Clearing the Air: Acute Invasive Fungal Rhinosinusitis in Hematologic Cancer Patients.

OBJECTIVES: Air quality has been shown to impact the rates of fungal infection of the airway, causing diseases such as acute invasive fungal rhinosinusitis (AIFRS), particularly in immunocompromised patients. We theorize that patients with hematologic malignancies in units with aging air handling units (AHUs) have a higher attack rate of AIFRS. METHODS: Retrospective chart review identified patients with hematologic malignancy and AIFRS in two distinct and equal time periods between 2013 and 2022, representing the presence of aging AHUs and new AHUs, respectively. Cubic feet per minute (CFM) air flows, AIFRS attack rates, and clinical data were compared between the two groups and statistical analyses performed. RESULTS: The older AHUs produce air flow of 27,610 CFM and the newer AHUs produce air flow of 80,000 CFM. There were 18 patients with air supplied by older AHUs and 7 patients with air supplied by new AHUs who developed AIFRS. There was a significantly higher AIFRS attack rate for patients supplied by the older AHUs compared with patients supplied by newer AHUs (p = 0.033). The patients supplied by the older AHUs tended to be younger. The white blood cell counts, absolute neutrophil counts, and the mean time to diagnosis did not differ between the two groups. CONCLUSIONS: To our knowledge, this is the first study to examine AIFRS in immunocompromised patients' inpatient environment. Further research should explore whether higher CFM AHUs can decrease this disease among our most vulnerable patients. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Identification of KDM4C as a gene conferring drug resistance in multiple myeloma.

Bortezomib (BTZ), a proteasome inhibitor, is a promising therapeutic option for multiple myeloma (MM) patients. However, drug resistance often occurs, leading to disease relapse and poor prognosis. In this study, we aimed to identify novel genes associated with drug resistance and investigate their roles in BTZ resistance. Through the screening of 26 genes frequently associated with chemosensitivity or drug resistance, we discovered that KDM4C, a histone demethylase, exhibited increased expression in BTZ-resistant MM cells compared to their sensitive counterparts. Overexpression of KDM4C enhanced the tolerance of a MM cell line to the drug, whereas the knockdown of KDM4C, using shRNA, increased the sensitivity of resistant cells to BTZ treatment. This suggests that KDM4C plays a pivotal role in conferring BTZ resistance. Our study offers fresh insights into BTZ resistance in MM and highlights KDM4C as a potential target for overcoming drug resistance.

Utilization and quality of palliative care in patients with hematological and solid cancers: a population-based study.

BACKGROUND: Palliative care (PC) contributes to improved end-of-life care for patients with hematologic malignancies (HM) and solid tumors (ST) by addressing physical and psychological symptoms and spiritual needs. Research on PC in HM vs. ST patients is fragmented and suggests less use. METHODS: We analyzed claims data of all deceased members of a large German health insurance provider for the year before death. First, we analyzed the frequency and the beginning of different types of PC and compared patients with HM vs. ST. Second, we analyzed the adjusted impact of PC use on several end-of-life quality outcomes in patients with HM vs. ST. We performed simple and multiple (logistic) regression analysis, adjusted for relevant covariates, and standardized for age and sex. RESULTS: Of the 222,493 deceased cancer patients from 2016 to 2020, we included 209,321 in the first analysis and 165,020 in the second analysis. Patients with HM vs. ST received PC less often (40.4 vs. 55.6%) and later (34 vs. 50 days before death). PC use significantly improved all six quality indicators for good end-of-life care. HM patients had worse rates in five of the six indicators compared with ST patients. Interaction terms revealed that patients with ST derived greater benefit from PC in five of six quality indicators than those with HM. CONCLUSION: The data highlight the need to integrate PC more often, earlier, and more effectively into the care of patients with HM.

CPX-351 Pharmacokinetics and Safety in Adults with Hematologic Malignancies and Renal Function Impairment: Phase 1 Trial.

