Characterization of Continuous Neutralization of a Chemical Warfare Agent and Its Simulants.

The persistent threat posed by chemical warfare agents (CWAs) necessitates the development of efficient and safe methods for their neutralization. In this study, we investigated the continuous neutralization of CWAs and their simulants using flow chemistry, which combines the benefits of safety, precise control over reaction parameters, and scalability. We focused on the integration of continuous-flow reactors to achieve controlled and rapid neutralization, thus addressing challenges such as the need for rapid reaction kinetics and the establishment of robust pathways for neutralization. Because the flow-chemistry approach can contribute significantly to the development of neutralization technologies for CWAs, we performed a thorough characterization in terms of reaction kinetics and neutralized product identification. The results demonstrated that the proposed continuous-flow-type neutralization reaction was faster and more efficient than batch-type neutralization reactions. Furthermore, in the early stages of the neutralization reaction, flow-type neutralization not only required less neutralizing agent than batch-type neutralization but was also faster. Thus, the chemical neutralization process proposed in this study can be used as a pragmatic foundation for developing demilitarization methods for CWAs.

Combination of rituximab and methotrexate followed by rituximab and cytarabine in elderly patients with primary central nervous system lymphoma.

The optimal treatment strategy for newly diagnosed primary central nervous system lymphoma (PCNSL) has yet to be established, especially in the elderly. In the current study, we conducted a phase II study to evaluate the efficacy and safety of rituximab plus high-dose MTX followed by rituximab plus cytarabine in patients aged ≥60 years newly diagnosed with PCNSL. Patients received an induction treatment of high-dose methotrexate plus rituximab followed by two cycles of a consolidation treatment of cytarabine plus rituximab. The primary end-point was a 2-year progression-free survival (PFS) rate. A total of 35 patients were recruited, and their median age was 73 (range: 60-81). After induction treatment, the complete and partial responses (PRs) were 56% and 20% respectively. Twenty-six patients proceeded to the consolidation treatment; the complete and PRs were 59% and 9% respectively. After a median follow-up duration of 36.0 months, the 2-year PFS rate was 58.7%. Treatment was generally well-tolerated as only three patients were withdrawn from the study due to toxicity, and no treatment-related mortality was reported. The 2-year overall survival rate was 77.9%. The current study may suggest the feasibility of administering high-dose MTX plus cytarabine in PCNSL patients aged ≥60 years and the potential role of additive rituximab.

Efficacy of ferric carboxymaltose or darbepoetin alfa for chemotherapy-induced anemia in patients with esophagogastric or pancreaticobiliary cancer: a retrospective comparative study.

Background: Esophagogastric and pancreaticobiliary cancers are associated with chronic blood loss, poor nutrition, and surgical interventions that interfere with iron absorption. Patients with these cancers often have a higher incidence of chemotherapy-induced anemia (CIA) than patients with other malignancies. Objectives: To investigate the efficacy of intravenous iron or erythropoietin-stimulating agents (ESA) for CIA treatment in patients with esophagogastric or pancreaticobiliary cancer. Design: Retrospective, comparative chart review of patients with esophagogastric or pancreaticobiliary cancer who received ferric carboxymaltose (FCM), or darbepoetin alfa (DA), and myelosuppressive chemotherapy at Chungbuk National University Hospital between June 2018 and December 2022. Methods: To assess the efficacy of FCM or DA over time, data on hemoglobin (Hb) levels were collected from the time of administration of FCM or DA (baseline) until 6 months post-baseline, when available. Results: In total, 214 patients (124 in the FCM and 90 in the DA group) were included in the analysis. The FCM group had a higher maximum Hb level and Hb changes for 3 months (mean ± standard deviation) following FCM or DA administration from baseline than the DA group (11.3 ± 1.5 versus 10.9 ± 1.2 g/dL, p = 0.02 and 2.0 ± 1.4 versus 1.5 ± 1.1 g/dL, p = 0.004, respectively). The FCM group had a higher proportion of Hb responders than the DA group (83.9% versus 68.9%, p = 0.013). Based on multivariable analysis, only the CIA treatment group was a significant factor for Hb response (odds ratio = 2.06, 95% confidence interval = 1.05-4.06, p = 0.036). Conclusion: Both FCM and DA are effective, and FCM showed a higher Hb response than DA for CIA treatment in patients with esophagogastric or pancreaticobiliary cancer. Therefore, further randomized controlled trials should determine the optimal treatment for CIA in patients with these cancers undergoing myelosuppressive chemotherapy.

