Hematologic Malignant Neoplasms Research Articles

The upconversion luminescence biomonitoring and biological properties of rare earth oxide-inorganic composite microspheres enhanced by lithium

Multiple myeloma is the second most common hematologic malignant tumor, which can result in complications such as osteolytic fractures and bacterial infections. The side effects of chemotherapy limit the dosage of drugs, which can easily lead to multidrug resistance. Moreover, the dose and distribution of drugs within the body significantly influence the therapeutic efficacy of drugs. Therefore, it is highly necessary to improve multidrug resistance and bacterial infection in the treatment of multiple myeloma, repair bone defects caused by bone pain, and monitor the real-time dynamics of drugs. This work proposes a novel rare earth oxide-inorganic composite (7Li-MBGs:2Er/2Yb-0.75MTO) as a drug delivery platform for the treatment of multiple myeloma. 7Li-MBG, which have bone repair functions, serve as inorganic matrix materials, while Er2O3 and Yb2O3 act as activators and sensitizers, respectively. MTO is used as a therapeutic drug for treating myeloma. The drug release process of MTO was successfully monitored by upconversion luminescence. Cell experiments confirmed that 7Li-MBGs:2Er/2Yb-0.75MTO has a certain long-term therapeutic effect on multiple myeloma, and its mechanism of action is consistent with its drug release kinetics. Moreover, the synergistic effect of rare earth oxides, alkali metal ions and MTO endows 7Li-MBGs:2Er/2Yb-0.75MTO with high antibacterial and osteoinductive abilities, and thus playing a role in enhancing the drug resistance of infectious bacteria, preventing bacterial infection, repairing bone defects and monitoring the real-time dynamics of drug release during multiple myeloma therapy. Therefore, the 7Li-MBGs:2Er/2Yb-0.75MTO multifunctional drug delivery platform synthesized in this work provides a new idea for the treatment of multiple myeloma and biomonitoring.

Oral mucositis assessment in pediatric and adolescent oncological patients: A systematic review.

Oral mucositis (OM) is a prevalent acute adverse effect of various cancer treatments. Accurate assessment of OM is vital for effective prevention and treatment strategies. However, a lack of validated pediatric instruments for evaluating OM can lead to unreliable data, and hinder interventional and epidemiological research. This study aims to evaluate the methods used for assessing OM in pediatric oncology patients. A systematic review of four databases and a manual search yielded 113 articles. Nine different scales were identified, with the World Health Organization (WHO) scale being the most commonly used (61.9%). The Children's International Mucositis Evaluation Scale (ChIMES) was used in 7.9% of the studies. Of the 8155 pediatric patients evaluated, 47.7% had both hematological malignancies and malignant solid tumors, while 46% had solely hematological malignancies. Despite the prevalence of the WHO scale, it lacks pediatric-specific criteria. Future OM research should incorporate validated tools like ChIMES for improved pediatric assessment.

Cardiovascular Events After Chimeric Antigen Receptor T-Cell Therapy for Advanced Hematologic Malignant Neoplasms

The frequency and clinical phenotypes of cardiotoxic events in chimeric antigen receptor (CAR) T-cell recipients remain poorly understood given that landmark approval trials typically exclude patients with high-risk cardiovascular profiles and data from nontrial settings are scarce. To summarize the prevalence of adverse cardiovascular events among adults receiving CAR T-cell therapies for advanced hematologic malignant neoplasms. MEDLINE, Embase, Cochrane Library, and Google Scholar were systematically searched from database inception until February 26, 2024. Observational studies were included if they comprised adult CAR T-cell recipients with advanced hematologic malignant neoplasms and if they systematically evaluated cardiovascular complications. Extraction of prespecified parameters related to the patient population, study design, and clinical events was performed at the study level by 2 independent reviewers in accordance with the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. Meta-analysis of single proportions was conducted using random-effect models with Freeman-Tukey double arcsine transformations to calculate pooled prevalence estimates. Sensitivity analysis was performed using generalized linear mixed models with logit transformations. Ventricular and supraventricular arrhythmias, heart failure events, reduction in left ventricular ejection fraction, myocardial infarction, and cardiovascular and all-cause mortality. Thirteen studies comprising 1528 CAR T-cell recipients (median [IQR] age, 61 [58.7-63.0] years; 1016 males [66%]; 80% patients with lymphoma) were included. The median (IQR) duration of follow-up was 487 (294-530) days. On random-effects meta-analysis, we observed a pooled prevalence of 0.66% (95% CI, 0.00%-2.28%) for ventricular arrhythmia, 7.79% (95% CI, 4.87%-11.27%) for supraventricular arrhythmia, 8.68% (95% CI, 2.26%-17.97%) for left ventricular dysfunction, 3.87% (95% CI, 1.77%-6.62%) for heart failure events, 0.62% (95% CI, 0.02%-1.74%) for myocardial infarction, and 0.63% (95% CI, 0.13%-1.38%) for cardiovascular death. The pooled prevalence of all-cause mortality was 30.01% (95% CI, 19.49%-41.68%). Sensitivity analyses generated similar findings. This meta-analysis found a low prevalence of ventricular arrhythmia, myocardial infarction, and cardiovascular death among CAR T-cell recipients over a short-term to midterm follow-up. Left ventricular dysfunction and supraventricular arrhythmia were the most commonly reported cardiovascular complications, suggesting that cardiovascular surveillance strategies should focus on decreases in ejection fraction and supraventricular arrhythmia.

