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Journal of Medical Microbiology Jun 2024Fluoroquinolone prophylaxis during haematopoietic cell transplantation (HCT) can lead to antimicrobial resistance (AMR). Identifying the groups of patients that have...
Fluoroquinolone prophylaxis during haematopoietic cell transplantation (HCT) can lead to antimicrobial resistance (AMR). Identifying the groups of patients that have the highest likelihood of benefiting from prophylactic antimicrobials is important for antimicrobial stewardship (AMS). We aimed to identify groups of HCT recipients that have the highest likelihood of benefiting from prophylactic fluroquinolones. All admissions for HCT in a tertiary centre between January 2020 and December 2022 ( = 400) were retrospectively studied. Allogeneic HCT (allo-HCT) recipients had prophylaxis with ciprofloxacin during the chemotherapy-induced neutropenia, while autologous HCT (auto-HCT) recipients did not. Bacteraemias were recorded when non-contaminant bacterial pathogens were isolated in blood cultures. Allo-HCT was performed for 43.3 % (173/400) of patients and auto-HCT was performed for 56.7 % (227/400). A bacteraemia was documented in 28.3 % (113/400) of cases. Allo-HCT recipients were more likely to have a Gram-positive bacteraemia (20.8%, 36/173, vs 10.1%, 23/227, = 0.03), while a difference was not observed for Gram-negative bacteraemias (18.5%, 32/173 vs 18.1%, 41/227, = 0.91). Among auto-HCT recipients not receiving ciprofloxacin prophylaxis, patients with germ cell tumours had the highest probability ( for trend 0.09) of recording any bacteraemia (43.5%, 10/23) followed by patients with lymphomas (32.5%, 13/40), other auto-HCT indications (22.2%, 2/9), multiple myeloma (22.1%, 29/131) and multiple sclerosis (12.5%, 3/24). The higher number of bacteraemias in patients with germ cell tumours was primarily driven by Gram-negative pathogens. Ciprofloxacin prophylaxis was associated with a reduced incidence of Gram-negative bacteraemias in allo-HCT recipients. Auto-HCT recipients due to germ cell tumours, not receiving ciprofloxacin prophylaxis, recorded the highest incidence of bacteraemias and represent a possible target group for this intervention.
PubMed: 38922673
DOI: 10.1099/jmm.0.001847 -
Current Oncology (Toronto, Ont.) May 2024Advanced non-small-cell lung cancer (NSCLC) can be treated with novel targeted therapies that are tailored to the genetic characteristics of malignancy. While...
BACKGROUND
Advanced non-small-cell lung cancer (NSCLC) can be treated with novel targeted therapies that are tailored to the genetic characteristics of malignancy. While tissue-based genomic testing is considered the gold standard for the detection of oncogenic driver mutations, several challenges like inadequate tissue availability, the invasiveness of procuring tumors, and prolonged turnaround time of analysis are encountered. Considering these limitations, guidelines have recognized liquid biopsies using circulating cell-free DNA (cfDNA) as a useful tool to complement conventional tissue testing. Even though cfDNA next-generation sequencing (NGS) can have high sensitivity and specificity, optimal patient benefit requires the interpretation of the molecular profiling results in the context of clinical and diagnostic features to achieve the best outcomes.
CASE DESCRIPTIONS
In this case series, we present six patients with advanced NSCLC whose plasma or tissue biopsy samples were analyzed with commercially available comprehensive NGS assays that elucidate the role of testing at various time points in the treatment journey. In all six cases, comprehensive genomic profiling (CGP) provided clinically useful information to guide treatment decisions.
CONCLUSION
Adding to the existing real-world evidence, this case series reinforces that CGP-driven treatment strategies in advanced NSCLC, coupled with other available clinical information, can optimize treatment decisions.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Male; Middle Aged; Female; Aged; High-Throughput Nucleotide Sequencing; Genomics
PubMed: 38920723
DOI: 10.3390/curroncol31060239 -
The Oncologist Jun 2024Daratumumab-hyaluronidase-fihj (Dara-SQ) is frequently used in the treatment of plasma cell disorders and is associated with improved outcomes. Dara-SQ was shown to be...
