Emerging roles for tRNAs in hematopoiesis and hematological malignancies.

tRNAs are central players in decoding the genetic code linking codons in mRNAs with cognate amino acids during protein synthesis. Recent discoveries have placed tRNAs as key regulators of gene expression during hematopoiesis, especially in hematopoietic stem cell (HSC) maintenance and immune development. These functions have been shown to be influenced by dynamic changes in tRNA expression, post-transcriptional base modifications, tRNA-interacting proteins, and tRNA fragmentation; these events underlie the complexity of tRNA-mediated regulatory events in hematopoiesis. In this review, we discuss these recent findings and highlight how deregulation of tRNA biogenesis can contribute to hematological malignancies.

T cell-redirecting therapies in hematological malignancies: Current developments and novel strategies for improved targeting.

T cell-redirecting therapies (TCRTs), such as chimeric antigen receptor (CAR) or T cell receptor (TCR) T cells and T cell engagers, have emerged as a highly effective treatment modality, particularly in the B and plasma cell-malignancy setting. However, many patients fail to achieve deep and durable responses; while the lack of truly unique tumor antigens, and concurrent on-target/off-tumor toxicities, have hindered the development of TCRTs for many other cancers. In this review, we discuss the recent developments in TCRT targets for hematological malignancies, as well as novel targeting strategies that aim to address these, and other, challenges.

Exploring the nexus of nuclear receptors in hematological malignancies.

Hematological malignancies (HM) represent a subset of neoplasms affecting the blood, bone marrow, and lymphatic systems, categorized primarily into leukemia, lymphoma, and multiple myeloma. Their prognosis varies considerably, with a frequent risk of relapse despite ongoing treatments. While contemporary therapeutic strategies have extended overall patient survival, they do not offer cures for advanced stages and often lead to challenges such as acquisition of drug resistance, recurrence, and severe side effects. The need for innovative therapeutic targets is vital to elevate both survival rates and patients' quality of life. Recent research has pivoted towards nuclear receptors (NRs) due to their role in modulating tumor cell characteristics including uncontrolled proliferation, differentiation, apoptosis evasion, invasion and migration. Existing evidence emphasizes NRs' critical role in HM. The regulation of NR expression through agonists, antagonists, or selective modulators, contingent upon their levels, offers promising clinical implications in HM management. Moreover, several anticancer agents targeting NRs have been approved by the Food and Drug Administration (FDA). This review highlights the integral function of NRs in HM's pathophysiology and the potential benefits of therapeutically targeting these receptors, suggesting a prospective avenue for more efficient therapeutic interventions against HM.

Subsequent malignant neoplasms after primary hematological malignancy in adult patients.

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.

Next-generation cytogenetics: Comprehensive assessment of 52 hematological malignancy genomes by optical genome mapping.

Somatic structural variants (SVs) are important drivers of cancer development and progression. In a diagnostic set-up, especially for hematological malignancies, the comprehensive analysis of all SVs in a given sample still requires a combination of cytogenetic techniques, including karyotyping, FISH, and CNV microarrays. We hypothesize that the combination of these classical approaches could be replaced by optical genome mapping (OGM). Samples from 52 individuals with a clinical diagnosis of a hematological malignancy, divided into simple (<5 aberrations, n = 36) and complex (≥5 aberrations, n = 16) cases, were processed for OGM, reaching on average: 283-fold genome coverage. OGM called a total of 918 high-confidence SVs per sample, of which, on average, 13 were rare and >100 kb. In addition, on average, 73 CNVs were called per sample, of which six were >5 Mb. For the 36 simple cases, all clinically reported aberrations were detected, including deletions, insertions, inversions, aneuploidies, and translocations. For the 16 complex cases, results were largely concordant between standard-of-care and OGM, but OGM often revealed higher complexity than previously recognized. Detailed technical comparison with standard-of-care tests showed high analytical validity of OGM, resulting in a sensitivity of 100% and a positive predictive value of >80%. Importantly, OGM resulted in a more complete assessment than any previous single test and most likely reported the most accurate underlying genomic architecture (e.g., for complex translocations, chromoanagenesis, and marker chromosomes). In conclusion, the excellent concordance of OGM with diagnostic standard assays demonstrates its potential to replace classical cytogenetic tests as well as to rapidly map novel leukemia drivers.