Research Progress on Ferroptosis in Multiple Myeloma.

Multiple myeloma (MM) is the second most common hematological malignant (HM) tumor, and a large proportion of patients still suffer from treatment failure and a poor prognosis despite the use of some newly approved drugs, a deeper understanding of the underlying mechanism is still needed. Ferroptosis is a new form of programmed cell death (PCD) that is different from other traditional forms of cell death such as apoptosis, necrosis and autophagy. With the continuous deepening of research on ferroptosis, ferroptosis has been found to be closely related to MM. This article reviews the regulatory mechanism of ferroptosis and research progress on ferroptosis in MM, providing a new theoretical basis and strategies for the diagnosis and treatment of MM.

Metabolic Function and Therapeutic Potential of CD147 for Hematological Malignancies: An Overview.

Hematological malignancies refer to a heterogeneous group of neoplastic conditions of lymphoid and hematopoietic tissues classified in leukemias, Hodgkin and non-Hodgkin lymphomas and multiple myeloma, according to their presumed cell of origin, genetic abnormalities, and clinical features. Metabolic adaptation and immune escape, which influence various cellular functions, including the proliferation and survival of hematological malignant tumor cells, are major aspects of these malignancies that lead to therapeutic drug resistance. Targeting specific metabolic pathways is emerging as a novel therapeutic strategy in hematopoietic neoplasms, particularly in acute myeloid leukemia and multiple myeloma. In this context, CD147, also known as extracellular matrix metalloproteinase inducer (EMMPRIN) or Basigin, is one target candidate involved in reprograming metabolism in different cancer cells, including hematological malignant tumor cells. CD147 overexpression significantly contributes to the metabolic transformation of these cancer cells, by mediating signaling pathway, growth, metastasis and metabolic reprogramming, through its interaction, direct or not, with various membrane proteins related to metabolic regulation, including monocarboxylate transporters, integrins, P-glycoprotein, and glucose transporter 1. This review explores the metabolic functions of CD147 and its impact on the tumor microenvironment, influencing the progression and neoplastic transformation of leukemias, myeloma, and lymphomas. Furthermore, we highlight new opportunities for the development of targeted therapies against CD147, potentially improving the treatment of hematologic malignancies.

Cognitive Trajectories in Older Adults Diagnosed With Hematologic Malignant Neoplasms

