines in NK cells, thereby augmenting the ability to lyse HMs. Clinically, heightened CD300A expression correlated with shorter survival and an “exhausted” phenotype of intratumoral NK cells in patients with HMs or solid tumors. Conclusions: These results propose CD300A as a potential target for invigorating NK cell-based treatments against HMs.

The effect of vaccination on severity of subsequent COVID-19 in patients with hematologic malignancies (HMs) is unknown. In this single-center retrospective cohort study, we found no difference in severity of COVID-19 disease in vaccinated (n = 16) versus unvaccinated (n = 54) HM patients using an adjusted multiple logistic regression model. Recent anti-B-cell therapy was associated with more severe illness.

Background: Patients with hematological malignancies often require multidrug therapy using a variety of antineoplastic agents and supportive care medications. This increases the risk of drug-related problems (DRPs). Determining DRPs in patients hospitalized in hematology services is important for patients to achieve their drug treatment goals and prevent adverse effects. This study aims to identify DRPs by the clinical pharmacist in the multidisciplinary team in patients hospitalized in the hematology service of a university hospital in Turkey. Methods: This study was conducted prospectively between December 2022 and May 2023 in the hematology service of Suleyman Demirel University Research and Application Hospital in Isparta, Turkey. DRPs were determined using the Pharmaceutical Care Network Europe (PCNE) 9.1 Turkish version. Results: This study included 140 patients. Older age, longer hospital stay, presence of acute lymphoblastic leukemia, presence of comorbidities, higher number of medications used, and polypharmacy rate were statistically significantly higher in the DRP group than in the non-DRP group (p < 0.05). According to multivariate logistic regression analysis, the probability of DRP in patients with polypharmacy was statistically significant 7.921 times (95% CI: 3.033–20.689) higher than in patients without polypharmacy (p < 0.001).Every 5-day increase in the length of hospital stay increased the likelihood of DRP at a statistically significant level (OR = 1.476, 95% CI: 1.125–1.938 p = 0.005). In this study, at least one DRP was detected in 69 (49.3%) patients and the total number of DRPs was 152. Possible or actual adverse drug events (96.7%) were the most common DRPs. The most important cause of DRPs was drug choice (94.7%), and the highest frequency within its subcategories was the combination of inappropriate drugs (93.4%). Conclusions: This study shows the importance of including a clinical pharmacist in a multidisciplinary team in identifying and preventing DRPs in the hematology service. [ABSTRACT FROM AUTHOR]

Introduction: Patients with hematologic malignancies (HMs) often face challenges in accessing palliative care (PC) and receiving quality end‐of‐life (EOL) care. We examined factors associated with referrals to tertiary PC and the effects of tertiary PC on EOL care in patients with HMs. Method: We included patients with HMs who were admitted to a university‐affiliated hospital and died during hospitalization between January 2018 and December 2021. We investigated the receipt of PC consultations, patient characteristics, and EOL care indicators. Results: Overall, 487 patients were included in the analysis, with 156 (32%) undergoing PC consultation. Sex, residence, disease status, and admission purpose were factors associated with the likelihood of PC consultation, and there has been an increasing trend in the frequency of consultations in recent cases. A higher proportion of patients who received PC completed advance statements and life‐sustaining treatment documents. Patients who received PC had lower rates of aggressive EOL care, including chemotherapy and intensive care unit admission, than those who did not receive PC. Notably, PC reduced the number of blood transfusions. Conclusion: Tertiary PC aims to reduce aggressive EOL care through patient‐centered goal‐of‐care discussions. Therefore, there is an imperative need for concerted efforts toward seamless integration of PC. [ABSTRACT FROM AUTHOR]