This open-label phase 1 study (clinicaltrials.gov, NCT03555955) assessed CPX-351 pharmacokinetics (PK) and safety in patients with hematologic malignancies with normal or impaired renal function. Patients were enrolled into three cohorts based on their creatinine clearance (CrCl): ≥90 mL/min (Cohort 1, normal renal function, n = 7), 30 to <59 mL/min (Cohort 2, moderate renal impairment, n = 8), or <30 mL/min (Cohort 3, severe renal impairment, n = 6). Patients received intravenous CPX-351 for initial induction; blood and urine samples were collected for PK analysis. The primary objective was to assess the PK parameters for cytarabine, daunorubicin, and their respective metabolites, arabinosyluracil (Ara-U) and daunorubicinol. Renal impairment did not significantly impact the cytarabine, daunorubicin, or daunorubicinol exposure, but it caused a slight increase in the Ara-U exposure. The CPX-351 side effect profile was similar in patients with impaired renal function compared to those with normal renal function. All the patients reported ≥1 treatment-emergent adverse event (TEAE), most commonly febrile neutropenia and nausea (57% each) and hyperglycemia (43%); no patients discontinued treatment due to TEAEs. These data suggest that CPX-351 dose adjustment is not required for patients with hematologic malignancies with moderate or severe renal impairment.

Genetic heterogeneity in p53-null leukemia increases transiently with spindle assembly checkpoint inhibition and is not rescued by p53.

Chromosome gains or losses often lead to copy number variations (CNV) and loss of heterozygosity (LOH). Both quantities are low in hematologic "liquid" cancers versus solid tumors in data of The Cancer Genome Atlas (TCGA) that also shows the fraction of a genome affected by LOH is ~ one-half of that with CNV. Suspension cultures of p53-null THP-1 leukemia-derived cells conform to these trends, despite novel evidence here of genetic heterogeneity and transiently elevated CNV after perturbation. Single-cell DNAseq indeed reveals at least 8 distinct THP-1 aneuploid clones with further intra-clonal variation, suggesting ongoing genetic evolution. Importantly, acute inhibition of the mitotic spindle assembly checkpoint (SAC) produces CNV levels that are typical of high-CNV solid tumors, with subsequent cell death and down-selection to novel CNV. Pan-cancer analyses show p53 inactivation associates with aneuploidy, but leukemias exhibit a weaker trend even though p53 inactivation correlates with poor survival. Overexpression of p53 in THP-1 does not rescue established aneuploidy or LOH but slightly increases cell death under oxidative or confinement stress, and triggers p21, a key p53 target, but without affecting net growth. Our results suggest that factors other than p53 exert stronger pressures against aneuploidy in liquid cancers, and identifying such CNV suppressors could be useful across liquid and solid tumor types.

Recomendaciones SER sobre la gestión de riesgo del tratamiento con FAME biológicos o sintéticos dirigidos en pacientes con artritis reumatoide / Recommendations by the Spanish Society of Rheumatology on risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis

Objetivo: Elaborar recomendaciones basadas en la evidencia disponible y el consenso de expertos, para la gestión del riesgo del tratamiento biológico y los inhibidores de las JAK en pacientes con artritis reumatoide. Métodos: Se identificaron preguntas clínicas de investigación relevantes para el objetivo del documento. Estas preguntas fueron reformuladas en formato PICO (paciente, intervención, comparación, outcome o desenlace) por un panel de expertos, seleccionados en base a su experiencia en el área. Se realizó una revisión sistemática de la evidencia, graduándose de acuerdo a los criterios GRADE (Grading of Recommendations Assessment, Development, and Evaluation). A continuación, se formularon las recomendaciones específicas. Resultados: Se propusieron por el panel de expertos 6preguntas PICO en base a su relevancia clínica y a la existencia de información reciente referentes al riesgo de aparición de infecciones graves, el riesgo de reactivación del virus de la hepatitisB, el riesgo de reactivación del virus varicela-zoster, el riesgo de aparición de cáncer de piel (melanoma y no melanoma) o hematológico, el riesgo de aparición de enfermedad tromboembólica y el riesgo de progresión del virus del papiloma humano. Se formularon un total de 29 recomendaciones, estructuradas por pregunta, basadas en la evidencia encontrada y el consenso de los expertos. Conclusiones: Se presentan las recomendaciones SER sobre la gestión del riesgo del tratamiento con terapias biológicas e inhibidores de las JAK en la artritis reumatoide.(AU)

