Leukemia & Lymphoma最新文献

VEXAS syndrome is a recently described entity characterized by systemic inflammatory and hematologic manifestations. The disease was first characterized by Beck et al. in 2020 in a study characterizing 25 patients with undiagnosed adult-onset inflammatory syndromes. While the literature regarding VEXAS syndrome has grown exponentially since 2020, there is still much to be understood. This lack of information leads to challenges in both the diagnosis and treatment of patients with VEXAS syndrome. Patients will often have a variety of clinical symptoms that can lead to missed or delayed diagnoses. Additionally, awareness of VEXAS syndrome is still developing among clinicians. In this comprehensive review, we summarize the current literature regarding VEXAS syndrome, and explore clinical updates of this emerging disease state. Our aim of this review is to increase awareness regarding this new disease state and identify research areas to better understand future treatment approaches for patients with VEXAS syndrome.

Outcomes in adult and pediatric patients with acute lymphoblastic leukemia (ALL) have improved over successive generations due to rigorously conducted clinical trials and incorporation of novel therapeutic agents. Despite these advances, approximately 20% of high-risk pediatric patients and 50% of adults with ALL will fail to achieve long-term remission with frontline chemotherapy protocols, mostly due to relapse. The ability to predict which patients with ALL are more likely to relapse allows for early intensification of therapy and/or incorporation of novel immunotherapies with the goal of relapse prevention. In this review, we outline the most robust clinical predictors of relapse in ALL with a focus on measurable residual disease (MRD) and genomics. We also discuss application of these prognostic tools in different clinical settings including frontline treatment, pre-/post-allogeneic stem cell transplant, and pre-/post-Chimeric Antigen Receptor T-cell therapy.

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and adolescents and in recent decades, the survival rates have risen to >90% in children largely due the introduction of risk adapted therapy. Therefore, knowledge of factors influencing risk of relapse is important. The transcription factor IKAROS is a regulator of lymphocyte development and alterations of its coding gene, IKZF1, are frequent in ALL and are associated with higher relapse risk. This concise review will discuss the normal function of IKAROS together with the effect of gene alterations in ALL such as relieved energy restriction and altered response to anti-leukemic drugs. Besides the biology, the clinical impact of gene alterations in the different subtypes of ALL will be discussed. Finally, possibilities for treating ALL with IKZF1 alterations will be considered including novel therapies like cell signaling inhibitors and immunotherapy.

Plasma cell neoplasms (PCN) have infrequently been reported in patients with myelodysplastic syndrome (MDS) and even more rarely in those with myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN). We report the clinicopathologic features of 26 patients with bone marrow myelodysplasia accompanied by PCN, including 21 patients with MDS and 5 with MDS/MPN. The clinicopathologic features of the MDS/MPN-PCN were compared to those of the MDS-PCN group and 68 cases of MDS/MPN without PCN, respectively. The MDS/MPN-PCN group was notable for increased reticulin fibrosis > grade 1 when compared to both the MDS/MPN (p = 0.007) and MDS-PCN (p = 0.02) groups. MDS/MPN-PCN was associated with worse overall survival when compared with MDS-PCN (p = 0.03) and but not with MDS/MPN. Notably, hemoglobin level <8 g/dl (p = 0.008), and IDH2 somatic mutation (p = 0.003) were independent predictors of poor overall survival in all patients with MDS/MPN. Analysis of larger cohorts is required to confirm these associations and provide an insight into the pathogenesis.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults and characterized by a highly heterogeneous clinical course. The CLL-IPI and the OCLL-1 scores are among the best validated tools to predict time-to-first-treatment. In both models, elevated beta-2-microglobulin plasma level (B2M) is an independent prognostic factor. Yet, B2M is commonly increased in patients with chronic kidney disease (CKD) per se and both models were not adjusted for CKD. We analyzed the clinical outcomes of 297 treatment-naive CLL patients between 2000 and 2022. B2M was more frequently elevated in CKD patients and lost prognostic significance at the threshold > 2.5 mg/L. Both CLL-IPI and OCLL-1 failed to facilitate prognostic segregation in CKD patients. 22.2% of CKD patients were assigned to a higher CLL-IPI risk group due to elevated B2M. Our results suggest that both models overestimate the risk for disease progression and need to be interpreted with caution in CKD patients.

In chronic lymphocytic leukemia (CLL), TP53 mutations or deletions on chromosome 17p lead to adverse prognosis and reduced levels of miR-34a, which targets NOTCH1. Also, hyperactivated NOTCH1 signaling is crucial for CLL progression. Here we explored the interaction between p53, miR-34a, and NOTCH1 in CLL. We investigated the effect of p53 and miR-34a on NOTCH1 signaling and expression in CLL cells with altered TP53. Our results indicate that miR-34a reduces NOTCH1 3' UTR activity but might not be a mediator between p53 signaling and NOTCH1. p53 activation increases miR-34a expression and NOTCH1 protein levels, correlating with decreased NOTCH1 and miR-34a levels in primary CLL cells with TP53 alterations. Some samples with high NOTCH1 levels presented increased BCL-2, suggesting an anti-apoptotic mechanism of a potentially direct p53-NOTCH1 relation in CLL. This study deepens the understanding of the p53-miR-34a-NOTCH1 signaling network, providing insights that could guide future therapeutic strategies for CLL.

Tumor lysis syndrome (TLS) in childhood leukemia was assessed retrospectively in 252 patients in a single tertiary center in Thailand during 2009-2019. Fifty-one (20.2%) developed TLS during their induction chemotherapy; 60.7% (31/51) were spontaneous TLS and 47% (24/51) developed clinical TLS. The predictive score model consisted of white blood cell (WBC) count more than 50,000 cells/mm³, glomerular filtration rate less than 90, and aspartate transaminase more than 44 units/L. The TLS development rates were 11.1%, 46.2%, and 78.5% in the low, intermediate, and high-risk groups, respectively. Death during the first induction phase in patients with TLS was significantly higher than in the patients without TLS. However, the 5-year overall survival rates for the children with and without TLS were not significantly different.

Reactive pleocytosis in the CSF has been observed with blinatumomab but has not been well-described. We performed a retrospective study of 88 patients who received intrathecal chemotherapy (IT) while on blinatumomab with CSF analyzed to determine if pleocytosis had an impact efficacy and safety. Blinatumomab was used for relapsed/refractory 62.5%, MRD-positive 31.8%, and consolidation in MRD-negative 5.7%. The incidence of pleocytosis in CSF was 51% and was more frequent after day 15 (55.8% vs. 18.2%, p = 0.025). Pleocytosis did not impact CR, clearance of MRD positivity, PFS and OS rates. Lower incidence of non-CNS extramedullary relapse was seen (3.7% vs. 30.8%, p = 0.011) with pleocytosis in CSF. Analysis of CSF by flow cytometry showed median CD4:CD8 ratio of 1.34. In conclusion, CSF pleocytosis is prevalent with blinatumomab but only demonstrated lower rates of non-CNS extramedullary relapse but no impact on CNS relapse or neurotoxicity.