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Patients with primary hematological malignancy (HM) are at an elevated risk of subsequent malignant neoplasms (SMNs), which is a common concern after treatment of primary cancer. We identified 45,533 patients aged ≥20 years and diagnosed with primary HM in Finland from 1992 to 2019 from the Finnish Cancer Registry and estimated standardized incidence ratios (SIR) and excess absolute risks per 1000 person‐years (EAR) for SMNs. A total of 6076 SMNs were found (4604 solid and 1472 hematological SMNs). The SIRs were higher for hematological SMNs (SIR 4.9, 95% confidence interval [CI] 4.7–5.2) compared to solid SMNs (SIR 1.5, 95% CI 1.4–1.5). The SIRs for hematological SMNs were highest in the young HM patients aged 20–39 years (SIR 9.2, 95% CI 6.8–12.2 in males and SIR 10.5, 95% CI 7.2–14.7 in females) and decreased by age of first primary HM. However, EARs for hematological SMNs were highest in the older patients, aged 60–79 years at their first primary HM (EAR 5.7/1000 and 4.7/1000 in male and female patients, respectively). In conclusion, the incidence of both hematological and solid SMNs were increased in hematological cancer patients. The relative risk (SIR) was highest among younger HM patients with hematological SMNs. The absolute second cancer burden reflected by high EAR arises from solid malignancies in older patients. Our results accentuate the need for vigilance in the surveillance of HM patients. [ABSTRACT FROM AUTHOR]

Background: Targeted protein degradation of neosubstrates plays a crucial role in hematological cancer treatment involving immunomodulatory imide drugs (IMiDs) therapy. Nevertheless, the persistence of inevitable drug resistance and hematological toxicities represents a significant obstacle to their clinical effectiveness. Methods: Phenotypic profiling of a small molecule compounds library in multiple hematological cancer cell lines was conducted to screen for hit degraders. Molecular dynamic-based rational design and cell-based functional assays were conducted to develop more potent degraders. Multiple myeloma (MM) tumor xenograft models were employed to investigate the antitumor efficacy of the degraders as single or combined agents with standard of care agents. Unbiased proteomics was employed to identify multiple therapeutically relevant neosubstrates targeted by the degraders. MM patient-derived cell lines (PDCs) and a panel of solid cancer cell lines were utilized to investigate the effects of candidate degrader on different stage of MM cells and solid malignancies. Unbiased proteomics of IMiDs-resistant MM cells, cell-based functional assays and RT-PCR analysis of clinical MM specimens were utilized to explore the role of BRD9 associated with IMiDs resistance and MM progression. Results: We identified a novel cereblon (CRBN)-dependent lead degrader with phthalazinone scaffold, MGD-4, which induced the degradation of Ikaros proteins. We further developed a novel potent candidate, MGD-28, significantly inhibited the growth of hematological cancer cells and induced the degradation of IKZF1/2/3 and CK1α with nanomolar potency via a Cullin-CRBN dependent pathway. Oral administration of MGD-4 and MGD-28 effectively inhibited MM tumor growth and exhibited significant synergistic effects with standard of care agents. MGD-28 exhibited preferentially profound cytotoxicity towards MM PDCs at different disease stages and broad antiproliferative activity in multiple solid malignancies. BRD9 modulated IMiDs resistance, and the expression of BRD9 was significant positively correlated with IKZF1/2/3 and CK1α in MM specimens at different stages. We also observed pronounced synergetic efficacy between the BRD9 inhibitor and MGD-28 for MM treatment. Conclusions: Our findings present a strategy for the multi-targeted degradation of Ikaros proteins and CK1α against hematological cancers, which may be expanded to additional targets and indications. This strategy may enhance efficacy treatment against multiple hematological cancers and solid tumors. [ABSTRACT FROM AUTHOR]

RGS (Regulator of G protein signaling) proteins have long captured the fascination of researchers due to their intricate involvement across a wide array of signaling pathways within cellular systems. Their diverse and nuanced functions have positioned them as continual subjects of scientific inquiry, especially given the implications of certain family members in various cancer types. Of particular note in this context is RGS20, whose clinical relevance and molecular significance in hepatocellular carcinoma we have recently investigated. These investigations have prompted questions into the prevalence of pathogenic mutations within the RGS20 gene and the intricate network of interacting proteins that could contribute to the complex landscape of cancer biology. In our study, we aim to unravel the mutations within the RGS20 gene and the multifaceted interplay between RGS20 and other proteins within the context of cancer. Expanding on this line of inquiry, our research is dedicated to uncovering the intricate mechanisms of RGS20 in various cancers. In particular, we have redirected our attention to examining the role of RGS20 within hematological malignancies, with a specific focus on multiple myeloma and follicular lymphoma. These hematological cancers hold significant promise for further investigation, as understanding the involvement of RGS20 in their pathogenesis could unveil novel therapeutic strategies and treatment avenues. Furthermore, our exploration has extended to encompass the latest discoveries concerning the potential involvement of RGS20 in diseases affecting the central nervous system, thereby broadening the scope of its implications beyond oncology to encompass neurobiology and related fields. [ABSTRACT FROM AUTHOR]