Novel diagnostic biomarkers for pancreatic cancer: assessing methylation status with epigenetic-specific peptide nucleic acid and KRAS mutation in cell-free DNA.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor with a poor prognosis that poses challenges for diagnosis using traditional tissue-based techniques. DNA methylation alterations have emerged as potential and promising biomarkers for PDAC. In this study, we aimed to assess the diagnostic potential of a novel DNA methylation assay based on epigenetic-specific peptide nucleic acid (Epi-sPNA) in both tissue and plasma samples for detecting PDAC. Materials and methods: The study involved 46 patients with PDAC who underwent surgical resection. Epi-TOP pancreatic assay was used to detect PDAC-specific epigenetic biomarkers. The Epi-sPNA allowed accurate and rapid methylation analysis without bisulfite sample processing. Genomic DNA extracted from paired normal pancreatic and PDAC tissues was used to assess the diagnostic efficacy of epigenetic biomarkers for PDAC. Subsequent validation was conducted on cell-free DNA (cfDNA) extracted from plasma samples, with 10 individuals represented in each group: PDAC, benign pancreatic cystic neoplasm, and healthy control. Results: The combination of seven epigenetic biomarkers (HOXA9, TWIST, WT1, RPRM, BMP3, NPTX2, and BNC1) achieved 93.5% sensitivity and 96.7% specificity in discerning normal pancreatic from PDAC tissues. Plasma cfDNA, analyzed using these markers and KRAS mutations, exhibited a substantial 90.0% sensitivity, 95.0% specificity, and an overall 93.3% accuracy for discriminating PDAC. Notably, cancer antigen 19-9 and carcinoembryonic antigen both had an accuracy of 90.0%. Conclusion: Our study suggests that analyzing seven differentially methylated genes with KRAS mutations in cfDNA using the novel Epi-TOP pancreatic assay is a potential blood-based biomarker for the diagnosis of PDAC.

Hypoglycemic and hypolipidemic effects of unsaponifiable matter from okra seed in diabetic rats.

BACKGROUND/OBJECTIVES: Okra seed is a rich source of various nutritional and bioactive constituents, but its mechanism of action is still unclear. The aim of this study was to evaluated the effects on glucose uptake and serum lipid profiles of unsaponifiable matter (USM) from okra seed in adipocytes and diabetic animal models. MATERIALS/METHODS: USM was prepared from okra seed powder by saponification. The contents of phytosterols and vitamin E in USM were measured. 3T3-L1 preadipocytes were cultured for 6 days with different concentrations of USM (0-200 µg/mL). The diabetic rats were administered with or without USM for 5 wk. RESULTS: In the USM, the contents of phytosterols and vitamin E were 394.13 mg/g USM and 31.16 mg/g USM, respectively. USM showed no cytotoxicity and led to an approximately 1.4-fold increase in glucose uptake in 3T3-L1 adipocytes. The treatment of USM also increased the expressions of peroxisome proliferator-activated receptor-γ and glucose transporter-4 in a dose-dependent manner in adipocytes. The body weight change was not significantly different in all diabetic rats. However, blood glucose and the weights of liver and adipose tissues were significantly reduced compared to those in the control diabetic rats. Treatment with USM decreased the levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol compared to the control group. The USM group also showed significantly decreased atherogenic indices and cardiac risk factors. CONCLUSION: These results suggest that USM from okra seed improves the hypoglycemic and hypolipidemic effects in diabetic rats, and provides valuable information for improving the functional properties of okra seed.

Therapeutic Effect of Anti-Inflammatory Tripeptide Cream in Hand-Foot Syndrome/Skin Reaction Related to Anticancer Drugs: a Randomized, Double-Blind, Placebo-Controlled Pilot Trial.

