Hematological Oncology最新文献

{"title":"EDUCATIONAL NEEDS OF SWISS PATIENTS WITH HEMATOLOGICAL DISEASES: FOCUS ON KNOWLEDGE REGARDING HEMATOLOGY LABORATORY RESULTS AND BIOMEDICAL CONCEPTS","authors":"C. Dedieu, H. Chanvrier, J. Carr-Klappert, A. Batista Mesquita Sauvage, S. Manciana, B. Van Meenen, M. Cote, T. Corbière, H. Auner, F. Solly, M. Eicher","doi":"10.1002/hon.70093_ON08","DOIUrl":"https://doi.org/10.1002/hon.70093_ON08","url":null,"abstract":"<p>C. Dedieu, H. Chanvrier, and F. Solly equally contributing author.</p><p><b>Introduction:</b> Patients with hematological diseases, including blood cancers such as lymphoma or myeloma, often face significant difficulties in navigating health information about their illness due to the complexity of these conditions.</p><p>One of the self-reported educational needs of patients with hematological cancer is receiving clear and comprehensive information about laboratory results. Although these patients often undergo procedures such as venipuncture, knowledge gaps regarding laboratory results and biological concepts have been highlighted.</p><p>However, repeated procedures in combination with knowledge gaps and lack of information tailoring regarding laboratory results can decrease patient adherence and increase anxiety.</p><p>Our aim is to assess hematology patients’ knowledge of laboratory results and biological concepts, and their educational needs (format and frequency). We are also investigating patients’ interest in a novel biomedical consultation.</p><p><b>Methods:</b> This cross-sectional study is based on a digital self-reported questionnaire. Inpatients and outpatients over 18 years of age with a hematological disease and their caregivers are recruited at the Lausanne University Hospital by direct approach, flyers, patient associations or mail. The sample size of 103 was determined using Cochran’s formula, referencing a similar study. The questionnaire is divided into four sections consisting of (i) demographic information, (ii) general health literacy and disease awareness, (iii) preferences for educational interventions, and (iv) patient self-efficacy in managing laboratory results/biomedical information.</p><p><b>Results:</b> Preliminary results were obtained from 36 patients between November and December 2024. The largest group of participants were aged 60–75 years (42%), followed by those aged 75 years or older (25%). Patients with lymphoma and myeloma represented 5.6% and 22% of the participants respectively. Most participants (56%) rated their knowledge of biological concepts as average or poor. Only 19% of participants reported having a good understanding of blood counts. Understanding technical language and the meaning of laboratory results for their health was challenging according to 69%. Most participants (67%) expressed a desire to receive additional information regarding their laboratory results while 50% were interested in an individual educational biomedical consultation about laboratory analyses.</p><p><b>Conclusion:</b> These preliminary results provide valuable insights into patients' knowledge, unmet educational needs and preferences regarding educational formats. Recruitment is still ongoing, and we aim to present the final results at the conference. Our study will ultimately contribute to the development of an educational intervention to improve patients’ knowledge and self-management of laboratory results. Further st","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_ON08","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CLONAL HEMATOPOIESIS IN DIFFUSE LARGE B-CELL LYMPHOMA","authors":"D. Piffaretti, I. Romano, J. Marquez de Almeida, M. Salehi, H. Javanmard Khameneh, R. Moia, A. Bruscaggin, F. Jauk, S. Bocchetta, A. Condoluci, G. Forestieri, M. C. Pirosa, L. Terzi di Bergamo, S. Schär, A. Zenobi, A. Stathis, S. Monticelli, G. Gaidano, G. Guarda, D. Rossi","doi":"10.1002/hon.70093_60","DOIUrl":"https://doi.org/10.1002/hon.70093_60","url":null,"abstract":"<p>D. Piffaretti and I. Romano equally contributing authors.