Hematological Oncology最新文献

Previous studies have shown that the pre-transplant C-reactive protein (CRP)/platelet ratio (CP ratio) is a predictor of survival. The aim of this multicenter retrospective study was to evaluate the clinical significance of CP ratio in patients with malignant lymphoma (ML) who underwent allogeneic hematopoietic stem cell transplantation (alloHCT). The cohort included patients with ML who underwent first alloHCT from 2007 to 2021. CP ratio was defined as CRP [mg/dL]/platelet [10^4/μL] and evaluated prior to alloHCT. The cutoff value for CP ratio was set at 0.05 based on previous studies. A total of 311 cases were analyzed, of which 134 were mature B cell lymphoma, 177 were T/NK cell lymphoma (including 70 cases of adult T-cell leukemia/lymphoma), and 17 were Hodgkin's lymphoma. The median age was 53 years (range: 17–69 years). High CP ratio was associated with status of disease, presence of infections, poor performance status at alloHCT, and high transfusion volume received prior to alloHCT. Overall survival (OS) at 2 years according to CP ratio (low vs. high) was 61.1% versus 30.1% (p < 0.001), non-relapse mortality (NRM) was 21.4% versus 40.7% (p = 0.001), and the relapse rate was 23.7% versus 32.6% (p = 0.061), respectively. In multivariate analysis, the high CP ratio group was associated with poor OS (HR = 2.20, 95% CI: 1.61–3.02, p < 0.001) and higher NRM (HR = 1.90, 95% CI: 1.28–2.81, p = 0.0014). High CP ratio was found to be associated with poor post-transplant OS and NRM, and was a suitable prognostic biomarker for stratifying the risk of patients with ML who are candidates for alloHCT.

Diffuse large B-cell lymphoma (DLBCL) is the most prevalent adult lymphoma, which exhibits aggressive clinical behavior with rapid progression. Accumulating evidence implicates microRNAs (miRNAs) in the pathogenesis of various human tumors. Investigating miR-29a-3p expression and mechanism may reveal novel therapeutic targets for DLBCL pathogenesis and monitoring. The levels of miR-29a-3p in DLBCL tissue, serum and cell samples were determined by PCR reactions. ROC curve reflected the screening ability of miR-29a-3p for DLBCL patients. The target of miR-29a-3p was verified by dual-luciferase activity assay. Transfection assays were employed to upregulate miR-29a-3p and MCL1 expression, followed by functional characterization using CCK-8, Transwell assays and flow cytometry. miR-29a-3p is downregulated in DLBCL, which has a high potential to identify DLBCL patients. MCL1 is a validated miR-29a-3p target prominently expressed in DLBCL. miR-29a-3p mimic notably suppressed DLBCL cell activity and adverse behavior, which was partially counteracted by MCL1 overexpression. High levels of miR-29a-3p target MCL1 to prevent DLBCL cell malignant behavior, highlighting that miR-29a-3p/MCL1 axis may be a candidate therapeutic and monitoring marker for DLBCL.

Although allogeneic hematopoietic stem cell transplantation (allo-HCT) is considered a potentially curative therapy for multiple myeloma, disease progression after allo-HCT remains a major limitation. Post-transplant maintenance therapy may help reduce the risk of relapse. Lenalidomide, an immunomodulatory agent, has demonstrated efficacy in multiple myeloma, but its use after allo-HCT is limited due to concerns regarding graft-versus-host disease (GVHD). To evaluate the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of lenalidomide when used as maintenance therapy after allo-HCT for multiple myeloma. This was a prospective, multicenter, phase I/II clinical trial conducted from 2014 to 2019. Lenalidomide maintenance therapy was initiated 100–365 days post-allo-HCT. Eligible patients received lenalidomide on days 1–21 of a 28-day cycle for at least four cycles, beginning at 5 mg/day. A standard 3 + 3 dose-escalation design (Fibonacci method) was used to determine DLT and MTD. The study included 10 patients; one was excluded due to early disease progression, leaving nine patients evaluable for toxicity. The phase II portion was not conducted due to expiration of the trial period. The median interval from allo-HCT to initiation of lenalidomide was 244 days (range, 169–330 days). At the 10 mg/day dose level, one patient experienced moderate chronic GVHD meeting the predefined criteria for DLT. No other DLTs occurred, establishing the MTD at 10 mg/day. No acute GVHD was observed. Two additional patients developed mild chronic GVHD, which resolved spontaneously without treatment. The 2-year progression-free survival (PFS) and overall survival (OS) rates from the start of maintenance therapy were 53% and 78%, respectively. Late initiation of lenalidomide maintenance therapy after allo-HCT for multiple myeloma was feasible at a dose of 10 mg/day and was associated with a low incidence of GVHD-related complications. However, further studies are required to confirm treatment efficacy.

Diffuse large B-cell lymphoma (DLBCL), the most aggressive non-Hodgkin lymphoma subtype, is cured in 60%–70% of patients with frontline chemoimmunotherapy. For refractory/relapsed cases, deciphering DLBCL's molecular drivers could unveil new therapies to overcome resistance and enhance survival. Interferon regulatory factor 3 (IRF3) is a transcription factor that drives type I interferon responses, crucial for antiviral defense against DNA and RNA viruses. Emerging evidences implicate IRF3 in the malignant progression of gastric cancer, hepatocellular carcinoma, and multiple myeloma. However, its biological role and prognostic significance in DLBCL need further investigation. Here, we examined the expression level of IRF3 in DLBCL patient samples. Functional impact on proliferation was assessed by MTS and EdU assays, while mechanistic insights were obtained through cell cycle analysis and apoptosis evaluation. As a result, IRF3 expression was significantly elevated in DLBCL patients compared to controls and correlated with poorer clinical outcomes. Notably, increased expression of IRF3 induced by poly I:C or poly dA:dT enhanced DLBCL cells proliferation, whereas IRF3 knockdown suppressed this effect. Furthermore, IRF3 promoted G1/S phase transition by upregulating cyclin D3 and CDK4 expression. Collectively, IRF3 regulates DLBCL cell proliferation by controlling G1/S transition via cyclin D3 and CDK4. Thus, our study identifies IRF3 as a novel regulator of DLBCL proliferation, highlighting its potential as a therapeutic target in DLBCL.

Retrospective subgroup analyses can introduce significant bias in the estimation of hazard ratios (HRs), particularly when patient distributions across treatment arms are imbalanced. Such disparities can distort the validity of HR outcomes, especially in the presence of unequal risk group compositions and varying treatment assignment probabilities. These factors may artificially shift HR estimates across different risk populations, leading to misleading correlations between subgroup classifications and treatment effects. To quantify this phenomenon, we conducted Monte Carlo simulations across 1000 trials, demonstrating how hazard ratios vary systematically with changes in the underlying risk group population. These findings underscore the need for caution in interpreting HRs from subgroup analyses and highlight the importance of robust trial design to mitigate bias.