Leukemia & Lymphoma最新文献

Second primary malignancies (SPMs) increasingly affect mantle cell lymphoma (MCL) survivors. In nationwide Danish and Swedish cohorts (2000-2020), we evaluated overall survival among MCL patients with SPMs versus matched non-lymphoma individuals with comparable malignancies and MCL patients without SPMs, respectively. Of 3094 MCL survivors, 19% in Denmark and 15% in Sweden developed an SPM, with a median of three years from MCL diagnosis to first SPM. MCL patients with SPMs had about double the mortality risk compared with non-lymphoma counterparts (pooled HR 2.1, 95% confidence interval (CI) 1.3-3.5), and worse survival than MCL patients without SPMs (pooled HR 1.6, 95% CI 1.4-1.9). In Swedish MCL patients with SPMs, deaths were attributed to subsequent hematologic malignancies (9%), solid cancers (14%), primary MCL (23%), non-cancer causes (11%), with 40% still alive. Development of SPMs in MCL is associated with substantially higher mortality, supporting long-term surveillance and proactive management of late complications.

Among patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL), those who failed to respond to CD19-directed immunotherapies, there are limited options available pre-HSCT. This study aimed to evaluate the efficacy and safety of Inotuzumab ozogamicin (InO) as the definitive treatment pre-HSCT in patients with R/R B-cell B-ALL. Sixteen patients were enrolled, ten of whom failed treatment with prior CD19-directed immunotherapies, and two of whom relapsed after first HSCT. All patients achieved morphologic complete remission; 13 patients achieved negative measurable residual disease after InO. After bridging to HSCT, the 1-year probabilities of leukemia-free survival and overall survival were 66.5% and 80.8%. One patient developed sinusoidal obstruction syndrome post-HSCT. The prognosis for patients with R/R B-ALL, particularly those who do not respond to prior immunotherapies, is very poor. InO serves as an effective and safe bridging therapy prior to HSCT.

This clinical trial evaluated assess the efficacy and safety of combination therapy with the BCL-2 antagonist venetoclax and the demethylase inhibitor azacitidine in 440 patients diagnosed with multiple myeloma. The primary endpoints included overall response rate (ORR), complete response (CR) rate, progression-free survival (PFS), and safety profile. The venetoclax-azacytidine combination demonstrated comparable efficacy, with enhanced depth of response in patients with high-risk cytogenetic abnormalities. Adverse events were generally manageable, with neutropenia observed in 25% and fatigue in 30% of patients. Minimal residual disease (MRD) negativity and specific cytogenetic markers, such as t(11;14), were identified as significant independent predictors of favorable treatment response. The therapy demonstrated clinical benefit with a manageable toxicity profile, suggesting potential utility as a treatment option in selected patient subgroups. However, the need for longer follow-up and expanded cohorts remains critical to validate these outcomes and optimize patient selection. These findings support the further exploration of venetoclax and azacitidine as a viable treatment option for patients with refractory or high-risk multiple myeloma, warranting additional prospective trials before consideration for standard-of-care implementation.

T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) remains a challenging malignancy with poor prognosis. Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains a key curative option, but the optimal conditioning regimen is unclear. We retrospectively analyzed 93 T-ALL/LBL patients undergoing allo-HCT between January 2010 and July 2023, including 72 with modified busulfan plus cyclophosphamide (mBuCy) and 21 with total body irradiation plus cyclophosphamide (TBI-Cy). Propensity score matching (PSM) was applied to adjust baseline differences. Prior to PSM, survival outcomes were not significantly different, though numerical trends favored TBI-Cy. After PSM, 3-year graft-versus-host disease-free, relapse-free survival (GRFS) was higher with TBI-Cy (52% vs. 22%; p = 0.036), while other endpoints remained comparable in terms of statistical significance. Among patients transplanted in first complete remission (CR1), outcomes were not significantly different between regimens. These findings suggest TBI-Cy may provide improved composite outcomes, mainly reflected by GRFS, and inform conditioning regimen selection in T-ALL/LBL.

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.