Objective: To present recommendations based on the available evidence and the consensus of experts, for risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis. Methods: Clinical research questions relevant to the purpose of the document were identified. These questions were reformulated in PICO format (patient, intervention, comparison, outcome) by a panel of experts, selected based on their experience in the area. A systematic review of the evidence was carried out, grading according to the GRADE criteria (Grading of Recommendations Assessment, Development, and Evaluation). Specific recommendations were then formulated. Results: Six PICO questions were proposed by the panel of experts based on their clinical relevance and the existence of recent information regarding the risk of occurrence of serious infections, the risk of reactivation of the hepatitisB virus, the risk of reactivation of the virus varicella-zoster, the risk of appearance of skin (melanoma and non-melanoma) or hematological cancer, the risk of appearance of thromboembolic disease and the risk of progression of the human papilloma virus. A total of 29 recommendations were formulated, structured by question, based on the evidence found and the consensus of the experts. Conclusions: The SER recommendations on risk management of treatment with biologic therapies and JAK inhibitors in rheumatoid arthritis are presented.(AU)

Recommendations by the Spanish Society of Rheumatology on risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis.

OBJECTIVE: To present recommendations based on the available evidence and the consensus of experts, for risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis. METHODS: Clinical research questions relevant to the purpose of the document were identified. These questions were reformulated in PICO format (patient, intervention, comparison, outcome or outcome) by a panel of experts, selected based on their experience in the area. A systematic review of the evidence was carried out, grading according to the GRADE criteria (Grading of Recommendations Assessment, Development, and Evaluation). Specific recommendations were then formulated. RESULTS: 6 PICO questions were proposed by the panel of experts based on their clinical relevance and the existence of recent information regarding the risk of occurrence of serious infections, the risk of reactivation of the hepatitis B virus, the risk of reactivation of the virus varicella-zoster, the risk of appearance of skin (melanoma and non-melanoma) or haematological cancer, the risk of appearance of thromboembolic disease and the risk of progression of the human papilloma virus. A total of 28 recommendations were formulated, structured by question, based on the evidence found and the consensus of the experts. CONCLUSIONS: The SER recommendations on risk management of treatment with biologic therapies and JAK inhibitors in rheumatoid arthritis are presented.

Role of the gut microbiota in hematologic cancer.

Hematologic neoplasms represent 6.5% of all cancers worldwide. They are characterized by the uncontrolled growth of hematopoietic and lymphoid cells and a decreased immune system efficacy. Pathological conditions in hematologic cancer could disrupt the balance of the gut microbiota, potentially promoting the proliferation of opportunistic pathogens. In this review, we highlight studies that analyzed and described the role of gut microbiota in different types of hematologic diseases. For instance, myeloma is often associated with Pseudomonas aeruginosa and Clostridium leptum, while in leukemias, Streptococcus is the most common genus, and Lachnospiraceae and Ruminococcaceae are less prevalent. Lymphoma exhibits a moderate reduction in microbiota diversity. Moreover, certain factors such as delivery mode, diet, and other environmental factors can alter the diversity of the microbiota, leading to dysbiosis. This dysbiosis may inhibit the immune response and increase susceptibility to cancer. A comprehensive analysis of microbiota-cancer interactions may be useful for disease management and provide valuable information on host-microbiota dynamics, as well as the possible use of microbiota as a distinguishable marker for cancer progression.

FLT3-ITD Mutation and Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia: A Case Study.