Stenotrophomonas maltophilia (SM) bloodstream infections (BSIs) contribute to significant mortality in hematologic malignancy (HM) and hematopoietic stem cell transplantation (HSCT) patients. A risk score to predict SM BSI could reduce time to appropriate antimicrobial therapy (TTAT) and improve patient outcomes. A single center cohort study of hospitalized adults with HM/HSCT was conducted. Patients had ≥ 1 blood culture with a Gram-negative (GN) organism. A StenoSCORE was calculated for each patient. The StenoSCORE2 was developed using risk factors for SM BSI identified via logistic regression. Receiver operating characteristic (ROC) curves were plotted. Sensitivity and specificity for the StenoSCORE and StenoSCORE2 were calculated. Thirty-six SM patients and 534 non-SM patients were assessed. A StenoSCORE ≥ 33 points was 80% sensitive, 68% specific, and accurately classified 69% of GN BSIs. StenoSCORE2 variables included acute leukemia, prolonged neutropenia, mucositis, ICU admission, recent meropenem and/or cefepime exposure. The StenoSCORE2 performed better than the StenoSCORE (ROC AUC 0.84 vs. 0.77). A StenoSCORE2 ≥ 4 points was 86% sensitive, 76% specific, and accurately classified 77% of GN BSIs. TTAT was significantly longer for patients with SM BSI compared with non-SM BSI (45.16 h vs. 0.57 h; p < 0.0001). In-hospital and 28-day mortality were significantly higher for patients with SM BSI compared to non-SM BSI (58.3% vs. 18.5% and 66.7% vs. 26.4%; p-value < 0.0001). The StenoSCORE and StenoSCORE2 performed well in predicting SM BSIs in patients with HM/HSCT and GN BSI. Clinical studies evaluating whether StenoSCORE and/or StenoSCORE2 implementation improves TTAT and clinical outcomes are warranted. [ABSTRACT FROM AUTHOR]

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Febrile neutropenia (FN) is common among hematologic malignancy patients, including recipients of hematopoietic cell transplantation (HCT) and cellular therapies such as chimeric antigen receptor (CAR)‐T‐cell therapy. Prompt empiric antibiotic use has been the mainstay for decades but a "one‐size‐fits‐all" approach is no longer broadly accepted, as treatment‐related infectious risk are more understood. Growing antimicrobial resistance is an increasing clinical challenge. Evolving strategies on de‐escalation of broad‐spectrum antibiotics in FN without identified infection are areas of particular interest. [ABSTRACT FROM AUTHOR]

Purpose: Patients with hematologic malignancy (HM) commonly develop critical illness. Their long-term survival and functional outcomes have not been well described. Methods: We conducted a prospective, observational study of HM patients admitted to seven Canadian intensive care units (ICUs) (2018–2020). We followed survivors at 7 days, 6 months and 12 months following ICU discharge. The primary outcome was 12-month survival. We evaluated functional outcomes at 6 and 12 months using the functional independent measure (FIM) and short form (SF)-36 as well as variables associated with 12-month survival. Results: We enrolled 414 patients including 35% women. The median age was 61 (interquartile range, IQR: 52–69), median Sequential Organ Failure Assessment (SOFA) score was 9 (IQR: 6–12), and 22% had moderate–severe frailty (clinical frailty scale [CFS] ≥ 6). 51% had acute leukemia, 38% lymphoma/multiple myeloma, and 40% had received a hematopoietic stem cell transplant (HCT). The most common reasons for ICU admission were acute respiratory failure (50%) and sepsis (40%). Overall, 203 (49%) were alive 7 days post-ICU discharge (ICU survivors). Twelve-month survival of the entire cohort was 21% (43% across ICU survivors). The proportion of survivors with moderate–severe frailty was 42% (at 7 days), 14% (6 months), and 8% (12 months). Median FIM at 7 days was 80 (IQR: 50–109). Physical function, pain, social function, mental health, and emotional well-being were below age- and sex-matched population scores at 6 and 12 months. Frailty, allogeneic HCT, kidney injury, and cardiac complications during ICU were associated with lower 12- month survival. Conclusions: 49% of all HM patients were alive at 7 days post-ICU discharge, and 21% at 12 months. Survival varied based upon hematologic diagnosis and frailty status. Survivors had important functional disability and impairment in emotional, physical, and general well-being. [ABSTRACT FROM AUTHOR]

Background: Aplastic anemia (AA), characterized by hematopoietic stem cell deficiency, can evolve into different hematologic malignancies. Our understanding of the genetic basis and mechanisms of this progression remains limited. Methods: We retrospectively studied 9 acquired AA patients who later developed hematologic malignancies. Data encompassed clinical, laboratory, karyotype, and next-generation sequencing (NGS) information. We explored chromosomal alterations and mutation profiles to uncover genetic changes underlying the transition. Results: Nine AA patients developed myelodysplastic syndrome (seven patients), acute myeloid leukemia (one patient), or chronic myelomonocytic leukemia (one patient). Among eight patients with karyotype results at secondary malignancy diagnosis, monosomy 7 was detected in three. Trisomy 1, der(1;7), del(6q), trisomy 8, and del(12p) were detected in one patient each. Among three patients with NGS results at secondary malignancy diagnosis, KMT2C mutation was detected in two patients. Acquisition of a PTPN11 mutation was observed in one patient who underwent follow-up NGS testing during progression from chronic myelomonocytic leukemia to acute myeloid leukemia. Conclusion: This study highlights the genetic dynamics in the progression from AA to hematologic malignancy. Monosomy 7's prevalence and the occurrence of PTPN11 mutations suggest predictive and prognostic significance. Clonal evolution underscores the complexity of disease progression. [ABSTRACT FROM AUTHOR]

