69 research outputs found
Phase II trial of daratumumab with DCEP in relapsed/refractory multiple myeloma patients with extramedullary disease
Extramedullary multiple myeloma (EMD) is an aggressive subentity of multiple myeloma (MM) with poor prognoâ
sis. As more innovative therapeutic approaches are needed for the treatment of MM with EMD, we conducted this
multicenter, non-randomized phase II trial of daratumumab in combination with dexamethasone, cyclophosphaâ
mide, etoposide and cisplatin (DARA-DCEP). A total of 32 patients (median age 59, range 35â73) were treated with
DARA-DCEP. Based on the best response during the study, the complete remission (CR) rate was 35.5% and overall
response rate (ORR) 67.7%. During the median follow-up of 11 months, the median progression-free survival (PFS) was
5 months and median overall survival (OS) 10 months. There were 7 long-term responders whose median PFS was not
reached. The most common gradeâ„3 hematologic AE was thrombocytopenia. The most common non-hematologic
AE was nausea (22.6%), followed by dyspepsia, diarrhea and stomatitis (all 12.9%). Gradeâ„3 daratumumab infusionrelated reaction was noted in 9.7% of the patients. Except for the planned 30% dose adjustment in cycle 1, only 2
patients required DCEP dose reduction. This is one of the very few prospective trials focusing on EMD and we successâ
fully laid grounds for implementing immunochemotherapy in MM treatment.This work was supported by grants from the Korea Health TechnolĂ ĂÂą ogy R&D Project through the Korea Health Industry Development
Institute (KHIDI, HI14C1277)
ITDetect: a method to detect internal tandem duplication of FMS-like tyrosine kinase (FLT3) from next-generation sequencing data with high sensitivity and clinical application
Abstract
Internal tandem duplication (ITD) of the FMS-like tyrosine kinase (FLT3) gene is associated with poor clinical outcomes in patients with acute myeloid leukemia. Although recent methods for detecting FLT3-ITD from next-generation sequencing (NGS) data have replaced traditional ITD detection approaches such as conventional PCR or fragment analysis, their use in the clinical field is still limited and requires further information. Here, we introduce ITDetect, an efficient FLT3-ITD detection approach that uses NGS data. Our proposed method allows for more precise detection and provides more detailed information than existing in silico methods. Further, it enables FLT3-ITD detection from exome sequencing or targeted panel sequencing data, thereby improving its clinical application. We validated the performance of ITDetect using NGS-based and experimental ITD detection methods and successfully demonstrated that ITDetect provides the highest concordance with the experimental methods. The program and data underlying this study are available in a public repository
Comparison of Monthly Ibandronate Versus Weekly Risedronate in Preference, Convenience, and Bone Turnover Markers in Korean Postmenopausal Osteoporotic Women
Patient preferences, convenience, and bone turnover markers were evaluated for the monthly ibandronate over the weekly risedronate regimen in Korean postmenopausal osteoporotic women. This was a 6-month, prospective, randomized, open-label, multicenter study with a two-period and two-sequence crossover treatment design. After a 30-day screening period, eligible participants with postmenopausal osteoporosis were randomized to receive either monthly oral ibandronate 150Â mg for 3Â months followed by weekly oral risedronate 35Â mg for 12Â weeks (sequence A) or the same regimen in reverse order (sequence B). Patient preference and convenience were evaluated by questionnaire. The changes in serum C-telopeptide after 3Â months of treatment were analyzed. A total of 365 patients were enrolled in this study (sequence A 182, sequence B 183). Of patients expressing a preference (83.4%), 74.8% preferred the monthly ibandronate regimen over the weekly regimen (25.2%). More women stated that the monthly ibandronate regimen was more convenient (84.2%) than the weekly regimen (15.8%). There was no significant difference in the change in bone turnover marker between the two treatments. The two regimens were similarly tolerable. There were fewer adverse events in the monthly ibandronate group compared to the weekly risedronate group in terms of gastrointestinal side effects (nausea and abdominal distension). This study revealed a strong preference and convenience for monthly ibandronate over weekly risedronate in Korean postmenopausal osteoporotic women. There was no significant difference in change of bone turnover marker and safety profile between the two regimens
