Minimal residual disease assessment in transplant-eligible patients with multiple myeloma: real-world applications of multiparametric flow cytometry-DURAClone (CAREMM-2104).

Not available.

Genomic insights into inherited bone marrow failure syndromes in a Korean population.

Inherited bone marrow failure syndromes (IBMFS) pose significant diagnostic challenges due to overlapping symptoms and variable expressivity, despite evolving genomic insights. The study aimed to elucidate the genomic landscape among 130 Korean patients with IBMFS. We conducted targeted next-generation sequencing (NGS) and clinical exome sequencing (CES) across the cohort, complemented by whole genome sequencing (WGS) and chromosomal microarray (CMA) in 12 and 47 cases, respectively, with negative initial results. Notably, 50% (n = 65) of our cohort achieved a genomic diagnosis. Among these, 35 patients exhibited mutations associated with classic IBMFSs (n = 33) and the recently defined IBMFS, aplastic anaemia, mental retardation and dwarfism syndrome (AmeDS, n = 2). Classic IBMFSs were predominantly detected via targeted NGS (85%, n = 28) and CES (88%, n = 29), whereas AMeDS was exclusively identified through CES. Both CMA and WGS aided in identifying copy number variations (n = 2) and mutations in previously unexplored regions (n = 2). Additionally, 30 patients were diagnosed with other congenital diseases, encompassing 13 distinct entities including inherited thrombocytopenia (n = 12), myeloid neoplasms with germline predisposition (n = 8), congenital immune disorders (n = 7) and miscellaneous genomic conditions (n = 3). CES was particularly effective in revealing these diverse diagnoses. Our findings underscore the significance of comprehensive genomic analysis in IBMFS, highlighting the need for ongoing exploration in this complex field.

The Inhibition Activity of Natural Methoxyflavonoid from Inula britannica on Soluble Epoxide Hydrolase and NO Production in RAW264.7 Cells.

Soluble epoxide hydrolase (sEH) is an enzyme targeted for the treatment of inflammation and cardiovascular diseases. Activated inflammatory cells produce nitric oxide (NO), which induces oxidative stress and exacerbates inflammation. We identify an inhibitor able to suppress sEH and thus NO production. Five flavonoids 1-5 isolated from Inula britannica flowers were evaluated for their abilities to inhibit sEH with IC50 values of 12.1 ± 0.1 to 62.8 ± 1.8 µM and for their effects on enzyme kinetics. A simulation study using computational chemistry was conducted as well. Furthermore, five inhibitors (1-5) were confirmed to suppress NO levels at 10 µM. The results showed that flavonoids 1-5 exhibited inhibitory activity in all tests, with compound 3 exhibiting the most significant efficacy. Thus, in the development of anti-inflammatory inhibitors, compound 3 is a promising natural candidate.

Analytical Performance Evaluation of a Digital Real-Time PCR for Quantifying Major BCR::ABL1 Transcripts.

BACKGROUND: Accurate quantification of the BCR::ABL1 transcripts is essential for measurable residual disease (MRD) monitoring in chronic myeloid leukemia (CML) after tyrosine kinase inhibitor (TKI) treatment. This study evaluated the newly developed digital real-time PCR method, Dr. PCR, as an alternative reverse transcription-PCR (qRT-PCR) for MRD detection. METHODS: The performance of Dr. PCR was assessed using reference and clinical materials. Precision, linearity, and correlation with qRT-PCR were evaluated. MRD levels detected by Dr. PCR were compared with qRT-PCR, and practical advantages were investigated. RESULTS: Dr. PCR detected MRD up to 0.0032%IS (MR4.5) with excellent precision and linearity and showed a strong correlation with qRT-PCR results. Notably, Dr. PCR identified higher levels of MRD in 12.7% (29/229) of patients than qRT-PCR, including six cases of MR4, which is a critical level for TKI discontinuation. Dr. PCR also allowed for sufficient ABL1 copies in all cases, while qRT-PCR necessitated multiple repeat tests in 3.5% (8/229) of cases. CONCLUSION: Our study provides a body of evidence supporting the clinical application of Dr. PCR as a rapid and efficient method for assessing MRD in patients with CML under the current treatment regimen.