CAR-T cell therapy is known as an effective therapy in patients with hematological malignancies. Since 2017, several autologous CAR-T cell (auto-CAR-T) drugs have been approved by the US Food and Drug Administration (FDA) for the treatment of some kinds of relapsed/refractory hematological malignancies. However, some patients fail to respond to these drugs due to high manufacturing time, batch-to-batch variation, poor quality and insufficient quantity of primary T cells, and their insufficient expansion and function. CAR-T cells prepared from allogeneic sources (allo-CAR-Ts) can be an alternative option to overcome these obstacles. Recently, several allo-CAR-Ts have entered into the early clinical trials. Despite their promising preclinical and clinical results, there are two main barriers, including graft-versus-host disease (GvHD) and allo-rejection that may decline the safety and efficacy of allo-CAR-Ts in the clinic. The successful development of these products depends on the starter cell source, the gene editing method, and the ability to escape immune rejection and prevent GvHD. Here, we summarize the gene editing technologies and the potential of various cell sources for developing allo-CAR-Ts and highlight their advantages for the treatment of hematological malignancies. We also describe preclinical and clinical data focusing on allo-CAR-T therapy in blood malignancies and discuss challenges and future perspectives of allo-CAR-Ts for therapeutic applications. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the most frequent primary liver tumor globally and a leading cause of mortality in cirrhotic patients. Our study aimed to estimate the diagnostic performance of triphasic CT and inter-observer reliability in the preoperative detection of microvascular invasion (MVI) in HCC. Two independent radiologists accomplished a retrospective analysis for 99 patients with HCC to assess the CT features for MVI in each lesion. Postoperative histopathology was considered the gold standard. Results: Multivariate regression analysis revealed that incomplete or absent tumor capsules, presence of TTPV, and absence of hypodense halo were statistically significant independent predictors of MVI. There was excellent agreement among observers in evaluating peritumoral enhancement, identifying intratumoral arteries, hypodense halo, TTPV, and macrovascular invasion. Also, our results revealed moderate agreement in assessing the tumor margin and tumor capsule. Conclusion: Triphasic CT features of MVI are reliable imaging predictors that may be helpful for standard preoperative interpretation of HCC. [ABSTRACT FROM AUTHOR]

Introduction: CD80, a co-stimulatory molecule required for optimal T cell activation, is expressed on antigen-presenting cells, including monocytes and dendritic cells, in dogs and humans. We hypothesized that CD80 would be expressed on tumor cells in dogs from acute myeloid leukemia (AML) but not dogs with lymphoid neoplasms. Methods and results: We first evaluated the cellular staining pattern of a hamster anti-murine CD80 antibody (clone 16-10A1, ThermoFisher Scientific Cat# 17– 0801-82, RRID: AB_469417) in blood and bone marrow aspirates from healthy dogs. Using flow cytometric analysis and examination of modified Wright’sstained cytologic smears of unsorted and flow cytometric or immunomagnetic bead-sorted leukocytes, we show that the antibody binds to mature and immature neutrophils and monocytes, but not lymphocytes or eosinophils, in blood and bone marrow. We then added the antibody to routine flow cytometric panels for immunophenotyping hematopoietic neoplasms in dogs. We found that the antibody labeled tumor cells in 72% of 39 dogs with AML and 36% of 11 dogs with acute leukemia expressing lymphoid and myeloid markers (“mixed lineage”) but none of the dogs with B (n  =  37) or T (n  =  35) lymphoid neoplasms. A higher proportion of tumor cells in dogs with AML were labeled with the anti-CD80 antibody vs antibodies against other myeloid-associated antigens, including CD4 (36%, p  =  0.003), CD11b (44%), CD11c (46%), CD14 (38%, p  =  0.006) and CD18 (59%, clone YFC118). In contrast, antibodies against CD11b and CD11c bound to tumor cells in 8–32% of the lymphoid neoplasms. Discussion: We show that CD80, as detected by antibody clone 16-10A1, is a sensitive and specific marker for AML and would be useful to include in flow cytometric immunophenotyping panels in dogs. [ABSTRACT FROM AUTHOR]

