Leukemia & Lymphoma最新文献

Polatuzumab vedotin combined with rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) is approved for the treatment of untreated diffuse large B-cell lymphoma (DLBCL); however, safety data in patients aged ≥80 years remain limited. This observational study analyzed Japanese claims data (August 2022-September 2023) to assess safety outcomes in 2,452 patients receiving first-line Pola-R-CHP (n = 843) or R-CHOP (n = 1,609), including 153 and 449 patients aged ≥80 years, respectively. The study focused on infectious events, including febrile neutropenia (FN). FN incidence in patients aged ≥80 years (Pola-R-CHP, 22.9%; R-CHOP, 22.5%) was lower than in those aged 70-79 years (29.7% and 28.5%). This likely reflects strategic dose reductions from Cycle 1, with 92.1% and 97.2% of elderly patients receiving reduced doxorubicin doses, compared with 43.2% and 53.3% in their 70s. With proactive dose adjustments, the safety profile of Pola-R-CHP in patients aged ≥80 years was manageable and comparable to that of younger groups and R-CHOP.

EZH2 is an important epigenetic regulator in malignant neoplasms. We investigated the tumorigenic roles of EZH2 and intracellular molecules in JAK2+/- myeloid neoplasms. EZH2 is upregulated in AML and non-leukemic myeloid neoplasms (M/N) and is associated with H3K27me3 co-expression. EZH2 overexpression is correlated with p-STAT3 and MYC upregulation in JAK2+ M/N, but only with MYC activation in JAK2- M/N. In JAK2+ myeloid neoplasms, p-STAT3, p-ERK1/2, and MYC showed a significantly elevated percentage of tumor cell positivity in AML compared to M/N group. In JAK2- cases, MYC, but not p-STAT3 or p-ERK1/2, showed significantly elevated percentage of tumor cell positivity in AML compared to M/N group. In conclusion, EZH2 plays an oncogenic role through overexpression in its wild-type myeloid neoplasms. EZH2, p-STAT3, MYC, and p-ERK1/2 upregulation associate differently with disease progression depending on JAK2 mutation status. EZH2 and related signaling molecules could serve as potential therapeutic targets in myeloid neoplasms.

Timely diagnosis and treatment are important in lymphoma care. This systematic review examined articles published up to April 2025 which reported intervals from symptom onset to treatment initiation and a subset examining associations with health-related outcomes. Of 11,606 articles screened, 67 were included (23 reported associations). Significant heterogeneity was noted, with 27 intervals reported across various lymphoma subtypes. Methodological issues included poor reporting of interval variability, small sample sizes, and arbitrary interval categorization. Commonly reported intervals included symptom onset to diagnosis (articles; median range), (27; 26-217 days), symptom onset to first presentation (23; 9-91 days), first presentation to diagnosis (17; 15-126 days), and diagnosis to treatment start (25; 1-42 days). Most association studies considered treatment interval and survival, finding inconsistencies. Only few examined the length of diagnostic or patient interval impacts on health outcomes. Future research should apply the Aarhus Checklist - a tool designed to enhance precision and transparency in early cancer diagnosis research to improve the consistency and quality of interval reporting. Further, non-linear interval-survival associations should be explored to capture paradoxical effects.

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare and biologically distinct subtype of diffuse large B-cell lymphoma (DLBCL). It is marked by rare neoplastic B-cells within a prominent inflammatory microenvironment. Historically it was associated with poor prognosis but contemporary reports show outcomes comparable if not better than DLBCL-NOS, especially with the use of chemo-immunotherapies. Autologous stem cell transplantation (auto-HCT) demonstrated favorable progression-free and overall survival in relapsed patients in comparison to matched DLBCL cohorts. The efficacy of CD19-directed CAR T-cell therapy in THRLBCL has been limited, with high relapse rates and poor durability of response, likely due to an immunosuppressive tumor microenvironment characterized by PD-1/PD-L1 pathway activation. Several case series and translational studies support the use of immune checkpoint blockade in selected patients, although prospective validation is needed. While bispecific antibodies, tafasitamab-lenalidomide, and antibody-drug conjugates show promise in R/R DLBCL, THRLBCL patients remain underrepresented in these pivotal trials. This review summarizes current insights into the prognosis of THRLBCL and underscores the need for novel, biologically informed strategies to improve outcomes in the relapsed setting through a deeper understanding of its biology and immune evasion mechanisms.

