HemaSphere最新文献

{"title":"Bortezomib before and after high-dose therapy in transplant-eligible patients with newly diagnosed multiple myeloma: Long-term overall survival after more than 10 years of follow-up from the phase III HOVON-65/GMMG-HD4 trial","authors":"Elias K. Mai, Axel Nogai, Henk M. Lokhorst, Bronno van der Holt, Sonja Zweegman, Katja C. Weisel, Sandra Croockewit, Anna Jauch, Jens Hillengass, Marian Stevens-Kroef, Marc S. Raab, Annemiek Broijl, Gerard M. J. Bos, Peter Brossart, Paula Ypma, Christine Hanoun, Uta Bertsch, Thomas Hielscher, Hans J. Salwender, Christoph Scheid, Hartmut Goldschmidt, Pieter Sonneveld","doi":"10.1002/hem3.70052","DOIUrl":"https://doi.org/10.1002/hem3.70052","url":null,"abstract":"<p>Life expectancy in patients with multiple myeloma (MM) has increased due to the availability of effective drugs such as proteasome inhibitors (PIs),<span><sup>1, 2</sup></span> immunomodulatory drugs (IMiDs),<span><sup>3-5</sup></span> and more recently, monoclonal antibodies.<span><sup>6-8</sup></span></p><p>While the progression-free survival (PFS) rates and the depth of response increase with the use of modern multi-drug combinations, it is not clear whether these effects will translate into an improved long-term overall survival (OS). To draw such conclusions, long-term follow-up analyses from trials are needed as comparators for future trials. Here, we report on the long-term overall survival of the HOVON-65/GMMG-HD4 trial including the OS after more than 10 years, and the role of established prognostic factors.</p><p>The investigator-sponsored, open-label, randomized HOVON-65/GMMG-HD4 phase III trial was conducted by the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and the German-speaking Myeloma Multicenter Group (GMMG) in 75 centers in the Netherlands, Belgium, and Germany from May 2005 to May 2008 and included 827 eligible patients. The trial was registered at www.trialregister.nl (until June 2022) and https://trialsearch.who.int/ as NTR213, at www.isrctn.com as ISRCTN64455289 and at www.clinicaltrialsregister.eu as EudraCT2004-000944-26. The ethics committees of the Erasmus University Medical Center, the University of Heidelberg, and all participating sites approved this trial. All patients gave written informed consent. The study was conducted in accordance with the European Clinical Trial Directive (2005) and the Declaration of Helsinki (1996).</p><p>Initial results of the trial have been published and include a detailed study protocol, inclusion and exclusion criteria, randomization procedures and toxicities,<span><sup>9</sup></span> and results after a median follow-up of 96 months.<span><sup>10</sup></span> After that, only OS data were collected on which we here report the final long-term survival data.</p><p>The aim of the trial was to investigate the use of bortezomib (BTZ) in induction and maintenance compared to treatment with classical cytotoxic agents as induction and thalidomide maintenance in transplant-eligible patients regarding the primary endpoint PFS, while OS was a secondary endpoint. Patients were randomized 1:1 to receive either vincristine, adriamycin, and dexamethasone (VAD) as induction therapy, followed by high-dose chemotherapy with melphalan and autologous stem-cell transplantation (ASCT), followed by maintenance therapy with thalidomide (VAD arm). In the PAD arm, BTZ, adriamycin, and dexamethasone were used in induction, followed by ASCT and maintenance with BTZ. Patients were stratified by center and International Staging System (ISS, I vs. II vs. III). A single ASCT was planned in the HOVON group, whereas in the GMMG, a tandem ASCT was planned. Patients with an HLA-identical sib","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"8 11","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The incidence and clinical significance of monoclonal and oligoclonal protein bands in multiple myeloma patients after BCMA–CAR-T cell therapy: A retrospective study based on LEGEND-2","authors":"Rui Liu,&nbsp;Gongzhizi Gao,&nbsp;Hongli Chen,&nbsp;Ruijun Dong,&nbsp;Wanggang Zhang,&nbsp;Wanhong Zhao,&nbsp;Jie Liu,&nbsp;Jianli Wang,&nbsp;Bo Lei,&nbsp;Baiyan Wang,&nbsp;Jiali Liu,&nbsp;Xuezhu Xu,&nbsp;Zujie Lin,&nbsp;Ruoyu Yang,&nbsp;Yiwen Wang,&nbsp;Aili He,&nbsp;Fangxia Wang,&nbsp;Ju Bai","doi":"10.1002/hem3.70054","DOIUrl":"https://doi.org/10.1002/hem3.70054","url":null,"abstract":"<p>The emergence of abnormal protein bands (APBs), also known as oligoclonal protein bands, has been documented in patients with multiple myeloma (MM) post hematopoietic stem cell transplantation. However, the incidence rate and clinical significance of APBs remain contentious. Few studies have explored the occurrence and prognostic implications of APBs in patients with MM treated with B-cell maturation antigen (BCMA)–specific chimeric antigen receptor (CAR)-T therapy. In this retrospective study, we examined the frequency, isotypes, and duration of APBs, as well as their correlation with MM disease characteristics, treatment response, clinical outcomes, and immune signature in patients with