Background/Aims: Inflammatory bowel disease (IBD) may contribute to the development of hematologic malignancies. In this study, the potential relationship between IBD and hematologic malignancies was investigated. Methods: We searched the PubMed, Web of Science, Embase, and Cochrane Library databases for all cohort studies comparing the incidence of hematologic malignancies in non-IBD populations with that in IBD patients, and we extracted relevant data from January 2000 to June 2023 for meta-analysis. Results: Twenty cohort studies involving 756,377 participants were included in this study. The results showed that compared with the non-IBD cohort, the incidence of hematologic malignancies in the IBD cohort was higher (standardized incidence ratio [SIR]=3.05, p<0.001). According to the specific types of IBD, compared with the non-IBD patients, the incidences of hematologic malignancies in ulcerative colitis patients (SIR=2.29, p=0.05) and Crohn's disease patients (SIR=3.56, p=0.005) were all higher. In the subgroup analysis of hematologic malignancy types, compared with the control group, the incidences of non-Hodgkin's lymphoma (SIR=1.70, p=0.01), Hodgkin's lymphoma (SIR=3.47, p=0.002), and leukemia (SIR=3.69, p<0.001) were all higher in the IBD cohort. Conclusions: The incidence of hematologic malignancies, including non-Hodgkin's lymphoma, Hodgkin's lymphoma, and leukemia is higher in patients with IBD (ulcerative colitis or Crohn's disease) than in non-IBD patients. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the utilization of hematopathology resources within our enterprise on axillary lymph node core biopsy (AxLNCB) specimens, particularly those obtained in the context of breast cancer screening. Methods The utilization of hematopathology resources was determined for all AxLNCB specimens over a 30-month period from across our enterprise, and chart review was performed for select patient demographics and radiographic features. The AxLNCB cases with benign histology were reviewed for subtyping of histologic patterns. Results Of the total 594 AxLNCB specimens, 61.6% were benign and 38.6% malignant. Of malignant cases, only 9.3% contained any hematologic malignancy, yet 94% of all cases received tissue triage for lymphoma, and 81% were reviewed at least in part by a hematopathologist. Six clinical parameters were found to independently predict risk of hematologic malignancy: male sex (P =.041), bilateral lymphadenopathy (P =.004), diffuse cortical thickening (P =.005), lack of breast cancer (P =.001), older age (P <.001), and history of hematologic malignancy (P <.001). Conclusions Our enterprise overused hematopathology resources in the evaluation of AxLNCB performed in the study period. Our process could improve from the application of a simple tool generated from this cohort to predict percent risk of the specimen containing hematologic malignancy using patient characteristics easily found via routine chart review. [ABSTRACT FROM AUTHOR]

Background When to perform echocardiography to rule out infective endocarditis (IE) in patients with viridans group streptococci (VGS) bloodstream infections (BSIs) is unclear. Objectives We aimed to identify independent risk factors for IE in patients with VGS BSI. Methods This retrospective study conducted at Seoul National University Hospital from January 2013 to December 2022 involved patients with VGS and nutritionally variant streptococcal BSI, excluding single positive blood cultures and polymicrobial BSI cases. Independent risk factors were identified by multivariate logistic regression and sensitivity analyses according to echocardiography results, VGS species or the inclusion of possible IE cases. Results Of 845 VGS BSI cases, 349 were analysed and 86 IE cases were identified (24.6%). In the multivariate analysis, heart valve disease [adjusted odds ratio (aOR), 14.14, 95% CI, 6.14–32.58; P  < 0.001], persistent bacteraemia (aOR, 5.12, 95% CI, 2.03–12.94; P  = 0.001), age (per year, aOR, 0.98; 95% CI, 0.96–1.00; P =  0.015), solid cancer (aOR, 0.26; 95% CI, 0.13–0.53; P <  0.001) and haematologic malignancy (aOR, 0.04; 95% CI, 0.01–0.41; P =  0.006) were independently associated with IE. Sensitivity analyses yielded consistent results; also, infection by a member of the mitis group was independent risk factor for IE (aOR, 6.50; 95% CI, 2.87–14.68; P  < 0.001). Conclusions Younger age, heart valve disease, persistent bacteraemia, absence of underlying malignancy and BSI by a member of the mitis group were independent risk factors for IE in patients with VGS BSI. Echocardiographic evaluation could be prudently considered based on these clinicomicrobiological risk factors. [ABSTRACT FROM AUTHOR]

Background: The mediating role of hope in the effects of spiritual wellbeing on life satisfaction in elderly haematologic cancer patients in Turkey was investigated in the present study. Methods: The study was conducted in a descriptive, cross‐sectional and correlational design. The study was conducted with 150 patients aged 65 and older who were diagnosed with haematologic cancer and who were referred to a university hospital haematology clinic and outpatient clinic. Research data were collected with Descriptive Information Form, Dispositional Hope Scale (DHS), Spiritual Well‐being Scale (FACIT‐Sp‐12) and Satisfaction with Life Scale (SWLS). Results: FACIT‐Sp‐12 score was 37.25 ± 7.29; DHS score was 40.42 ± 8.29, SWLS score was 16.24 ± 8.79. FACIT‐Sp‐12 (β = 0.668) and DHS (β = 0.226) were found to affect SWLS positively. In terms of the effect of FACIT‐Sp‐12 on SWLS, DHS has a mediating role and makes the positive effect of FACIT‐Sp‐12 on SWLS stronger (β = 0.771). Conclusions: Spiritual wellbeing levels of the participants in our study were found to be high, while their levels of satisfaction with life and hope were found to be moderate. It was also concluded that spiritual wellbeing had a direct effect on satisfaction with life and an indirect effect through the mediating role of hope. [ABSTRACT FROM AUTHOR]

