Leukemia & Lymphoma最新文献

The R-MPV regimen-comprising rituximab, methotrexate, procarbazine (PCZ), and vincristine-followed by reduced-dose whole-brain radiotherapy and high-dose cytarabine, is an established treatment for primary central nervous system lymphoma (PCNSL). However, PCZ is occasionally omitted due to adverse events, and its prognostic impact remains unclear. Among 91 patients with PCNSL treated at our institution between 2008 and 2020, we analyzed 60 adults who completed the R-MPV regimen. The 5-year progression-free survival (PFS) rate for the entire cohort was 67.6%. PCZ was discontinued in 17 of the 60 patients. The 5-year PFS rate was significantly higher in patients who completed PCZ compared with those who discontinued it (81.2% vs. 46.3%; p = 0.00487). PCZ discontinuation was associated with inferior PFS in both univariable and multivariable analyses. These findings suggest that maintaining the full PCZ dose during R-MPV treatment may be critical for achieving favorable survival outcomes in patients with PCNSL.

The t(16;21)(q24;q22) translocation creates the RUNX1::RUNX1T3 (also known as CBFA2T3, MTG16) fusion gene, representing a rare but clinically significant subtype of myeloid neoplasms. This comprehensive study presents detailed clinical, immunophenotypic, cytogenetic, and molecular data from 10 new cases while integrating findings from 35 previously reported cases. Patients showed a median age of 48 years with notable female predominance. Immunophenotypic analysis consistently demonstrated a distinctive hybrid myeloid/B-lymphoid phenotype characterized by CD19 co-expression with myeloid markers. Cytogenetic evaluation revealed additional chromosomal abnormalities in 75.6% of cases, with trisomy 8 being most frequent (42.2%). Next-generation sequencing identified recurrent mutations in ASXL1 (50%), TET2, JAK2, and NRAS (each 25%). Clinically, this fusion strongly correlated with therapy-related myeloid neoplasms and demonstrated significantly worse survival outcomes compared to RUNX1::RUNX1T1 AML, highlighting its distinct clinicopathological features and adverse prognostic implications.

Autologous stem cell transplantation (ASCT) remains central in multiple myeloma, yet the optimal CD34⁺ infusion dose is uncertain. We retrospectively analyzed 176 newly diagnosed patients undergoing ASCT. Survival was estimated by Kaplan-Meier, and predictors were assessed by Cox regression. Among ASCT patients, a high CD34⁺ dose (≥5 × 10⁶/kg) was associated with superior progression-free survival (PFS, p = 0.020), OS (p < 0.001), deeper responses (p = 0.034), and sustained minimal residual disease (MRD) negativity (p = 0.001). High dose correlated with oligoclonal bands formation (OB, p = 0.038), indicating immune reconstitution. Patients exhibiting both high CD34⁺ dose and OB constituted the best OS (p < 0.001). In multivariate analysis, CD34⁺ ≥5 × 10⁶/kg independently predicted superior PFS (p = 0.014) and OS (p < 0.001). In sum, CD34⁺ ≥5 × 10⁶/kg is a practical dosing target that couples immune reconstitution via OB formation to durable post-ASCT survival, with no incremental benefit above 10.64 × 10⁶/kg.

High-dose cytarabine given on days 1, 3, and 5 (HDAC-135) is a mainstay of consolidation treatment for acute myeloid leukemia (AML). Recent evidence indicates that consecutive daily dosing (HDAC-123) accelerates hematologic recovery and reduces hospitalization duration without compromising survival. However, the impact of HDAC-123 on infection outcomes is unclear. We performed a retrospective analysis of 73 AML patients undergoing HDAC consolidation, including 24 (33%) patients aged ≥60 years. Thirty-six patients received HDAC-135, and 37 received HDAC-123. HDAC-123 was associated with a shorter duration of neutropenia (8 versus 10 days, p < .001), fewer neutropenic infections (58% versus 79%, p = .02), and a reduced cumulative number of bacteremia episodes per patient (1.54 versus 3.30, p = .03), particularly from Gram-negative pathogens (1.22 versus 3.15, p = .003) compared to HDAC-135. HDAC-123 was well tolerated across all ages and demonstrated improvements in infection-related complications, supporting its use as a safe and effective consolidation strategy in AML.

Vincristine remains central in adult acute lymphoblastic leukemia (ALL) therapy but frequently requires dose adjustments due to toxicity. We retrospectively analyzed 96 adults (median age 29.5 years, range 17-68) treated from 2014-2023 at a Mexican tertiary center. Overall, 79.2% had at least one vincristine dose reduction, more frequent with pediatric-inspired regimens (87.3% vs. 63.6%, OR 3.93, 95% CI 1.41-10.96, p = 0.015). Clinically significant peripheral neuropathy (PN) was reported in 35.1% before maintenance and persisted in 37% at last follow-up, associated with age ≥30 years (OR 6.78, 95% CI 2.07-22.2, p = 0.002) and cumulative vincristine >53 mg (OR 5.29, 95% CI 1.41-19.85, p = 0.014). Despite these adjustments, outcomes were unaffected: median OS was 55.2 months with dose reduction vs. 44.5 months without (HR 0.87, p = 0.707), and median EFS 40.1 vs. 19.0 months (HR 0.64, p = 0.158). Vincristine reductions did not compromise survival, supporting reevaluation of dosing to balance efficacy and long-term toxicity.

Acute lymphoblastic leukemia (ALL) has high relapse rates, requiring new therapies. Quercetin, a natural flavonoid, exhibits anti-cancer potential, but its mechanisms in ALL, particularly involving miRNAs, are unclear. This study explores quercetin's effects and its role in regulating the miR-367/KLF4/JNK axis. Using ALL cell lines and xenograft models, quercetin's efficacy was assessed. It inhibited tumor growth in mice and induced apoptosis and autophagy in vitro. Mechanistically, quercetin downregulated miR-367, leading to upregulation of KLF4, which subsequently suppressed JNK signaling to promote cell death. In vivo results confirmed that quercetin suppresses ALL progression via this pathway. These findings identify quercetin as a potent anti-leukemic agent targeting the miR-367/KLF4/JNK axis to induce cell death. This reveals a novel regulatory pathway in ALL and highlights quercetin's potential as a miRNA-based therapy.

Acute lymphoblastic leukemia (ALL) is among the most curable pediatric cancers, yet relapse involving the central nervous system (CNS) remains a major therapeutic obstacle. In this prospective cohort, 97 children (aged 1.1-18.2 years) experiencing their first CNS relapse were enrolled in the ALL-IC REL study. Relapses were classified as isolated CNS (i-CNS, n = 43) or combined CNS (c-CNS, n = 54), and patients received treatment through standard- or high-risk regimens, encompassing chemotherapy, cranial irradiation, and allogeneic stem cell transplantation. The estimated 2-year event-free survival was 40.0%, and overall survival 49.4%, closely matching outcomes reported internationally. Survival rates were comparable across i-CNS and c-CNS relapses, while induction failure occurred more frequently in c-CNS. Multivariable analysis identified female sex, T-cell phenotype, and very early relapse as independent predictors of poor prognosis. These results underscore the critical necessity for risk-adapted therapy techniques and the incorporation of innovative medicines into forthcoming procedures.