Acute myeloid leukemia (AML) is a hematologic cancer that is characterized by unchecked myeloid precursor cell growth in the bone marrow and peripheral circulation, which results in an overabundance of immature myeloid cells. The 22-year-old man featured in this case report had a fever, tiredness, and easy bruising. Pancytopenia was discovered through laboratory testing, and an AML diagnosis was confirmed by a bone marrow biopsy, with myeloid blasts making up 85% of the nucleated cells. FLT3-ITD and NPM1 mutations were found by genetic testing. After receiving induction chemotherapy using the drugs daunorubicin and cytarabine, the patient experienced complete remission after just one cycle of treatment. He then had an allogeneic stem cell transplant and was still in remission during follow-up. This example highlights the significance of early AML diagnosis and detection, as well as the function of molecular profiling and risk stratification in directing treatment choices. It emphasizes the requirement for continued study to produce novel treatments and enhance results for AML patients. In general, this case study advances knowledge of AML and its management techniques. For AML patients to experience the best results, early diagnosis, risk assessment, and individualized therapy plans based on molecular profiling are essential. AML patients' prognosis and quality of life can be improved by the development of targeted medicines, which require ongoing study to better understand the disease.

Successful Treatment of Persistent Symptomatic Coronavirus Disease 19 Infection With Extended-Duration Nirmatrelvir-Ritonavir Among Outpatients With Hematologic Cancer.

Persistent symptomatic coronavirus disease 2019 (COVID-19) is a distinct clinical entity among patients with hematologic cancer and/or profound immunosuppression. The optimal medical management is unknown. We describe 2 patients who had symptomatic COVID-19 for almost 6 months and were successfully treated in the ambulatory setting with extended courses of nirmatrelvir-ritonavir.

Association between high galectin expression and poor prognosis in hematologic cancers: a systematic review and meta-analysis.

BACKGROUND: Galectin (Gal) is considered a promising immune checkpoint molecule. More and more studies have shown that high expression levels of galectins in hematologic cancer are positively correlated with poor clinical prognosis. However, the exact prognostic significance of galectins remains unclear. METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched for studies addressing the correlation of galectin expression levels with prognosis of hematologic cancers. Stata software was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULT: Hematologic cancer patients with high galectin expression levels showed poor overall survival (OS, HR = 2.43, 95% CI: 1.95, 3.04), disease-free survival (DFS, HR = 3.29, 95% CI: 1.61, 6.71), and event-free survival (EFS, HR = 2.20, 95% CI: 1.47, 3.29) outcomes. Subgroup analysis revealed that high expression levels of galectins pointed to relatively poor OS in MDS (HR = 5.44, 95% CI: 2.09, 14.18), as compared to AML, CHL and CLL. No correlation was found between galectins and OS in NHL and MM. Among the three galectins, Gal-9 (HR = 3.60, 95% CI: 2.03, 6.38) showed higher correlation with poor prognosis than Gal-1 and Gal-3. In addition, use of peripheral blood (HR = 2.96, 95% CI: 2.07, 4.22) samples and qRT-PCR (HR = 2.80, 95% CI: 1.96, 4.01) method for galectin detection were shown to improve its prognostic correlation in hematologic cancers. CONCLUSION: Meta-analysis revealed high expression of galectins was associated with poor prognosis in hematologic cancer patients and galectins can be considered a promising prognostic predictive marker.

Multidisciplinary Antenatal Management of a Late Pregnancy Complicated With Advanced Stage Breast Burkitt Lymphoma - Case Report and a Review of the Literature.

The multidisciplinary team (MDT) plays a pivotal role in establishing the diagnosis and tailoring treatment for challenging, complicated, rare obstetrical cases. At 28 weeks of gestation, a lady presented with an unresolved unilateral proptosis and sustained severe mastitis. MDT managed the patient at a tertiary care hospital for primary breast Burkitt lymphoma (PBBL). It is a rare and highly malignant condition requiring an aggressive therapeutic approach. Antenatal chemotherapy (ANC) with an aggressive regimen of R-hyper-CVAD/MA was started. A healthy baby was vaginally delivered after completing the second therapy cycle at 32+ weeks, weighing 1.6kg with a good Apgar score. Postnatally, the central nervous system (CNS) prophylaxis was added; after completing eight chemo cycles, our patient remained stabilized for nine months. Unfortunately, due to the refractory and aggressive nature of malignancy, it relapsed, giving an overall survival (OS) of two years. MDT care should be considered at the earliest possible period to expedite the entire process. Positive results can be achieved with timely aggressive treatment and early management of such cases.