Performance Evaluation of a Novel Artificial Intelligence-Assisted Digital Microscopy System for the Routine Analysis of Bone Marrow Aspirates.

Bone marrow aspiration (BMA) smear analysis is essential for diagnosis, treatment, and monitoring of a variety of benign and neoplastic hematological conditions. Currently, this analysis is performed by manual microscopy. We conducted a multicenter study to validate a computational microscopy approach with an artificial intelligence-driven decision support system. A total of 795 BMA specimens (615 Romanowsky-stained and 180 Prussian blue-stained) from patients with neoplastic and other clinical conditions were analyzed, comparing the performance of the Scopio Labs X100 Full Field BMA system (test method) with manual microscopy (reference method). The system provided an average of 1,385 ± 536 (range, 0-3,131) cells per specimen for analysis. An average of 39.98 ± 19.64 fields of view (range, 0-140) per specimen were selected by the system for analysis, of them 87% ± 21% (range, 0%-100%) were accepted by the qualified operators. These regions were included in an average of 17.62 ± 7.24 regions of interest (range, 1-50) per specimen. The efficiency, sensitivity, and specificity for primary and secondary marrow aspirate characteristics (maturation, morphology, and count assessment), as well as overall interuser agreement, were evaluated. The test method showed a high correlation with the reference method for comprehensive BMA evaluation, both on Romanowsky- (90.85% efficiency, 81.61% sensitivity, and 92.88% specificity) and Prussian blue-stained samples (90.0% efficiency, 81.94% sensitivity, and 93.38% specificity). The overall agreement between the test and reference methods for BMA assessment was 91.1%. For repeatability and reproducibility, all standard deviations and coefficients of variation values were below the predefined acceptance criteria both for discrete measurements (coefficient of variation below 20%) and differential measurements (SD below 5%). The high degree of correlation between the digital decision support system and manual microscopy demonstrates the potential of this system to provide a high-quality, accurate digital BMA analysis, expediting expert review and diagnosis of BMA specimens, with practical applications including remote BMA evaluation and possibly new opportunities for the research of normal and neoplastic hematopoiesis.

Ulcerating skin lesions from blastic plasmacytoid dendritic cell neoplasm responding to low-dose radiotherapy-a case report and literature review.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that can manifest with skin nodules and erythematous plaques. In most cases BPDCN progresses rapidly, causing multiple skin lesions and also affecting internal organs and bone marrow, warranting initiation of systemic therapies or hematopoietic stem cell transplantation (HCT). Although not curative, radiotherapy for isolated lesions might be indicated in case of (imminent) ulceration and large or symptomatic lesions. To this end, doses of 27.0-51.0 Gy have been reported. Here, we present the case of an 80-year-old male with BPDCN with multiple large, nodular, and ulcerating lesions of the thorax, abdomen, and face. Low-dose radiotherapy of 2â€¯× 4.0 Gy was administered to several lesions, which resolved completely within 1 week with only light residual hyperpigmentation of the skin in affected areas and reliably prevented further ulceration. Radiotoxicity was not reported. Therefore, low-dose radiotherapy can be an effective and low-key treatment in selected cases of BPDCN, especially in a palliative setting, with a favorable toxicity profile.

Exploring the promise of regulator of G Protein Signaling 20: insights into potential mechanisms and prospects across solid cancers and hematological malignancies.

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.

Charting a path forward: Promising outcomes of convalescent plasma therapy in the care of severely B-cell depleted patients with persistent COVID-19.