More people are surviving long-term after diagnosis with hematologic malignant neoplasm (HMN), yet there are limited data on cancer-related cognitive impairment in people with HMN. Better understanding cognitive outcomes after HMN in older adults is important for patient counseling and management. To model cognitive trajectories and rates of cognitive decline before and after HMN diagnosis in older adults compared with a matched noncancer cohort. In this population-based cohort study, older adults from the Health and Retirement Study (HRS) diagnosed with HMN between 1998 and 2016 after age 65 years were matched 1:3 to participants without cancer from the same HRS wave using propensity scores incorporating variables relevant to cognition. Cognitive trajectories were modeled with piecewise linear splines, and rates of cognitive decline before, during, and after diagnosis were compared in the 2 groups. Data were analyzed from April 2022 to April 2024. HMN diagnosis by Medicare diagnosis codes. Cognitive function was assessed by the Langa-Weir cognitive summary score from 1992 to 2020. Sociodemographic and health-related variables relevant to cognition were incorporated into propensity scores. At baseline, there were 668 participants in the HMN cohort (mean [SD] age, 76.8 [7.6] years; 343 [51.3%] male; 72 [10.8%] Black, 33 [4.9%] Hispanic, and 585 [87.6%] White) and 1994 participants in the control cohort (mean [SD] age, 76.5 [7.3] years; 1020 [51.2%] male; 226 [11.3%] Black, 91 [4.6%] Hispanic, and 1726 [86.6%] White). The HMN cohort consisted predominantly of more indolent diagnoses, and only 96 patients (14.4%) received chemotherapy. Before and in the 2 years around the time of diagnosis, the HMN and control cohorts had similar rates of cognitive decline. At 1 year postdiagnosis and beyond, the rate of cognitive decline was slower in the HMN cohort (-0.18; 95% CI, -0.23 to -0.14) than in the control group (-0.24; 95% CI, -0.26 to -0.23) (P = .02), but this difference was no longer significant after accounting for the competing risk of death (HMN group, -0.27; 95% CI, -0.34 to -0.19; control group, -0.30; 95% CI, -0.33 to -0.27; P = .48). In this cohort study of older adults, the HMN and matched noncancer control cohorts had similar rates of cognitive decline before, during, and after diagnosis after accounting for the competing risk of death.

Chinese expert consensus on minimal residual disease detection in multiple myeloma based on bone marrow samples (2024)

Multiple myeloma (MM) is the second most common hematologic malignant tumor. Standard holistic treatment model and new drug-based regimens have greatly improved the survival of patients with MM; however, minimal residual disease (MRD) causes relapse in most patients. Therefore, combining MRD testing on the basis of traditional serological efficacy evaluation is necessary to achieve a more accurate assessment of the patient's disease status. At present, next-generation flow cytometry (NGF) and next-generation sequencing (NGS) are the mainstream technologies for detecting MRD based on bone marrow samples. To standardize and normalize MRD detection, the expert group discussed and formulated Chinese expert consensus on the application of NGF and NGS technology for bone marrow MRD detection in patients with MM.

Patient-Reported Outcomes in Phase 3 Clinical Trials for Blood Cancers: A Systematic Review

Published research suggests that patient-reported outcomes (PROs) are neither commonly collected nor reported in randomized clinical trials (RCTs) for solid tumors. Little is known about these practices in RCTs for hematological malignant neoplasms. To evaluate the prevalence of PROs as prespecified end points in RCTs of hematological malignant neoplasms, and to assess reporting of PROs in associated trial publications. All issues of 8 journals known for publishing high-impact RCTs (NEJM, Lancet, Lancet Hematology, Lancet Oncology, Journal of Clinical Oncology, Blood, JAMA, and JAMA Oncology) between January 1, 2018, and December 13, 2022, were searched for primary publications of therapeutic phase 3 trials for adults with hematological malignant neoplasms. Studies that evaluated pretransplant conditioning regimens, graft-vs-host disease treatment, or radiotherapy as experimental treatment were excluded. Data regarding trial characteristics and PROs were extracted from manuscripts and trial protocols. Univariable analyses assessed associations between trial characteristics and PRO collection or reporting. Ninety RCTs were eligible for analysis. PROs were an end point in 66 (73%) trials: in 1 trial (1%) as a primary end point, in 50 (56%) as a secondary end point, and in 15 (17%) as an exploratory end point. PRO data were reported in 26 of 66 primary publications (39%): outcomes were unchanged in 18 and improved in 8, with none reporting worse PROs with experimental treatment. Trials sponsored by for-profit entities were more likely to include PROs as an end point (49 of 55 [89%] vs 17 of 35 [49%]; P < .001) but were not significantly more likely to report PRO data (20 of 49 [41%] vs 6 of 17 [35%]; P = .69). Compared with trials involving lymphoma (18 of 29 [62%]) or leukemia or myelodysplastic syndrome (18 of 28 [64%]), those involving plasma cell disorders or multiple myeloma (27 of 30 [90%]) or myeloproliferative neoplasms (3 of 3 [100%]) were more likely to include PROs as an end point (P = .03). Similarly, compared with trials involving lymphoma (3 of 18 [17%]) or leukemia or myelodysplastic syndrome (5 of 18 [28%]), those involving plasma cell disorders or multiple myeloma (16 of 27 [59%]) or myeloproliferative neoplasms (2 of 3 [67%]) were more likely to report PROs in the primary publication (P = .01). In this systematic review, almost 3 of every 4 therapeutic RCTs for blood cancers collected PRO data; however, only 1 RCT included PROs as a primary end point. Moreover, most did not report resulting PRO data in the primary publication and when reported, PROs were either better or unchanged, raising concern for publication bias. This analysis suggests a critical gap in dissemination of data on the lived experiences of patients enrolled in RCTs for hematological malignant neoplasms.