Clinical significance of decreased or loss of ABO blood group expression in acute myeloid leukaemia: A single-centre retrospective study.

BACKGROUND AND OBJECTIVES: Decreased or loss of ABO blood group antigen expression has been observed in acute myeloid leukaemia (AML) patients. We studied the clinical significance of this group in AML patients. MATERIALS AND METHODS: This was a retrospective, single-centre cohort study in which the data were retrieved from April 2009 to December 2019. A total of 1592 AML patients with normal ABO blood group antigen (Group I) and 65 patients of decreased or loss of ABO blood group antigen (Group II) group were enrolled. Data were collected at the time of initial admission for pathological diagnosis. To interrogate the underlying mechanism, publicly available The Cancer Genome Atlas AML data were downloaded. RESULTS: Group II consisted of 3.9% (65/1657) of AML patients. The 90-day survival (D90) probability was higher for Group II with a mean survival of 86.4 days compared to 80.6 days for Group I (p = 0.047). Group II had higher haematocrit (28.6 vs. 27.4%) and lower d-dimer, fibrinogen degradation production and C-reactive protein. Publicly available data revealed that among 11 CpG methylation sites within the ABO gene, 4 sites with elevated methylation level were associated with improved D90 survival probability and demonstrated an inverse correlation with ABO gene expression. Lower expression of the ABO gene showed improved survival trends for D90 (p = 0.058) and 180-day survival (p = 0.072). CONCLUSION: AML with decreased expression or loss of ABO blood group showed better early survival during D90. Transfusion support for this subgroup of AML patients should be meticulously performed considering serum typing.

Prognostic value of European LeukemiaNet 2022 criteria and genomic clusters using machine learning in older adults with acute myeloid leukemia.

This study aimed to validate the new European Leukemia Net (ELN) 2022 criteria for genetic risk stratification in older adults with acute myeloid leukemia (AML) and to determine the most likely set of clusters of similar cytogenetic and mutation properties correlated with survival outcomes in three treatment groups: intensive chemotherapy (IC), hypomethylating agents (HMA) alone, and HMA plus venetoclax (HMA/VEN). The study included 279 patients (aged ≥60 years) who received IC (N=131), HMA (N=76), and HMA/VEN (N=72) between July 2017 and October 2021. No significant differences were observed in survival among the groups according to ELN 2022 risk stratification. Unsupervised hierarchical clustering analysis identified nine genomic clusters (C1-9) with varying survival outcomes depending on treatment type. For example, C4 (predominant for core binding factor-AML) displayed a favorable prognosis in the IC group, but not in the HMA or HMA/VEN groups. The HMA/VEN group had better outcomes than the HMA group in many clusters (C1, 2, 3, and 5); however, the addition of VEN to HMA or IC did not improve the survival outcomes compared with those of HMA alone in C7 and C9 (predominant for -5, del(5q), -7, -17/abn(17p), complex karyotypes, and mutated TP53). The study highlights the limitations of ELN genetic risk stratification in older adults with AML. It emphasizes the need for a more comprehensive approach that considers co-occurring somatic mutations to guide treatment selection in older adults with AML.

Analytical performance of the Abbott ID NOW 2.0 assay for SARS-CoV-2 detection in clinical samples from symptomatic patients.

