Leukemia & Lymphoma最新文献

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.

AMN006 is a prospective, single-arm, phase 2 study evaluating the efficacy and safety of daratumumab, bortezomib, and dexamethasone (DVd) in elderly, transplant-ineligible (TI) patients with newly diagnosed multiple myeloma (NDMM). The primary end point was overall response rate (ORR); secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. 27 patients were enrolled between October 2019 and September 2021. Treatment comprised fixed-duration DVd (9 months) followed by daratumumab maintenance until progression or toxicity. At a median follow-up of 27 months, the ORR was 96.3%, ≥CR in 29.6% and VGPR in 51.9%. Among patients achieving ≥ CR, 7/8 were MRD-negative (sensitivity 10^-5). Median PFS was 36.5 months; median OS was not reached. The regimen was well tolerated, with treatment-emergent adverse events related to study drugs in 22% of patients. These findings support the feasibility of time-limited DVd and daratumumab maintenance as an effective and tolerable frontline approach for TI NDMM patients.

Trial Registration: NCT03695744.

Acute myeloid leukemia (AML) cells depend on nicotinamide adenine dinucleotide (NAD⁺) biosynthesis via nicotinamide phosphoribosyltransferase (NAMPT) for survival. Single-cell RNA sequencing revealed robust NAMPT expression across diverse AML subtypes. Proteomic profiling showed that NAMPT inhibition with KPT-9274 induced adaptive upregulation of BCL2, an anti-apoptotic protein, highlighting a survival mechanism. BH3 profiling confirmed that AML cells hierarchically depend on BCL2, followed by MCL1 and BCLxL, for survival. Combining KPT9274 with the BCL2 inhibitor venetoclax synergistically enhanced mitochondrial dysfunction, cytochrome C release, and apoptotic death in AML blasts. Additionally, NAMPT inhibition reduced PARP activity and impaired DNA repair pathways, sensitizing AML cells to cytarabine and hypomethylating agents. Together, these results demonstrate that NAMPT inhibition both potentiates venetoclax activity and enhances the cytotoxic effects of standard chemotherapies by targeting metabolic and DNA repair vulnerabilities. These findings provide strong preclinical support for evaluating NAMPT and BCL2 dual inhibition strategies in future AML clinical trials.

Febrile neutropenia (FN) is a common complication of chemotherapy and potentially fatal. It is often associated with mucositis. Timely recognition of complications enables early supportive treatment and potentially reduces mortality. Common diagnostic parameters are often nonspecific or have slow kinetics. This study examines the applicability of mucosa-related biomarkers in the recognition of complicated course among 78 adult hematologic patients with FN after intensive chemotherapy. Plasma concentrations of citrulline, intestinal fatty acid binding protein (I-FABP), zonula occludens-1 (ZO-1) and alpha-1 acid glycoprotein (α₁AGP), as well as C-reactive protein (CRP) and procalcitonin (PCT), were measured at the onset of fever and the following two days. All except ZO-1 showed a significant trend. Concentrations of CRP, PCT, citrulline and α₁AGP were higher with a complicated course. Patients with severe sepsis had higher levels of PCT and lower levels of I-FABP. In conclusion, measurement of mucosa-related biomarkers might help predict the course of FN.

We retrospectively analyzed 293 adults with multiple myeloma treated at a tertiary public center (2002-2024; 65% men; median age 58). Kaplan-Meier for survival estimation and Cox proportional-hazards models for associations. Median follow-up was 2.9 years; 47 (16%) underwent autologous stem-cell transplantation (ASCT). Overall survival (OS) at 3, 5, and 10 years were 84%, 76%, and 60%. ASCT was associated with higher unadjusted 10-year OS (74.1% vs 56.1%; p = 0.007), but was not significant after adjustment (p = 0.20). In multivariable analyses, higher hemoglobin was protective (HR 0.79; 95% CI 0.67-0.92; p = 0.003), and higher lactate dehydrogenase was associated with mortality (HR 1.63 per 100 U/L; 95% CI 1.13-2.36; p = 0.010). Progression-free survival (PFS) was assessed in all patients; 134 PFS events occurred, and the median PFS was 3.9 years. Findings support LDH-informed risk stratification and timely ASCT referral in resource-limited settings and suggest a pragmatic, FISH-free prognostic approach incorporating hemoglobin where cytogenetics are unavailable.