Socioeconomic Status and Overall Survival Among Patients With Hematological Malignant Neoplasms

In recent years, there has been a focus on reducing the socioeconomic gap in survival for hematological malignant neoplasms. Understanding recent developments is important to develop further intervention to improve care. To investigate the temporal trend in associations of socioeconomic status (SES) with survival among 3 aggressive hematological malignant neoplasms: multiple myeloma (MM), acute myeloid leukemia (AML), and diffuse large B-cell lymphoma (DLBCL). This nationwide, population-based cohort study used retrospectively collected data from 3 clinical registries of patients diagnosed in Denmark between January 1, 2005, and December 31, 2020, with follow-up until December 31, 2021. Analyses were stratified by diagnosis year (2005-2009, 2010-2014, and 2015-2020). Participants were patients aged 25 to 65 years with hematological malignant neoplasms. Patients with missing data on education were excluded. Data were analyzed from October 14, 2022, to January 2, 2024. Education was used as a proxy for SES and defined low- and high-SES groups based on the completion of tertiary education. The main outcome was overall survival (OS), analyzed using Kaplan-Meier (log rank) method and Cox proportional hazards regression adjusted for age, sex, performance status, comorbidities, and disease-specific prognostic indices. Two-year OS through time and survival difference were estimated using flexible parametric survival models. A total of 5677 patients (median [IQR] age, 58 [51-62] years; 3177 [57.0%] male) were assessed, including 1826 patients with MM, 1236 patients with AML, and 2509 patients with DLBCL. The 2-year OS increased over time for patients with MM (78.8% [95% CI, 75.4%-82.3%] to 91.4% [95% CI, 89.3%-93.5%]), AML (42.2% [95% CI, 37.8%-47.1%] to 52.7% [95% CI, 48.0%-57.9%]), and DLBCL (80.1% [95% CI, 77.4%-82.8%] to 88.1% [95% CI, 86.0%-90.3%]). For MM and DLBCL, no association of SES with survival was observed after adjustment (MM: hazard ratio [HR], 0.99 [95% CI, 0.85-1.15]; DLBCL: HR, 1.08 [95% CI, 0.91-1.29]). For AML, a negative association was observed between low SES and survival (HR, 1.49 [95% CI, 1.25-1.76]), but the association was attenuated in recent years. The difference in hazard for patients with low SES and AML was observed in the first 2 years after diagnosis. These findings suggest that survival has improved among patients with these hematological malignant neoplasms. While patients with MM and DLBCL had increased survival in all groups, disparities were observed in AML outcomes, primarily in the first years after diagnosis. These results suggest that differences originate in factors specific to AML.

Risk factors and predictive model for mortality in patients undergoing allogeneic hematopoietic stem cell transplantation admitted to the intensive care unit.

Hematological malignant tumors represent a group of major diseases carrying a substantial risk to the lives of affected patients. Risk factors for mortality in critically ill patients have garnered substantial attention in recent research endeavors. The present research aimed to identify factors predicting intensive care unit (ICU) mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Furthermore, the present study analyzed and compared the mortality rate between patients undergoing haploidentical hematopoietic stem cell transplantation (Haplo-SCT) and those undergoing identical sibling donor (ISD) transplantation. A total of 108 patients were included in the present research, 83 (76.9%) of whom underwent Haplo-SCT. ICU mortality was reported in 58 (53.7%) patients, with the values of 55.4 and 48.0% associated with Haplo-SCT and ISD, respectively (P=0.514). The mortality rate of patients undergoing Haplo-SCT was comparable to that of patients undergoing ISD transplantation. The present study found that reduced hemoglobin, elevated total bilirubin, elevated brain natriuretic peptide, elevated fibrinogen degradation products, need for vasoactive drugs at ICU admission, need for invasive mechanical ventilation and elevated APACHE II scores were independent risk factors for ICU mortality. Among patients presenting with 5-7 risk factors, the ICU mortality reached 100%, significantly exceeding that of other patients. The present research revealed that ICU mortality rates remain elevated among patients who underwent allo-HSCT, especially those presenting multiple risk factors. However, the outcome of patients undergoing Haplo-SCT were comparable to those of patients undergoing ISD transplants.