Interconnectivity of fear of progression and generalized anxiety - Network analysis among a sample of hematological cancer survivors.

PURPOSE: Fear of cancer progression and recurrence (FoP) and generalized anxiety disorder (GAD) are syndromes commonly seen in cancer patients. This study applied network analysis to investigate how symptoms of both concepts are interconnected. METHODS: We used cross-sectional data from hematological cancer survivors. A regularized Gaussian graphical model including symptoms of FoP (FoP-Q) and GAD (GAD-7) was estimated. We investigated (i) the overall network structure and (ii) tested on pre-selected items whether both syndromes could be differentiated based on their worry content (cancer related vs. generalized). For this purpose, we applied a metric named bridge expected influence (BEI). Lower values mean that an item is only weakly connected with the items of the other syndrome, which can be an indication of its distinctive characteristic. RESULTS: Out of 2001 eligible hematological cancer survivors, 922 (46%) participated. The mean age was 64 years and 53% were female. The mean partial correlation within each construct (GAD: r = .13; FoP: r = .07) was greater than between both (r = .01). BEI values among items supposed to discriminate between the constructs (e.g., worry about many things within GAD and fear not to endure treatment within FoP) were among the smallest so our assumptions were confirmed. CONCLUSIONS: Our findings based on the network analysis support the hypothesis that FoP and GAD are different concepts within oncology. Our exploratory data needs to be validated in future longitudinal studies.

Nanomechanical Signatures of Extracellular Vesicles from Hematologic Cancer Patients Unraveled by Atomic Force Microscopy for Liquid Biopsy.

Cells release extracellular vesicles (EVs) as the carriers for intercellular communications to regulate life activities. Particularly, it is increasingly apparent that mechanical forces play an essential role in biological systems. The nanomechanical properties of EVs and their dynamics in cancer development are still not fully understood. Herein, with the use of atomic force microscopy (AFM), the nanomechanical signatures of EVs from the liquid biopsies of hematologic cancer patients were unraveled. Single native EVs were probed by AFM under aqueous conditions. The elastic and viscous properties of EVs were measured and visualized to correlate EV mechanics with EV geometry. Experimental results remarkably reveal the significant differences in EV mechanics among multiple myeloma patients, lymphoma patients, and healthy volunteers. The study unveils the unique nanomechanical signatures of EVs in hematologic cancers, which will benefit the studies of liquid biopsies for cancer diagnosis and prognosis with translational significance.

Premature ovarian insufficiency in female adolescent and young adult survivors of non-gynecological cancers: a population-based cohort study.