</p><p><b>Introduction:</b> Clonal Hematopoiesis (CH) may promote diffuse large B-cell lymphoma (DLBCL) in two ways: by seeding mutations in the B-cells progenitors, potentially contributing to malignant transformation. Alternatively, lymphoma may be promoted by the clonal and pro-inflammatory tumor microenvironment derived from CH. In this study we aimed to determine: (i) CH prevalence in newly diagnosed DLBCL; (ii) clinical impact of CH; (iii) correlation between CH and DLBCL genetic lesions; (iv) co-occurrence frequency of DLBCL driver and CH mutations at the single cell level; (v) enrichment of CH in cells of the lymphoma microenvironment compared to blood.</p><p><b>Methods:</b> Patients (<i>n</i> = 387) from the IOSI-EMA003 and SAKK38/19 trials were analyzed. CH mutations were identified in genomic DNA using a myeloid panel, while a lymphoid panel detected DLBCL mutations, somatic copy number abnormalities, and <i>BCL6</i> fusions in plasma cfDNA. Multiomic scDNA-seq and immunophenotyping of paired peripheral blood (PB) or bone marrow (BM) and disaggregated lymph nodes of 6 patients were performed. A custom Tapestri (MissionBio) panel targeted CH mutations and barcoded the dominant DLBCL clone by covering trunk oncogene mutations, enabling simultaneous genotyping and phenotyping of B cells, T cell subtypes, and myeloid cells. To assess whether CH-bearing myeloid cells support DLBCL in vitro: (i) BM cells from <i>Tet2</i> knockout (KO) and control mice were differentiated into macrophages and co-cultured with a <i>Tp53</i> KO murine B-cell lymphoma line; (ii) biallelic <i>TET2-</i>KO human THP1 monocytic cells, were differentiated into macrophages and co-cultured with DLBCL cell lines. Additionally, lymphoma-prone <i>Klf2</i><sup><i>fl/fl</i></sup><i>/Notch2IC</i><sup><i>fl/+</i></sup><i>/Cd19Cre</i><sup><i>+/</i>−</sup>/<i>Cd</i>45<i>.2</i><sup>+/+</sup> oncogenic and <i>Cd19Cre</i><sup><i>+/</i>−</sup>/<i>Cd45.2</i><sup>+/−</sup> control mice were adoptively transplanted with BM cells from <i>Tet</i>2<sup>+/+</sup>, <i>Tet</i>2<sup>+/−</sup>, and <i>Tet2</i><sup>−/−</sup> C57BL/6 <i>Cd45.1</i><sup>+/−</sup> mice without conditioning.</p><p><b>Results:</b> The analysis was done including patients per the CONSORT diagram (Figure 1A). CH mutations (VAF > 1%) were found in 38% of patients, primarily in <i>DNMT3A</i> and <i>TET2</i>, and correlated with age (Figure 1B). However, CH showed no association with features of lymphoma aggressiveness (clinical stage, B-symptoms, IPI) or DLBCL subtypes (cell of origin, C1-C5). Cox analyses (univariate/multivariate, adjusted for IPI), revealed no impact of CH on progression-free survival or lymphoma-specific survival. In vitro, lymphoma cell survival was limitedly affected by <i>TET2</i> status in macrophages. Engraftment in control mice mirrored the typical load of CH in humans (∼1% PB leukocytes at 3 months), whereas <i>Tet</i>2<sup>+/−</su","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_60","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A PHASE II TRIAL OF PEMBROLIZUMAB CONCURRENT WITH RADIOTHERAPY FOR FRAIL PATIENTS WITH NEWLY DIAGNOSED EARLY-STAGE NATURAL KILLER/T-CELL LYMPHOMA (IELSG50)","authors":"H. Zhong, C. Chen, S. Cheng, G. Cai, P. Sun, P. Liu, P. Xu, M. Cai, H. Yang, J. Xiong, Y. Wang, Y. Huang, J. Zhao, H. Yang, J. Chen, L. Wang, S. Luminari, E. Zucca, F. Cavalli, Z. Li, W. Zhao","doi":"10.1002/hon.70093_62","DOIUrl":"https://doi.org/10.1002/hon.70093_62","url":null,"abstract":"<p>H. Zhong, C. Chen, S. Cheng, G. Cai, P. Sun, P. Liu Z. Li, and W. Zhao equally contributing authors.</p><p><b>Introduction:</b> Natural killer/T-cell lymphoma (NKTCL) is highly aggressive and characterized by Epstein-Barr virus (EBV) infection and overexpression of immune checkpoints. The therapeutic options were limited for patients unsuitable for chemotherapy. Immune checkpoint inhibitors have been shown effective in refractory and relapsed NKTCL. This study aims to investigate the efficacy and safety of programmed death 1 (PD-1) antibody pembrolizumab concurrent with radiotherapy as a first-line treatment in newly diagnosed early-stage frail NKTCL patients.