Severe COVID-19 in Vaccinated Adults With Hematologic Cancers in the Veterans Health Administration

With SARS-CoV-2 transforming into an endemic disease and with antiviral treatments available, it is important to establish which patients remain at risk of severe COVID-19 despite vaccination. To quantify the associations of clinical and demographic variables with odds of severe COVID-19 among patients with hematologic cancers. This case-control study included all patients with hematologic malignant neoplasms in the national Veterans Health Administration (VHA) who had documented SARS-CoV-2 infection after vaccination. Groups of patients with severe (cases) vs nonsevere (controls) COVID-19 were compared. Data were collected between January 1, 2020, and April 5, 2023, with data on infection collected between January 1, 2021, and September 30, 2022. All patients with diagnostic codes for hematologic malignant neoplasms who had documented vaccination followed by documented SARS-CoV-2 infection and for whom disease severity could be assessed were included. Data were analyzed from July 28 to December 30, 2023. Clinical (comorbidities, predominant viral variant, treatment for malignant neoplasm, booster vaccination, and antiviral treatment) and demographic (age and sex) variables shown in prior studies to be associated with higher or lower rates of severe COVID-19. Comorbidities included Alzheimer disease or dementia, chronic kidney disease, chronic obstructive pulmonary disease, diabetes, heart failure, and peripheral vascular disease. The main outcome was severe COVID-19 compared with nonsevere SARS-CoV-2 infection. Severe COVID-19 was defined as death within 28 days, mechanical ventilation, or hospitalization with use of dexamethasone or evidence of hypoxemia or use of supplemental oxygen. Multivariable logistic regression was used to estimate the associations of demographic and clinical variables with the odds of severe COVID-19, expressed as adjusted odds ratios (aORs) with 95% CIs. Among 6122 patients (5844 [95.5%] male, mean [SD] age, 70.89 [11.57] years), 1301 (21.3%) had severe COVID-19. Age (aOR per 1-year increase, 1.05; 95% CI, 1.04-1.06), treatment with antineoplastic or immune-suppressive drugs (eg, in combination with glucocorticoids: aOR, 2.32; 95% CI, 1.93-2.80), and comorbidities (aOR per comorbidity, 1.35; 95% CI, 1.29-1.43) were associated with higher odds of severe disease, whereas booster vaccination was associated with lower odds (aOR, 0.73; 95% CI, 0.62-0.86). After oral antiviral drugs became widely used in March 2022, 20 of 538 patients (3.7%) with SARS-CoV-2 infection during this period had progression to severe COVID-19. In this case-control study of patients with hematologic cancers, odds of severe COVID-19 remained high through mid-2022 despite vaccination, especially in patients requiring treatment.

Risk of hematologic malignant neoplasms from head CT radiation in children and adolescents presenting with minor head trauma: a nationwide population-based cohort study.

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. 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. 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. Radiation exposure from head CTs in children and adolescents with minor head trauma was associated with an increased incidence of hematologic malignant neoplasms. 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. • 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.

Clonal Hematopoiesis Risk Score and All-Cause and Cardiovascular Mortality in Older Adults.