BACKGROUND: Patients with severe B-cell depletion related to hematological malignancies or B-cell targeted therapy suffer from impaired antibody responses to SARS-CoV-2 and are at risk for prolonged COVID-19. In this population, COVID-19 convalescent plasma (CCP) may provide passive immunity, enhance immune response, and promote virus neutralization. This study evaluated outcomes of B-cell depleted patients with persistent COVID-19 treated with CCP. STUDY DESIGN AND METHODS: This analysis included all consecutive severely B-cell depleted patients with persistent COVID-19, receiving CCP at Rambam between 01.2022-02.2023. Persistent COVID-19 was defined as the presence of symptoms for ≥14 days in patients with negative SARS-CoV-2 nucleocapsid antibody test results. RESULTS: Twenty patients met inclusion criteria, 17 of whom had hematological malignancies, two suffered from rheumatoid arthritis and one had both. Twelve patients received anti-CD-20 treatment, one - CAR-T cells and three underwent stem cell transplantation. The median duration of COVID-19 symptoms was 27.5 days (range 14-97); 12 patients had mild-to-moderate COVID-19 and 8 had severe infection. Sixteen patients required hospitalization. The majority of patients received other COVID-19 therapies before CCP. Within a median of two days (range 1-16) post-infusion, 19/20 patients clinically improved. No CCP-associated adverse events were documented. COVID-19 symptoms recurred in 3 of the improved patients. Two patients died from COVID-19 on days 1 and 90 following the first CCP infusion. DISCUSSION: In severely B-cell depleted patients with persistent COVID-19, CCP is safe and associated with rapid clinical improvement. This subset of immunocompromised patients could particularly benefit from CCP administration.

Prognostic value of hyperlactatemia and lactate clearance in septic patients with hematological malignancies.

BACKGROUND: The coexistence of sepsis and hematological malignancies increases patient vulnerability, revealing the need for precise prognostic markers. This study explores the prognostic significance of lactate levels and clearance in septic patients with hematological malignancies. MATERIALS AND METHODS: A retrospective cohort study from January 2016 to December 2019 in a tertiary hematological intensive care unit (ICU) included 167 adults with hematological malignancies and sepsis. The relationship between lactate levels, hyperlactatemia, lactate clearance, and ICU outcomes was investigated. ICU survivors and non-survivors were compared to identify the factors affecting ICU mortality. RESULTS: Patients were primarily with lymphoma and acute leukemia (66%) and had frequent hyperlactatemia (64%) on ICU admission. ICU non-survivors demonstrated higher lactate levels and hyperlactatemia frequency at various time points (0, 6, and 12 h) than survivors. Lactate clearance and liver function tests did not differ significantly between the two groups. Invasive mechanical ventilation [OR (95% confidence interval-CI): 20.4 (2.4-79.8), p < 0.01], requirement of vasopressors [OR (95% CI): 5.6 (1.3-24.5), p < 0.01], lactate level at the 6th hour [OR (95% CI): 1.51 (1.1-2.07), p = 0.01], and APACHE II score (OR (95% CI): 1.16 (1.01-1.34), p = 0.05) were independent risk factors for ICU mortality. The Area Under the Curve for APACHE II score and lactate level at the 6th hour were 0.774 (95% CI: 0.682-0.866) and 0.703 (95% CI: 0.602-0.804), respectively. CONCLUSION: While elevated lactate levels correlate with mortality rate and lactate level at the 6th hour is an independent risk factor for mortality, the absence of a significant difference in lactate clearance challenges traditional assumptions. These results question the commonly accepted perspective regarding lactate dynamics in sepsis among individuals with hematological malignancies. ORAL PRESENTATION: Inci K, et al. "Hyperlactatemia, lactate clearance and outcome in critically ill patients with hematological malignancies," 22nd international intensive care symposium, 2019.

