Leukemia & Lymphoma最新文献

The therapeutic landscape of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is rapidly evolving. Novel immunotherapies and targeted therapies have expanded treatment options and improved outcomes for patients with historically limited effective options. These advances raise important questions regarding sequencing, patient selection, and mechanisms of resistance. At the same time, frontline therapy is shifting toward biomarker-informed and risk-adapted approaches, with interim imaging and circulating tumor DNA increasingly incorporated into trial design. As advanced therapies move earlier in the treatment paradigm, the biology of relapse is expected to evolve, requiring reevaluation of therapeutic sequencing in the R/R setting. This review summarizes relevant prognostic factors and highlights the evolving therapeutic landscape, with a focus on both current practice and future directions in the management of R/R DLBCL.

Acute graft-versus host disease (aGVHD) is a major early complication of allogeneic hematopoietic cell transplantation and is associated with substantial morbidity and mortality, particularly in severe cases. The use of corticosteroids as first-line therapy remains standard of care, despite limited efficacy in high-risk cases and associated toxicities. Ruxolitinib has emerged as the treatment of choice for patients who fail corticosteroids, but there remains a need for novel treatment strategies. In this review, we examine the evolving therapeutic landscape of aGVHD and summarize emerging approaches including small molecule inhibitors, biologics, and cellular- and microbiome-modulating therapies. We explore how improved understanding of aGVHD pathophysiology continues to inform new interventions while also addressing the operational and conceptual challenges that constrain clinical trial design and regulatory progress. Finally, we discuss new innovations in biomarker-driven strategies and adaptive clinical trial designs that may facilitate future therapeutic development and advance outcomes for patients with aGVHD.

We evaluated serum soluble B-cell maturation antigen (sBCMA) levels in 67 Waldenström macroglobulinemia (WM) patients, healthy controls, and individuals with IgM-MGUS, IgM-multiple myeloma, other B-cell neoplasms, and reactive hypergammaglobulinemia. WM patients had higher sBCMA levels (median 100 ng/mL) compared to healthy controls (41.4 ng/mL, p < 0.001). Symptomatic WM patients had a higher level of sBCMA than asymptomatic patients (133 vs 73.8 ng/mL, p < 0.001). Asymptomatic WM did not progress to symptomatic disease when sBCMA was in MGUS level (<65 ng/mL). There was strong correlation between bone marrow CD20+ cell counts and sBCMA levels (ρ = 0.73), while serum IgM levels showed weaker correlation (ρ = 0.55). sBCMA levels demonstrated parallel changes with IgM levels when assessing treatment efficacy. Notably, IgM flares following rituximab administration or plasma exchanges had a minimal impact on sBCMA levels. These findings suggest that sBCMA is a decent biomarker of tumor burden, offering a reliable predictor of clinical outcomes in WM patients.

Patients treated with intensive induction therapy for acute myeloid leukemia (AML) traditionally remain admitted until count recovery, however, select patients may be safe for 'early' discharge. We evaluated sequential patients with newly diagnosed AML treated with intensive induction at Yale Cancer Center from December 2016 to January 2024 and eligible for an early discharge program (EDP). Amongst 185 patients, 99 (53.5%) were discharged with an absolute neutrophil count (ANC) <0.5 x 10³/µL. An ANC ≤0.1 x 10³/µL at discharge (N = 54) was used to define patients furthest from hematologic recovery. These patients had fewer inpatient days accounting for re-admissions (23%) before count recovery (23.5 vs 28.0 days, p = 0.0003). Most readmissions (92%) were for febrile neutropenia and uncomplicated. Ultimately, there were no differences in 90-day mortality, or median overall survival between patients with ANC ≤0.1 x 10³/µL at discharge and non-EDP patients. An EDP is feasible and safe for select patients.

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.