</p><p><b>Methods:</b> This is a multicenter phase II study. Eligible patients met the following criteria: (1) age ≥ 18 years; (2) newly diagnosed NKTCL with Ann Arbor stage I-II disease; (3) presence of at least one risk factor (age > 60 years, elevated serum lactate dehydrogenase, Ann Arbor stage II or primary tumor invasion); (4) unsuitable for systemic chemotherapy. All patients received induction treatment with pembrolizumab (200 mg intravenously on day 1 in each 21-day cycle for 6 cycles) concurrently with radiotherapy (a total dose of 50–54 Gy). The patients achieved complete remission (CR), partial remission (PR), or stable disease (SD) have been given pembrolizumab 200 mg every 21 days as a maintenance up to 2 years. The primary endpoint was 2-year progression-free survival (PFS) rate. The main secondary endpoints included CR rate (CRR), overall response rate (ORR), adverse events and plasma EBV DNA change.</p><p><b>Results:</b> From August 2020 to January 2025, a total of 30 patients with median age of 62 (20–74) years were enrolled in Shanghai Ruijin Hospital and Guangzhou Sun Yat Sen University Cancer Center. All patients were intermediate (60%, <i>n</i> = 18) and high (40%, <i>n</i> = 12) risk according to nomogram-revised risk index. Until February 2025, 62.5% CRR (95% CI: 40.6%–81.2%) and 91.7% ORR (95% CI: 73.0%–99.0%) have been achieved in twenty-four evaluable patients after induction treatment. With median follow-up time of 10.2 months (not yet mature for the analysis of the primary endpoint), the best CRR and ORR were 83.3% (95% CI: 62.6%–95.3%) and 91.7% (95% CI: 73.0%%–99.0%), respectively (Figure). The responses improved with the increase of cycles. The most common adverse events were lymphocytopenia, leukopenia, oral mucositis, radiodermatitis and dry mouth. Grade 3/4 adverse events were low, including lymphocytopenia (16.6%) and oral mucositis (13.3%). The treatment was well-tolerated. Among patients who were EBV DNA positive before treatment, 70% achieved EBV DNA negativity following induction therapy.</p><p><b>Conclusion:</b> Pembrolizumab concurrent with radiotherapy was effective and safe in newly diagnosed early-stage frail NKTCL patients, even in those with intermediate or high risk. Immune checkpoint inhibitors could be applied as first-line alternative ","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_62","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FREQUENCY OF FUSION GENES AND THEIR CLINICAL IMPACTS IN CHINESE PEDIATRIC PATIENTS WITH T-CELL LYMPHOBLASTIC LYMPHOMA","authors":"Y. Li, L. Jin, Y. Duan, W. Liu, J. Zhou, F. Li, X. Yang, Y. Jia, K. Yang, Y. Liu, Y. Dai, L. Yang, A. Liu, P. Wu, R. Liu, L. Jiang, X. Yuan, J. Jiang, S. Zhuang, J. Wang, Z. Xu, H. Gao, Q. Zheng, Y. Zhang","doi":"10.1002/hon.70093_36","DOIUrl":"https://doi.org/10.1002/hon.70093_36","url":null,"abstract":"<p>Y. Li, L. Jin, Q. Zheng, and Y. Zhang equally contributing authors.</p><p><b>Introduction:</b> T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive malignancy with a high incidence among children and adolescents. Despite its prevalence, research on fusion genes in T-LBL, particularly their distribution and prognostic implications, remains limited. This study aimed to elucidate the frequency of fusion genes in Chinese pediatric T-LBL patients and explore their potential impact on prognosis, thereby providing new insights for clinical management.</p><p><b>Methods:</b> We collected data from 552 pediatric T-LBL patients (aged ≤ 16 years) treated at multiple centers of the China Network of Childhood Lymphoma (CNCL), with fusion gene testing results available for 180 patients. Sequencing-based methods were used to detect fusion genes, and statistical analysis was performed to investigate their associations with patient clinical outcomes.</p><p><b>Results:</b> Among the 180 patients analyzed, 105 (58.3%) were found to harbor fusion genes, with a total of 40 distinct fusion genes identified. The higher percentage of fusion genes were <i>SIL</i>::<i>TAL1</i> (<i>n</i> = 40, 22.2%), <i>MLL</i> fusions (<i>n</i> = 20, 11.1%), <i>TCR</i> partner-related fusions (<i>n</i> = 11, 6.1%), <i>ABL1</i> fusions (<i>n</i> = 9, 5%), <i>NOTCH1</i> fusions (<i>n</i> = 7, 3.9%), and <i>SET</i>::<i>CAN</i> (<i>n</i> = 7, 3.9%) (Figure 1a). These findings highlight the genetic heterogeneity of T-LBL in pediatric patients.