Leukemia & Lymphoma最新文献

Multiple myeloma (MM) is a plasma cell cancer characterized by genomic instability and drug resistance. The FOXM1 transcription factor and the BUB1B kinase are pivotal drivers of this malignancy. FOXM1 promotes cell cycle progression and is upregulated by oncogenic pathways like mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT, correlating with aggressive disease. BUB1B ensures proper chromosome segregation, and its dysregulation fuels genomic instability. Critically, FOXM1 transcriptionally regulates BUB1B, forming an oncogenic axis that enhances proliferation, drug resistance, and survival. This FOXM1-BUB1B pathway is a promising therapeutic target, with inhibitors under preclinical investigation. Future research must validate its clinical relevance, explore combination therapies, and assess its potential as a biomarker to overcome challenges like toxicity and resistance.

Waldenström macroglobulinemia (WM) is the most common malignancy associated with an IgM paraprotein, but in rare cases, a clonal IgM may be the result of IgM multiple myeloma (IgM-MM). Although there are some overlapping features associated with these two entities, there are specific characteristics that can help differentiate IgM-MM from WM. In each patient a thorough clinical, pathologic, and genomic evaluation is required to distinguish these conditions and allow for accurate diagnosis and appropriate treatment.

This study aimed to identify the clinical characteristics, risk factors, and prognostic determinants of intracranial hemorrhage (ICH) in adult patients with acute leukemia (AL). We conducted a retrospective analysis of 3751 AL patients (aged ≥14 years) treated at our institution between 2010 and 2024. Independent risk factors for ICH included AL subtype, platelet count (PLT) <50 × 10⁹/L, leukocytosis (WBC >100 × 10⁹/L), elevated lactate dehydrogenase (LDH >245 IU/L), and prolonged prothrombin time (PT ≥3 s). The median overall survival (OS) in the ICH group was markedly shorter than in the NICH group (1.0 vs. 38.0 months, p < 0.001). Among non-APL patients, leukocytosis (WBC >100 × 10⁹/L), thrombocytopenia (PLT <50 × 10⁹/L), APTT prolongation ≥10 s, and increased D-dimer (DDI) level (≥9 μg/mL) were independent risk factors for ICH, while increased DDI level (≥9 μg/mL) was associated with poor prognosis. These findings emphasize the importance of early risk stratification and targeted interventions to reduce the risk of ICH.

Chronic lymphocytic leukemia (CLL) exhibits heterogeneous clinical outcomes influenced by chromosomal aberrations and genetic mutations. NOTCH1 and SF3B1 mutations are critical prognostic markers linked to disease progression and therapy resistance. This study analyzed 60 CLL patients from Hiwa Hospital (Sulaymaniyah, Iraq). Hematological parameters were assessed, and genomic DNA was sequenced for NOTCH1 exon 34 and SF3B1 exons 15-16. In silico pathogenicity was predicted using I-Mutant and PolyPhen-2. Mutations were found in 23.3% of patients (14/60), including the recurrent NOTCH1 c.7541_7542delCT (p.P2514Rfs) (10%) and SF3B1 c.2098A > G (p.K700E) (6.6%). Two novel NOTCH1 variants (PX317668 and PX317669) were also identified. Mutated cases showed advanced Binet stages, elevated LDH, and reduced hemoglobin (HGB) and platelet (PLT) counts. These findings reveal a notable prevalence of NOTCH1 and SF3B1 mutations associated with adverse features, expanding the CLL mutational spectrum and offering valuable prognostic and therapeutic insights.

This prospective, phase I trial evaluated the safety and efficacy of linperlisib plus chidamide in patients with relapsed/refractory peripheral T-cell lymphoma (r/r PTCL). Linperlisib was administered at three dose levels (40, 60, and 80 mg) following a standard "3 + 3" scheme. Fourteen patients were enrolled, including six with peripheral T-cell lymphoma, not otherwise specified and eight with nodal T-follicular helper lymphoma. No dose-limiting toxicities occurred. Linperlisib 80 mg daily was selected as the recommended phase II dose. The most common grade ≥3 adverse events were hematologic. Gastrointestinal toxicities improved with chidamide dose reduction. Among 14 efficacy-evaluable patients, the overall response rate was 64.3%, with a complete response rate (CRR) of 50.0%. With a median follow-up time of 13.0 months, median duration of response (DOR), progression-free survival, and overall survival (OS) were not reached. In conclusion, linperlisib plus chidamide demonstrated a favorable safety profile and encouraging preliminary efficacy in r/r PTCL.

Characterization of real-world outcomes in ruxolitinib-treated patients with myelofibrosis and anemia is limited. This retrospective analysis of the US Flatiron Health electronic health record-derived deidentified database focused on patients with myelofibrosis who did or did not have anemia and received ruxolitinib. More baseline anemic vs nonanemic patients received <20 mg/day of ruxolitinib throughout the first 3 months post baseline (25% vs 16%), and baseline anemic patients had numerically shorter times to first dose reduction (median, 5.6 vs 12.8 months) and discontinuation (16.7 vs 24.8 months). Median survival was significantly shorter in baseline anemic vs nonanemic patients (37.4 vs 64.9 months [p < .001]) and in patients receiving ruxolitinib <20 vs ≥20 mg/day (40.1 vs 53.1 months [p<.05]). Regardless of baseline anemia, patients with new/worsening anemia on ruxolitinib had significantly worse survival (HR, 1.68 [95% CI, 1.18-2.40]; p<.01), suggesting that alternative therapies to ruxolitinib warrant evaluation in patients with myelofibrosis and anemia.

Outcomes for adults with Philadelphia chromosome positive pre-B cell acute lymphoblastic leukemia (Ph + B-ALL) have improved dramatically, but questions remain regarding the optimal induction regimen and role of allogeneic hematopoietic cell transplantation (alloHCT). We analyzed 60 consecutive patients who received reduced-intensity (RII) or hyper-CVAD induction with continuous, second-generation tyrosine kinase inhibitors (TKIs). Reduced hematologic toxicity occurred after RII. Measurable residual disease (MRD) clearance by multicolor flow cytometry (MFC, 61 vs. 94%, p = 0.02) favored hyper-CVAD, but subsequent MRD-directed blinatumomab negated this difference. Four-year relapse-free survival (RFS) was 72.3% (95% confidence interval: 57.4-91.0%) and 79.8% (65.4-97.3%, p = 0.3) in RII and hyper-CVAD groups, respectively. AlloHCT, predominantly using reduced-intensity conditioning, bone marrow grafts, and post-transplant cyclophosphamide, was the only variable associated with improved overall survival on multivariate analysis. Concurrent chemotherapy and TKIs followed by blinatumomab for MRD positivity and alloHCT, all in less intensive forms, yield excellent outcomes for patients with Ph + B-ALL.