Purpose: Hand-foot syndrome (HFS) and hand-foot skin reaction (HFSR) are relatively common toxicities that interfere with the quality of life (QoL) of patients with cancer. Anti-inflammatory tripeptide cream (ATPC) is a complex formulation of anti-inflammatory tripeptides, the CD99-agonist BinterinTM and the Wnt-antagonist WinhibinTM. The present study aimed to assess the therapeutic effects of ATPC in HFS/HFSR associated with anticancer drugs. Materials and Methods: This was a single-center, randomized, double-blind, placebo-controlled trial. Patients who developed grade 1 HFS/HFSR after systemic anticancer treatments were enrolled, and randomly assigned to receive either ATPC or placebo cream (PC) and followed up at 3-week intervals for up to nine weeks. Primary endpoint was the development of grade ≥ 2 HFS/HFSR. Results: Between April 2019 and July 2022, 60 patients (31 in the ATPC and 29 in the PC group) completed the study. The incidence of grade ≥ 2 HFS/HFSR was significantly lower in the ATPC than in the PC group (25.8% vs. 51.7%, p=0.039). The ATPC showed trends towards a better QoL score, assessed by a HFSR and QoL questionnaire at 9 weeks (26.0 vs. 29.9, p=0.574), and a lower frequency of discontinuation, interruption, or dose reduction of anticancer drugs (51.6% vs. 58.6%, p=0.586) than the PC group over 9 weeks, though without statistical significance. Conclusion: Our results showed that ATPC significantly decreased the development of grade ≥ 2 HFS/HFSR in patients already with HFS/HFSR. Therefore, ATPC may be an effective treatment for HFS/HFSR associated with anticancer drugs.

Asian variant intravascular large B-cell lymphoma with highly suspected central nervous system involvement: A case report.

BACKGROUND: Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of extranodal lymphoma. In particular, the Asian variant of IVLBCL is characterized by hemophagocytic lymphohistiocytosis along with bone marrow involvement. However, central nervous system (CNS) involvement is uncommon in this variant compared to the Western variant. Here, we report a case of typical Asian variant IVLBCL with highly suspected CNS involvement and discuss the nature of the disease and its genetic aberration. CASE SUMMARY: A 67-year-old female patient complained of gradually worsening cognitive impairment. While hospitalized, she developed a high fever and showed marked bicytopenia. Intracranial imaging revealed a suspected leptomeningeal disease. Although no malignant cells were found in the cerebrospinal fluid (CSF), the protein and lactate dehydrogenase levels in CSF were increased. Bone marrow examination revealed an increased number of hemophagocytic histiocytes, and 18F-fluorodeoxyglucose (FDG) positron emission tomography with computerized tomography scan revealed increased FDG uptake in both adrenal glands, the liver, and the right ethmoid sinus. A tissue biopsy showed atypical large lymphoid cells with prominent nucleoli in the vessels, and the tumor cells were positive for CD20, BCL2, BCL6, and IRF4/MUM1. In addition, targeted sequencing identified MYD88, TET2, and PIM1 mutations. Consequently, we diagnosed the patient with the Asian variant of IVLBCL with highly suspected CNS involvement. CONCLUSION: Suspicion of IVLBCL and immediate diagnosis lead to timely treatment. Moreover, careful CNS examination at diagnosis is recommended.

Current Treatment Patterns and the Role of Upfront Autologous Stem Cell Transplantation in Patients with Peripheral T-Cell Lymphoma: A Korean Nationwide, Multicenter Prospective Registry Study (CISL 1404).

PURPOSE: We conducted a nationwide, multicenter, prospective registry study for newly diagnosed patients with peripheral T-cell lymphoma (PTCL) to better define the clinical characteristics, treatment patterns, survival outcomes, and the role of upfront autologous stem cell transplantation (ASCT) in these patients. Materials and Methods: Patients with PTCL receiving chemotherapy with curative intent were registered and prospectively monitored. All patients were pathologically diagnosed with PTCL. RESULTS: A total of 191 patients with PTCL were enrolled in this prospective registry study. PTCL, not otherwise specified (PTCL-NOS) was the most common pathologic subtype (n=80, 41.9%), followed by angioimmunoblastic T-cell lymphoma (AITL) (n=60, 31.4%). With a median follow-up duration of 3.9 years, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 39.5% and 60.4%, respectively. The role of upfront ASCT was evaluated in patients who were considered transplant-eligible (n=59). ASCT was performed as an upfront consolidative treatment in 32 (54.2%) of these patients. There were no significant differences in PFS and OS between the ASCT and non-ASCT groups for all patients (n=59) and for patients with PTCL-NOS (n=26). However, in patients with AITL, the ASCT group was associated with significantly better PFS than the non-ASCT group, although there was no significant difference in OS. CONCLUSION: The current study demonstrated that the survival outcomes with the current treatment options remain poor for patients with PTCL-NOS. Upfront ASCT may provide a survival benefit for patients with AITL, but not PTCL-NOS.