Vaccine challenges in CLL: a comprehensive exploration of efficacy of SARS-CoV-2 immunization for patients with chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is characterized by disease- and treatment-related immunosuppression. Patients with CLL comprise a vulnerable population to coronavirus disease 2019 (COVID-19), while the protective effect of COVID-19 vaccination remains uncertain.We conducted a systematic review to evaluate published data reporting response to COVID-19 vaccination in patients with CLL. The primary outcome was the rate of seropositivity after full primary vaccination, while secondary outcomes were rates of positive neutralizing antibodies, cellular responses, and adverse events. Response after booster doses of vaccination was also evaluated.Twenty-three studies of full primary vaccination (12 CLL-specific with 1747 patients, 11 with mixed hematologic diseases including 1044 patients with CLL) with a total of 2791 patients, and eight studies on booster doses with 389 patients were included in the analysis. The serologic response varied between studies with a median of 55%. Where reported, the median neutralizing antibody response rate was 61.2% and the cellular response rate was 44.2%. Poor serologic response was noted in patients under active treatment with anti-CD20 monoclonal antibodies, BCL2, and BTK inhibitors.The present review highlights the substantially impaired humoral and cellular response to COVID-19 vaccination in patients with CLL with patients under active treatment being the most vulnerable.

Changing patterns of bacterial profile and antimicrobial resistance in high-risk patients during the COVID-19 pandemic at a tertiary oncology hospital.

The widespread evolution of phenotypic resistance in clinical isolates over the years, coupled with the COVID-19 pandemic onset, has exacerbated the global challenge of antimicrobial resistance. This study aimed to explore changes in bacterial infection patterns and antimicrobial resistance during the COVID-19 pandemic. This study involved the periods before and during COVID-19: the pre-pandemic and pandemic eras. The surveillance results of bacterial isolates causing infections in cancer patients at an Egyptian tertiary oncology hospital were retrieved. The Vitek®2 or Phoenix systems were utilized for species identification and susceptibility testing. Statistical analyses were performed comparing microbiological trends before and during the pandemic. Out of 2856 bacterial isolates, Gram-negative bacteria (GNB) predominated (69.7%), and Gram-positive bacteria (GPB) comprised 30.3% of isolates. No significant change was found in GNB prevalence during the pandemic (P = 0.159). Elevated rates of Klebsiella and Pseudomonas species were demonstrated during the pandemic, as was a decrease in E. coli and Acinetobacter species (P < 0.001, 0.018, < 0.001, and 0.046, respectively) in hematological patients. In surgical patients, Enterobacteriaceae significantly increased (P = 0.012), while non-fermenters significantly decreased (P = 0.007). GPB species from either hematological or surgical wards exhibited no notable changes during the pandemic. GNB resistance increased in hematological patients to carbapenems, amikacin, and tigecycline and decreased in surgical patients to amikacin and cefoxitin (P < 0.001, 0.010, < 0.001, < 0.001, and 0.016, respectively). The study highlights notable shifts in the microbial landscape during the COVID-19 pandemic, particularly in the prevalence and resistance patterns of GNB in hematological and surgical wards.

CAR-T cell therapy in hematological malignancies: Where are we now and where are we heading for?

Chimeric antigen receptor T (CAR-T) therapy has emerged as a revolutionary new pillar in cancer care, particularly in relapsed/refractory (r/r) B-cell malignancies. Following impressive clinical outcomes in hematological malignancies, the FDA-approved six CAR-T cell products for indications such as lymphoma, leukemia, and myeloma. Despite the numerous advantages of CAR-T cell treatment, several challenges exist that interfere with its therapeutic efficacy. Serious adverse effects connected with the treatment continue to be a major concern. In addition, poor persistence of therapeutics and antigen escape frequently result in tumor relapse. Exorbitant treatment cost further remains a significant barrier to its effective implementation, limiting its accessibility. This review presents progress of CAR-T research, the key obstacles that hamper promising outcomes for patients with hematological malignancies, and a few strategies to overcome them.

Application of thromboelastography to predict the severity of bleeding after chimeric antigen receptor (CAR)-T cell therapy in patients with hematological malignancy.