</p><p>Prognostic analysis revealed that patients with <i>NOTCH1</i> fusions had significantly poorer event-free survival (EFS) and overall survival (OS) compared to those without <i>NOTCH1</i> fusions (EFS, <i>p</i> < 0.0001; OS, <i>p</i> = 0.00013, Figure 1b,c). The identified <i>NOTCH1</i> fusion types included <i>IKZF2</i>::<i>NOTCH1</i> (<i>n</i> = 4, 57%), <i>MIR142</i>::<i>NOTCH1</i> (<i>n</i> = 2, 29%) and <i>IKZF1</i>::<i>NOTCH1</i> (<i>n</i> = 1, 14%), all of which are associated with poor outcomes. We further analyzed the relationship between <i>NOTCH1</i> mutations and <i>NOTCH1</i> fusions, and there was no obvious evidence of co-occurrence or mutual exclusivity between these genetic events. Notably, although <i>NOTCH1</i> mutations are generally associated with favorable outcomes in pediatric T-LBL patients, the cooccurrence of <i>NOTCH1</i> fusions appeared to diminish this benefit, showing a trend toward poorer prognosis (<i>p</i> = 0.056). These findings indicate that <i>NOTCH1</i> fusions may serve as potential biomarkers for adverse prognosis in pediatric patients with T-LBL. Additionally, <i>SIL::TAL1</i> and <i>MLL</i> fusions were observed but showed no prognostic significance in this cohort, warranting further study in larger cohorts.</p><p><b>Conclusion:</b> Our study provides the comprehensive overview of fusion gene distribution in Chinese pediatric T-LBL patients and highlights the significant prognostic impact of ","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_36","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SEQUOIA 5-YEAR FOLLOW-UP IN ARM C: FRONTLINE ZANUBRUTINIB IN PATIENTS WITH DEL(17P) AND TREATMENT-NAIVE CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA (CLL/SLL)","authors":"C. S. Tam, P. Ghia, M. Shadman, T. Munir, S. S. Opat, P. A. Walker, M. Lasica, I. W. Flinn, T. Tian, S. Agresti, J. Hirata, J. R. Brown","doi":"10.1002/hon.70093_72","DOIUrl":"https://doi.org/10.1002/hon.70093_72","url":null,"abstract":"<p><b>Introduction:</b> Zanubrutinib is a next-generation Bruton tyrosine kinase inhibitor that is approved for five indications, including CLL/SLL. Initial results from the SEQUOIA study (NCT03336333), at a median follow-up of 26.2 months, demonstrated superior progression-free survival (PFS) by independent review with zanubrutinib versus bendamustine + rituximab (arms A and B) in patients with treatment-naive CLL/SLL without del(17p) as well as high overall response rate (ORR) and PFS benefit in patients with del(17p) (arm C). Additionally, the 5-year follow-up in arm A demonstrated durable PFS benefit, with estimated 54- and 60-month PFS rates of 80% and 76%, respectively. Here we report updated results in SEQUOIA arm C, in patients with del(17p), after approximately 5 years of follow-up (data cutoff: Apr 30, 2024).</p><p><b>Methods:</b> Arm C is a nonrandomized cohort of SEQUOIA patients with del(17p) that received zanubrutinib monotherapy. Investigator-assessed PFS, overall survival (OS), ORR, and safety/tolerability were evaluated. Adverse events (AEs) were recorded until disease progression or start of next-line therapy.</p><p><b>Results:</b> Between Feb 2018 and Mar 2019, 111 treatment-naive patients with del(17p) were enrolled to receive zanubrutinib. The median age was 71 years (range, 42–87 years), 79 (71%) were male, 67 (60%) were IGHV unmutated, and 47 (42%) had both del(17p) and <i>TP53</i> mutation. At a median follow-up of 65.8 months (range, 5–75 months), median PFS was not reached. The estimated 60-month PFS rate was 72.2% (62.4%–79.8%) (Figure), or 73.0% (63.3%–80.6%) when adjusted for COVID-19. Median OS was also not reached. The estimated 60-month OS rate was 85.1% (76.9%–90.6%), or 87.0% (79.0%–92.1%) when adjusted for COVID-19. The ORR was 97.3%, and the complete response/complete response with incomplete hematologic recovery rate was 18.2%. Zanubrutinib treatment was ongoing in 62.2% of patients. The most common causes for treatment discontinuation were AEs and progressive disease (in 17.1% and 15.3%, respectively). Key AEs of interest (AEI) included any-grade infection (82%), bleeding (60%), neutropenia (19%), hypertension (18%), anemia (9%), thrombocytopenia (8%), and atrial fibrillation/flutter (7%). Grade ≥ 3 AEI included infection (33%), neutropenia (16%), hypertension (8%), bleeding (6%), atrial fibrillation/flutter (5%), and thrombocytopenia (2%).