Outcomes in Refractory Diffuse Large B-Cell Lymphoma: Results from Two Prospective Korean Cohorts.

PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal. MATERIALS AND METHODS: We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation. RESULTS: Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529). CONCLUSION: In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.

Usefulness of Genetic Aberration and Shorter Telomere Length in Myelodysplastic Syndrome: A Pilot Study.

OBJECTIVE: We aimed to evaluate the clinical usefulness of genetic aberration and shorter telomere length (TL) in individuals with myelodysplastic syndrome (MDS). METHODS: A targeted sequencing panel with 49 genes and TL measurement by quantitative real-time polymerase chain reaction were performed for 46 subjects. RESULTS: According to the revised International Prognostic Scoring System (IPSS-R) subtypes, the mutation frequency was 33.3%, 57.9%, and 100% in the very low/low, intermediate, and very high/high risk groups, respectively. A shorter telomere was detected in 43.5%. We defined group 1 as IPSS-R-high or -very high risk, group 2 as having 1 or more genetic aberrations, group 3 as having a shorter TL, and group 4 as having a longer TL than the age-matched reference. Group 1 and group 2 showed an adverse prognosis. The TL was not strongly correlated with MDS prognosis. However, it may be related to a poor long-term prognosis. CONCLUSION: Genetic variation and shorter TL may be helpful in reclassifying non-high-risk groups.

The new diagnostic criteria for myelodysplasia-related acute myeloid leukemia is useful for predicting clinical outcome: comparison of the 4th and 5th World Health Organization classifications.

Mutations in myelodysplasia-related (MR) genes, rather than morphological features, have been included in the diagnostic criteria of the new 5th World Health Organization (WHO) classification for myelodysplastic syndrome (MDS)-associated acute myeloid leukemia (AML). This study compares the clinical relevance of the new criteria with those of the previous version. In a cohort of 135 patients with newly diagnosed AML, the MDS-related AML patients were classified according to the 5th and 4th edition of the WHO classification (AML, myelodysplasia-related [AML-MR5th] and AML with myelodysplasia-related changes [AML-MRC4th], respectively). The median age of the patients was 70.4 years. MR gene mutations were found in 48 patients (35.6%). Sixty-one patients (46.6%) were diagnosed with AML-MRC4th, while 71 patients (53.0%) were diagnosed with AML-MR5th. Patients with AML-MR5th were significantly older with significantly lower treatment response rate, higher recurrence rate, and shorter relapse-free survival after chemotherapy, whereas AML-MRC4th patients did not show any association with the treatment outcome. Overall, the following prognostic factors for survival were identified: age over 75 years, antecedent MDS or MDS/myeloproliferative neoplasm, chromosome 5 or 7 abnormalities, and KRAS and ZSZR2 mutations. The 5th WHO classification is more useful for predicting the treatment response of patients with AML-MR than the previous version. Among the MR genes, ZSZR2 mutations were found to be independent prognostic factors affecting survival.

Sequential eradication of Helicobacter pylori as a treatment for immune thrombocytopenia in patients with moderate thrombocytopenia: a multicenter prospective randomized phase 3 study.

Due to several issues, standard treatments are not recommended for asymptomatic patients with moderate immune thrombocytopenia (ITP). Since platelet responses are reported in some patients with Helicobacter pylori (H. pylori)-positive ITP after eradication, we conducted a multicenter, phase 3 study to evaluate the safety and efficacy of recently established sequential eradication for these patients having moderate thrombocytopenia. Persistent or chronic ITP patients with platelet count (30 × 103 ~ 80 × 103/µL) and confirmed active H. pylori infection were randomly assigned to a treatment and a control group. The former received 10-day sequential treatment. Eradication was assessed by urea breath test at 3 months after treatment. Primary endpoint was the overall platelet response rate at 3 months in successfully eradicated treatment group and control group. Secondary endpoints were platelet response time, H. pylori eradication success rate, etc. The patient enrollment terminated early because of the change of national insurance and treatment guideline for H. pylori-positive patients in Korea during the study. Of the 28 H. pylori-positive ITP patients, 17 were randomized to the treatment group, and eradication was achieved for 15 (88.2%) at 3 months, and seven in control group after withdrawal. Statistically, significant difference in platelet response rates between the two groups were observed (p = 0.017). Our study verifies that H. pylori eradication was an effective ITP treatment for patients with H. pylori-associated moderate ITP. This sequential eradication regimen showed not only a high H. pylori eradication rate, but also a remarkable platelet response for ITP patients. Trial registration number and date of registration for these prospectively registered trials is ClinicalTrials.gov number, NCT03177629 and June 6, 2017.

