Objective Diffuse large B-cell lymphoma (DLBCL) features significant clinical and molecular heterogeneity, and current molecular biomarkers are insufficient for precise prognostic stratification. DNA methylation is well-validated in solid tumor diagnosis but its value in DLBCL prognosis remains unclear. The purpose of this study was to evaluate the predictive value of bone marrow RASSF1A, P16, and PAX5 methylation detection for prognosis in patients with diffuse large B-cell lymphoma (DLBCL). Methods A total of 60 newly diagnosed DLBCL patients and 61 controls were retrospectively enrolled. Methylation-specific real-time fluorescent PCR (MS-PCR) was used to detect the methylation status of RASSF1A, P16, and PAX5 in pre-treatment bone marrow samples. The optimal threshold and AUC values were determined by ROC curve analysis. The correlations between methylation results and complete blood count, endocrine-related metabolic indicators, treatment regimens, and immunohistochemical markers were analyzed. Factors affecting patient prognosis were screened through LASSO and Cox regression. Results The methylation levels of RASSF1A, P16, and PAX5 showed varying degrees of correlation with pre-treatment complete blood count and endocrine-related metabolic indicators. In the CART treatment group, the positive rates of P16 and PAX5 methylation were significantly lower than those in the untreated group (P < 0.05), while in the transplantation treatment group, only the positive rate of P16 methylation was significantly reduced (P = 0.011). In terms of immunohistochemistry, the positive rates of RASSF1A and P16 methylation were significantly elevated in the Ki67-positive group (P < 0.05), the positive rates of all three methylation markers were significantly elevated in the CD34-positive group (all P < 0.05), the positive rates of P16 and PAX5 methylation were significantly elevated in the CD56-positive group (P < 0.01), and only the positive rate of P16 methylation was significantly elevated in the P53-positive group (P = 0.047). LASSO regression and multivariate Cox regression analysis showed that RASSF1A methylation (HR=0.921, P = 0.022), P16 methylation (HR=0.933, P = 0.042), and Ki67 proliferation index (HR=1.042, P < 0.001) were independent predictors of PFS, while CD56 expression showed a positive correlation trend (HR=2.866, P = 0.062). Conclusion Bone-marrow-based gene methylation markers may act as candidate epigenetic biomarkers for risk stratification in DLBCL. Given limitations of this single-center retrospective study with limited outcome events, our results cannot yet support direct clinical judgement for hematopoietic stem cell transplantation. Further multi-center external validation is required before clinical translation. Bone marrow gene methylation detection shows promising research value for prognostic evaluation of DLBCL.
Background This study compared real-world outcomes of patients with chronic myeloid leukemia in chronic phase (CML-CP) treated with asciminib and first/second generation (1 G/2 G) tyrosine kinase inhibitors (TKI) as second-line treatment (2 L) in the US. Methods A retrospective panel-based chart review from oncologists/hematologists was conducted on adult patients with CML-CP in 2 L treated with asciminib or 1 G/2 G TKIs between January 2022-June 2023 (index period). Entropy balancing was used to adjust baseline characteristics between asciminib and 1 G/2 G TKI cohorts. Time to discontinuation, progression to accelerated phase/blast crisis (AP/BC), BCR::ABL1 ≤ 0.1% (MMR), and BCR::ABL1 ≤ 0.01% (MR4) post-index were assessed using weighted Kaplan-Meier analyses and Gehan-Breslow tests. Results De-identified data on 255 patients (median age: 62.0, female: 43.5%, White: 56.1%) in the asciminib cohort were collected from 76 physicians (community/academic: 47.4/52.6%) and 233 patients (median age: 62.0, female: 43.3%, White: 56.2%) in the 1 G/2 G TKI cohort from 72 physicians (community/academic: 41.7/58.3%). By 48 weeks post-index, fewer patients in the asciminib (4.6%) versus 1 G/2 G TKI (10.4%) cohort experienced discontinuations (p = 0.07), and no patients progressed to AP/BC in the asciminib versus 4.2% in the 1 G/2 G TKI cohort (p < 0.05). By 48 weeks post-index, 68.3% of the asciminib versus 59.8% of the TKI cohort achieved or maintained MMR, and 40.6% versus 22.0% for MR4. Median time to MMR (MR4) was 30.7 (59.7) and 39.7 (72.7) weeks for the asciminib and 1 G/2 G TKI cohorts, respectively (all p < 0.05). Conclusions Findings from this large real-world US study suggest that 2 L asciminib offers favorable tolerability and better effectiveness compared with 1 G/2 G TKIs for patients with CML-CP.