</p><p><b>Conclusions:</b> With this 5-year follow-up in SEQUOIA, the efficacy of zanubrutinib in treatment-naive higher-risk patients with del(17p) was maintained, and patients continue to demonstrate PFS benefits consistent with the randomized cohort of patients without del(17p) (arm A). Additionally, with longer-term follow-up, no new safety signals were identified. This update, in the largest cohort of uniformly treated patients with del(17p), suggests that zanubrutinib remains a valuable frontline treatment option for patients with or without del(17p) CLL/SLL.</p><p><b","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_72","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"THE ASSOCIATION OF SOCIAL DISADVANTAGE WITH OUTCOMES IN PATIENTS WITH ADVANCED-STAGE, CLASSIC HODGKIN LYMPHOMA ENROLLED IN THE PHASE 3 INTERGROUP TRIAL S1826","authors":"J. M. Kahn, J. M. Unger, H. Li, S. M. Castellino, H. Dillon, T. Hernandez, S. C. Rutherford, A. Punnett, M. LeBlanc, J. Y. Song, S. M. Smith, A. M. Evens, K. M. Kelly, J. W. Friedberg, A. Herrera","doi":"10.1002/hon.70094_368","DOIUrl":"https://doi.org/10.1002/hon.70094_368","url":null,"abstract":"<p>J. M. Unger, H. Li, S. M. Castellino, H. Dillon, T. Hernandez, S. C. Rutherford, A. Punnett, M. LeBlanc, J. Y. Song, S. M. Smith, A. M. Evens, K. M. Kelly, J. W. Friedberg, and A. Herrera equally contributing author.</p><p><b>Background</b>: The phase 3 randomized trial S1826 showed that among patients with advanced-stage classic Hodgkin lymphoma (cHL), nivolumab plus doxorubicin, vinblastine, and dacarbazine (N+AVD) resulted in longer progression-free survival (PFS) compared to brentuximab vedotin plus AVD (BV+AVD). We assessed whether the treatment benefits of N+AVD applied to potentially socioeconomically vulnerable populations.</p><p><b>Methods:</b> S1826 was a multicenter trial for patients ≥ 12 years old with stage III or IV newly diagnosed cHL. The trial was stopped early at its pre-specified second interim analysis due to efficacy of the N+AVD arm (hazard ratio [HR] for progression or death, 0.48; 95% confidence interval [CI], 0.27–0.87, <i>p</i> = 0.001). We assessed whether there was any evidence of differential benefit of N+AVD with respect to PFS according to categories of race/ethnicity (Black race and/or Hispanic ethnicity vs. others), rural versus urban residence, area-level socioeconomic deprivation (Area Deprivation Index [ADI] above median, yes vs. no), and insurance status (Medicaid or no insurance vs. others) using interaction tests. Analyses were conducted using Cox regression adjusting for the study-specified stratification variables including age (12 –17 vs. 18–60 vs. > 60 years), the international prognostic score (IPS; 0–3 vs. 4–7), and intent to use radiation (yes vs. no). An overall Type I error rate of alpha = 0.10 was used; multiplicity was accounted for by specifying each individual test at the two-sided alpha = 0.025 level using Bonferroni. If no interaction was found, the marginal association of socioeconomic variables and PFS using multivariable Cox regression was examined.</p><p><b>Results:</b> Of N = 970 eligible patients, 90% were < 60 years, and 56% were male; 11.8% were Black, 12.7% were Hispanic, and 32% had IPS 4–7. Among socioeconomic variables, the combined Black and/or Hispanic patients comprised 24.5%, 13.3% were from rural areas, 50% lived in areas above the median ADI level, and 23.2% had Medicaid or no insurance. In survival analyses, there was no statistically significant evidence that the effect of treatment on PFS differed between levels of the socioeconomic variables (Table). For instance, the PFS HR was 0.52 for Black and/or Hispanic patients and 0.41 for other patients (interaction <i>p</i>-value = 0.60). Across all patients, there was no statistically significant association of Black and/or Hispanic race/ethnicity (HR = 1.10, 95% CI: 0.72–1.69, <i>p</i> = 0.65), rural geography (HR = 1.11, 95% CI: 0.67–1.85, <i>p</i> = 0.67), high ADI (HR = 1.30, 95% CI: 0.89–1.88, <i>p</i> = 0.17), or Medicaid/no insurance (HR = 1.01, 95% CI: 0.63–1.60, <i>p</i> = 0.98) with PFS.