Type I Interferon Signaling Regulates Ly6Chi Monocytes and Neutrophils during Acute Viral Pneumonia in Mice
Type I interferon (IFN-I) plays a critical role in the homeostasis of hematopoietic stem cells and influences neutrophil influx to the site of inflammation. IFN-I receptor knockout (Ifnar1â/â) mice develop significant defects in the infiltration of Ly6Chi monocytes in the lung after influenza infection (A/PR/8/34, H1N1). Ly6Chi monocytes of wild-type (WT) mice are the main producers of MCP-1 while the alternatively generated Ly6Cint monocytes of Ifnar1â/â mice mainly produce KC for neutrophil influx. As a consequence, Ifnar1â/â mice recruit more neutrophils after influenza infection than do WT mice. Treatment of IFNAR1 blocking antibody on the WT bone marrow (BM) cells in vitro failed to differentiate into Ly6Chi monocytes. By using BM chimeric mice (WT BM into Ifnar1â/â and vice versa), we confirmed that IFN-I signaling in hematopoietic cells is required for the generation of Ly6Chi monocytes. Of note, WT BM reconstituted Ifnar1â/â chimeric mice with increased numbers of Ly6Chi monocytes survived longer than influenza-infected Ifnar1â/â mice. In contrast, WT mice that received Ifnar1â/â BM cells with alternative Ly6Cint monocytes and increased numbers of neutrophils exhibited higher mortality rates than WT mice given WT BM cells. Collectively, these data suggest that IFN-I contributes to resistance of influenza infection by control of monocytes and neutrophils in the lung
International Consensus Statement on Rhinology and Allergy: Rhinosinusitis
Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICARâRS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICARâRSâ2021 as well as updates to the original 140 topics. This executive summary consolidates the evidenceâbased findings of the document. Methods: ICARâRS presents over 180 topics in the forms of evidenceâbased reviews with recommendations (EBRRs), evidenceâbased reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICARâRSâ2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidenceâbased management algorithm is provided. Conclusion: This ICARâRSâ2021 executive summary provides a compilation of the evidenceâbased recommendations for medical and surgical treatment of the most common forms of RS
P1157: PHASE II STUDY OF GLOFITAMAB, POSELTINIB AND LENALIDOMIDE IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE B CELL LYMPHOMAS
PB2130: MAGNETISMM-6: A PHASE 3 STUDY OF ELRANATAMAB + DARATUMUMAB + LENALIDOMIDE VS DARATUMUMAB + LENALIDOMIDE + DEXAMETHASONE IN TRANSPLANT INELIGIBLE PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA
The Inhibition of Stress-Induced c-fos Expression by Superior Cervical Ganglion Block in Rat Brain
Mobilization of hematopoietic stem cells with lenograstim in multiple myeloma patients: Prospective multicenter observational study (KMM122)
Abstract Background Current guidelines recommend using filgrastim or tboâfilgrastim to mobilize hematopoietic progenitor cells in an autologous setting. However, previous studies have suggested other forms of granulocyte colonyâstimulating factor (GâCSF) are equally efficacious, possibly with fewer leukaphereses required. Thus, we prospectively studied the efficacy of lenograstim, a glycosylated recombinant form of GâCSF, in multiple myeloma (MM) patients. Methods From November 2011 to January 2020, 98âMM patients undergoing autologous stem cell transplant (ASCT) from five academic centers in Korea were enrolled. Patients were mobilized with subcutaneous lenograstim (NeutroginÂź) with fixed doses of 10 Όg/kg for 4âdays. Results Most of the patients ( N  = 90, 91.8%) achieved at least the targets of 2âĂâ106 CD34+ cells/kg body weight, and more than half of MM patients ( N  = 57, 58.2%) reached a target of 5âĂâ106 CD34+ cells/kg body weight. The mobilization failure rate was 8.2% ( N  = 8). The median number of CD34â+âcell/kg using GâCSF only was 5.25âĂâ106/kg (range 0.49â13.47). Adverse events included transfusion (TF, N  = 53, 54.1%), bone pain ( N  = 6, 6.1%), fever ( N  = 2, 2.0%), and gastrointestinal troubles ( N  = 2, 2.0%). There were no grade 3 or 4 adverse events during mobilization. Body surface area (BSA) at mobilization and platelet TF were factors associated with CD34+ collection. Most patients achieved neutrophil ( N  = 93, 98.9%) and platelet ( N  = 89, 95.7%) engraftment. Conclusion Lenograstim can safely and effectively mobilize stem cells in MM autologous settings
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