Safety and efficacy of nilotinib in adult patients with chronic myeloid leukemia: a post-marketing surveillance study in Korea.

Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph+ CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). Conclusion: This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph+ CML in routine clinical practice settings.

Short-chain fluorocarbon-based polymeric coating with excellent nonwetting ability against chemical warfare agents.

The ongoing concerns and regulations on long-chain fluorinated compounds (C8 or higher) for nonwetting coatings have driven the market to search for sustainable alternative chemistries. In this study, a copolymeric coating containing short-chain fluorinated groups was synthesized to achieve excellent nonwetting ability against hazardous chemical warfare agents (CWAs). A copolymer of 1H,1H,2H,2H-perfluorooctyl methacrylate (PFOMA) and ethylene glycol dimethacrylate (EGDMA, crosslinker) was directly coated onto a textile fabric via initiated chemical vapor deposition. The p(PFOMA-co-EGDMA) coating shows a rough-textured morphology with a bumpy, raspberry-like structure leading to high contact angles (θ water > 150° and θ dodecane = 113.8°) and a small water shedding angle (<5°). Moreover, the p(PFOMA-co-EGDMA) coating was further analysed for application in military fabrics: air permeability, tensile strength, and safety against toxic perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS). Outstanding nonwetting was noticeably achieved against different CWAs, including bis(2-chloroethyl)sulfide (HD), pinacolyl methylfluorophosphonate (GD), and O-ethyl S-(2-diisopropylaminoethyl)methylphosphonothioate (VX) (θ HD = 119.1°, θ GD = 117.0°, and θ VX = 104.1°). The coating retained its nano-structuration and nonwetting ability for water and n-dodecane despite being subjected to 250 cycles of Martindale abrasion and harsh chemicals (NaOH and HCl). The robustness and scalable straightforward preparation route of the coating make it an ideal approach for designing durable next-generation CWA nonwetting coatings for fabrics with favorable health and environmental properties.

A case report of nilotinib-induced irreversible interstitial lung disease.

RATIONALE: Nilotinib is a second line tyrosine kinase inhibitor to treat patients with chronic myeloid leukemia after imatinib resistance or intolerance. Drug related pulmonary complication is known to be rare. We discuss a case of nilotinib-induced interstitial lung disease presenting with nonspecific interstitial pneumonia on the unilateral lung. PATIENT CONCERNS: A 46-year-old man with chronic-phase chronic myeloid leukemia presented with cough and weight loss for 2 months. He had been treated with nilotinib for 52 months. DIAGNOSIS: Computed tomography scan showed right lung dominant consolidations, ground glass opacities and traction bronchiectasis. Bronchoalveolar lavage fluid analysis revealed no evidence of infection or malignancy. Surgical lung biopsy specimen was consistent with fibrosing nonspecific interstitial pneumonia. The patient was diagnosed with nilotinib induced interstitial lung disease. INTERVENTIONS: Corticosteroid treatment was initiated with prednisolone (50 mg daily) and slowly tapered down for 2 months. OUTCOMES: Cough improved after the course of corticosteroid treatment. However, fibrotic lung lesions persisted. Reinitiation of nilotinib resulted in the worsening of lung lesions. LESSONS: We report a case of irreversible interstitial lung disease that caused by nilotinib. Clinicians should have suspicion of this potential pulmonary complication in patients with respiratory symptoms and abnormal radiologic findings during nilotinib treatment, albeit rarely.

Pegfilgrastim Prophylaxis Is Effective in the Prevention of Febrile Neutropenia and Reduces Mortality in Patients Aged ≥ 75 Years with Diffuse Large B-Cell Lymphoma Treated with R-CHOP: A Prospective Cohort Study.

