Leukemia & Lymphoma最新文献

In chronic lymphocytic leukemia (CLL), T cell dysfunction is a hallmark feature and includes impaired proliferation, reduced cytotoxicity, defective immunological synapse formation, and metabolic exhaustion. While these alterations have been well described, the underlying mechanisms remain incompletely understood. By contrast, in the field of solid tumor immunotherapy, extensive research has yielded detailed mechanistic insights into how tumors evade T cell immunity, particularly by interfering with T cell receptor (TCR) signaling at multiple levels. This review examines whether the mechanisms of T cell dysfunction uncovered in solid oncology can inform our understanding of T cell failure in CLL. By aligning TCR defects in CLL with insights from solid tumors, we identify mechanistic explanations for T cell failure in CLL that warrant further investigation. These include non-canonical checkpoint signaling, recruitment of inhibitory phosphatases, and impaired propagation of activation signals. Understanding these pathways may enable rational design of next-generation immunotherapies for CLL.

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.

We classified 45 AML patients not considered fit for intensive treatment into 3 groups: standard dose VEN (Group A), shorter duration of VEN (Group B), and dose reduction of VEN (Group C). CRc rates were 58, 73, and 72% in Groups A, B, and C, respectively. EFS and OS were significantly shorter in Group A than in Groups B and C. The incidence of FN and severe neutropenia was lower in Groups B (73% and 27%) and C (78% and 44%) than in Group A (92% and 67%). The number of treatment cycles was lower in Group A (7.5) than in Groups B (10.2) and C (15.5). The present study showed that shortening the duration and reducing the dose of VEN may reduce the risk of complications and be as effective as standard dose VEN for the treatment of AML patients not considered fit for intensive treatment.

Cord blood transplantation (CBT) is an alternative donor option for patients lacking suitable matched donors, particularly in high-risk acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). We retrospectively analyzed 76 adults undergoing reduced-intensity conditioning allogeneic transplantation using one of five donor types: CBT with ultra-low-dose methotrexate (uldMTX; n = 47), matched related donor (MRD), matched unrelated donor (MUD), mismatched unrelated donor (MMUD), or mismatched related donor (MMRD) (n = 29 across the four donor types). Two-year overall survival (OS) with uldMTX-CBT (58.8%) was significantly superior to MRD, MUD, and MMRD transplantation, with similar patterns for disease-free survival (DFS). In multivariate analyses, CBT remained independently associated with improved OS and DFS. Neutrophil and platelet recovery were comparable across donor types, as were the incidences of graft-versus-host disease and non-relapse mortality. These findings indicate that CBT provides a safe and effective donor platform with competitive outcomes across diverse alternative donor settings in high-risk AML/MDS.