</p><p><b>Conclusion:","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_368","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"INVESTIGATING NEUTROPHIL EXTRACELLULAR TRAPS AS A POSSIBLE PROGNOSTIC MARKER IN DIFFUSE LARGE B-CELL LYMPHOMA AND CLASSICAL HODGKIN LYMPHOMA","authors":"E. Pettersson, K. Vemuri, M. Berglund, J. Collin, M. Herre, R. Amini, D. Molin, A. Olsson, G. Enblad","doi":"10.1002/hon.70094_205","DOIUrl":"https://doi.org/10.1002/hon.70094_205","url":null,"abstract":"<p><b>Introduction:</b> Neutrophil extracellular traps (NETs) are complexes of decondensed chromatin and granule proteins that can be released from activated neutrophils during infections or in inflammatory conditions, including cancer. Accumulation of NETs in tissues and blood can contribute to increased inflammation, thrombosis and organ damage. In several types of solid cancers, NETs have been shown to facilitate metastasis and tumour growth, leading to a worse prognosis. However, little is known about the role of NETs in malignant lymphomas.</p><p><b>Methods:</b> The concentration of NETs was analysed in plasma samples taken at diagnosis from patients with diffuse large B-cell lymphoma (DLBCL, <i>n</i> = 227) and classical Hodgkin lymphoma (cHL, <i>n</i> = 117) in the Uppsala Umeå Comprehensive Cancer Consortium (U-CAN) biobank. Plasma from blood donors (<i>n</i> = 54) were used as healthy controls. NETs were measured using a commercial enzyme-linked immunosorbent assay (ELISA) targeting complexes of citrullinated histones and extracellular DNA, a biomarker with high specificity for NETs. Clinical data, including blood counts at diagnosis and treatment outcome, was extracted from patient records and analysed in relation to the plasma concentrations of NETs.</p><p><b>Results:</b> Higher concentrations of NETs were seen in plasma from DLBCL patients (range 0.62 to 200 ng/ml) compared to cHL patients (<i>p</i> < 0.01, range 0.58 to 62 ng/ml) and healthy controls (<i>p</i> < 0.001, range 1.0 to 37 ng/ml). The level of NETs in cHL was not significantly higher than in control samples. In both DLBCL and cHL, a poorer overall survival was seen in patients with concentrations of NETs above median (7.4 and 5.6 ng/ml respectively, <i>p</i> < 0.05). There was no significant correlation between progression free survival and NETs. In cHL, there was a positive correlation between elevated levels of NETs and age above 45 years (<i>p</i> < 0.05), but no correlation to age was shown in DLBCL. The NET levels did not significantly differ between the sexes. A trend, although not significant, could be seen with increased NET levels in higher stages of both DLBCL and cHL. The plasma concentration of NETs in both lymphoma diseases showed a positive correlation with the neutrophil count in blood (<i>p</i> < 0.05), as well as erythrocyte sedimentation rate (ESR) above 50 mmHg (<i>p</i> < 0.01) at diagnosis.</p><p><b>Conclusions:</b> In line with previous studies on NETs in cancer, we show that high levels of NETs in plasma correlates with worse survival for both DLBCL and cHL patients. However, plasma concentrations were only significantly increased in DLBCL compared to healthy controls, with no correlation to age or sex. Based on the results, NETs could be a possible prognostic marker to further investigate in malignant lymphoma. In both DLBCL and cHL, higher levels of NETs were seen in patients with elevated neutrophil count and high ESR, a sign of","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_205","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PEMBROLIZUMAB AND RADIATION THERAPY ALONE AS AN ALTERNATIVE TO TRANSPLANT FOR LOCALIZED FAILURE AFTER CHEMOTHERAPY IN HODGKIN LYMPHOMA: A MULTICENTER PHASE II STUDY","authors":"A. D. Dreyfuss, N. Ganesan, B. S. Imber, M. LaRiviere, D. Isrow, J. Plastaras, J. Svoboda, J. Yahalom, C. H. Moskowitz, A. Moskowitz","doi":"10.1002/hon.70093_129","DOIUrl":"https://doi.org/10.1002/hon.70093_129","url":null,"abstract":"<p><b>Background:</b> Chemotherapy (chemo) followed by stem cell transplant (SCT) is standard of care for relapsed/refractory (RR) Hodgkin Lymphoma (HL). In a phase II study, we evaluated pembrolizumab (pembro) with involved site radiation therapy (ISRT) as an alternative salvage approach for localized favorable relapse.</p><p><b>Methods:</b> Patients with RR stage IA/IIA, non-bulky (< 10cm) HL after one line of therapy had a PETCT simulation followed by pembro 200 mg IV q 21d for 4 cycles and PETCT simulation 3 wks later. Patients then received ISRT per response as follows: (1) 20 Gy for complete metabolic response (CMR) defined by Deauville Score (DS) 1–3; (2) 30 Gy for partial metabolic response (PMR) or stable disease (SD) (DS 4–5) and negative biopsy; or (3) 36–40 Gy for PMR/SD and positive biopsy. Patients who progressed (PD) were taken off study. PETCT response was documented 4–6 weeks after ISRT. The primary endpoint was CMR rate after pembro-RT. Secondary endpoints were response to single agent pembro, 2-year progression free survival (PFS), and toxicity.