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.

This study aimed to identify germline pathogenic variants in the KMT2A, SAMD9, SAMD9L, ANKRD26, and ATG2B genes among patients with acute myeloid leukemia. The study included 92 patients with de novo AML. A novel, likely pathogenic germline variant was identified in the SAMD9 gene in one patient. Additionally, germline variants of uncertain significance were detected in four patients: one in KMT2A, two in ANKRD26, and one in ATG2B. The median age at AML diagnosis was six years younger in patients carrying germline variants compared to those without. The identification of AML susceptibility genes enhances our understanding of the disease pathogenesis, aids help with recognizing in recognizing individuals at elevated risk, forms the basis for genetic counseling and patient management, assists in selecting suitable donors for allogeneic hematopoietic stem cell transplantation, and supports the development of targeted therapeutic strategies.

Smoldering multiple myeloma (SMM) is a biologically diverse precursor to multiple myeloma (MM), characterized by varying risks of progression. Several validated risk stratification models help identify patients at the highest risk, who may benefit from early treatment at the precursor stage. Current guidelines recommend treatment with lenalidomide, with or without dexamethasone, or participation in clinical trials for patients with high-risk SMM. Recent data also support using daratumumab monotherapy, which has been shown to significantly delay progression to MM. However, uncertainties remain about the long-term benefits of early intervention, especially regarding its effects on overall survival, quality of life, and the risk-benefit ratio in this asymptomatic group. This review discusses current risk stratification models for SMM, summarizes evidence from key clinical trials on prevention strategies, and highlights the evolving landscape of ongoing research.

Multiple myeloma (MM) remains incurable, largely owing to the lack of effective therapeutic targets. Wilms' tumor 1-associated protein (WTAP) has been implicated in MM tumorigenesis, but its underlying molecular mechanisms remain unclear. This study aimed to elucidate the role of WTAP in MM progression. Bone marrow samples from newly diagnosed MM patients were analyzed. WTAP expression was assessed via Quantitative real-time PCR (qRT-PCR) and Western blot. Cell proliferation was evaluated using EdU and flow cytometry assays, while RNA immunoprecipitation (RIP) confirmed protein interactions. WTAP was overexpressed in MM patients and correlated with poor survival. Its knockdown significantly suppressed MM cell proliferation and inflammation. RIP assays identified MAP6D1 as a potential WTAP target. RNA-seq analysis suggested WTAP regulates MM proliferation via the Hippo signaling pathway. WTAP promotes MM proliferation by targeting MAP6D1 and modulating the Hippo pathway, highlighting its potential as a therapeutic target.

Patients with non-Hodgkin lymphoma (NHL), especially younger individuals, can face fertility risks from treatment. We assessed rates and predictors of fertility counseling and preservation in this population. The LEO cohort prospectively enrolled newly diagnosed NHL patients (2015-2020) at eight U.S. academic centers. We assessed responses to a 3-year survivorship questionnaire in those aged 18-50 at diagnosis; logistic regression evaluated predictors of fertility counseling. Of 77 respondents included (46% female, median age 40), 72.2% of females and 58.5% of males recalled having a fertility discussion at diagnosis. Fertility counseling was more likely to occur in those aged 18-39 versus 40-50 (OR 10.2, 95% CI 3.3-39.2) and in those receiving alkylating therapy (OR 9.0, 95% CI 2.3-45.5). Interventions are still needed to ensure adequate survivorship care.

Adult histiocytic disorders are rare, and limited data exists on spectrum, clinical presentation and real-world management strategies. Here, we present Canadian single-center experience spanning over 23 years. Ninety-six patients were identified, with Langerhans Cell Histiocytosis (LCH; n = 60), Erdheim-Chester disease (ECD; n = 11); Rosai-Dorfman disease (RDD; n = 19) constituting the majority. At a median follow-up of 38 months, median OS of our cohort was not reached with encouraging 5-year OS of 96.3%, 79.5% and 86% amongst LCH, ECD and RDD patients respectively. Although, 5-year PFS rates were higher for LCH and RDD compared to ECD patients (61.7% vs 47% vs 24.2%; p = 0.320), these were not statistically significant. LCH patients with RO involvement had inferior 2-year PFS compared to those without (33.3% vs 75.8%; p = 0.042). A high incidence of concomitant hematological malignancies, (n = 3/11 in ECD and n = 3/60 in LCH) in our cohort warrants the need for further translational studies to explore possible association.