Clonal hematopoiesis (CH) with acquired pathogenic variants in myeloid leukemia driver genes is common in older adults but of unknown prognostic value. To investigate the prevalence of CH and the utility of the CH risk score (CHRS) in estimating all-cause and disease-specific mortality in older adults with CH. This population-based prospective cohort study involved community-dwelling older adults (aged 67-90 years) without hematologic malignant neoplasms (HMs) who were participants in the Atherosclerosis Risk in Communities Visit 5 at 4 US centers: Forsyth County, North Carolina; Jackson, Mississippi; Minneapolis, Minnesota; and Washington County, Maryland. Samples were collected from 2011 to 2013, sequencing was performed in 2022, and data analysis was completed in 2023. The exposure was a diagnosis of CH. CHRS scores (calculated using 8 demographic, complete blood cell count, and molecular factors) were used to categorize individuals with CH into low-risk (CHRS ≤9.5), intermediate-risk (CHRS >9.5 to <12.5), and high-risk (CHRS ≥12.5) groups. The primary outcome was all-cause mortality, and secondary outcomes were HM mortality, cardiovascular disease mortality, and death from other causes. Among 3871 participants without a history of HM (mean [SD] age, 75.7 [5.2] years; 2264 [58.5%] female individuals; 895 [23.1%] Black individuals; 2976 White individuals [76.9%]), 938 (24.2%) had CH. According to the CHRS, 562 (59.9%) were low risk, 318 (33.9%) were intermediate risk, and 58 (6.2%) were high risk. During a median (IQR) follow-up of 7.13 (5.63-7.78) years, 570 participants without CH (19.4%) and 254 participants with CH (27.1%) died. Mortality by CHRS risk group was 128 deaths (22.8%) for low risk, 93 (29.2%) for intermediate risk, and 33 (56.9%) for high risk. By use of multivariable competing risk regression, subdistribution hazard ratios (sHRs) for all-cause mortality were 1.08 (95% CI, 0.89-1.31; P = .42) for low-risk CH, 1.12 (95% CI, 0.89-1.41; P = .31) for intermediate-risk CH, and 2.52 (95% CI, 1.72-3.70; P < .001) for high-risk CH compared with no CH. Among individuals in the high-risk CH group, the sHR of death from HM (6 deaths [10.3%]) was 25.58 (95% CI, 7.55-86.71; P < .001) and that of cardiovascular death (12 deaths [20.7%]) was 2.91 (95% CI, 1.55-5.47; P < .001). In this cohort study, the CHRS was associated with all-cause, HM-related, and cardiovascular disease mortality in older adults with CH and may be useful in shared decision-making to guide clinical management and identify appropriate candidates for clinical trials.

Higher Expression of Human Endogenous Retrovirus-K was Observed in Peripheral B Lymphocytes of Leukemia and Lymphoma Patients.

Hematological malignant tumors (HMTs) are serious diseases that threaten human health and life with high mortality. Therefore, it is necessary to develop novel strategies for diagnosis and treatment. Human endogenous retroviruses (HERVs) have recently attracted increasing attention as potential targets for cancer diagnosis and therapy. In this study, we explored the association between HERV-K expression levels and HMTs development. Clinical data and peripheral blood samples were collected from 236 leukemia, 384 lymphoma patients, and 69 healthy controls. Quantitative polymerase chain reaction was used to detect the expression of HERV-K gag, pol, and env genes in peripheral blood mononuclear cells or different cell subpopulations. Differently expressed HERV-K genes were further tested by using deep sequencing method, and further analyzed with gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. B cell- and T cell-related cytokines in patients were also detected by enzyme-linked immunosorbent assay (ELISA). The results showed that the expression levels of the HERV-K gag, pol, and env genes in patients were significantly higher than in healthy controls. There was a correlation between the expression level of HERV-K and the clinicopathological parameters of leukemia patients. HERV-K expression was increased in the B lymphocytes of leukemia and lymphoma patients, but not in the T cells or neutrophils. The GO and KEGG analyses showed that abnormal expression of the HERV-K locus in patients affected immune regulation. The analysis of cytokines proved that the B cell-related cytokines, including interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon-gamma, were significantly decreased in patients, while the T cell-related cytokines, including IL-3, IL-12, and TNF-β, were not significantly changed. In conclusion, HERV-K genes might participate in the occurrence and development of leukemia and lymphoma, and might be biomarkers for the detection or evaluation of leukemia and lymphoma.

Gene amplification in neoplasia: A cytogenetic survey of 80 131 cases.

Gene amplification is a crucial process in cancer development, leading to the overexpression of oncogenes. It manifests cytogenetically as extrachromosomal double minutes (dmin), homogeneously staining regions (hsr), or ring chromosomes (r). This study investigates the prevalence and distribution of these amplification markers in a survey of 80 131 neoplasms spanning hematologic disorders, and benign and malignant solid tumors. The study reveals distinct variations in the frequency of dmin, hsr, and r among different tumor types. Rings were the most common (3.4%) sign of amplification, followed by dmin (1.3%), and hsr (0.8%). Rings were particularly frequent in malignant mesenchymal tumors, especially liposarcomas (47.5%) and osteosarcomas (23.4%), dmin were prevalent in neuroblastoma (30.9%) and pancreatic carcinoma (21.9%), and hsr frequencies were highest in head and neck carcinoma (14.0%) and neuroblastoma (9.0%). Combining all three amplification markers (dmin/hsr/r), malignant solid tumors consistently exhibited higher frequencies than hematologic disorders and benign solid tumors. The structural characteristics of these amplification markers and their potential role in tumorigenesis and tumor progression highlight the complex interplay between cancer-initiating gene-level alterations, for example, fusion genes, and subsequent amplification dynamics. Further research integrating cytogenetic and molecular approaches is warranted to better understand the underlying mechanisms of these amplifications, in particular, the enigmatic question of why certain malignancies display certain types of amplification. Comparing the present results with molecular genetic data proved challenging because of the diversity in definitions of amplification across studies. This study underscores the need for standardized definitions in future work.