</p><p><b>Results:</b> 22 of planned 22 patients enrolled with median age of 36 (range 22–66) and 10 (45%) males. 3 (14%) had stage I, 18 (82%) stage II, and 1 had an unspecified limited stage at initial diagnosis. Frontline therapy was chemotherapy alone in 19 (86%) and combined modality in 3 (14%). 21 (95%) received adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD), 17 (81%) with < 6 cycles. 14 (64%) had relapsed and 8 (36%) had refractory disease.</p><p>7 (32%) had CMR after pembro, 3 (14%) had PMR/SD with negative biopsy, 6 (27%) had PMR with positive biopsy, 1 (5%) had PMR without biopsy, and 5 (23%) had PD. 17 patients proceeded to ISRT, of whom 7 (41%) with CMR received 20 Gy, 3 (18%) with PMR/SD and negative biopsy received 30 Gy, and 7 (41%) with PMR/SD and positive/no biopsy received 36–40 Gy. Of the 14 with post-RT PET, 12 (86% of these patients, 67% overall) achieved CMR. After median follow up of 34 months (6–79), 2-year PFS was 65% (95% CI: 47–91).</p><p>Five patients progressed on pembro and three relapsed after a median of 12 months (range 7–70) from completion of pembro-RT. Among the patients with PD during or after pembro-RT, three are currently in remission, one is currently undergoing therapy, and the status for the others are unknown. Subsequent treatments included pembro plus gemcitabine/vinorelbine/liposomal doxorubicin followed by ASCT (<i>n</i> = 2), brentuximab vedotin (BV) plus nivolumab followed by ASCT (<i>n</i> = 1) and 2 doses of BV followed by additional RT (<i>n</i> = 1).</p><p>Immune-related toxicities were 3 (14%) grade 1 rash, and 3 (14%) grade 2 hypo/hyperthyroidism. Grade > 2 toxicities were 1 (5%) grade 3 headache, 1 (5%) grade 3 urinary tract infection, 1 (5%) grade 3 encephalopathy, and 1 (5%) grade 4 lipase elevation.</p><p><b>Conclusion:</b> Pembro-RT yielded excellent CMR rates and minimal toxicity. These data suggest pembro-R","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SYSTEMATIC INVESTIGATION OF DISEASE- AND GENOTYPE-SPECIFIC VULNERABILITIES IN PRIMARY BLOOD CANCER USING HIGH-THROUGHPUT EX VIVO DRUG SCREENING","authors":"K. D. Hofer,&nbsp;S. Scheinost,&nbsp;L. Ben-Taarit,&nbsp;J. Hüllein,&nbsp;T. Walther,&nbsp;K. Putzker,&nbsp;L. Sellner,&nbsp;M. W. Kühn,&nbsp;T. Kindler,&nbsp;F. Nguyen-Khac,&nbsp;M. Crespo Maull,&nbsp;F. Bosch,&nbsp;A. Theocharides,&nbsp;M. G. Manz,&nbsp;J. Bourquin,&nbsp;B. Bornhauser,&nbsp;S. Dietrich,&nbsp;J. Lewis,&nbsp;W. Huber,&nbsp;J. Lu,&nbsp;T. Zenz","doi":"10.1002/hon.70093_114","DOIUrl":"https://doi.org/10.1002/hon.70093_114","url":null,"abstract":"<p>K. D. Hofer and S. Scheinost equally contributing author.</p><p>Ex vivo drug screening may leverage the cellular response to drugs for disease understanding, identification of new targets and improved treatment. Precise stratification of patients with hematologic malignancies based on molecular profiling can improve treatment selection and outcome.</p><p>Here, we perform a large-scale drug screen across a range of hematologic malignancies to link drug response to diseases and subgroups, identify pathway dependencies and define determinants of drug response. We analyze sequential samples to assess the dynamics of drug response phenotypes over time and compare ex vivo results to clinical outcomes.</p><p>For 722 patient samples from 17 blood cancers we assessed drug response to 63 different compounds. The analysis of 143,640 data points shows that drug response is strongly linked to disease entities. We link functional pathway dependencies to individual blood cancers and genetic subgroups. In CLL, trisomy(12) confers susceptibility to inhibition of MEK/ERK and PI3K-AKT-mTOR pathways. DDX3X mutations are associated with increased sensitivity to BTK and SYK inhibition. Longitudinal assessment shows stable drug response over time in untreated patients. Patients receiving BCR signaling inhibitors acquire sensitivities to BET and dual MCL-1/BCL-2 inhibition.