Blood Cancer Journal最新文献

The prognostic influence of socioeconomic status (SES) on the survival of diffuse large B-cell lymphoma (DLBCL) patients remains controversial. This observational study examines the potential impact of regional SES inequalities on overall survival (OS) among DLBCL patients in Germany. We analyzed data from the German nationwide population-based dataset spanning 2004-2019 sourced from the German Center for Cancer Registry Data (n = 49,465). The primary objective was to assess the 5-year OS among patients with low SES compared to those living in middle and high SES areas. SES was grouped according to quintiles of the German Index of Socioeconomic Deprivation, which summarized nine indicators covering aspects of regional education, employment, and income. DLBCL patients in low SES areas had significantly impaired 5-year OS compared to those in middle and high SES regions (59.2% vs. 61.8% vs. 64.1%, p < 0.0001). Yet, additionally accounting for regional premature mortality removed the impact of SES on survival (Hazard Ratio 0.94, 95% CI 0.87–1.01). Our findings indicate that the prognostic impact of socioeconomic deprivation on long-term survival is not due to variations in diagnosis and treatment of DLBCL itself but rather a higher comorbidity burden.

MGTA-145 or GROβT, a CXCR2 agonist, has shown promising activity for hematopoietic stem cell (HSC) mobilization with plerixafor in pre-clinical studies and healthy volunteers. Twenty-five patients with multiple myeloma enrolled in a phase 2 trial evaluating MGTA-145 and plerixafor for HSC mobilization (NCT04552743). Plerixafor was given subcutaneously followed 2 h later by MGTA-145 (0.03 mg/kg) intravenously with same day apheresis. Mobilization/apheresis could be repeated for a second day in patients who collected <6 ×10⁶ CD34+ cells/kg. Lenalidomide and anti-CD38 antibody were part of induction therapy in 92% (n = 23) and 24% (n = 6) of patients, respectively. Median total HSC cell yield (CD34+ cells/kg × 10⁶) was 5.0 (range: 1.1–16.2) and day 1 yield was 3.4 (range: 0.3–16.2). 88% (n = 22) of patients met the primary endpoint of collecting 2 ×10⁶ CD34+ cells/kg in ≤ two days, 68% (n = 17) in one day. Secondary endpoints of collecting 4 and 6 × 10⁶ CD34+ cells/kg in ≤ two days were met in 68% (n = 17) and 40% (n = 10) patients. Grade 1 or 2 adverse events (AE) were seen in 60% of patients, the most common AE being grade 1 pain, usually self-limited. All 19 patients who underwent transplant with MGTA-145 and plerixafor mobilized HSCs engrafted successfully, with durable engraftment at day 100. 74% (17 of 23) of grafts with this regimen were minimal residual disease negative by next generation flow cytometry. Graft composition for HSCs and immune cells were similar to a contemporaneous cohort mobilized with G-CSF and plerixafor.

This study sheds light on the pivotal role of the oncoprotein DEK in B-cell lymphoma. We reveal DEK expression correlates with increased tumor proliferation and inferior overall survival in cases diagnosed with low-grade B-cell lymphoma (LGBCL). We also found significant correlation between DEK expression and copy number alterations in LGBCL tumors, highlighting a novel mechanism of LGBCL pathogenesis that warrants additional exploration. To interrogate the mechanistic role of DEK in B-cell lymphoma, we generated a DEK knockout cell line model, which demonstrated DEK depletion caused reduced proliferation and altered expression of key cell cycle and apoptosis-related proteins, including Bcl-2, Bcl-xL, and p53. Notably, DEK depleted cells showed increased sensitivity to apoptosis-inducing agents, including venetoclax and staurosporine, which underscores the therapeutic potential of targeting DEK in B-cell lymphomas. Overall, our study contributes to a better understanding of DEK’s role as an oncoprotein in B-cell lymphomas, highlighting its potential as both a promising therapeutic target and a novel biomarker for aggressive LGBCL. Further research elucidating the molecular mechanisms underlying DEK-mediated tumorigenesis could pave the way for improved treatment strategies and better clinical outcomes for patients with B-cell lymphoma.

Aggressive B-cell non-Hodgkin lymphomas (NHL) in children, adolescents, and young adults (CAYA) include Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), and a subset of high-grade tumors with features intermediate between these entities whose genetic and molecular profiles have not been completely elucidated. In this study, we have characterized 37 aggressive B-NHL in CAYA, 33 with high-grade morphology, and 4 DLBCL with MYC rearrangement (MYC-R), using targeted next-generation sequencing and the aggressive lymphoma gene expression germinal center B-cell-like (GCB), activated B-cell-like (ABC), and dark zone signatures (DZsig). Twenty-two tumors had MYC-R without BCL2 breaks, and two MYC-non-R cases had BCL6 translocations. MYC-R cases, including DLBCL, carried BL-related mutations and copy number alterations. Conversely, MYC-non-R lymphomas had alterations in the B-cell receptor signaling/NF-κB pathway (71%). DZsig was expressed in 12/13 of MYC-R tumors but only in 2/10 of MYC-non-R GCB tumors (P < 0.001). The 3-year event-free survival (EFS) of the whole cohort was 79.6%. TP53 and KMT2C mutations conferred inferior outcome (3-year EFS P < 0.05). Overall, MYC-R lymphomas in CAYA have a molecular profile similar to BL regardless of their high-grade or DLBCL morphology, whereas MYC-non-R has more heterogeneous genetic alterations closer to that of DLBCL.

MRD2STOP is a pragmatic trial evaluating maintenance therapy cessation guided by measurable residual disease (MRD) negativity in multiple myeloma (MM). Eligible patients had previous MRD < 10⁻⁵, received ≥1 year of maintenance, and were prospectively confirmed to have undetectable disease by positron emission tomography, bone marrow (BM) flow cytometry (limit of detection [LoD] 10⁻⁵), and BM clonoSEQ (LoD 10⁻⁶). BM aspirates enriched for CD138⁺ cells were analyzed by clonoSEQ to achieve MRD 10⁻⁷ sensitivity. We evaluated the incidence of disease resurgence and progression-free survival (PFS), stratified by 10⁻⁷ status. Forty-seven patients discontinued maintenance after a median of 36 months. Baseline MRD ≥ 10⁻⁷ was observed in 19% (9/47). The median follow-up post-discontinuation was 30 months. Disease resurgence (MRD 10 ≥ ⁻⁶) occurred in 11 patients, including 5 disease progressions. One patient died from a second cancer. The estimated 3-year cumulative incidence of disease resurgence was 20% for patients with baseline MRD < 10⁻⁷ compared to 75% for MRD ≥ 10⁻⁷ (HR 7.8, 95% CI 2.2-27.6, p = 0.001). Baseline MRD ≥ 10⁻⁷ was associated with inferior PFS compared to MRD < 10⁻⁷ (HR 10.1, 95% CI 1.6–62.3; 3-year PFS 49% vs 92%). Maintenance discontinuation in patients with MM and MRD < 10⁻⁶ led to low rates of disease resurgence. MRD < 10⁻⁷ may be a superior cessation threshold, requiring further validation.