PURPOSE: Febrile neutropenia (FN) can cause suboptimal treatment and treatment-related mortality (TRM) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). MATERIALS AND METHODS: We conducted a prospective cohort study to evaluate the effectiveness of pegfilgrastim prophylaxis in DLBCL patients receiving R-CHOP, and we compared them with the PROCESS cohort (n=485). RESULTS: Since January 2015, 986 patients with DLBCL were enrolled. Pegfilgrastim was administered at least once in 930 patients (94.3%), covering 90.3% of all cycles. FN developed in 137 patients (13.9%) in this cohort (23.7% in the PROCESS cohort, p<0.001), and 4.2% of all cycles (10.2% in the PROCESS cohort, p<0.001). Dose delay was less common (≥3 days: 18.1% vs. 23.7%, p=0.015; ≥5 days: 12.0% vs. 18.3%, p=0.023) in this cohort than in the PROCESS cohort. The incidence of TRM (3.2% vs. 5.6%, p=0.047) and infection-related death (1.8% vs. 4.5%, p=0.004) was lower in this cohort than in the PROCESS cohort. The 4-year overall survival (OS) and progression-free survival (PFS) rates of the two cohorts were not different (OS: 73.0% vs. 71.9%, p=0.545; PFS: 69.5% vs. 68.8%, p=0.616). However, in patients aged ≥75 years, the 4-year OS and PFS rates were higher in this cohort than in the PROCESS cohort (OS: 49.6% vs. 33.7%, p=0.032; PFS: 44.2% vs. 30.3% p=0.047). CONCLUSION: Pegfilgrastim prophylaxis is effective in the prevention of FN and infection-related death in DLBCL patients receiving R-CHOP, and it also improves OS in patients aged ≥75 years.

E-Cadherin and Angiopoietin-2 as Potential Biomarkers for Colorectal Cancer With Peritoneal Carcinomatosis.

BACKGROUND/AIM: E-Cadherin has been implicated in cell-cell adhesion, and soluble E-cadherin is involved in angiogenesis and resistance to anti-angiogenic therapy in several cancer types. This study aimed to investigate the expression and clinical significance of soluble E-cadherin and other angiogenesis-related factors in plasma and malignant ascites of colorectal cancer (CRC) in patients with peritoneal carcinomatosis (PC). MATERIALS AND METHODS: Multiplex enzyme-linked immunosorbent assay was performed on 95 body fluid samples (57 plasma and 38 malignant ascites) from patients with CRC. The status of E-cadherin and angiopoietin-2 (AGNPT2) was retrospectively evaluated by immunohistochemistry in primary CRC and paired metastatic peritoneal tissues or cell blocks of malignant ascites of 30 patients with peritoneal metastases of CRC. RESULTS: The expression levels of soluble E-cadherin and ANGPT2 in plasma samples were significantly increased in patients with PC compared with those without. E-Cadherin concentration was significantly lower and ANGPT2 concentration was significantly higher in malignant ascites than plasma samples. Expression of E-cadherin was strongly positive, whilst that of ANGPT2 was negative in primary colorectal tissues, metastatic peritoneal tissues, and cell blocks of malignant ascites by immunohistochemistry. High levels of soluble E-cadherin or ANGPT2 in ascites were negatively associated with overall survival in patients with CRC with malignant ascites. CONCLUSION: Our findings suggest that soluble E-cadherin and ANGPT2 may be surrogate biomarkers for clinical outcome in patients with PC from CRC.

The Prognostic Ability of RAS Pathway-Related Gene Mutations in Patients with Myeloid Neoplasms Treated with Hypomethylating Agents.

INTRODUCTION: This study aimed to identify genetic predictors of treatment response and survival in patients with myeloid neoplasms treated with hypomethylating agents (HMAs). METHODS: We performed next-generation sequencing on bone marrow aspiration samples of 59 patients diagnosed with acute myeloid leukemia (AML), myelodysplastic syndrome with excess blasts-2, or chronic myelomonocytic leukemia and treated with decitabine or azacitidine as a frontline therapy. RESULTS: A single gene with the most common mutations was TP53 (14 of 59 patients), and mutations in RAS pathway-related genes including KRAS, NRAS, FLT3, PTPN11, CBL, and KIT were found in 28.8% of patients. The overall response rate to HMAs was 33.9%. Predictive factors for a poor response were an age >75 years (p = 0.007), 3 or more gene mutations (p = 0.004), mutations in RAS pathway-related genes (p = 0.033), and a mutated NRAS gene (p = 0.042). An age >75 years (hazard ratio 2.946), diagnosis of AML (hazard ratio 2.915), and mutations in NRAS (hazard ratio 4.440) were identified as poor prognostic factors for survival. CONCLUSION: In conclusion, mutations in RAS pathway-related genes were predictors of a poor response to HMAs. Particularly, mutated NRAS was associated with inferior survival rates.