Leukemia & Lymphoma最新文献

Chimeric Antigen Receptor T-Cell (CAR-T) therapy is an effective therapy and promising frontier in the treatment of hematologic malignancies. However, this revolutionary treatment has led to new challenges for patients, caregivers, and the healthcare system. In this review article, we discuss the various difficulties patients face both in the acute and long-term period following CAR-T infusion. We highlight the various ways these difficulties are addressed, as well as further areas of research and support needed to improve patient experience. Additionally, we consider the difficulties and burdens placed on caregivers and healthcare systems, as well as barriers to accessing CAR-T therapy. Finally, we address future directions of research and intervention development to meet patient and caregiver needs and improve equitable access. We pose early integration of specialty palliative care for individuals and their caregivers undergoing CAR-T therapy as one promising strategy to help improve patient experience and meet their needs.

Treatment of chronic lymphocytic leukemia (CLL) has been revolutionized with the introduction of small molecule inhibitors targeting both the B-cell receptor (BCR) signaling pathway and B-cell lymphoma-2 (BCL-2) family of proteins. Inhibitors of Bruton's tyrosine kinase (BTK) and the BH3 mimetic venetoclax are bothcurrently used as the standard of care for patients in the frontline and relapsed/refractory setting of CLL. With the clinical success of both these classes of therapies, sequencing of these agents has become a major challenge in treatment of CLL. In this review we will discuss the current data available for both classes of agents in the front-line and relapsed/refractor setting, considerations when giving these agents, and how we can continue to improve the treatment landscape for CLL.

Patients with relapsed/refractory primary central nervous system lymphoma (R/R PCNSL) usually have a poor prognosis and limited treatment options. We respectively reviewed 38 patients with R/R PCNSL treated with zanubrutinib-based regimens in our center. The overall response rate, complete response rate and disease control rate were 76.3%, 47.4% and 92.1%, respectively. The median progression-free survival (PFS) was 31.0 months, the median overall survival (OS) was not reached. Unitivariate analysis by Cox's proportional hazards model revealed that overall response (vs. no response, HR = 0.18, 95%CI:0.07,0.48, p = 0.001), long duration of zanubrutinib (≥6months vs 2-5 months, HR = 0.20, 95%CI:0.06,0.63, p = 0.006) were independent factors for prolonged PFS. The log-rank analysis indicated a prolongation of PFS among patients exhibiting a higher Tumor mutational burden (TMB, ≥14.75muts/Mb) following zanubrutinib-based treatment (p = 0.016). Our data showed promising efficacy with tolerable safety of zanubrutinib-based therapies in patients with R/R PCNSL. Long duration of zanubrutinib may be associated with prolonged PFS.

Various aspects of myeloproliferative chronic myelomonocytic leukemia (MP-CMML) and myelodysplastic CMML (MD-CMML) have been reported but inconsistencies remain. This study conducted a comprehensive retrospective analysis of clinical, pathological, and molecular data from a cohort of CMML. The results revealed a higher frequency of ASXL1 and NRAS mutations and a greater mutation burden in MP-CMML, characterized by more tier 1 or 2 variants and dominant mutations. Significant genotype-phenotype correlations were observed, including distinct patterns within MD-CMML subgroups. Additionally, NRAS or RUNX1 mutations and an abnormal karyotype were associated with worse overall survival or progression-free survival. These findings underscore the distinct molecular and pathological differences between MP-CMML and MD-CMML, highlighting the more aggressive nature of MP-CMML and the need for tailored treatment strategies.

In this study, we aimed to uncover novel biomarkers in acute myeloid leukemia (AML) that could serve as prognostic indicators or therapeutic targets. We analyzed AML microarray datasets from the Gene Expression Omnibus (GEO) repository, identifying key differentially expressed genes (DEGs) through the robust rank aggregation (RRA) approach. The functions of these DEGs were elucidated through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Additionally, the CIBERSORT algorithm was employed to assess immune cell infiltration in AML. Six hub genes were identified using the cytoHubba plugin, and their clinical significance, survival impact, and meta-analyses were conducted. Through comprehensive bioinformatics and qPCR analyses, we gained new insights into AML pathogenesis and metastasis, identifying FCGR3B, FLT3, EREG, and MMP9 as potential prognostic biomarkers. Antagonists targeting FCGR3B, FLT3, and MMP9, or agonists for EREG, hold promise as therapeutic and preventative strategies for AML.