OBJECTIVES: We aim to analyze the predictive value of thromboelastography on bleeding severity of patients with chimeric antigen receptor (CAR)-T cell therapy. METHODS: A total of 80 patients with refractory/relapsed hematological malignancy were enrolled and divided into two groups: the severe bleeding group and the non-severe bleeding group. The thromboelastography data was collected on the day of CAR-T infusion and the 3rd, 7th, 10th, 13th, 17th, and 20th day after CAR-T cell infusion. RESULTS: The patients of the severe bleeding group had lower platelet (p < .007), maximum amplitude (p = .002), coagulation index (p = .005), and longer coagulation time (p = .019). Increasing trend in reaction time and coagulation time and decreasing trend in Alpha, maximum amplitude, and coagulation index on Days 0-10, opposite on Days 10-20. Univariate logistic regression analysis and multivariable logistic regression analysis showed maximum amplitude on the 3rd day after CAR-T cell infusion (MA3) (OR = 0.9; 95% CI = 0.84-0.95; p < .001) and cytokine release syndrome grade (OR = 2.57; 95% CI = 1.35-5.32; p = .006) were significantly associated with high bleeding severity. CONCLUSIONS: Thromboelastography was considered to be a good predictor of bleeding severity.

Health-related quality of life in older hematological cancer survivors (70+) compared to older general population-A German cancer-register-based cross-sectional comparative study.

OBJECTIVES: The extent of health-related quality of life (HRQOL) impairments in older hematological cancer survivors (HCS) has not been sufficiently studied. We therefore examined HRQOL in older HCS compared to a community sample (CS) and investigated sociodemographic, disease- and treatment-specific, geriatric, and psychosocial factors associated with reduced HRQOL. MATERIALS AND METHODS: In this cancer-register-based cross-sectional comparative study 200 HCS, aged ≥70 years, and 252 persons of an age- and gender-matched CS completed validated questionnaires including the EORTC QLQ-C30 and EORTC QLQ-ELD14. RESULTS: Older HCS reported a reduced HRQOL in the dimensions of global QOL, physical, role, and social functioning (small clinical significance) and higher symptom burden of fatigue, nausea and vomiting, appetite loss, and poorer mobility compared to the CS (fatigue and mobility with medium, the others with small clinical significance). Perceived disease burden of comorbidities, functional disabilities, psychological distress, and depression showed statistical significance for reduced HRQOL in older HCS in multiple linear regression analysis (R2 = .602, p < .001). DISCUSSION: The screening and treatment of functional limitations and individual symptoms and the integration of a geriatric assessment into oncological practice can help to identify supportive care needs, to implement individualized, patient-centered cancer survivorship care programs and to improve older HCS's HRQOL.

Microbiological risk factors, ICU survival, and 1-year survival in hematological patients with pneumonia requiring invasive mechanical ventilation.

PURPOSE: To identify pathogenic microorganisms and microbiological risk factors causing high morbidity and mortality in immunocompromised patients requiring invasive mechanical ventilation due to pneumonia. METHODS: A retrospective single-center study was performed at the intensive care unit (ICU) of the Department of Internal Medicine at Heidelberg University Hospital (Germany) including 246 consecutive patients with hematological malignancies requiring invasive mechanical ventilation due to pneumonia from 08/2004 to 07/2016. Microbiological and radiological data were collected and statistically analyzed for risk factors for ICU and 1-year mortality. RESULTS: ICU and 1-year mortality were 63.0% (155/246) and 81.0% (196/242), respectively. Pneumonia causing pathogens were identified in 143 (58.1%) patients, multimicrobial infections were present in 51 (20.7%) patients. Fungal, bacterial and viral pathogens were detected in 89 (36.2%), 55 (22.4%) and 41 (16.7%) patients, respectively. Human herpesviruses were concomitantly reactivated in 85 (34.6%) patients. As significant microbiological risk factors for ICU mortality probable invasive Aspergillus disease with positive serum-Galactomannan (odds ratio 3.1 (1.2-8.0), p = 0.021,) and pulmonary Cytomegalovirus reactivation at intubation (odds ratio 5.3 (1.1-26.8), p = 0.043,) were identified. 1-year mortality was not significantly associated with type of infection. Of interest, 19 patients had infections with various respiratory viruses and Aspergillus spp. superinfections and experienced high ICU and 1-year mortality of 78.9% (15/19) and 89.5% (17/19), respectively. CONCLUSIONS: Patients with hematological malignancies requiring invasive mechanical ventilation due to pneumonia showed high ICU and 1-year mortality. Pulmonary Aspergillosis and pulmonary reactivation of Cytomegalovirus at intubation were significantly associated with negative outcome.