BACKGROUND: The risk of premature ovarian insufficiency (POI) is increased in adolescent and young adult (AYA) cancer survivors, with the prevalence depending on cancer diagnosis, treatment, and patient factors. Prior studies are limited by sample size and type of cancer included. The objective of this study was to assess the risk of POI in female AYA survivors of non-gynecologic cancers, using a population-based approach. METHODS: This population-based retrospective cohort study comprises 21,666 females, 15-39 years old, diagnosed with a single non-gynecologic cancer in Ontario, Canada from 1995 to 2015. Through health administrative data linkage, participants were followed until their 40th birthday, December 31, 2018, bilateral oophorectomy, loss of health insurance eligibility or death. Each cancer survivor was matched to 5 females who were not diagnosed with cancer (unexposed, n = 108,330). Women with bilateral oophorectomy or a prior menopause diagnosis were excluded. POI was identified through use of the ICD-9 code for menopause (ICD9-627). Modified Poisson regression models were used to calculate the adjusted relative risk (aRR) of POI for AYA cancer survivors compared to unexposed individuals, adjusted for income, parity, age, and immigration status. RESULTS: The occurrence of POI was higher in survivors of AYA cancer versus unexposed patients (5.4% vs. 2.2%). Survivors of AYA cancer had an increased risk of POI relative to unexposed patients (aRR 2.49; 95% CI 2.32-2.67). Risk varied by type of cancer: breast (4.32; 3.84-4.86), non-Hodgkin's lymphoma (3.77; 2.88-4.94), Hodgkin's lymphoma (2.37; 1.91-2.96), leukemia (14.64; 10.50-20.42), thyroid (1.26; 1.09-1.46) and melanoma (1.04; 0.82-1.32). Risk varied by age at time of cancer diagnosis, with a higher risk among females diagnosed at age 30-39 years (3.07; 2.80-3.35) than aged 15-29 years (1.75; 1.55-1.98). CONCLUSIONS: AYA survivors of non-gynecologic cancers are at an increased risk of POI, particularly survivors of lymphomas, leukemia, breast, and thyroid cancer. The risk of POI is increased for those diagnosed with cancer at an older age. These results should inform reproductive counseling of female AYAs diagnosed with cancer.

Premature ovarian insufficiency is the onset of premature menopause in individuals less than 40-years-old. Previous research has shown that there is a higher risk of premature ovarian insufficiency in adolescent and young adult cancer survivors, due to the toxicity of cancer treatments on reproductive organs. Prior research was limited in its applicability by having small sample sizes, only including childhood cancer, excluding young adults, and studying fewer types of cancer. This study was conducted using a large population-based approach, on all females aged 15­39 years old with cancer in Ontario, Canada from 1995 to 2015. We found that there was nearly a 2.5 times greater risk of premature ovarian insufficiency in cancer survivors compared patients without cancer. Compared to patients without cancer, this risk was highest for survivors of leukemia (14 times higher risk), followed by breast cancer (4 times higher risk), lymphomas (2­4 times higher risk), and thyroid cancer (1.2 times higher risk). There is no increased risk in melanoma survivors. The risk was higher in individuals diagnosed with cancer at a later age (30­39 years), with a risk 3 times higher than the population without cancer, while a younger age of diagnosis (15­29 years) carries a risk only 1.75 times higher than the population without cancer. These results should help improve healthcare provider and patient understanding of the risk of premature ovarian insuficiency in young cancer survivors, and guide counseling at the time of cancer diagnosis and during survivorship on future reproductive function.

Histone deacetylases (HDACs) as the promising immunotherapeutic targets for hematologic cancer treatment.

Bone marrow transplantation is regarded as the most effective immunotherapy for hematologic cancer, but it generally faces difficulties in matching. Aberrant expression of histone deacetylases (HDACs) is closely related to the occurrence and development of hematological cancer. Recent studies suggested that HDACs might play a critical role in initiating anti-cancer immune response or enhancing anti-cancer immunotherapy. Besides, combining HDAC inhibition and immunotherapy could prevent immunotherapy resistance in some degree and reach an extended treatment window. This review summarized the relationship between HDACs and immune and described the current understanding of HDACs in immunotherapy for hematologic cancer.

The efficacy of selinexor (KPT-330), an XPO1 inhibitor, on non-hematologic cancers: a comprehensive review.

PURPOSE: Selinexor is a novel XPO1 inhibitor which inhibits the export of tumor suppressor proteins and oncoprotein mRNAs, leading to cell-cycle arrest and apoptosis in cancer cells. While selinexor is currently FDA approved to treat multiple myeloma, compelling preclinical and early clinical studies reveal selinexor's efficacy in treating hematologic and non-hematologic malignancies, including sarcoma, gastric, bladder, prostate, breast, ovarian, skin, lung, and brain cancers. Current reviews of selinexor primarily highlight its use in hematologic malignancies; however, this review seeks to summarize the recent evidence of selinexor treatment in solid tumors. METHODS: Pertinent literature searches in PubMed and the Karyopharm Therapeutics website for selinexor and non-hematologic malignancies preclinical and clinical trials. RESULTS: This review provides evidence that selinexor is a promising agent used alone or in combination with other anticancer medications in non-hematologic malignancies. CONCLUSION: Further clinical investigation of selinexor treatment for solid malignancies is warranted.