Bridging radiotherapy (BR) prior to CAR-T for non-Hodgkin lymphoma (NHL) can achieve durable cytoreduction, but optimal dosing remains undefined. We evaluated correlates of local progression (LP) among 33 patients (25 large B-cell lymphoma [LBCL], 8 Mantle Cell Lymphoma [MCL]) with relapsed/refractory NHL who received BR at our institution. Using image-guided radiotherapy (IGRT), we defined 'rapid bridging response' (RBR) as ≥10% volume reduction within 5 fractions. We estimated the cumulative incidence of LP with death as a competing risk. Five of 19 LBCL and 5/7 MCL patients with IGRT experienced RBR. LP occurred in 6 patients (all LBCL, 18-month cumulative incidence 19%), none of whom had RBR, and was increased for tumors with metabolic tumor volume > 100 mL. Among LBCL patients, median volume change during radiation for tumors with LP was 0% vs -4% for those without. Histology, radiomic features, and real-time radiotherapy response may guide a personalized approach to BR.

Primary cutaneous T-cell lymphomas (CTCL) are a rare and heterogeneous group, associated with significant morbidity and mortality. Mycosis fungoides (MF), the most common subtype, typically follows an indolent course, whereas Sézary syndrome (SS) is a leukemic and aggressive variant. Treatment strategies for MF are diverse, stage-dependent, and individualized to the patient. While early-stage disease can be effectively managed with skin-directed therapies, advanced or relapsed/refractory disease is associated with a poorer prognosis and frequently necessitates multiple sequential therapies. Current systemic therapeutic options include immunomodulatory drugs, targeted therapies, and chemotherapy, and are aimed at achieving disease control rather than disease cure. Presently, the only potentially curative treatment option is allogeneic stem-cell transplantation. Regional variation in drug access impacts treatment decisions, whilst the evolving landscape of novel agents continues to challenge current paradigms. This review discusses the underlying biology, clinical features, current and emerging therapeutic strategies for relapsed or refractory MF/SS.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome marked by defective cytotoxic lymphocyte function. While its immunologic features are recognized, the contribution of immunothrombosis is less defined. We analyzed plasma from 12 HLH patients with viral, lymphomatous, and autoimmune etiologies. Hallmark features included hyperferritinemia, cytopenias, hypertriglyceridemia, elevated sIL-2Rα, and acute-phase reactants. Cytokine profiling showed high IL-6, IL-8, IL-10, TNF-α, CRP, and IL-18, with variable IFN-γ. Coagulation studies revealed compensated DIC, elevated FVIIa/antithrombin complexes, and microparticle-bound tissue factor, implying in extrinsic pathway activation. Thrombomodulin shedding and reduced Protein S indicated impaired protein C anticoagulant function. The fibrinolytic system is impaired based on high levels of PAI-1/tPA, and complement activation with consumption of C3. Endothelial dysfunction was evidenced by elevated sVCAM-1, sICAM-1, angiopoietin-2, and decreased ADAMTS13. Elevated plasma SVEP-1 and immunohistochemical evidence of pS6 supported mTORC1 activation in histiocytes. In conclusion, HLH is more accurately described as a "cytokine storm" with pronounced immunothrombosis. The interplay between these 2 processes through multiple, redundant, and reciprocal mechanisms may represent a unifying pathway in HLH pathogenesis and reveal novel therapeutic targets.