We evaluated the analytical performance of ID NOW™ COVID-19 2.0 assay versus conventional real-time reverse transcription-polymerase chain reaction (RT-PCR) using a total of 792 clinical samples from nasopharyngeal and oropharyngeal swabs, stored in frozen universal transport medium samples. Positive percent agreement (PPA) and negative percent agreement of ID NOW were 97.6 % and 100 %, respectively. The overall percent agreement between ID NOW and RT-PCR was 99.5 %. The PPA of ID NOW in detecting SARS-CoV-2 in 164 RT-PCR positive patients, all of whom had symptoms related COVID-19, was 97.1 % within 8 days since symptom onset, 97.9 % from 8 to 14 days since symptom onset, and 97.6 % after 14 days since symptom onset, with no significant difference between the days since symptom onset. The ID NOW assay demonstrated good performance, providing a rapid and randomly accessible alternative to conventional RT-PCR for timely SARS-CoV-2 detection, particularly in situations requiring rapid results for patient care.

Effectiveness of leukapheresis on early survival in acute myeloid leukemia: An observational propensity score matching cohort study.

BACKGROUND: The association between leukapheresis (LK) as a treatment option for hyperleukocytosis (HL) in patients with acute myeloid leukemia (AML) remains controversial. METHODS: Data were extracted from the electronic medical record for 2801 patients with AML between April 2009 and December 2019. LK was performed when the leukocyte count was ≥100 × 109 /L at the time initial bone marrow examination. RESULTS: A comparison between the patients with HL in the non-LK (n = 1579) and LK (n = 208) groups revealed survival probabilities (%) of 93.2% and 90.4% (P = .130) for day 30 (D30), 85.4% and 84.2% (P = .196) for D60, and 83.6% and 80.8% (P = .258) for D90, respectively. After propensity score matching, a comparison between the patients with HL in the non-LK (n = 192) and LK (n = 192) groups revealed survival probabilities (%) of 83.9% and 91.2% (P = .030) for D30, 75.0% and 84.9% (P = .015) for day 60 (D60), and 62.4% and 81.3% (P = .034) for day 90 (D90), respectively. After D150, the observed effect of LK appeared to be mitigated without a survival benefit. DISCUSSION: LK was associated with improved early survival outcomes at D30, D60, and D90 among patients with AML exhibiting HL. Thus, it may be considered a treatment option for reducing cell mass in such patients.

Machine Learning Predicts 30-Day Outcome among Acute Myeloid Leukemia Patients: A Single-Center, Retrospective, Cohort Study.

Acute myeloid leukemia (AML) is a clinical emergency requiring treatment and results in high 30-day (D30) mortality. In this study, the prediction of D30 survival was studied using a machine learning (ML) method. The total cohort consisted of 1700 survivors and 130 non-survivors at D30. Eight clinical and 42 laboratory variables were collected at the time of diagnosis by pathology. Among them, six variables were selected by a feature selection method: induction chemotherapy (CTx), hemorrhage, infection, C-reactive protein, blood urea nitrogen, and lactate dehydrogenase. Clinical and laboratory data were entered into the training model for D30 survival prediction, followed by testing. Among the tested ML algorithms, the decision tree (DT) algorithm showed higher accuracy, the highest sensitivity, and specificity values (95% CI) of 90.6% (0.918-0.951), 70.4% (0.885-0.924), and 92.1% (0.885-0.924), respectively. DT classified patients into eight specific groups with distinct features. Group 1 with CTx showed a favorable outcome with a survival rate of 97.8% (1469/1502). Group 6, with hemorrhage and the lowest fibrinogen level at diagnosis, showed the worst survival rate of 45.5% (25/55) and 20.5 days. Prediction of D30 survival among AML patients by classification of patients with DT showed distinct features that might support clinical decision-making.

Comparison of Quality, Antioxidant Capacity, and Anti-Inflammatory Activity of Adlay [Coix lacryma-jobi L. var. ma-yuen (Rom. Caill.) Stapf.] Sprout at Several Harvest Time.