BACKGROUND
Daratumumab-hyaluronidase-fihj (Dara-SQ) is frequently used in the treatment of plasma cell disorders and is associated with improved outcomes. Dara-SQ was shown to be non-inferior to intravenous daratumumab (Dara-IV) in efficacy, safety, and associated with fewer administration-related reactions (ARRs). Despite the lower ARR risk with Dara-SQ, package labeling still recommends indefinite premedication. In this study, we investigated the safety of premedication discontinuation after one cycle of Dara-SQ.
MATERIALS AND METHODS
This pre-post interventional quality improvement study included all patients aged 18 years and older diagnosed with multiple myeloma or light chain (AL) amyloidosis who received at least one dose of Dara-SQ. Patients in Arm 1 received Dara-SQ per package labeling, while patients in Arm 2 had premedication omitted (excluding dexamethasone) after cycle 1. The primary endpoint was the incidence of ARR after cycle 1. Overall ARR rate and therapy time saved were also evaluated.
RESULTS
A total of 102 patients (63 in Arm 1 and 39 in Arm 2) were included. There were zero reactions in either arm after cycle 1 across 1479 Dara-SQ doses administered over a 30-month period with or without premedication omission. The overall ARR rate was 2.9% (3/102), which all occurred prior to premedication omission. Therapy timed saved from premedication omission was 194 hours in a 6-month period, equating to approximately $140 000 USD.
CONCLUSION
ARRs to Dara-SQ were rare, mild, and occurred during cycle 1 prior to premedication omission. Omission of noncorticosteroid premedication is safe, feasible, and carries substantial time and cost savings for patients and infusion centers.
PubMed: 38920281
DOI: 10.1093/oncolo/oyae158 -
Annals of the Academy of Medicine,... Nov 2023AL amyloidosis is the most common form of systemic amyloidosis. However, the non-specific nature of presenting symptoms requires the need for a heightened clinical... (Review)
Review
AL amyloidosis is the most common form of systemic amyloidosis. However, the non-specific nature of presenting symptoms requires the need for a heightened clinical suspicion to detect unexplained manifestations in the appropriate clinical setting. Early detection and treatment are crucial as the degree of cardiac involvement emerges as a primary prognostic predictor of survival in a patient with AL amyloidosis. Following the diagnosis of AL amyloidosis with appropriate tissue biopsies, prompt treatment with a bortezomib, cyclophosphamide and dexamethasone-based first-line induction with or without daratumumab should be initiated. The goal of treatment is to achieve the best haematologic response possible, ideally with involved free light chain <20 mg/L, as it offers the best chance of organ function improvement. Treatment should be changed if patients do not achieve a partial response within 2 cycles of treatment or very good partial response after 4 cycles or after autologous stem cell transplant, as achievement of profound and prolonged clonal responses translates to better organ response and long-term outcomes. Early involvement of multidisciplinary subspecialists such as renal physicians, cardiologists, neurologists, and gastroenterologists for optimal maintenance and support of involved organs is recommended for optimal management of patients with AL amyloidosis.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Dexamethasone; Singapore; Bortezomib; Cyclophosphamide; Antineoplastic Combined Chemotherapy Protocols; Consensus; Antibodies, Monoclonal; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation
PubMed: 38920149
DOI: 10.47102/annals-acadmedsg.2023101 -
Annals of the Academy of Medicine,... Nov 2023This study aimed to evaluate the clinical utility of positron emission tomography/magnetic resonance imaging (PET/MRI), especially in comparison with PET/computed... (Comparative Study)
Comparative Study
INTRODUCTION
This study aimed to evaluate the clinical utility of positron emission tomography/magnetic resonance imaging (PET/MRI), especially in comparison with PET/computed tomography (CT), which has been widely used in clinical practice in multiple myeloma.
