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While survival has improved for Burkitt lymphoma patients, potential differences in outcome between pediatric and adult patients remain unclear. In both age groups, survival remains poor at relapse. Therefore, we conducted a comparative study in a large pediatric cohort, including 191 cases and 97 samples from adults. While TP53 and CCND3 mutation frequencies are not age related, samples from pediatric patients showed a higher frequency of mutations in ID3 , DDX3X, ARID1A and SMARCA4 , while several genes such as BCL2 and YY1AP1 are almost exclusively mutated in adult patients. An unbiased analysis reveals a transition of the mutational profile between 25 and 40 years of age. Survival analysis in the pediatric cohort confirms that TP53 mutations are significantly associated with higher incidence of relapse (25 ± 4% versus 6 ± 2%, p-value 0.0002). This identifies a promising molecular marker for relapse incidence in pediatric BL which will be used in future clinical trials. Survival outcomes in Burkitt lymphoma differ between adult and paediatric patients. Here, the authors show differences in mutational frequencies between age groups, and a transition between mutational profiles which occurs between 25 and 40 years.

Background In response to the prioritization of healthcare resources towards the COVID-19 pandemic, routine cancer screening and diagnostic have been disrupted, potentially explaining the apparent COVID-era decline in cancer cases and mortality. In this study, we identified temporal trends in public interest in cancer-related health information using the nowcasting tool Google Trends. Methods We used Google Trends to query search terms related to cancer types for short-term (September 2019–September 2020) and long-term (September 2016–September 2020) trends in the US. We compared average relative search volumes (RSV) for specified time ranges to detect recent and seasonal variation. Results General search interest declined for all cancer types beginning in March 2020, with changes in search interest for “Breast cancer,” “Colorectal cancer,” and “Melanoma” of − 30.6%, − 28.2%, and − 26.7%, respectively, and compared with the mean RSV of the two previous months. In the same time range, search interest for “Telemedicine” has increased by + 907.1% and has reached a 4-year peak with a sustained increased level of search interest. Absolute cancer mortality has declined and is presently at a 4-year low; however, search interest in cancer has been recuperating since July 2020. Conclusion We observed a marked decline in searches for cancer-related health information that mirrors the reduction in new cancer diagnoses and cancer mortality during the COVID-19 pandemic. Health professions need to be prepared for the coming demand for cancer-related healthcare, foreshadowed by recovering interest in cancer-related information on Google Trends.

Abstract Patients with high-risk or relapsed aggressive B-cell lymphomas are characterized by poor prognosis. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) can induce durable remissions in these patients and is potentially curative. Two hundred forty-seven patients with aggressive B-cell lymphomas treated with high-dose chemotherapy and ASCT, either as consolidation after first-line therapy or after salvage therapy for relapsed disease, between 2002 and 2019 at the University Hospital Muenster, were analyzed. The median follow-up of surviving patients was 36 months (range 0–163). Progression-free survival (PFS) and overall survival (OS) after 3 years was 63% and 68%, respectively. After ASCT, 28% of all patients experienced a relapse. The cumulative incidence of non-relapse mortality at day 100 after ASCT was 4%. Multivariate analysis identified remission status at ASCT, age at ASCT, and the numbers of infused CD34+ cells as independent prognostic factors for both PFS and OS. Patients with mantle cell lymphoma (MCL) or primary CNS lymphoma (PCNSL) treated with ASCT in first-line had a superior OS and PFS when compared to patients treated with ASCT in relapsed disease. For patients with diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL), early relapse (< 12 months) after first-line therapy showed a trend towards an inferior PFS and OS. Deaths after ASCT were predominantly caused by lymphoma relapse and/or progression (64%) or due to infections (23%). In conclusion, high-dose chemotherapy followed by ASCT in the era of novel targeted agents remains a feasible and effective approach for patients with high-risk or relapsed aggressive B-cell lymphomas. Remission status and age at ASCT, and the number of infused stem cells were of prognostic relevance.

