Leukemia & Lymphoma最新文献

Multiple myeloma is a hematologic malignancy that predominantly affects older individuals, in whom frailty is prevalent. Frailty is a clinical syndrome characterized by decreased reserve and increased vulnerability to stressors, leading to decreased functional capacity. Frailty is prevalent in older individuals and negatively impacts treatment outcomes. In this review, we summarize the tools and strategies used to assess frailty in patients with multiple myeloma, review data describing treatment outcomes in frail adults with multiple myeloma using clinical trial and real-world evidence and evaluate the potential relationship of frailty with quality of life and patient-reported outcomes during therapy for multiple myeloma. Frailty-adapted therapy for MM has the potential to improve treatment outcomes for older adults with myeloma.

Myelodysplastic syndromes (MDSs) treatment focuses on improving quality of life (QOL), affected by anemia and transfusion dependence (TD). Using the MDS-CAN registry, we studied how changes in transfusion status - TD to transfusion independence (TI) (group A), or vice versa (group B), and maintaining TD (group C) or TI (group D) - affected OS and QOL in 1120 MDS patients. Analysis showed superior OS for those remaining TI, poorer for those remaining TD, and intermediate for those with changes. Among 656 treated patients, group A (n = 54) showed improved QOL, with trends toward improved physical and social function scores. Group B (n = 151) experienced declines in global QOL measures after switching to TD, particularly in fatigue and physical, role, and social functioning. Group C had notable fatigue worsening, while group D showed milder declines across multiple QOL aspects. Achieving TI in MDS correlates with improved QOL, whereas reverting to TD more significantly worsens overall QOL and function scores.

Acute myeloid leukemia (AML) is a heterogeneous group of malignancies with poor prognosis. AML result from the proliferation of immature myeloid cells blocked at a variable stage of differentiation. Beyond inter-patient heterogeneity, AMLs are characterized by genetic and phenotypic intra-patient heterogeneity. Despite major advances in deciphering AML biology with bulk sequencing studies, pivotal questions remain unanswered. Analyses at the single-cell level could thus transform our understanding of these neoplasms. We review recent progresses in single-cell sequencing technologies from cell processing to bioinformatic pipelines. We next discuss how single-cell applications have helped understand the genetic and functional intra-leukemic heterogeneity, emphasizing aspects related to leukemic stem cells, clonal evolution and measurable residual disease (MRD) monitoring. We finally delineate how single-cell technologies could be implemented in routine clinical practice to improve patient management.

For fixed-duration therapies against chronic lymphocytic leukemia (CLL), undetectable measurable residual disease (MRD) predicts overall and progression-free survival more accurately than complete remission. For indefinite therapies, MRD status can direct discontinuation of treatment. We systematically reviewed the relationship between antineoplastic drug exposures and undetectable MRD in CLL. Seventeen trials from MEDLINE and EMBASE met the inclusion criteria; four of which evaluated drug exposures in relation to MRD status. Undetectable MRD was associated with higher trough concentrations of ofatumumab and alemtuzumab, as well as increased maximum concentration and area under the plasma concentration curve (AUC) of ibrutinib. One study found an association between high rituximab AUC and undetectable MRD until adjusting for tumor burden. The limited studies, lack of exposure measurements of concomitant drugs, and high heterogeneity in designs limit the results' generalizability. Further research is needed to explore the exposure-MRD relationship and the possibility for therapeutic drug monitoring in CLL.

Multiple myeloma (MM), a malignant plasma cell disorder, remains incurable due to inevitable chemo-resistance development, including carfilzomib (CFZ) leading to relapse and poor patient outcomes. Therefore, new treatment strategies, including using FDA-approved alcohol deterrent disulfiram (DSF) are under investigation. The present study investigated the effect of DSF on ferroptosis and CFZ resistance in MM cells. Our findings indicate that DSF increases the production of cytosolic and mitochondrial reactive oxygen species, and causes a loss of mitochondrial Δψ and an elevation in lipid peroxidation in MM cells. DSF treatment in MM cell lines led to the significant downregulation of ferroptotic genes, including glutathione peroxidase 4. Moreover, ferroptosis inhibitor liproxstatin-1rescued DSF-induced ferroptosis by promoting glutathione peroxidase 4 upregulation. DSF alone overcomes CFZ resistance through lipid peroxidation elevation and acts synergistically with CFZ in CFZ-resistant MM cell lines. Our results suggest that DSF is a promising anti-myeloma agent for overcoming CFZ resistance in MM through ferroptosisinduction.