Leukemia & Lymphoma最新文献

Waldenström macroglobulinemia (WM) is the most common malignancy associated with an IgM paraprotein, but in rare cases, a clonal IgM may be the result of IgM multiple myeloma (IgM-MM). Although there are some overlapping features associated with these two entities, there are specific characteristics that can help differentiate IgM-MM from WM. In each patient a thorough clinical, pathologic, and genomic evaluation is required to distinguish these conditions and allow for accurate diagnosis and appropriate treatment.

Tonsillar enlargement in chronic lymphocytic leukemia (CLL) either with or without symptoms has been rarely reported. We describe 22 cases of CLL with tonsillar involvement and demonstrate this is a CLL disease site that may be under-recognized in routine practice. Tonsillar involvement can be divided into three categories: (1) symptomatic CLL tonsillar involvement with upper airway obstruction (UAO) requiring therapy managed with: (a) tonsillectomy without systemic therapy when tonsillar enlargement is disproportionate to overall disease state, (b) tonsillectomy and systemic CLL therapy, and (c) standard systemic CLL therapy alone for both UAO and overall CLL state; (2) asymptomatic CLL tonsillar enlargement in proportion to other CLL disease sites not necessarily requiring imminent therapy; and finally, (3) tonsils as the site of Richter's transformation (RT). Tonsillar involvement in CLL can be evaluated by simple clinical examination in most cases, with imaging utilized if there is concern for UAO or RT.

To understand the recent, evolving treatment landscape for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), we retrospectively analyzed US claims data from MarketScan Commercial Claims and Encounters and Medicare databases and Symphony Health Solutions database for adult patients who initiated first-line DLBCL therapy from January 2017 through June 2023 (MarketScan) or May 2024 (Symphony). The MarketScan analysis included 3552 patients (median follow-up: 15 months). The Symphony analysis included 49,370 patients (median follow-up: 35 months). Results from this contemporary real-world analysis showed heterogeneity in DLBCL treatments administered, with a lack of standard of care in the third-line/fourth-line setting. In both analyses, most patients (>50% per line) received rituximab-based therapy as second-line or later-line therapy. These results highlight a need for new regimens that demonstrate clinical benefit and improve overall survival in patients with R/R DLBCL, while also being feasible and widely applicable in routine practice.

B-cell acute lymphoblastic leukemia harboring MEF2D-translocations represents an aggressive subtype with poor prognosis. MEF2D fusion proteins drive leukemogenesis via super enhancer mediated transcriptional dysregulation, making them promising target for epigenetic intervention. BET proteins, especially BRD4, are key regulators of oncogenic enhancer activity. Here, we explored the potential of BET protein inhibition as a targeted therapeutic strategy in MEF2D-HNRNPUL1 translocated B-ALL. Our study revealed that BET inhibitor inhibited proliferation and triggered apoptosis in leukemic cells, by targeting pre-BCR genes in addition to previously demonstrated targets, c-myc and IL-7R. A novel finding is that BET inhibitor induces DNA damage by downregulating DNA repair genes. These findings highlight that anti-leukemic activity of BET inhibitors offers a promising strategy to improve outcomes in this high-risk leukemia subtype.

Leukemia is the most common cancer among children and young adults, accounting for 30% of cases worldwide. Although global studies report geographic and demographic differences in incidence, long-term patterns in northern England remain insufficiently examined. This study investigates leukemia incidence among individuals aged 0-24 years in northern England from 1968 to 2021, considering age, sex, socioeconomic status, and urban-rural residence. Data were obtained from the Northern Region Young Persons Malignant Disease Registry. Incidence rates were calculated by age group (0-14, 15-24 years), sex, deprivation quintiles (Townsend Deprivation Score), and urban-rural status. Temporal trends were assessed using Joinpoint regression to estimate annual percentage changes, and Poisson regression was applied to evaluate demographic and socioeconomic effects. Higher incidence occurred in 0-14-year-olds, especially ages 0-4. Males consistently showed higher rates. Incidence increased annually in 0-14-year-olds but declined after 1995 in 15-24-year-olds. Rural areas showed increased incidence in 2016-2021, whilst there was no significant association with deprivation.

Systemic mastocytosis is a malignant neoplasm classically driven by the KIT D816V mutation. Due to the range of clinical outcomes in these patients, the diagnosis and subclassification of the disease is complex but critical to understanding management, prognosis and therapeutic approaches. In those with non-advanced systemic mastocytosis, treatment decisions are tailored towards symptom improvement, whereas in advanced disease antiproliferative agents become more critical as outcomes resemble that of other myeloid neoplasms. With the advent of novel targeted therapies, the use of these agents have begun to expand their use in both non-advanced and advanced disease. This review will highlight the pathophysiology of systemic mastocytosis and offer a simplified approach to the clinical evaluation and diagnostic criteria to stratify patients by subtype. Further, management approaches in non-advanced, symptomatic disease and those with advanced disease in the era of targeted therapies are reviewed in detail.

Second primary malignancies (SPMs) increasingly affect mantle cell lymphoma (MCL) survivors. In nationwide Danish and Swedish cohorts (2000-2020), we evaluated overall survival among MCL patients with SPMs versus matched non-lymphoma individuals with comparable malignancies and MCL patients without SPMs, respectively. Of 3094 MCL survivors, 19% in Denmark and 15% in Sweden developed an SPM, with a median of three years from MCL diagnosis to first SPM. MCL patients with SPMs had about double the mortality risk compared with non-lymphoma counterparts (pooled HR 2.1, 95% confidence interval (CI) 1.3-3.5), and worse survival than MCL patients without SPMs (pooled HR 1.6, 95% CI 1.4-1.9). In Swedish MCL patients with SPMs, deaths were attributed to subsequent hematologic malignancies (9%), solid cancers (14%), primary MCL (23%), non-cancer causes (11%), with 40% still alive. Development of SPMs in MCL is associated with substantially higher mortality, supporting long-term surveillance and proactive management of late complications.