Purpose: Data on short courses of antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients are limited. The aim of the study was to describe and compare the frequency of bacteremia relapse, 30-day overall and infection-related mortality, Clostridiodes difficile infection and length of hospital stay since bacteremia among those who received antibiotic therapy for 7 or 14 days. Methods: This is a multicenter, prospective, observational cohort study in adult high-risk neutropenic patients with hematologic malignancies or hematopoietic stem cell transplant and monomicrobial Enterobacterales bacteremia. They received appropriate empirical antibiotic therapy, had a clinical response within 7 days, and infection source control. Clinical, epidemiological and outcomes variables were compared based on 7 or 14 days of AT. Results: Two hundred patients were included (100, 7-day antibiotic therapy; 100, 14-day antibiotic therapy). Escherichia coli was the pathogen most frequently isolated (47.5%), followed by Klebsiella sp. (40.5%). Among those patients that received 7-day vs. 14-day antibiotic course, a clinical source of bacteremia was found in 54% vs. 57% (p = 0.66), multidrug-resistant Enterobacterales isolates in 28% vs. 30% (p = 0.75), and 40% vs. 47% (p = 0.31) received combined empirical antibiotic therapy. Overall mortality was 3% vs. 1% (p = 0.62), in no case related to infection; bacteremia relapse was 7% vs. 2% (p = 0.17), and length of hospital stay since bacteremia had a median of 9 days (IQR: 7–15) vs. 14 days (IQR: 13–22) (p = < 0.001). Conclusions: These data suggest that seven-day antibiotic therapy might be adequate for patients with high-risk neutropenia and Enterobacterales bacteremia, who receive appropriate empirical therapy, with clinical response and infection source control. [ABSTRACT FROM AUTHOR]

Background: India is a vast and diverse country with existing variations in the frequency and distribution of cancers across its various parts. In regions lacking population-based cancer registries (PBCRs) in a vast country like India, hospital-based cancer registry (HBCR) data become an important source of information on the trends and patterns of a region. To determine the numerical trends of cases of the top ten cancer sites reporting to HBCR of a tertiary care cancer center in Bihar from 2014 to 2021. Materials and Methods: The details of all histopathologically confirmed cancer cases registered in the HBCR department of radiation oncology, State Cancer Institute, Indira Gandhi Institute of Medical Sciences, Patna, India between January 2014 and December 2021 were included in this retrospective observational study. All these cases were grouped site-wise and listed in descending order of the total number of cases reported in each group. Cross-tabulation with age and sex distribution was done. The frequency distribution of the top ten leading cancers for every consecutive calendar year was plotted in line diagrams for time trend analysis. Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.). was used for analysis. Annual percent change (APC) was determined for the number of cases of all ten cancer sites using joinpoint regression analysis (Joinpoint Regression Software, Version 4.0.4--May 2013; Statistical Methodology and Applications Branch, Surveillance Research Program of the US National Cancer Institute; Bethesda, MD, USA). Results: Out of 32,057 total cancer cases registered between Jan 2014 and Dec 2021, 21,848 patients (68.2%) cases constituted the top ten cancers. The top ten cancers among both sexes were cancer gallbladder (n = 4204, 13.1%), head and neck (n = 3395, 10.6%), breast (n = 3392, 10.6%), lung (n = 2069, 6.5%), cervix (n = 2039, 6.4%), hematolymphoid (n = 1930, 6.0%), liver (n = 1572, 4.9%), stomach (n = 1116, 3.5%), ovary (n = 1103, 3.4%), and colon-rectum (n = 1028, 3.2%). Except for cervical and hematolymphoid cancers, the rest all showed a rising trend over consecutive years. Conclusion: Cancer of the gallbladder continues to be among the most common cancers in the region. Focused research in all aspects of this deadly disease is needed. Strengthening of prevention and screening programs for common cancers and upliftment of the existing infrastructure for diagnosis and treatment of cancer in the region are necessitated. [ABSTRACT FROM AUTHOR]

Objectives: Patients with hematologic cancer experience severe symptoms (i.e. insomnia, fatigue, pain, distress). Few interventions addressing insomnia and other symptoms exist for this population. Mindfulness-Based Therapy for Insomnia (MBTI) may be appropriate but has only been tested in healthy outpatients. This study aimed to develop and test an adapted MBTI protocol for hematologic cancer patients. Methods: Patient (n = 3) and clinician (n = 1) focus groups, and user-testing (N = 5) informed adaptation of Mindful Night-to-Day (MBTI+). A single-arm pilot trial (N = 32) evaluated feasibility (accrual, attrition, adherence), acceptability (intervention satisfaction), and changes to insomnia symptom severity (Insomnia Severity Index; primary outcome) and secondary outcomes (fatigue, pain, distress, pre-sleep arousal, mindfulness, symptom management self-efficacy) at baseline, post-intervention, and 1-month post-intervention. Descriptive statistics and paired sample t-tests were conducted. Results: Qualitative feedback informed MBTI+ content, format, and delivery. Mindfulness was used to increase symptom awareness (sleepiness vs. fatigue). Meditations and behavioral skills were applied to inpatient treatment. MBTI+ met feasibility (N = 32/12 months; 8.1% attrition; 83.8% adherence) and acceptability (M = 3.52/4.00) benchmarks. Insomnia symptom severity decreased (d = 1.20) from baseline to post-intervention, as did most secondary outcomes. Conclusions: MBTI+ was feasible, acceptable, and showed promise for benefits throughout inpatient and outpatient treatment. Findings warrant further evaluation in a randomized trial. [ABSTRACT FROM AUTHOR]