Background Myelodysplastic syndromes (MDS) can impose indirect and out-of-pocket costs on patients and informal carers despite NHS treatment being free at the point of care. No MDS-specific estimate of this burden has been identified for England. Methods A prevalence-based, bottom-up cost-of-illness model was developed for England in 2024 GBP. Costs were stratified by transfusion dependence and included gross out-of-pocket travel and parking costs, informal caregiver time valued at the National Living Wage, and an illustrative patient productivity scenario. Parameters were taken from NICE documents, published MDS literature, ONS earnings data, HMRC mileage rates and NHS parking guidance. Results The prevalent MDS population in England was estimated at 9000 patients, including 3150 transfusion-dependent (TD) and 5850 transfusion-independent (TI) patients. Gross annual direct costs were £ 469 per TD patient and £ 170 per TI patient, giving a population total of £ 2.5 million. Informal caregiver time was the main cost component, at £ 12,625 per TD patient and £ 3032 per TI patient, or £ 57.5 million nationally. Direct and carer costs totalled £ 60.0 million per year. An illustrative productivity scenario added £ 6.7 million, raising the total to £ 66.7 million. Combined direct and carer costs were 4.1 times higher for TD than TI patients. Conclusions MDS-related financial burden in England is driven mainly by informal carer time and is concentrated among TD patients. These findings support prospective measurement of financial toxicity and caregiver burden in MDS studies, and highlight the patient-side economic value of achieving transfusion independence.
Adult acute lymphoblastic leukemia (ALL) outcomes remain inferior to pediatric results, motivating adoption of pediatric-inspired regimens (PIR) in adults. The optimal frontline regimen for high-risk subgroups, such as Philadelphia chromosome-like (Ph-like) ALL, has not been established. In this retrospective analysis, 160 adults with Philadelphia chromosome-negative B-cell or T-cell ALL treated between 2013 and 2024 received either the USC-ALL regimen, a pediatric-inspired protocol incorporating synchronized pegaspargase and high-dose methotrexate during two induction and six consolidation cycles followed by two years of POMP maintenance, or Hyper-CVAD. The cohort was predominantly Hispanic (77.2%) and 33.8% Ph-like, with median age 34 years and median follow-up 40.3 months. The USC-ALL regimen resulted in significantly higher rates of measurable residual disease (MRD) negativity by flow cytometry at complete remission (80.7% vs 50.0%, p = 0.002) and at the end of induction (79.5% vs 54.3%, p = 0.004). Three-year disease-free survival (DFS) favored USC-ALL (62.3% vs 36.7%; HR 2.15, p = 0.004), with a lower cumulative incidence of relapse (CIR; 34.3% vs 57.7%; HR 1.95, p = 0.019) and no difference in overall survival (OS). The DFS advantage remained significant in multivariate analysis adjusting for age, ALL subtype, and end-of-induction MRD status (HR 1.84, p = 0.031). The benefits were most pronounced in patients younger than 40 years and with Ph-like disease, where USC-ALL improved 3-year OS (89.8% vs 59.3%), DFS (65.3% vs 22.0%), and CIR (30.4% vs 68.4%). Pegaspargase toxicities were consistent with previous PIR experience. These results support pediatric-inspired, asparaginase-based regimens as preferred frontline therapy in adult ALL, particularly for Ph-like disease.