Super Enhancer Regulatory Gene FYB1 Promotes the Progression of T Cell Acute Lymphoblastic Leukemia by Activating IGLL1.

Arising from T progenitor cells, T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignant tumor, accounting for 15% of childhood ALL and 25% of adult ALL. Composing of putative enhancers in close genomic proximity, super enhancer (SE) is critical for cell identity and the pathogenesis of multiple cancers. Belonging to the cytosolute linker protein group, FYB1 is essential for TCR signaling and extensively studied in terms of tumor pathogenesis and metastasis. Dissecting the role of FYN binding protein 1 (FYB1) in T-ALL holds the potential to improve the treatment outcome and prognosis of T-ALL. In this study, SEs were explored using public H3K27ac ChIP-seq data derived from T-ALL cell lines, AML cell lines and hematopoietic stem and progenitor cells (HSPCs). Downstream target of FYB1 gene was identified by RNA-seq. Effects of shRNA-mediated downregulation of FYB1 and immunoglobulin lambda-like polypeptide 1 (IGLL1) on self-renewal of T-ALL cells were evaluated in vitro and/or in vivo. As an SE-driven gene, overexpression of FYB1 was observed in T-ALL, according to the Cancer Cell Line Encyclopedia database. In vitro, knocking down FYB1 led to comprised growth and enhanced apoptosis of T-ALL cells. In vivo, downregulation of FYB1 significantly decreased the disease burden by suppressing tumor growth and improved survival rate. Knocking down FYB1 resulted in significantly decreased expression of IGLL1 that was also an SE-driven gene in T-ALL. As a downstream target of FYB1, IGLL1 exerted similar role as FYB1 in inhibiting growth of T-ALL cells. Our results suggested that FYB1 gene played important role in regulating self-renewal of T-ALL cells by activating IGLL1, representing a promising therapeutic target for T-ALL patients.

SARS-CoV-2 Infection, Hospitalization, and Mortality in Adults With and Without Cancer

Patients with cancer are at increased risk of SARS-CoV-2-associated adverse outcomes. To determine the associations of tumor type with SARS-CoV-2 infection, hospitalization, intensive care unit (ICU) admission, and death. This retrospective, population-based cohort study included community-dwelling adults aged at least 18 years in Ontario, Canada, ICES-linked provincial health databases from January 1, 2020, to November 30, 2021. Data were analyzed from December 1, 2021, to November 1, 2022. Cancer diagnosis. The primary outcome was SARS-CoV-2 infection, and secondary outcomes included all-cause 14-day hospitalization, 21-day ICU admission, and 28-day death following SARS-CoV-2 infection. Cox proportional hazards models were used to obtain adjusted hazard ratios (aHRs) and 95% CIs. Of 11 732 108 people in the ICES-linked health databases, 279 287 had cancer (57.2% female; mean [SD] age, 65.9 [16.1] years) and 11 452 821 people did not have cancer (45.7% female; mean [SD] age, 65.9 [16.0] years). Overall, 464 574 individuals (4.1%) developed SARS-CoV-2 infection. Individuals with hematologic malignant neoplasms (33 901 individuals) were at increased risk of SARS-CoV-2 infection (aHR, 1.19; 95% CI, 1.13-1.25), 14-day hospitalization (aHR, 1.75; 95% CI, 1.57-1.96), and 28-day mortality (aHR, 2.03; 95% CI, 1.74-2.38) compared with the overall population, while individuals with solid tumors (245 386 individuals) were at lower risk of SARS-CoV-2 infection (aHR, 0.93; 95% CI, 0.91-0.95) but increased risk of 14-day hospitalization (aHR, 1.11; 95% CI, 1.05-1.18) and 28-day mortality (aHR, 1.31; 95% CI, 1.19-1.44). The 28-day mortality rate was high in hospitalized patients with hematologic malignant neoplasms (163 of 321 hospitalized patients [50.7%]) or solid tumors (486 of 1060 hospitalized patients [45.8%]). However, the risk of 21-day ICU admission in patients with hematologic malignant neoplasms (aHR, 1.14; 95% CI, 0.93-1.40) or solid tumors (aHR, 0.93; 95% CI, 0.82-1.05) was not significantly different from that among individuals without cancer. The SARS-CoV-2 infection risk decreased stepwise with increasing numbers of COVID-19 vaccine doses received (1 dose: aHR, 0.63; 95% CI, 0.62-0.63; 2 doses: aHR, 0.16; 95% CI, 0.16-0.16; 3 doses: aHR, 0.05; 95% CI, 0.04-0.06). These findings highlight the importance of prioritization strategies regarding ICU access to reduce the mortality risk in increased-risk populations, such as patients with cancer.