Background The CXCR4 receptor antagonist plerixafor (AMD3100) is raising interest as an anti-cancer agent that disrupts the CXCL12-CXCR4 chemokine – receptor interaction between neoplastic cells and their microenvironment in tumor progression and metastasis. Here, we investigated plerixafor for anti-cancer activity in Ewing sarcoma, a rare and aggressive cancer of bone and soft tissues. Methods We used a variety of methods such as cell viability and migration assays, flow cytometry, phospho-tyrosine arrays and western blotting to determine plerixafor effects on five characterized Ewing sarcoma cell lines and a low-passage culture in vitro. Results Unexpectedly, plerixafor led to an increase in cell viability and proliferation in standard cell growth conditions, and to chemotactic migration towards plerixafor. Exploring potential molecular mechanisms underlying this effect, we found that Ewing sarcoma cell lines divided into classes of high- and low-level CXCR4 surface expression. Proliferative plerixafor responses were observed in both groups, maintained despite significant CXCR4 down-regulation or inhibition of Gαi-protein signal transduction, and involved activation of multiple receptor tyrosine kinases (DDR2, MERTK, MST1R, NTRK1, RET), the most prominent being platelet-derived growth factor receptor beta (PDGFRB). PDGFRB was activated in response to inhibition of the CXCL12-CXCR4 axis by plerixafor and/or pertussis toxin (Gαi-protein inhibitor). Dasatinib, a multi-kinase inhibitor of both PDGFRB and the CXCR4 downstream kinase SRC, counteracted this activation in some but not all cell lines. Conclusion These data suggest a feedback interaction between the CXCR4 chemokine receptor and RTK signaling cascades that elicits compensatory cell survival signaling and can shift the net effect of plerixafor towards proliferation. PDGFRB was identified as a candidate driver RTK and potential therapeutic co-target for CXCR4 in Ewing sarcoma. Although as yet limited to in vitro studies, these findings call for further investigation in the cancer – microenvironment interplay in vivo.

CD19‐directed chimeric antigen receptor (CAR)‐T cell therapy has become a standard treatment for relapsed/refractory diffuse large B‐cell lymphoma (r/r DLBCL). While the benefits of CAR‐T cell treatment are clear in the general patient population, there remains a relative scarcity of real‐world evidence regarding its efficacy and toxicity in patients (pts) aged ≥70 years with DLBCL. We conducted a multicenter retrospective analysis including 172 r/r DLBCL pts with CAR‐T cell treatment, axicabtagene ciloleucel or tisagenlecleucel, between 2019 and 2023 at three tertiary centers. Pts were grouped by age at CAR‐T infusion (<70 vs. ≥70 years). Subsequently, descriptive and survival analyses, including propensity score matching, were performed to compare outcomes between both age groups. We identified 109 pts aged <70 and 63 pts aged ≥70 years. Overall response rates for both age groups were comparable (77.7% vs. 78.3%; p = 0.63). With a median follow‐up of 8.3 months, median progression‐free survival was 10.2 months (95% confidence interval [CI]: 6.5–21.8) and 11.1 months (95% CI: 4.9–NR) (p = 0.93) for both cohorts. Median overall survival reached 21.8 months (95% CI: 11.8–NR) and 34.4 months (95% CI: 10.1–NR) (p = 0.97), respectively. No significant differences in the incidence of cytokine release syndrome (p = 0.53) or grade ≥3 neurotoxicity (p = 0.56) were observed. Relapse and nonrelapse mortality were not significantly different between both groups. Our findings provide additional support that CAR‐T cell therapy is feasible and effective in patients with r/r DLBCL aged 70 years or older, demonstrating outcomes comparable to those observed in younger patients. CAR‐T cell therapy should be not withheld for elderly patients with r/r DLBCL.

Stagnating COVID-19 vaccination rates and vaccine hesitancy remain a threat to public health. Improved strategies for real-time tracking and estimation of population-level behavior regarding vaccinations are needed. The aim of this study was to evaluate whether online search trends for COIVD-19 and influenza mirror vaccination rates. State-level weekly fraction of online searches for top vaccination-related search terms and CDC vaccination data were obtained from June 1, 2020, to May 31, 2021. Next, trends in online search and vaccination data for COVID-19 and influenza were analyzed for visual and quantitative correlation patterns using Spearman’s rank correlation analysis. Online searches in the US for COVID-19 vaccinations increased 2.71-fold (95% CI: 1.98-3.45) in the 4 weeks after the FDA emergency authorization compared to the precedent 4 weeks. In March-April 2021, US online searches reached a plateau that was followed by a decline of 83.3% (95% CI: 31.2%-135.3%) until May 31, 2021. The timing of peaks in online searches varied across US states. Online searches were strongly correlated with vaccination rates (r=0.71, 95% CI: 0.45 - 0.87), preceding actual reported vaccination rates in 44 of 51 states. Online search trends preceded vaccination trends by a median of 3.0 weeks (95% CI: 2.0-4.0 weeks) across all states. For influenza vaccination searches, seasonal peaks in September-October between 2016-2020 were noted. Influenza search trends highly correlated with the timing of actual vaccinations for the 2019-2020 (r=0.82, 95% CI: 0.64 – 0.93) and 2020-2021 season (r=0.91, 95% CI: 0.78 – 0.97). Search trends and real-world vaccination rates are highly correlated. Temporal alignment and correlation levels were higher for influenza vaccinations; however, only online searches for COVID-19 vaccination preceded vaccination trends. These findings indicate that US online search data can potentially guide public health efforts, including policy changes and identifying geographical areas to expand vaccination campaigns.