Patient-Derived Multiple Myeloma 3D Models for Personalized Medicine-Are We There Yet?

Despite the wide variety of existing therapies, multiple myeloma (MM) remains a disease with dismal prognosis. Choosing the right treatment for each patient remains one of the major challenges. A new approach being explored is the use of ex vivo models for personalized medicine. Two-dimensional culture or animal models often fail to predict clinical outcomes. Three-dimensional ex vivo models using patients' bone marrow (BM) cells may better reproduce the complexity and heterogeneity of the BM microenvironment. Here, we review the strengths and limitations of currently existing patient-derived ex vivo three-dimensional MM models. We analyze their biochemical and biophysical properties, molecular and cellular characteristics, as well as their potential for drug testing and identification of disease biomarkers. Furthermore, we discuss the remaining challenges and give some insight on how to achieve a more biomimetic and accurate MM BM model. Overall, there is still a need for standardized culture methods and refined readout techniques. Including both myeloma and other cells of the BM microenvironment in a simple and reproducible three-dimensional scaffold is the key to faithfully mapping and examining the relationship between these players in MM. This will allow a patient-personalized profile, providing a powerful tool for clinical and research applications.

Flavones, Flavonols, Lignans, and Caffeic Acid Derivatives from Dracocephalum moldavica and Their In Vitro Effects on Multiple Myeloma and Acute Myeloid Leukemia.

Phenolic plant constituents are well known for their health-promoting and cancer chemopreventive properties, and products containing such constituents are therefore readily consumed. In the present work, we isolated 13 phenolic constituents of four different compound classes from the aerial parts of the Moldavian dragonhead, an aromatic and medicinal plant with a high diversity on secondary metabolites. All compounds were tested for their apoptotic effect on myeloma (KMS-12-PE) and AML (Molm-13) cells, with the highest activity observed for the flavone and flavonol derivatives. While diosmetin (6) exhibited the most pronounced effects on the myeloma cell line, two polymethylated flavones, namely cirsimaritin (1) and xanthomicrol (3), were particularly active against AML cells and therefore subsequently investigated for their antiproliferative effects at lower concentrations. At a concentration of 2.5 µM, cirsimaritin (1) reduced proliferation of Molm-13 cells by 72% while xanthomicrol (3) even inhibited proliferation to the extent of 84% of control. In addition, both compounds were identified as potent FLT3 inhibitors and thus display promising lead structures for further drug development. Moreover, our results confirmed the chemopreventive properties of flavonoids in general, and in particular of polymethylated flavones, which have been intensively investigated especially over the last decade.

COVID-19 vaccination in patients with cancer: Opportunities and challenges.

The rapid spread of the SARS-Cov-2 virus, the increase in the number of patients with severe COVID-19, and the high mortality rate created the basis for the production of safe and effective vaccines. Studies have confirmed the increased risk of severe Covid-19 disease and mortality in cancer patients. It is logical that cancer patients should be the first to receive the primary vaccination and the booster vaccine for Covid-19. Since studies related to cancer patients and the effectiveness of existing Covid-19 vaccines have not been widely conducted, there are significant uncertainties about the effectiveness of the vaccine and the level of humoral and cellular immune responses in these patients. As a result, the possible risks and side effects of existing vaccines are not clear for patients with different cancers who are undergoing special treatments. In this study, we will discuss the effectiveness and safety of existing vaccines on cancer patients. In addition, we highlight factors that could affect the effectiveness of vaccines in these patients and finally discuss opportunities and challenges related to vaccination in cancer patients.