Purpose: Patients with hematologic malignancies (HM) typically rely on informal caregivers for support. Caregivers experience distress, poorer health, and lower quality of life. This study aimed to understand caregivers' experiences adapting to, and making meaning of, their family members' cancer diagnosis and treatment. Approach: Qualitative, constructivist approach. Participants: Caregivers (N = 28) of patients with HM within three months of diagnosis. Methods: A descriptive content analysis was used to analyze semi-structured interview responses and generate themes. Findings: Six themes emerged: power and control (powerlessness, empowerment, relinquishing control/accepting help), protection (gatekeeping, protective buffering), integrating the diagnosis, tolerating uncertainty, preparedness for the caregiver role, and maintaining positivity. Conclusions: Findings highlight challenges and resilience-promoting processes for caregivers adapting to HM diagnosis and treatment. Implications for Psychosocial Providers: Psychological and supportive care interventions can promote acceptance of the diagnosis, preparation for caregiving, navigation of power and control, and targeted coping strategies. [ABSTRACT FROM AUTHOR]

Purpose: Patients with acute myeloid leukemia (AML) experience significant distress. Expressive writing is an intervention designed to improve well-being by encouraging expression of emotions related to traumatic experiences. Expressive writing has been shown to be generally feasible and effective at improving the cancer experience but has not been examined in patients with recently diagnosed hematologic malignancies. We examined the feasibility of an expressive writing intervention for hospitalized patients with AML receiving induction chemotherapy. Methods: Fifteen hospitalized AML patients were randomized to complete expressive writing or neutral prompts. Feasibility was defined as 80% of enrolled subjects completing the study. Participants completed validated questionnaires measuring depression, anxiety, resilience, rumination, and quality of life at baseline, completion of the second and fourth writing exercises, and 3 months after enrollment. Participants also completed post-writing surveys following the writing exercise to reflect on the experience. Findings: We enrolled 15 participants and 8 of 15 subjects (53%) completed the study. Due to low enrollment, we examined the pre-to-post intervention changes, rather than comparing results across intervention arms. Pre-to-post intervention changes in the expected direction were seen at the second assessment for depression and resilience, at the fourth assessment for rumination, emotional well-being, and social well-being, and at the 3-month follow-up for anxiety and emotional well-being. Similar changes in patient-reported outcomes were also seen in the control condition. Participants who completed the intervention reported the experience was meaningful and were able to express their deepest thoughts and feelings, more so than participants in the control arm. Conclusion: In our work, the expressive writing intervention was not found to be feasible. The trial was interrupted by the COVID-19 pandemic which likely impacted the feasibility. Future studies should aim to identify ways to make the intervention more accessible, such as developing an electronic application for expressive writing. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T cell therapy has shown promising results in hematologic malignancies, but its effectiveness in solid cancers remains challenging. Macrophages are immune cells residing within the tumor microenvironment. They can phagocytose tumor cells. Recently, CAR macrophages (CAR-M) have been a promising candidate for treating solid cancers. One of the common cancer antigens overexpressed in various types of cancer is CD147. CAR-T and NK cells targeting CD147 antigen have shown significant efficacy against hepatocellular carcinoma. Nevertheless, CAR-M targeting the CD147 molecule has not been investigated. In this study, we generated CAR targeting the CD147 molecule using the THP-1 monocytic cell line (CD147 CAR-M). The CD147 CAR-M exhibited typical macrophage characteristics, including phagocytosis of zymosan bioparticles and polarization ability toward M1 and M2 phenotypes. Furthermore, the CD147 CAR-M demonstrated enhanced anti-tumor activity against K562 and MDA-MB-231 cells without exhibiting off-target cytotoxicity against normal cells. Our research provides valuable insights into the potential of CD147 CAR-M as a promising platform for cancer immunotherapy, with applications in both hematologic malignancies and solid cancers. [ABSTRACT FROM AUTHOR]

This document is a letter to the editor published in the journal Leukemia & Lymphoma. The authors conducted a retrospective analysis to understand the nature of TRBC1-dim populations, which are T-cell clones of uncertain significance (T-CUS), detected in peripheral blood samples. They aimed to estimate the prevalence of these populations, document their immunophenotypic features, and document the clinical characteristics of patients with these populations. The study found that 6.7% of samples and 6.1% of patients had TRBC1-dim populations, with the average age of patients with these populations being 70 years. The authors concluded that these populations are unlikely to represent a circulating T-cell neoplasm and are more likely to be a recurrent artifact. [Extracted from the article]

The tumor microenvironment's cells can promote or inhibit tumor formation, and there are no reports on the CD4/CD8 ratio's association with outcomes post allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively evaluated the pre-transplant peripheral blood CD4/CD8 ratio in 168 patients who underwent their first allo-HSCT for hematological malignancies at our institution. When patients were divided into two groups according to the median CD4/CD8 ratio 1.35 (range, 0.09–19.89), the high CD4/CD8 ratio group had a higher incidence of relapse, equivalent non-relapse mortality and worse overall survival (OS) than the low CD4/CD8 ratio group. In a multivariate analysis, the CD4/CD8 ratio was significantly associated with an increased risk of relapse, although there was a marginally significant difference in OS. The pre-transplant peripheral blood CD4/CD8 ratio could be a novel biomarker for predicting the prognosis of allo-HSCT. [ABSTRACT FROM AUTHOR]