Research Progress on Pyroptosis in Hematological Malignancies.

Pyroptosis is a kind of programmed cell death dependent on the caspase pathway that is different from apoptosis and necrosis. Recent studies have shown that pyroptosis can be involved in the pathological processes of many diseases, such as cancers, atherosclerosis, diabetic nephropathy, and blood diseases. However, the specific mechanisms by which pyroptosis participates in the occurrence and development of hematological malignant tumors still need further exploration. This article reviews the characteristics of pyroptosis and the regulatory mechanisms promoting or inhibiting pyroptosis and discusses the role of pyroptosis in hematological malignant tumors, which could provide ideas for the clinical treatment of such tumors in the future.

Measuring Safety and Outcomes for the Use of Compassionate and Off-Label Therapies for Children, Adolescents, and Young Adults With Cancer in the SACHA-France Study

Innovative anticancer therapies for children, adolescents, and young adults are regularly prescribed outside their marketing authorization or through compassionate use programs. However, no clinical data of these prescriptions is systematically collected. To measure the feasibility of the collection of clinical safety and efficacy data of compassionate and off-label innovative anticancer therapies, with adequate pharmacovigilance declaration to inform further use and development of these medicines. This cohort study included patients treated at French pediatric oncology centers from March 2020 to June 2022. Eligible patients were aged 25 years or younger with pediatric malignant neoplasms (solid tumors, brain tumors, or hematological malignant neoplasms) or related conditions who received compassionate use or off-label innovative anticancer therapies. Follow up was conducted through August 10, 2022. All patients treated in a French Society of Pediatric Oncology (SFCE) center. Collection of adverse drug reactions and anticancer activity attributable to the treatment. A total of 366 patients were included, with a median age of 11.1 years (range, 0.2-24.6 years); 203 of 351 patients (58%) in the final analysis were male. Fifty-five different drugs were prescribed, half of patients (179 of 351 [51%]) were prescribed these drugs within a compassionate use program, mainly as single agents (74%) and based on a molecular alteration (65%). Main therapies were MEK/BRAF inhibitors followed by multi-targeted tyrosine kinase inhibitors. In 34% of patients at least a grade 2 clinical and/or grade 3 laboratory adverse drug reaction was reported, leading to delayed therapy and permanent discontinuation of the innovative therapy in 13% and 5% of patients, respectively. Objective responses were reported in 57 of 230 patients (25%) with solid tumors, brain tumors, and lymphomas. Early identification of exceptional responses supported the development of specific clinical trials for this population. This cohort study of the SACHA-France (Secured Access to Innovative Medicines for Children with Cancer) suggested the feasibility of prospective multicenter clinical safety and activity data collection for compassionate and off-label new anticancer medicines. This study allowed adequate pharmacovigilance reporting and early identification of exceptional responses allowing further pediatric drug development within clinical trials; based on this experience, this study will be enlarged to the international level.

Ferroptosis in hematological malignant tumors.

Ferroptosis is a kind of iron-dependent programmed cell death discovered in recent years. Its main feature is the accumulation of lipid reactive oxygen species in cells, eventually leading to oxidative stress and cell death. It plays a pivotal role in normal physical conditions and the occurrence and development of various diseases. Studies have shown that tumor cells of the blood system, such as leukemia cells and lymphoma cells, are sensitive to the response to ferroptosis. Regulators that modulate the Ferroptosis pathway can accelerate or inhibit tumor disease progression. This article reviews the mechanism of ferroptosis and its research status in hematological malignancies. Understanding the mechanisms of ferroptosis could provide practical guidance for treating and preventing these dreaded diseases.