Clinical characteristics and mortality of mucormycosis in hematological malignancies: a retrospective study in Eastern China.

BACKGROUND: Mucormycosis is a significant cause of morbidity and mortality in patients with hematological malignancies, but its characteristics are not fully understood. This study aimed to gain a better understanding of the clinical features of mucormycosis in patients with hematological malignancies in eastern China. METHODS: A single-center retrospective analysis was conducted on the demographic profile, microbiology, management, and 90-day mortality of mucormycosis patients with hematological malignancies between 2018 and 2023. RESULTS: A total of 50 cases were included in the study, consisting of 11 proven and 39 probable cases of mucormycosis. The median age of the patients was 39.98 ± 18.52 years, with 52% being male. Among the cases, 46% had acute myeloid leukemia (AML), 16% had acute lymphoblastic leukemia (ALL), and 16% had myelodysplastic syndrome. The most common manifestations of mucormycosis were pulmonary (80%), disseminated (16%), and rhinocerebral (4%). The diagnosis was confirmed through histology, culture, microscopy, and molecular diagnostic techniques. The most commonly identified fungal species were Cunninghamella (40%), Rhizopus (26%), and Rhizomucor (22%). Treatment involved antifungals in 84% of cases and surgery in 10% of cases. The 90-day mortality rate was 76%. Logistic regression analysis revealed that treatment with amphotericin B and surgery was associated with improved survival, while neutropenia and administration of voriconazole prior to diagnosis was associated with higher mortality. CONCLUSIONS: Mucormycosis continues to have a high mortality rate in patients with hematological malignancies. Early diagnosis using various techniques, including molecular biology, along with the appropriate use of amphotericin B and surgery when possible, is vital for the successful treatment of mucormycosis.

Epidemiology of pediatric hematological malignancies in Kazakhstan: Data from Unified National Electronic Healthcare System 2014-2021.

We aimed to describe incidence and all-cause mortality of hematological pediatric malignancies (leukemia and lymphomas) in Kazakhstan based on nationwide large-scale healthcare data from the Unified National Electronic Healthcare System (UNEHS) for the 2014-2021 year period. The cohort included data of patients less than 18 years old with the diagnosis of hematological malignancies registered in the UNEHS (inpatient and outpatient registries) for the year period 2014-2021. Descriptive statistics were conducted to indicate socio-demographic characteristics of the cohort. Incidence and all-cause mortality were calculated per 100,000 population. Cox proportional hazard regression analysis was performed to investigate the association between determinants with the all-cause mortality. The total cohort consisted of 3357 children with leukemia and 1474 children with lymphomas. The mean age at diagnosis of leukemia and lymphomas was 7.3 ± 4.7 and 9.9 ± 4.9 years, respectively. The incidence rate of hematological malignancies was 6.8 per 100,000 in 2021. Patients with ALL had a higher incidence rate than patients with AML (3.4 and 1.2 per 100,000 in 2021, respectively). The incidence rate of HL and NHL was relatively similar which varied from 0.6 to 2.6 per 100,000 in 2014-2021. All-cause mortality of pediatric hematological malignancies varied from 1.1 to 1.5 per 100,000 in 2014-2021, with the peak in 2016 (1.7 per 100,000). Younger age is significantly associated with increased risk of all-cause mortality in children with AML. CONCUSION: Patients with ALL had a higher incidence rate than patients with AML. The incidence rate of HL and NHL was relatively similar. All-cause mortality rates for leukemia and lymphomas were quite stable during the study period. Younger age is significantly associated with increased all-cause mortality among AML patients. However, there is no significant association of age with all-cause mortality among ALL, HL and NHL. In order to obtain more reliable data and analysis on pediatric (hematological) malignancies, specific registries for childhood tumors (including detailed information on relapses, treatments, short and long-term side effects, and specific death causes) should be implemented. WHAT IS KNOWN: • Leukemias and lymphomas together account for around 45% of all pediatric malignancies. • Lymphoma accounts for 12% of all childhood malignancies; non-Hodgkin's lymphomas (NHL) are more frequent than Hodgkin's lymphomas (HL). WHAT IS NEW: • The incidence rate of ALL was higher than the incidence rate of AML throughout the whole study period, whereas all-cause mortality of ALL and AML was quite stable. • According to Cox PH analysis, younger age (0-5 years old) was associated with a higher risk of death among AML children compared to older children, and no significant association of age was observed with all-cause mortality among ALL and lymphomas.

