Leukemia & Lymphoma最新文献

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.

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.

EZH2 is an important epigenetic regulator in malignant neoplasms. We investigated the tumorigenic roles of EZH2 and intracellular molecules in JAK2+/- myeloid neoplasms. EZH2 is upregulated in AML and non-leukemic myeloid neoplasms (M/N) and is associated with H3K27me3 co-expression. EZH2 overexpression is correlated with p-STAT3 and MYC upregulation in JAK2+ M/N, but only with MYC activation in JAK2- M/N. In JAK2+ myeloid neoplasms, p-STAT3, p-ERK1/2, and MYC showed a significantly elevated percentage of tumor cell positivity in AML compared to M/N group. In JAK2- cases, MYC, but not p-STAT3 or p-ERK1/2, showed significantly elevated percentage of tumor cell positivity in AML compared to M/N group. In conclusion, EZH2 plays an oncogenic role through overexpression in its wild-type myeloid neoplasms. EZH2, p-STAT3, MYC, and p-ERK1/2 upregulation associate differently with disease progression depending on JAK2 mutation status. EZH2 and related signaling molecules could serve as potential therapeutic targets in myeloid neoplasms.

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare and biologically distinct subtype of diffuse large B-cell lymphoma (DLBCL). It is marked by rare neoplastic B-cells within a prominent inflammatory microenvironment. Historically it was associated with poor prognosis but contemporary reports show outcomes comparable if not better than DLBCL-NOS, especially with the use of chemo-immunotherapies. Autologous stem cell transplantation (auto-HCT) demonstrated favorable progression-free and overall survival in relapsed patients in comparison to matched DLBCL cohorts. The efficacy of CD19-directed CAR T-cell therapy in THRLBCL has been limited, with high relapse rates and poor durability of response, likely due to an immunosuppressive tumor microenvironment characterized by PD-1/PD-L1 pathway activation. Several case series and translational studies support the use of immune checkpoint blockade in selected patients, although prospective validation is needed. While bispecific antibodies, tafasitamab-lenalidomide, and antibody-drug conjugates show promise in R/R DLBCL, THRLBCL patients remain underrepresented in these pivotal trials. This review summarizes current insights into the prognosis of THRLBCL and underscores the need for novel, biologically informed strategies to improve outcomes in the relapsed setting through a deeper understanding of its biology and immune evasion mechanisms.

Bruton tyrosine kinase inhibitors (BTKi) have a unique cardiovascular toxicity profile. We investigated pericardial effusion and tamponade (PE/T) as a potential cardiac complication associated with BTKi therapy. We employed a multi-modal approach: (1) a case series (2) a prevalence analysis using institutional and National Health Oragnization Maintanance (HMO) registry data; and (3) a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing BTKi- and non-BTKi-based regimens in CLL. We identified 15 cases of PE/T during BTKi therapy. In our institutional cohort (n = 750), PE/T prevalence was 2.6% among BTKi-treated patients vs. 0.17% in non-BTKi-treated patients (RR 15.48; p = 0.0072). In the HMO registry (n = 5917), BTKi-associated PE/T prevalence was 0.78%, with an RR of 3.09 (p = 0.029). The meta-analysis showed a significantly increased risk of PE/T with BTKi therapy (OR 3.25; 95% CI 1.02-10.35; p = 0.01; I²=0%). These results suggest that PE/T may represent a rare but clinically meaningful cardiac toxicity of BTKi therapy.

Bridging radiotherapy (BR) prior to CAR-T for non-Hodgkin lymphoma (NHL) can achieve durable cytoreduction, but optimal dosing remains undefined. We evaluated correlates of local progression (LP) among 33 patients (25 large B-cell lymphoma [LBCL], 8 Mantle Cell Lymphoma [MCL]) with relapsed/refractory NHL who received BR at our institution. Using image-guided radiotherapy (IGRT), we defined 'rapid bridging response' (RBR) as ≥10% volume reduction within 5 fractions. We estimated the cumulative incidence of LP with death as a competing risk. Five of 19 LBCL and 5/7 MCL patients with IGRT experienced RBR. LP occurred in 6 patients (all LBCL, 18-month cumulative incidence 19%), none of whom had RBR, and was increased for tumors with metabolic tumor volume > 100 mL. Among LBCL patients, median volume change during radiation for tumors with LP was 0% vs -4% for those without. Histology, radiomic features, and real-time radiotherapy response may guide a personalized approach to BR.