Recently, there has been a growing interest in the consumption of plant-based foods such as vegetables and grains for the purpose of disease prevention and treatment. Adlay seeds contain physiologically active substances, including coixol, coixenolide, and lactams. In this study, adlay sprouts were cultivated and harvested at various time points, specifically at 3, 5, 7, 9, and 11 days after sowing. The antioxidant activity of the extracts was evaluated using assays such as DPPH radical scavenging, ABTS radical scavenging, reducing power, and total polyphenol contents. The toxicity of the extracts was assessed using cell culture and the WST-1 assay. The aboveground components of the sprouts demonstrated a significant increase in length, ranging from 2.75 cm to 21.87 cm, weight, ranging from 0.05 g to 0.32 g, and biomass, ranging from 161.4 g to 1319.1 g, as the number of days after sowing advanced, reaching its peak coixol content of 39.38 mg/g on the third day after sowing. Notably, the antioxidant enzyme activity was highest between the third and fifth days after sowing. Regarding anti-inflammatory activity, the inhibition of cyclooxygenase 2 (COX-2) expression was most prominent in samples harvested from the ninth to eleventh days after sowing, corresponding to the later stage of growth. While the overall production mass increased with the number of days after sowing, considering factors such as yield increase index per unit area, turnover rate, and antioxidant activity, harvesting at the early growth stage, specifically between the fifth and seventh days after sowing, was found to be economically advantageous. Thus, the quality, antioxidant capacity, and anti-inflammatory activity of adlay sprouts varied depending on the harvest time, highlighting the importance of determining the appropriate harvest time based on the production objectives. This study demonstrates the changes in the growth and quality of adlay sprouts in relation to the harvest time, emphasizing the potential for developing a market for adlay sprouts as a new food product.

Genetic Variants Associated with Drug Resistance of Cytomegalovirus in Hematopoietic Cell Transplantation Recipients.

Cytomegalovirus (CMV) infection is a serious complication in hematopoietic cell transplantation (HCT) recipients. Drug-resistant strains make it more challenging to treat CMV infection. This study aimed to identify variants associated with CMV drug resistance in HCT recipients and assess their clinical significance. A total of 123 patients with refractory CMV DNAemia out of 2271 HCT patients at the Catholic Hematology Hospital between April 2016 and November 2021 were analyzed, which accounted for 8.6% of the 1428 patients who received pre-emptive therapy. Real-time PCR was used to monitor CMV infection. Direct sequencing was performed to identify drug-resistant variants in UL97 and UL54. Resistance variants were found in 10 (8.1%) patients, and variants of uncertain significance (VUS) were found in 48 (39.0%) patients. Patients with resistance variants had a significantly higher peak CMV viral load than those without (p = 0.015). Patients with any variants had a higher risk of severe graft-versus-host disease and lower one-year survival rates than those without (p = 0.003 and p = 0.044, respectively). Interestingly, the presence of variants reduced the rate of CMV clearance, particularly in patients who did not modify their initial antiviral regimen. However, it had no apparent impact on individuals whose antiviral regimens were changed due to refractoriness. This study highlights the importance of identifying genetic variants associated with CMV drug resistance in HCT recipients for providing appropriate antiviral treatment and predicting patient outcomes.

Metabolic profiles of lung adenocarcinoma via peripheral blood and diagnostic model construction.

The metabolic profile of cancerous cells is shifted to meet the cellular demand required for proliferation and growth. Here we show the features of cancer metabolic profiles using peripheral blood of healthy control subjects (n = 78) and lung adenocarcinoma (LUAD) patients (n = 64). Among 121 detected metabolites, diagnosis of LUAD is based on arginine, lysophosphatidylcholine-acyl (Lyso.PC.a) C16:0, and PC-diacyl (PC.aa) C38:3. Network analysis revealed that network heterogeneity, diameter, and shortest path were decreased in LUAD. On the contrary, these parameters were increased in advanced-stage compared to early-stage LUAD. Clustering coefficient, network density, and average degree were increased in LUAD compared to the healthy control, whereas these topologic parameters were decreased in advanced-stage compared to early-stage LUAD. Public LUAD data verified that the genes encoding enzymes for arginine (NOS, ARG, AZIN) and for Lyso.PC and PC (CHK, PCYT, LPCAT) were related with overall survival. Further studies are required to verify these results with larger samples and other histologic types of lung cancer.