Evidence on mortality rates and causes of death associated with extrapulmonary nontuberculous mycobacteria (NTM) infection is limited. This nationwide register-based study in Denmark used diagnostic codes to match adult patients with extrapulmonary NTM infection 1:4 to controls. During 2000–2017, we identified 485 patients, who had significantly more comorbidities than controls. The 5-year mortality rate for patients was 26.8% (95% CI 23.1%–31.0%) and for controls, 10.9% (95% CI 9.6%–12.4%). The median age at death was 76 (interquartile range 63–85) years for patients and 84 (interquartile range 73–90) years for controls. The adjusted hazard rate of death for patients was 1.34 (95% CI 1.10–1.63; p = 0.004). Patients and controls mainly died of cardiovascular disease and solid malignant neoplasms. Hematologic malignancies and HIV were more frequently causes of death in patients. Mortality rates are substantial among patients with extrapulmonary NTM infection, predominantly caused by underlying conditions. [ABSTRACT FROM AUTHOR]

Objectives: The carcinogenic risks of CT radiation in children and adolescents remain debated. We aimed to assess the carcinogenic risk of CTs performed in children and adolescents with minor head trauma. Methods: In this nationwide population-based cohort study, we included 2,411,715 patients of age 0–19 with minor head trauma from 2009 to 2017. We excluded patients with elevated cancer risks or substantial past medical radiation exposure. Patients were categorized into CT-exposed or CT-unexposed group according to claim codes for head CT. The primary outcome was development of hematologic malignant neoplasms. Secondary outcomes included development of malignant solid neoplasms and benign neoplasms in the brain. We measured the incidence rate ratio (IRR) and incidence rate difference (IRD) using G-computation with Poisson regression adjusting for age, sex, hospital setting, and the type of head trauma. Results: Hematologic malignant neoplasms developed in 100 of 216,826 patients during 1,303,680 person-years in the CT-exposed group and in 808 of 2,194,889 patients during 13,501,227 person-years in the CT-unexposed group. For hematologic malignant neoplasms, the IRR was 1.29 (95% CI, 1.03–1.60) and the IRD was 1.71 (95% CI, 0.04–3.37) per 100,000 person-years at risk. The majority of excess hematologic malignant neoplasms were leukemia (IRR, 1.40 [98.3% CI, 1.05–1.87]; IRD, 1.59 [98.3% CI, 0.02–3.16] per 100,000 person-years at risk). There were no between-group differences for secondary outcomes. Conclusions: Radiation exposure from head CTs in children and adolescents with minor head trauma was associated with an increased incidence of hematologic malignant neoplasms. Clinical relevance statement: Our study provides a quantitative grasp of the risk conferred by CT examinations in children and adolescents, thereby providing the basis for cost–benefit analyses and evidence-driven guidelines for patient triaging in head trauma. Key Points: • This nationwide population-based cohort study showed that radiation exposure from head CTs in children and adolescents was associated with a higher incidence of hematologic malignant neoplasms. • The incidence rate of hematologic malignant neoplasms in the CT-exposed group was 29% higher than that in the CT-unexposed group (IRR, 1.29 [95% CI, 1.03–1.60]), and there were approximately 1.7 excess neoplasms per 100,000 person-years at risk in the CT-exposed group (IRD, 1.71 [0.04–3.37]). • Our study provides a quantified grasp of the risk conferred by CT examinations in children and adolescents, while controlling for biases observed in previous studies via specifying CT indication and excluding patients with predisposing conditions for cancer development. [ABSTRACT FROM AUTHOR]

Acute leukemia is a hematological malignancy affecting different organ systems including the eye and orbit through direct infiltration of tissues or secondary to hematological abnormalities. Ophthalmological manifestations in acute leukemia are variable ranging from asymptomatic presentation to serious manifestations that can alter the disease course and treatment. The purpose of this study is to detect the incidence of different ophthalmological manifestations in newly diagnosed acute leukemia patients and to assess the relationship between ocular findings and hematological characteristics and the sequel of these neoplasms. A cross-sectional study with analytical components was conducted on 222 newly diagnosed acute myeloid and acute lymphoblastic leukemia patients who presented at Oncology Center Mansoura University (OCMU) between January 2022 and February 2023. All patients underwent a complete ophthalmic evaluation at Mansoura Ophthalmology Center (MOC). The mean age was 43.45 ± 17.35 years (range, 17–85), and M/F was 137 (61.7%)/85 (38.3%). One-hundred and forty-four (64.9%) had acute myeloid leukemia (AML), and 78 (35.1%) had acute lymphoblastic leukemia (ALL). Ophthalmic manifestations were detected in 96 patients (43.2%). Among them, 4 (1.8%) had poor visual acuity. Retinal hemorrhage (19.8%) and Roth spots (17.1%) were the most common ocular manifestations. Other ophthalmological manifestations observed were orbital involvement (3.2%), ocular motility issues (1.4%), subconjunctival hemorrhage (5.9%), conjunctival chemosis (0.9%),lid swelling (4.1%), lid ecchymosis (3.2%), lagophthalmos (0.5%), lid ptosis (1.8%), retinal venous congestion & tortuosity (4.1%), preretinal hemorrhage (3.2%), vitreous hemorrhage (3.2%), macular affection (2.3%), retinal infiltration (1.8%), exudative retinal detachment (ERD) (1.8%), cotton-wool spots (0.9%), retinal vein occlusion (0.5%), papilledema (2.8%), optic disc infiltration (1.8%), disc pallor (1.8%).AML patients were significantly associated with a higher frequency of ocular affection, retinal hemorrhages, and Roth spots (P 0.028, 0.003, and 0.046, respectively) compared to ALL patients. Retinal hemorrhage was statistically significantly associated with anemia (P 0.021). Ophthalmological manifestations of acute leukemia are heterogeneous; they can be detected at initial presentations or relapse. Some manifestations are asymptomatic, others can affect visual acuity or even alter the disease course. Cooperation between ophthalmologists and haemato-oncologists is crucial for recognizing ocular involvement and disease management. [ABSTRACT FROM AUTHOR]