Raman spectroscopy is a molecular spectroscopic technique able to provide detailed information about the chemical structure, phase, crystallinity, and molecular interactions of virtually any analyzed sample. Although its medical applications have been studied for several decades, only recent advances in microscopy, lasers, detectors, and better understanding of the principles of the Raman effect have successfully expanded its applicability to clinical settings. The promise of a rapid, label-free diagnostic method able to evaluate the metabolic status of a cell in vivo makes Raman spectroscopy particularly attractive for hematology and oncology. Here, we review widely studied hematological applications of Raman spectroscopy such as leukocyte activation status, evaluation of treatment response, and differentiation between cancer and non-malignant cells, as well as its use in still unexplored areas in hematology. We also discuss limitations and challenges faced by Raman spectroscopy-based diagnostics as well as recent advances and modifications of the method aimed to increase its applicability to clinical hematooncology. [ABSTRACT FROM AUTHOR]

Background The fourth-generation (4th-gen) human immunodeficiency virus (HIV)-1/2 antibody/antigen (Ab/Ag) combination immunoassay currently used for HIV screening offers greater sensitivity than previous assays, but false-reactive results occur in up to 20% of patients. Large-scale observations in cancer patients are lacking. Methods We conducted a retrospective study of cancer patients seen at the University of Texas MD Anderson Cancer Center (March 2016–January 2023) who had reactive 4th-gen ARCHITECT HIV-1/2 Ab/Ag combination immunoassay results. We analyzed characteristics of patients with true-reactive and false-reactive results, defined based on Centers for Disease Control and Prevention criteria. Results A total of 43 637 patients underwent 4th-gen HIV screening, and 293 had reactive 4th-gen HIV test results. Twenty-one patients were excluded because they did not have cancer. Among the remaining 272 patients, 78 (29%) had false-reactive results. None of these patients experienced delays in their cancer treatment, but 26% experienced mental distress. Multivariate logistic regression analysis identified 5 predictors of having false-reactive results: age >60 years (adjusted odds ratio [aOR], 6.983; P <.0001), female sex (aOR, 6.060; P <.0001), race/ethnicity (Black: aOR, 0.274; Hispanic: aOR, 0.236; P =.002), syphilis coinfection (aOR, 0.046; P =.038), and plant alkaloids therapy (aOR, 2.870; P =.013). Conclusions False-reactive 4th-gen HIV test results occur in almost one-third of cancer patients. Physicians should be aware of the high rates of false-reactive HIV screening results in this patient population. These findings may have implications for counseling regarding testing, especially among those at low risk for HIV infection. [ABSTRACT FROM AUTHOR]

Streptococcus mitis commonly causes bloodstream infections (BSIs) in neutropenic patients but infrequently results in infective endocarditis (IE) in this population. Among 210 patients with neutropenia and S. mitis BSI, 55% underwent cardiac imaging. None were diagnosed with S. mitis IE; 3 had recurrent S. mitis BSI within 12 weeks. [ABSTRACT FROM AUTHOR]

There is lack of nationwide data on the cumulative incidence and timing of subsequent cutaneous squamous cell carcinomas (cSCCs) among patients with a first cSCC. To investigate the cumulative incidence and timing of subsequent cSCCs. Patients with a first cSCC in 2007/2008 from the Netherlands Cancer Registry were linked to the Netherlands Pathology Registry for subsequent cSCCs and the Netherlands Organ Transplant Registry. Cumulative incidence function curves were calculated for subsequent cSCCs and stratified for immune status. Among the 12,345 patients, second to sixth cSCC occurred in 4325, 2010, 1138, 739, and 501 patients, with median time intervals of 1.4, 1.2, 0.9, 0.6, and 0.5 years after the previous cSCC, respectively. The cumulative incidence of a subsequent cSCC at 5 years increased from 28% to 67% for the second to sixth cSCC. For solid organ transplant recipients, the cumulative incidences increased from 74% to 92% and from 41% to 64% for patients with hematologic malignancy. Only histopathologically confirmed cSCCs were included. The risk of a subsequent cSCC steeply rises with the number of prior cSCCs and immune status, while the time interval decreases. This can support more informed decisions about follow-up management. [ABSTRACT FROM AUTHOR]