Clinical outcomes of therapeutic leukapheresis in acute promyelocytic leukemia: A single-center retrospective cohort study.

BACKGROUND: In acute promyelocytic leukemia (APL), increased cell burden in the peripheral blood due to either the disease itself or early treatment with all-trans retinoic acid could cause hyperleukocytosis (HL) before induction chemotherapy. However, therapeutic leukapheresis has seldom been used because of concerns of subsequent coagulopathy after this invasive procedure. The aim of this study was to evaluate the effects of leukapheresis in APL, especially for efficacy and safety. METHODS: We retrospectively analyzed newly diagnosed patients with APL from January 2009 to March 2022. Among 323 patients, 85 had white blood cell count above 40 × 109/L before induction chemotherapy. Thirty-nine patients were initially treated with leukapheresis, whereas the other 46 were not. Clinical and laboratory parameters between these groups were compared. RESULTS: There was a trend toward favorable 30-day survival rate for the leukapheresis group compared with the non-leukapheresis group (76.9% and 67.4%; P = 0.24). The complications including subsequent intensive unit care (P = 0.23), severe hemorrhagic events (P = 0.13) showed no significant differences between the two groups. The patients were divided into subcohorts, and the survival rates of the leukapheresis and non-leukapheresis groups were 92.3% (95% confidence interval [CI], 77.8%-100.0%) versus 58.3% (95% CI, 38.6%-78.1%) (P = 0.03) in "sequential HL" and 76.7% (95% CI, 61.5%-91.8%) versus 54.8% (95% CI, 37.3%-72.4%) (P = 0.03) in "symptomatic HL," respectively. Moreover, in the "sequential HL" subcohort, the cumulative incidence of differentiation syndrome and following adverse events were significantly lower in the leukapheresis group. CONCLUSIONS: In APL with "sequential HL" or "symptomatic HL" from either the disease itself or the effect of all-trans retinoic acid, therapeutic leukapheresis could be applied to reduce leukemic cell burden without significant risks.

Regulatory Mechanism between Ferritin and Mitochondrial Reactive Oxygen Species in Spinal Ligament-Derived Cells from Ossification of Posterior Longitudinal Ligament Patient.

Primary spinal ligament-derived cells (SLDCs) from cervical herniated nucleus pulposus tissue (control, Ctrl) and ossification of the posterior longitudinal ligament (OPLL) tissue of surgical patients were analyzed for pathogenesis elucidation. Here, we found that decreased levels of ferritin and increased levels of alkaline phosphatase (ALP), a bone formation marker, provoked osteogenesis in SLDCs in OPLL. SLDCs from the Ctrl and OPLL groups satisfied the definition of mesenchymal stem/stromal cells. RNA sequencing revealed that oxidative phosphorylation and the citric acid cycle pathway were upregulated in the OPLL group. SLDCs in the OPLL group showed increased mitochondrial mass, increased mitochondrial reactive oxygen species (ROS) production, decreased levels of ROS scavengers including ferritin. ROS and ferritin levels were upregulated and downregulated in a time-dependent manner, and both types of molecules repressed ALP. Osteogenesis was mitigated by apoferritin addition. We propose that enhancing ferritin levels might alleviate osteogenesis in OPLL.

Transfusion support in hematopoietic stem cell transplantation.

Transfusion support for hematopoietic stem cell transplantation (HSCT) is an essential part of supportive care, and compatible blood should be transfused into recipients. As leukocyte antigen (HLA) matching is considered first and as the blood group does not impede HSCT, major, minor, bidirectional, and RhD incompatibilities occur that might hinder transfusion and cause adverse events. Leukocyte reduction in blood products is frequently used, and irradiation should be performed for blood products, except for plasma. To mitigate incompatibility and adverse events, local transfusion guidelines, hospital transfusion committees, and patient management should be considered.