METHOD
F-18 fluorodeoxyglucose PET/MRI and PET/ CT studies were done at baseline and when at least a partial response to treatment was achieved. These were done for newly-diagnosed myeloma patients who have not had more than 1 cycle of anti-myeloma treatment, or for relapsed and/or refractory myeloma patients before the start of next line of therapy.
RESULTS
PET/MRI correlated significantly with PET/CT, in terms of number of lesions detected, standardised uptake value (SUVmean and SUVmax, both at baseline and post-treatment. PET/MRI and PET/CT correlated with survival at baseline, but not post-treatment.
CONCLUSION
In this study, PET/MRI was more sensitive in detecting early disease and disease resolution post-treatment, compared with PET/CT. However, PET/MRI was less sensitive in detecting lesions in the ribs, clavicle and skull.
Topics: Multiple Myeloma; Humans; Magnetic Resonance Imaging; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Male; Female; Middle Aged; Aged; Positron-Emission Tomography; Multimodal Imaging; Radiopharmaceuticals; Adult; Sensitivity and Specificity; Aged, 80 and over
PubMed: 38920148
DOI: 10.47102/annals-acadmedsg.2022414 -
Annals of the Academy of Medicine,... Nov 2023
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Quality Improvement
PubMed: 38920144
DOI: 10.47102/annals-acadmedsg.2023370 -
Journal of Blood Medicine 2024Immune checkpoint inhibitor-related thrombocytopenia (irTCP) is a relatively rare immune-related adverse event (irAE); however, overall survival may worsen when it...
Successful Treatment of Steroid-Refractory Immune Thrombocytopenia in a Patient Developing Multiple Myeloma While on Immune Checkpoint Inhibitor Therapy for Lung Cancer: A Case Report.
Immune checkpoint inhibitor-related thrombocytopenia (irTCP) is a relatively rare immune-related adverse event (irAE); however, overall survival may worsen when it occurs. Prolonged use of high-dose steroids can diminish the effectiveness of immune checkpoint inhibitor (ICI) therapy on the primary disease because of T lymphocyte suppression, thus early tapering is necessary. We experienced a rare case of a 79-year-old male who concurrently developed irTCP and multiple myeloma (MM) during treatment with ICIs for lung adenocarcinoma. The patient exhibited severe thrombocytopenia and elevated serum IgA levels. Based on various tests, we diagnosed MM and irTCP. Despite administering the standard bortezomib plus dexamethasone (Bd therapy) treatment for MM, there was no response and the irTCP was steroid-resistant. Consequently, we administered a regimen including daratumumab (DPd therapy) for steroid-resistant irTCP and refractory MM, which resulted in a response. As a result, we were able to avoid prolonged use of high-dose steroids and the patient is stable without exacerbation of lung adenocarcinoma for 1 year and 5 months after the onset of MM. To our knowledge, there are no cases of MM developing during ICI treatment and this is the first case report in which daratumumab was effective for the treatment of irTCP.
PubMed: 38919949
DOI: 10.2147/JBM.S468921 -
South Asian Journal of Cancer Apr 2024Karuna Jha Multiple myeloma is a cytogenetically heterogeneous, evolving, and incurable disease. Differences in prevalence of myeloma already exist in Indian...
Karuna Jha Multiple myeloma is a cytogenetically heterogeneous, evolving, and incurable disease. Differences in prevalence of myeloma already exist in Indian subcontinent as compared with Western world countries. This study attempts to investigate differences in incidence of cytogenetic abnormalities (CA) in Eastern Indian patients and study differences in incidence with respect to age and gender. Interphase fluorescence in situ hybridization (FISH) was applied on purified plasma cells of 280 newly diagnosed myeloma cases using specific probes. Data was analyzed using SPSS software version 25. Note that 51.07% patients were FISH positive. Del13q was the most common CA. Significant association of del 13q with t(4;14), del 17p, and gain of 1q was seen. The frequencies of FISH positive and negative groups differed in the different age groups; higher number of cases in 41 to 50 years group in FISH positive group ( < 0.05) and lower number of cases in FISH positive group in 61 to 70 years ( < 0.05) as compared with FISH negative group. Del 17p had higher number of cases in age group 41 to 50 years and 51 to 60 years as compared with other age groups. Incidence of t(11;14) was in 5th to 7th decade while del 13q and t(4;14) had the widest range of age at presentation. Gender disparities were seen in high-risk cytogenetics like del 17p and 1q gain. The differences in incidence rate of CAs per se in myeloma cases diagnosed in Indian subcontinent and the differences in incidence with respect to age and gender warrant further multicentric studies.
