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.

As the survival of patients with Chronic Myeloid Leukemia (CML) on tyrosine kinase inhibitors (TKIs) is comparable to healthy counterparts, it is now being treated as a chronic disease. Hence, there is significant concern of the effect of TKI on fertility and pregnancy outcomes. While the teratogenic effects of TKIs are well established, data on their impact on male fertility remain limited. With a growing number of CML patients of reproductive age being diagnosed annually, understanding the effect of Imatinib on male fertility is crucial. To study the effect of Imatinib (TKI) on the Pituitary gonadal axis and sperm parameters in CML patients, as there is limited data in this area. A prospective cohort study (Oct 2018-Jan 2021) included 30 male CML-CP patients (18-60 years). Patients were excluded if they had known dysfunction of the pituitary-gonadal axis, structural abnormalities of the gonads, or a history of prior sterilizing treatments. After receiving imatinib treatment for 3 months, out of these 30 patients, sperm concentration declined in 22 (73.3%), though only 5 (22.7%) had oligospermia (<15 million/ml), and none had severe oligospermia (<5 million/ml). Among these 5 patients, 4 were aged ≤35 years, while 1 was older than 35 years. Progressive motility decreased in 11 patients, with 6 (54.5%) dropping below the reference range (<32%), potentially causing infertility. Vitality decreased in 13 patients. Out of these, in 10 patients, vitality dropped below the reference range (<58%). Normal sperm morphology declined in 16 patients, but in only 2 patients it fell below 4%. Post-Imatinib treatment, two patients had elevated FSH, while LH and testosterone levels remained normal in all. Although there was a mild decrease in mean values of post-imatinib samples, there was no statistically significant decrease in mean FSH (p-value = 0.106), LH (p-value = 0.080), or testosterone levels (p = 0.313). Mean sperm concentration reduced after imatinib treatment, though it was not significant (p-value = 0.080). Mean progressive motility increased, but the change was not significant (p = 0.059). Mean sperm vitality increased, but it was not significant (p-value = 0.264). Also, there was no significant correlation found between hormonal changes and sperm parameters. Imatinib therapy was associated with a decline in sperm concentration, progressive motility, vitality, and normal morphology in some patients; however, no statistically significant changes were observed in mean hormonal or semen parameters. Patients planning families should nonetheless be counselled regarding the potential impact of TKIs on sperm quality. While sperm cryopreservation is not routinely recommended, its role in selected patients warrants evaluation in larger and long-term studies.

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.