With advancements in novel therapeutics, it is unclear whether third hematopoietic cell transplantation (HCT3) has a place in the treatment of recurrent hematopoietic malignancies. We evaluated patients with hematologic malignancies who underwent HCT3 between 2000–2020. Nine patients, with a median age of 18 (9—68) years at HCT3 with acute myelogenous leukemia (n = 5), acute lymphoblastic leukemia (n = 2), myelodysplastic syndrome (n = 1), or undifferentiated acute leukemia (n = 1), were identified. The median time between first HCT and HCT3 was 3.9 (0.7—13.6) years. Indication for HCT3 was relapse (n = 8) or graft failure (n = 1) after second HCT. At HCT3, seven of nine patients were in complete remission by flow cytometry. All experienced robust donor engraftment by one month after HCT3 (≥ 90% CD3) while one died at day + 24 of multi-organ failure and was not evaluable for chimerism. In total, eight patients died from relapse (n = 4), non-relapse, (n = 3) or unknown (n = 1) causes at a median of 0.6 (range, 0.1 – 9.9) years after HCT3. After HCT3, estimated overall survival at 6 months, 1 year, and 5 years was 88%, 63%, and 22%, respectively. In this highly selected group, HCT3 provided a treatment option although long-term survival was still dismal. [ABSTRACT FROM AUTHOR]

Eosinophilic dermatosis of hematologic malignancy (EDHM) is a cutaneous manifestation seen in patients with hematoproliferative and lymphoproliferative disorders, most commonly chronic lymphocytic leukemia. This systematic review aimed to summarize the therapeutic interventions of EDHM. A comprehensive search yielded 71 studies, predominantly case reports and series. The most frequently reported modalities were systemic and topical corticosteroids, as well as treatment of the underlying malignancy. Responses to these treatments varied. Targeted therapies, including dupilumab and omalizumab, showed promise, as did other modalities such as montelukast, dapsone, doxycycline, and phototherapy. Higher‐quality studies should be conducted to facilitate higher‐quality management recommendations for EDHM. [ABSTRACT FROM AUTHOR]

Background and Objective: Multiple myeloma is a rare incurable hematological cancer in which most patients relapse or become refractory to treatment. This systematic literature review aimed to critically review the existing economic models used in economic evaluations of systemic treatments for relapsed/refractory multiple myeloma and to summarize how the models addressed differences in the line of therapy and exposure to prior treatment. Methods: Following a pre-approved protocol, literature searches were conducted on 17 February, 2023, in relevant databases for models published since 2014. Additionally, key health technology assessment agency websites were manually searched for models published as part of submission dossiers since 2018. Reported information related to model conceptualization, structure, uncertainty, validation, and transparency were extracted into a pre-defined extraction sheet. Results: In total, 49 models assessing a wide range of interventions across multiple lines of therapy were included. Only five models specific to heavily pre-treated patients and/or those who were refractory to multiple treatment classes were identified. Most models followed a conventional simple methodology, such as partitioned survival (n = 28) or Markov models (n = 9). All included models evaluated specific interventions rather than the whole treatment sequence. Where subsequent therapies were included in the model, these were generally only considered from a cost and resource use perspective. The models generally used overall and progression-free survival as model inputs, although data were often immature. Sensitivity analyses were frequently reported (n = 41) whereas validation was only considered in less than half (n = 19) of the models. Conclusions: Published economic models in relapsed/refractory multiple myeloma rarely followed an individual patient approach, mainly owing to the higher need for complex data assumptions compared with simpler modeling approaches. As many patients experience disease progression on multiple treatment lines, there is a growing need for modeling complex treatment strategies, leading to more sophisticated approaches in the future. Maintaining transparency, high reporting standards, and thorough analyses of uncertainty are crucial to support these advancements. [ABSTRACT FROM AUTHOR]

We report a case of chronic myeloid leukemia (CML), which was diagnosed during the management of proliferative retinopathy (PR) in a patient with type I diabetes mellitus due to the fulminant nature of the PR. This case highlights the importance of vigilance on the part of the ophthalmologist in the diagnosis of co-existing systemic disorders, notably hematological malignancy, which aggravates the posterior segment vasculopathy of the eye and the management of which is crucial for the patient. We also describe a short literature review on the clinical features, mechanism of the posterior segment vasculopathy of the eye, and management of PR co-existing in a patient with CML. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T-cell therapy is a human gene therapy product where T cells from a patient are genetically modified to enable them to recognize desired target antigen(s) more effectively. In recent years, promising antitumor activity has been seen with autologous CAR T cells. Since 2017, six CAR T-cell therapies for the treatment of hematological malignancies have been approved by the Food and Drug Administration (FDA). Despite the rapid progress of CAR T-cell therapies, considerable statistical challenges still exist for this category of products across all phases of clinical development that need to be addressed. These include (but not limited to) dose finding strategy, implementation of the estimand framework, use of real-world data in contextualizing single-arm CAR T trials, analysis of safety data and long-term follow-up studies. This paper is the first step in summarizing and addressing these statistical hurdles based on the development of the six approved CAR T-cell products. [ABSTRACT FROM AUTHOR]