PubMed: 38919660
DOI: 10.1055/s-0043-1761441 -
Frontiers in Oncology 2024Multiple myeloma (MM) exhibits considerable heterogeneity in treatment responses and survival rates, even when standardized care is administered. Ongoing efforts are...
BACKGROUND
Multiple myeloma (MM) exhibits considerable heterogeneity in treatment responses and survival rates, even when standardized care is administered. Ongoing efforts are focused on developing prognostic models to predict these outcomes more accurately. Recently, neutrophil extracellular traps (NETs) have emerged as a potential factor in MM progression, sparking investigation into their role in prognostication.
METHODS
In this study, a multi-gene risk scoring model was constructed using the intersection of NTEs and differentially expressed genes (DEGs), applying the least absolute shrinkage and selection operator (LASSO) Cox regression model. A nomogram was established, and the prognostic model's effectiveness was determined via Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). The ESTIMATE algorithm and immune-related single-sample gene set enrichment analysis (ssGSEA) were employed to evaluate the level of immune infiltration. The sensitivity of chemotherapy drugs was assessed using the Genomics of Drug Sensitivity in Cancer (GDSC) database. Ultimately, the presence of the detected genes was confirmed through quantitative real-time polymerase chain reaction (qRT-PCR) analysis in MM cell specimens.
RESULTS
64 NETs-DEGs were yielded, and through univariate Cox regression and LASSO regression analysis, we constructed a risk score composed of six genes: CTSG, HSPE1, LDHA, MPO, PINK1, and VCAM1. MM patients in three independent datasets were classified into high- and low-risk groups according to the risk score. The overall survival (OS) of patients in the high-risk group was significantly reduced compared to the low-risk group. Furthermore, the risk score was an independent predictive factor for OS. In addition, interactions between the risk score, immune score, and immune cell infiltration were investigated. Further analysis indicated that patients in the high-risk group were more sensitive to a variety of chemotherapy and targeted drugs, including bortezomib. Moreover, the six genes provided insights into the progression of plasma cell disorders.
CONCLUSION
This study offers novel insights into the roles of NETs in prognostic prediction, immune status, and drug sensitivity in MM, serving as a valuable supplement and enhancement to existing grading systems.
PubMed: 38919521
DOI: 10.3389/fonc.2024.1365460 -
Iranian Journal of Public Health Mar 2024Multiple Myeloma (MM) is a neoplastic hematologic disorder caused by the excessive proliferation of plasma cells and leads to bone lesions, anemia, and kidney failure.... (Review)
Review
Multiple Myeloma (MM) is a neoplastic hematologic disorder caused by the excessive proliferation of plasma cells and leads to bone lesions, anemia, and kidney failure. No definite etiology has been proposed for MM, but several environmental and genetic risk factors have been implicated so far. Exposure to pesticides, benzene, and organic solvents like methyl chloride have been considered a potential risk factor. Asbestos, ionizing radiation, and wood dust exposure have also been associated with MM. As MM is a relatively rare condition, the number of studies is insufficient, and in many studies, only a few study participants recall exposure to any agents. Therefore, establishing a definite risk factor is cumbersome and further studies with large study samples are needed. By recognizing these occupational risk factors, clinicians can encourage employees to reduce their exposure as more as possible and implement precautionary measures. In this review, we highlighted the current research on the potential association between occupational exposures and MM. Because of these studies, new regulations with the goal of occupational exposure reduction are anticipated in the future.
PubMed: 38919290
DOI: 10.18502/ijph.v53i3.15137