BackgroundDespite recent advances in the treatment of aggressive lymphomas, a significant fraction of patients still succumbs to their disease. Thus, novel therapies are urgently needed. As the anti-CD20 antibody rituximab and the CD19-targeting antibody tafasitamab share distinct modes of actions, we investigated if dual-targeting of aggressive lymphoma B-cells by combining rituximab and tafasitamab might increase cytotoxic effects.MethodsAntibody single and combination efficacy was determined investigating different modes of action including direct cytotoxicity, antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) in in vitro and in vivo models of aggressive B-cell lymphoma comprising diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL).ResultsThree different sensitivity profiles to antibody monotherapy or combination treatment were observed in in vitro models: while 1/11 cell lines was primarily sensitive to tafasitamab and 2/11 to rituximab, the combination resulted in enhanced cell death in 8/11 cell lines in at least one mode of action. Treatment with either antibody or the combination resulted in decreased expression of the oncogenic transcription factor MYC and inhibition of AKT signaling, which mirrored the cell line-specific sensitivities to direct cytotoxicity. At last, the combination resulted in a synergistic survival benefit in a PBMC-humanized Ramos NOD/SCID mouse model.ConclusionThis study demonstrates that the combination of tafasitamab and rituximab improves efficacy compared to single-agent treatments in models of aggressive B-cell lymphoma in vitro and in vivo .

Natural killer (NK)/T‐cell lymphomas (NKTCLs) are rare, aggressive lymphomas prevalent in East Asia and South America. Despite improvements, largely due to asparaginase‐based therapies, outcomes for advanced disease remain poor, and the role of autologous stem cell transplantation (auto‐HCT) remains controversial. This study evaluated real‐world outcomes of auto‐HCT in NKTCL patients across Asia and Europe. We included 130 adult NKTCL patients undergoing auto‐HCT between 2011 and 2022 using data from the European Society for Blood and Marrow Transplantation (EBMT) registry and South Korean registry data. Median age was 51.3 years; 66.9% were male. Most patients (95.1%) had an Eastern Cooperative Oncology Group (ECOG) score 0–1; 65.3% had Stage III–IV disease. One prior therapy line was reported in 53.1%, and ≥2 lines in 46.9%. Asparaginase‐based regimens were used in 79.5% pretransplant. Responses at auto‐HCT included complete (59.7%), partial (27.9%) remission, and stable/progressive disease (12.4%). Epstein–Barr virus (EBV)‐DNA in the peripheral blood was reported in 37.3%. With a median follow‐up of 4.6 years, 3‐year overall survival (OS) and progression‐free survival (PFS) were 63.8% and 47.6%. Relapse and NRM rates at 3 years were 46.7% and 5.7%. Patients in complete remission had improved 3‐year OS (75.2%) compared to PR (52.8%) and stable/progressive disease (32.0%) (P = 0.007). Detectable EBV‐DNA in the blood at auto‐HCT was associated with poor outcomes (3‐year OS: 26.7% vs. 78.1% in patients with undetectable EBV‐DNA; P < 0.0001). Patients achieving complete remission and undetectable EBV‐DNA in the blood before auto‐HCT had a favorable survival, suggesting auto‐HCT may be a treatment option in selected high‐risk patients. This is the largest multinational cohort evaluating prognostic factors for auto‐HCT for NKTCL.

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a standard treatment for patients with AML and MDS. The combination of fractionated total body irradiation(8GyTBI/Flu) with fludarabine is an established conditioning regimen, but fludarabine/treosulfan(Flu/Treo) constitutes an alternative in older/comorbid patients. We conducted a retrospective analysis of 215 AML(in CR) and 96 MDS patients undergoing their first allo-HCT between 2011 and 2022, identifying 53 matched Flu/Treo and 8GyTBI/Flu patients through propensity score matching. Median follow-up of survivors was 3.3 years and 4.1 years. For the Flu/Treo group, 1-year non-relapse mortality (2% vs. 10%, p = 0.03) was lower, while 1-year relapse incidence (16% vs. 13%, p = 0.81) was similar. Three-year outcomes, including relapse-free survival and graft-versus-host disease incidence, were comparable (OS: 81% vs. 74%, p = 0.70; RFS: 78% vs. 66%, p = 0.28; chronic GvHD: 34% vs. 36%, p = 0.97; acute GvHD (100 days): 11% vs. 23%, p = 0.11). Multivariable analysis, considering age, ECOG, HCT-CI, and MRD status, revealed no associations with main outcomes. Dose-reduced conditioning with Flu/Treo or 8GyTBI/Flu demonstrated favorable and comparable survival rates exceeding 70% at 3 years with 1-year NRM rates below 10% and low relapse rates in the matched cohort. These data underline the need for further evaluation of TBI and Treo-based conditionings in prospective trials.