Concomitant use of calcitonin gene-related peptide (CGRP) antagonists with azole antifungals in patients with hematological malignancies.

OBJECTIVE: Small molecule calcitonin gene-related peptide (CGRP) antagonists such as rimegepant, ubrogepant, and atogepant have been approved for migraine treatment and/or prevention. These molecules are metabolized by cytochrome P-450 3A4 (CYP3A4) enzymes in vivo, hence they are contraindicated or recommended to be avoided in combination with strong/moderate CYP3A4 inhibitors, namely posaconazole (strong) and isavuconazonium (moderate). However, no literature has been published on the impact this interaction has on patient safety and tolerability. In this case series, we report five cases in which CGRP antagonists and azole antifungal therapy were given concurrently, to provide real-world outcomes of this interaction. DATA SOURCES: Electronic medical records at our hospital system were reviewed between January 2021 and December 2023 to find patients who met the criteria of hematological malignancy, taking CGRP-antagonist and azole antifungal therapy. Records were then further investigated to find cases where CGRP antagonists and azole antifungals were used concomitantly. DATA SUMMARY: Concurrent use of CGRP antagonists and azole antifungal therapy was feasible for patients with migraines and hematological malignancies. None of the patients experienced any grade 3 or higher non-hematological toxicity from the proposed over-exposure to CGRP antagonist. The combination was well tolerated without any need for therapy discontinuation or dose modifications. CONCLUSIONS: It is recommended to follow the manufacturers' guidance on drug interactions, however, in the setting where there are no other options, concomitant use of CGRP antagonists with azole antifungals is possible with monitoring and observation for adverse effects.

Investigation of polypharmacy, antimicrobial-related potential drug-drug interactions in patients with hematological malignancies.

PURPOSE: Drug-drug interactions (DDIs) occur when one drug interferes with the pharmacological activity of another and can lead to increased side effects. The purpose of this study was to examine potential interactions between antimicrobials and other drugs in patients with hematological malignancies (HMs). METHOD: The medications used by 233 patients with HMs before and during hospitalization in Ankara City Hospital Hematology Clinic services between January 2021 and July 2021 were examined. Potential DDIs (pDDIs) were identified through UptoDate, Drugs.com, and MedScape databases. The effects of major antimicrobial-related pDDIs on patients were examined. Agreement between the two interaction systems was judged based on the kappa test. SPSS R Version 4.0.2 was used in the statistical analysis of the data, p<.05 was considered significant. RESULTS: The prevalence of polypharmacy before hospitalization was determined as 22.7%. Diagnosed with acute leukemia and multiple myeloma, more antimicrobial-related pDDIs were detected during hospitalization (p<.001). A total of 758 antimicrobial-related pDDIs, which were in the major category in at least one of the three databases, were detected in 72.5% (169/233) of the participants. It was determined that the total hospitalization period of patients with major antimicrobial-related pDDIs was longer (p<.001). There was negligible agreement between UptoDate and Dugs.com and between Drugs.com and MedScape (kappa: 0.008 for both). There was no compatibility between UptoDate and MedScape (kappa<0). CONCLUSION: Interactions between antimicrobials and other drugs are undesirable problems. Further studies are required to evaluate the clinical and economic effects of the interactions on patients with HMs.