The term "multiple primary (MP) cancers" refers to the existence of more than one cancer in the same patient. The combination of MP cancers with hematological malignancies is relatively uncommon. In this study, we present five patients diagnosed with MP cancers concomitant with hematological malignancies. We comprehensively analyzed their clinical characteristics, cytogenetic profiles, and germline and somatic variants. As first primaries, two patients had solid cancer not followed by cytotoxic therapy and three had hematologic cancer, followed by cytotoxic therapy. The second primaries were all hematologic malignancies that did not meet the criteria for therapy-related myeloid neoplasm. Notably, two (40%) out of the five patients harbored pathogenic potential/presumed germline variants in cancer predisposition genes. Therefore, germline variant testing should be considered when MP cancers with hematological malignancies require consideration for related donor stem cell transplantation. [ABSTRACT FROM AUTHOR]

Adoptive cell therapy (ACT) achieves substantial efficacy in the treatment of hematological malignancies and solid tumours, while enormous endeavors have been made to reduce relapse and extend the remission duration after ACT. For the genetically engineered T cells, their functionality and long-term anti-tumour potential depend on the specificity of the T cell receptor (TCR) or chimeric antigen receptor (CAR). In addition, the therapeutic benefit is directly to sufficient activation and proliferation of engineered T cells. Artificial antigen-presenting cells (aAPCs), as powerful boosters for ACT, have been applied to provide sustained stimulation of the cognate antigen and facilitate the expansion of sufficient T cells for infusion. In this review, we summarize the aAPCs used to generate effector cells for ACT and underline the mechanism by which aAPCs enhance the functionality of the effector cells. The manuscript includes investigations ranging from basic research to clinical trials, which we hope will highlight the importance of aAPCs and provide guidance for novel strategies to improve the effectiveness of ACT. [ABSTRACT FROM AUTHOR]

Background: Telomere shortening and epigenetic modifications are key factors in aging and hematologic diseases. This study investigates the relationship of telomere length and epigenetic age acceleration (EAA) with hematologic cancers, blood cells, and biochemical markers through the epigenetic clocks. Methods: This study primarily utilizes genome-wide association studies of populations of European descent as instrumental variables, exploring the causal relationships between exposures and outcomes through a bidirectional two-sample Mendelian randomization (MR) approach. MR techniques include inverse variance weighted (IVW), MR Egger, and weighted median modes. Heterogeneity and pleiotropy in MR are assessed using Cochran's Q test and the MR Egger intercept, with the robustness of the conclusions further validated by multivariable MR (MVMR). Results: Our research shows that longer telomere lengths significantly increase the risk of multiple myeloma, leukemia, and lymphoma (OR > 1, P < 0.05) and establish a causal relationship between telomere length and red blood cell indices such as RBC (OR = 1.121, PIVW = 0.034), MCH (OR = 0.801, PIVW = 2.046e-06), MCV (OR = 0.801, PIVW = 0.001), and MCHC (OR = 0.813, PIVW = 0.002). Additionally, MVMR analysis revealed an association between DNA methylation PhenoAge acceleration and alkaline phosphatase (OR = 1.026, PIVW = 0.007). Conclusion: The study clarifies the relationships between telomere length, EAA, and hematological malignancies, further emphasizing the prognostic significance of telomere length and EAA. This deepens our understanding of the pathogenesis of hematological diseases, which can inform risk assessment and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Myelofibrosis (MF), a complex hematological malignancy, presents a diverse array of symptoms, including anemia, constitutional symptoms, bone marrow insufficiency, and splenomegaly. The latter, often necessitating blood transfusions, poses an essential obstacle to MF management. While conventional approaches predominantly involve the use of JAK inhibitors, the potential for exacerbating anemia introduces complexity to the treatment. Nonetheless, Momelotinib stands out as a promising pharmaceutical compound with the potential to revolutionize the field. Momelotinib is an ACVR1 antagonist and a dual inhibitor of the JAK1 and JAK2 enzymes. By targeting MF's hematological and fibrotic aspects, Momelotinib influences iron metabolism by regulating hepcidin. This results in reduced hepcidin expression and increased iron availability, ultimately leading to improved anemia and reduced dependency on blood transfusion. This study aims to provide a concise overview of the pathogenesis of MF and elucidate the mechanism of action of Momelotinib. Subsequently, our review offers a practical summary encompassing the effects of Momelotinib in monotherapy, combined comparative drug therapy, and its associated side effects. Additionally, we explore the application of Momelotinib in other cancer types and investigate predictors for treatment success. Furthermore, we examine the utilization of Momelotinib in patients with liver and kidney failure. Highlights: MF is a complex hematological malignancy that has the potential to transform into acute myeloid leukemia in 20 % of cases Anemia occurs in approximately one-third of MF patients Momelotinib is a novel ACVR1 antagonist and a dual inhibitor of the JAK1 and JAK2 enzymes just FDA approved on September 15 A comprehensive applied review of this novel agent is lacking [ABSTRACT FROM AUTHOR]