</p><p>We have generated an accessible resource of ex vivo drug profiling across different hematologic malignancies that can be leveraged for functional analyses and biomarker-stratified treatment strategies.</p><p><b>Research</b> <b>funding declaration:</b> Jacques and Gloria Gossweiler Foundation, Swiss Academy of Medical Sciences, University Hospital Zurich</p><p><b>Keywords:</b> bioinformatics; computational and systems biology; tumor biology and heterogeneity</p><p><b>No potential sources of conflict of interest.</b></p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BOOM-BOOM RADIATION PRIOR TO LISOCABTAGENE MARALEUCEL IS FEASIBLE AND CONTRIBUTES TO HIGH COMPLETE RESPONSE RATES FOR AGGRESSIVE B-CELL NON-HODGKIN LYMPHOMA","authors":"C. D'Angelo,&nbsp;C. Enke,&nbsp;J. Vose,&nbsp;R. G. Bociek,&nbsp;S. Ananth,&nbsp;E. Lyden,&nbsp;F. Yu,&nbsp;M. Schissel,&nbsp;M. Lunning","doi":"10.1002/hon.70093_111","DOIUrl":"https://doi.org/10.1002/hon.70093_111","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Introduction:&lt;/b&gt; Low dose radiation therapy (RT), 4 Gray administered over 2 fractions (BOOM-BOOM), has demonstrated efficacy and low toxicity in B-cell lymphoma. Pre-clinical experiments demonstrate that BOOM-BOOM RT prior to CAR T-cell therapy successfully enhances CAR T-cell efficacy, suggesting engagement of immunotherapeutic mechanisms. We hypothesized that BOOM-BOOM radiation would be safe and effective as bridging therapy prior to liso-cel infusion.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; We performed an investigator-initiated study of BOOM-BOOM bridging RT prior to liso-cel. Eligible patients included adults with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma at the University of Nebraska Medical Center. Subjects received BOOM-BOOM RT to disease sites 7–10 days prior to liso-cel. No other bridging therapy beyond steroids was allowed. The primary endpoint was feasibility, defined as the percentage of subjects enrolled who received BOOM-BOOM RT and liso-cel.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; The trial has completed recruitment, and this is the first analysis of feasibility and efficacy for the whole cohort. The median follow-up is 146 days. Thirty-two subjects were enrolled and 30 subjects received BOOM-BOOM RT and liso-cel (30/32, 94%), meeting the prespecified feasibility threshold of &gt; 70%. The median age was 70 (range 23–84), 22 (69%) subjects were male. Three subjects were diagnosed with high-grade B-cell lymphoma, 1 with grey zone lymphoma, 1 with Richter’s transformation, and 27 with DLBCL. Fourteen subjects (18/32, 56%) had a LDH above the upper limit of normal. Twenty-nine subjects (29/32, 91%) received liso-cel as second line therapy. Twenty-one subjects (21/32, 66%) had extranodal disease, 20/32 (63%) were advanced stage, and 16/32 (50%) were refractory to frontline therapy.&lt;/p&gt;&lt;p&gt;Twenty-nine subjects receiving per-protocol therapy were evaluable for response using Lugano criteria for PET/CT. Responses to BOOM-BOOM and liso-cel were observed in 25/29 (86%) subjects, and the complete response (CR) rate was 24/29 (83%). Two subjects had stable disease, and 2 subjects experienced progressive disease as best response. Progression-free survival (PFS) and overall survival (OS) curves are depicted in Figure 1. A landmark analysis by response at D30 for PFS and OS is depicted in Figure 1C/D and demonstrates a 200-day PFS and OS rate for patients obtaining a CR of 75% (95% CI: 46%–90%) and 89% (95% CI: 62%–97%), respectively.&lt;/p&gt;&lt;p&gt;Thirty subjects were evaluable for safety. CRS was observed in 15 subjects and was G1–2 in 14 and G5 in one. Immune effector cell-associated neurotoxicity was observed in 8 subjects and G3–4 in 5/8. Two subjects died, 1 due to intestinal perforation and 1 due to septic shock prior to D100.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; The combination of BOOM-BOOM RT and liso-cel met our primary endpoint of feasibility and produced a high CR rate of 83%. These data suggest that the use of low-dose RT as bridging therapy is safe, feasible, a","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70093_111","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144299760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}