Leukemia & Lymphoma最新文献

In this review, we focus on the pro-oncogene MYC, the modes of deregulation in mouse and human B-cells, its undisputable importance in the evaluation of biological prognostication of patients, but also how it impacts on response to modern therapeutics, and how it should be targeted to improve the overall survival of chronic lymphocytic lymphoma (CLL) patients. After an overview of the current understanding of the molecular dysregulation of c-MYC, we will show how CLL, both in its indolent and transformed phases, has developed among other B-cell lymphomas a tight regulation of its expression through the chronic activation of B-Cell Receptors (among others). This is particularly important if one desires to understand the mechanisms at stake in the over-expression of c-MYC especially in the lymph nodes compartment. So doing, we will show how this oncogene orchestrates pivotal cellular functions such as metabolism, drug resistance, proliferation and histologic transformation (Richter syndrome).

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity accounting for ≈5% of all Hodgkin lymphoma (HL) cases. As some characteristics of NLPHL resemble B-cell non-Hodgkin lymphoma (B-NHL), nodular lymphocyte-predominant B-cell lymphoma has been proposed as alternative name. Unlike classical HL (cHL), NLPHL is mostly diagnosed in early stages. The clinical course is usually indolent. Overall, NLPHL patients have an excellent prognosis and the majority experiences long-term survival. Except for stage IA disease which is sufficiently treated with radiotherapy alone, treatment of newly diagnosed NLPHL is often very similar to cHL. However, activity has also been demonstrated for rituximab-containing protocols applied in B-NHL. Second-line treatment is chosen individually and mostly less intensive than in cHL. Chimeric antigen receptor T-cell therapy and bispecific antibodies may be part of future treatment strategies for NLPHL. This review aims at summarizing recent data on treatment approaches and discussing future perspectives in NLPHL.

Alterations in the RAS pathway underscore the pathogenic complexity of acute myeloid leukemia (AML), yet the full spectrum, including CBL, NF1, PTPN11, KRAS, and NRAS, remains to be fully elucidated. In this retrospective study of 735 adult AML patients, the incidence of RAS pathway alterations was 32.4%, each with distinct clinical characteristics. Venetoclax combined with hypomethylating agents (VEN + HMA) did not significantly improve response rates compared to intensive chemotherapy (IC) group. In the IC group, PTPN11 mutations in the N-SH2 domain showed a trend toward poorer prognosis, though not statistically significant in multivariate analysis, while NRAS mutations correlated with improved outcomes. In the VEN + HMA group, PTPN11 mutations in the N-SH2 domain emerged as an independent adverse prognostic marker. NRAS or KRAS mutations showed no survival advantage compared to wild-type, aligning with their intermediate-risk classification in the 2024 ELN guidelines. These findings emphasize the need for treatment-specific risk stratification for RAS pathway mutations in AML.

Anti-CD19 chimeric antigen receptor (CAR) T-cell therapies have demonstrated high efficacy in pediatric patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Despite this success, the challenge of post-infusion relapse persists. In our study, we evaluate 116 children with R/R B-ALL who received anti-CD19 CAR T-cell therapy at our center. All patients were included in the response analysis and assessed for survival and toxicity. The CR rate was 98.3%, with 90.5% achieving minimal residual disease negative (MRD)^- CR by day 28 (d28). The overall survival (OS) and event-free survival (EFS) were 69.3%±4.5% and 59.0%±4.6%, respectively, with a median follow-up duration of 47.9 months. The patients with pre-infusion MRD ≥ 1% was associated with lower 4-year OS (p = 0.006) and EFS (p = 0.027) comparing to those with MRD < 1%. The incidences of grade ≥ 3 cytokine release syndrome (CRS) and neurotoxicity were21.6 and 5.0%, respectively. Therefore, pre-infusion disease burden is a predictor of long-term outcome following anti-CD19 CAR T-cell therapy for pediatric R/R B-ALL.

Despite significant advancements in multiple myeloma (MM) treatment, including novel therapies and combination strategies, the translation of findings from randomized controlled trials (RCTs) into real-world clinical practice has been associated with several challenges. Specifically, the principles and criterion that shape the current design of MM RCTs have left out a sizable portion of patients that would particularly benefit from trial inclusion. In addition, RCTs may use primary outcomes which only partially cover patient-relevant endpoints important for evaluating treatment efficacy and quality of life. In this review, we explore the current MM RCT landscape and suggest possible solutions to improve generalizability of trial results, mitigate logistical pitfalls, and integrate real-world evidence into trials. Together, these strategies are designed to refine MM treatment guidelines and improve outcomes for all patient populations.