Whilst T-cell directed therapies have revolutionized the therapeutic landscape in triple-class refractory multiple myeloma, ongoing long-term safety concerns remain, including the risk of second primary malignancy (SPM) development. We systematically evaluated the incidence and distribution of SPMs in R/R MM patients post T-cell-directed therapy. MEDLINE, EMBASE, and Cochrane CENTRAL databases were searched for clinical trial and real-world studies reporting outcomes for patients infused with either chimeric antigen receptor (CAR) T-cell or bispecific antibody therapies reported until March 2025. Patient-specific characteristics and SPM outcomes were extracted from eligible studies with calculation of point estimate confidence intervals (CIs) achieved via the Clopper-Pearson Exact Method. A total of 12 studies (7 RCTs and 5 RWS) were eligible for analysis, encompassing a total of 2743 adult R/R MM patients. Eleven studies were related to CAR T-cell therapy, with only 1 study reporting on bispecific antibody therapy. The pooled SPM point estimate for CAR T-cell therapy was 6.3%, with hematological malignancies representing the most common subtype. This highlights the potential risk of SPMs in patients eligible for T-cell directed therapy. Further robust, prospective clinical trial and pharmacovigilance data will continue to inform the true level of risk in this cohort of patients.

T-cell engagers (TCE) have altered the therapeutic landscape for relapsed/refractory multiple myeloma (MM). Yet, patients in the real-world may have been ineligible for pivotal studies and TCEs are not widely accessible. A single-center retrospective study of 79 patients treated with teclistamab, talquetamab, or elranatamab was conducted. Forty-six percent had high-risk cytogenetics, 42% had EMD, and 44% had prior BCMA-exposure. ORR was similar to trials, 64%. PFS and OS were 4.44 and 13.3 months, respectively - both substantially shorter than clinical trials. On univariate analysis, having Medicare supplemental, secondary insurance, or advantage plans was associated with improved OS, but this did not persist on multivariate. Income below the NJ median and lack of accompaniment trended toward inferior OS. Achieving less than a PR to the last line was associated with inferior PFS/OS. Prospective studies should evaluate earlier utilization of TCEs and increasing early access for patients with low income.

We report on a series of three patients diagnosed with secondary acute lymphoblastic leukemia (sALL) following treatment for multiple myeloma (MM) where serial, commercially available, next-generation sequencing (NGS) based tracking of measurable residual disease (MRD) using the clonoSEQ assay provided valuable clinical insight. Each of the patients in this series had been treated for their MM with regimens that had included autologous stem cell transplantation following high dose melphalan chemotherapy and had been on maintenance treatment with the immunomodulatory drug lenalidomide for at least one year.

Radiotherapy (RT) is increasingly used as bridging therapy before CD19-targeted CAR-T infusion in large B-cell lymphoma, but its clinical role remains uncertain. We conducted a systematic review and meta-analysis of 16 studies involving 488 patients with large B-cell non-Hodgkin lymphoma who received bridging RT. Pooled estimates showed an overall response rate (ORR) of 74.6% and complete response (CR) rate of 55%. The 1-year progression-free survival (PFS) and overall survival (OS) rates were 57.7% and 72.1%, respectively. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 76.8% and 36.9% of patients, with grade ≥3 events in 6.7% and 19.1%, respectively. Compared with systemic bridging, RT was associated with superior survival, while outcomes were comparable to non-bridging cohorts. These findings suggest that bridging RT is a feasible, well-tolerated, and potentially advantageous in selected patients undergoing CAR-T therapy.