relapsed/refractory MM who had received LCAR-B38M therapy at the Xi'an site of the phase 1 LEGEND-2 trial. Among 47 patients assessed, 23 (48.9%) developed APBs following CAR-T therapy, with IgG being the most common isotype. The median onset and duration of APBs post-CAR-T infusion were 3.6 and 5.8 months, respectively. Patients with APBs demonstrated significantly improved response to LCAR-B38M therapy, along with longer overall and progression-free survival. Furthermore, those with APBs exhibited enhanced recovery rates of immunoglobulins and higher absolute counts of white blood cells, neutrophils, and lymphocytes post-CAR-T treatment compared to those without APBs. However, no significant differences were observed between the two groups in the percentages of various T-cell subsets and natural killer cells. Overall, the presence of APBs in patients with MM following CAR-T treatment was associated with deeper remission and a more favorable prognosis, suggesting a robust humoral response and subsequent immune reconstitution.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"8 11","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoclonal gammopathy of undetermined significance with multiple paraproteins: A population-based screening study","authors":"Sæmundur Rögnvaldsson,&nbsp;Jón Þ. Óskarsson,&nbsp;Sigrun Thorsteinsdóttir,&nbsp;Malin Hultcrantz,&nbsp;Robert Palmason,&nbsp;Ingigerdur S. Sverrisdottir,&nbsp;Elias Eythorsson,&nbsp;Thorir E. Long,&nbsp;Isleifur Olafsson,&nbsp;Ingunn Thorsteinsdottir,&nbsp;Brynjar Vidarsson,&nbsp;Pall T. Onundarson,&nbsp;Bjarni A. Agnarsson,&nbsp;Margret Sigurdardottir,&nbsp;Asbjorn Jonsson,&nbsp;Brian G. M. Durie,&nbsp;Stephen Harding,&nbsp;Ola Landgren,&nbsp;Thorvardur J. Love,&nbsp;Sigurdur Y. Kristinsson","doi":"10.1002/hem3.70046","DOIUrl":"https://doi.org/10.1002/hem3.70046","url":null,"abstract":"<p>Monoclonal gammopathy of undetermined significance (MGUS) is the precursor of multiple myeloma (MM) and related disorders. MGUS is characterized by asymptomatic paraproteinemia. In some cases, multiple paraproteins can be identified but the clinical implications of this phenomenon are poorly understood. In this study, we aim to inform the approach to this challenging MGUS subgroup by utilizing data from iStopMM, a population-based screening study and randomized trial of follow-up strategies. In total, 75,422 Icelanders over the age of 40 were screened for MGUS with 3389 (4.4%) having at least one paraprotein of whom 303 (9%) had multiple paraproteins. IgM paraproteins were more common in those with multiple paraproteins (49% vs. 27% of paraproteins, <i>p</i> &lt; 0.001), and IgM and non-IgM paraproteins frequently co-occurred (60% of cases). Two-thirds of these participants were randomized to active follow-up where only 31% of multiple paraproteins were persistent. Paraprotein concentrations were mostly independent, and although progression events were few, the progression rate was similar between those with multiple paraproteins and a single paraprotein. In a next-generation flow cytometry (NGF) sub-study, two phenotypically distinct aberrant plasma cell populations could be identified in some with multiple paraproteins. The findings suggest that multiple paraproteins often reflect independent ongoing disease processes that should be monitored independently but otherwise treated similarly to other MGUS cases. Specifically, the findings highlight the need for independent monitoring of IgM and non-IgM paraproteins in these individuals. The study provides novel insights into the management of this understudied MGUS subset.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"8 11","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A single-chain variable fragment-based bispecific T-cell activating antibody against CD117 enables T-cell mediated lysis of acute myeloid leukemia and hematopoietic stem and progenitor cells","authors":"Laura Volta,&nbsp;Renier Myburgh,&nbsp;Mara Hofstetter,&nbsp;Christian Koch,&nbsp;Jonathan D. Kiefer,&nbsp;Celeste Gobbi,&nbsp;Francesco Manfredi,&nbsp;Kathrin Zimmermann,&nbsp;Philipp Kaufmann,&nbsp;Serena Fazio,&nbsp;Christian Pellegrino,&nbsp;Norman F. Russkamp,&nbsp;Danielle Villars,&nbsp;Mattia Matasci,&nbsp;Monique Maurer,&nbsp;Jan Mueller,&nbsp;Florin Schneiter,&nbsp;Paul Büschl,&nbsp;Niclas Harrer,&nbsp;Jacqueline Mock,&nbsp;Stefan Balabanov,&nbsp;César Nombela-Arrieta,&nbsp;Timm Schroeder,&nbsp;Dario Neri,&nbsp;Markus G. Manz","doi":"10.1002/hem3.70055","DOIUrl":"https://doi.org/10.1002/hem3.70055","url":null,"abstract":"<p>Acute myeloid leukemia (AML) derives from hematopoietic stem and progenitor cells (HSPCs). To date, no AML-exclusive, non-HSPC-expressed cell-surface target molecules for AML selective immunotherapy have been identified. Therefore, to still apply surface-directed immunotherapy in this disease setting, time-limited combined immune-targeting of AML cells and healthy HSPCs, followed by hematopoietic stem cell transplantation (HSCT), might be a viable therapeutic approach. To explore this, we generated a recombinant single-chain variable fragment-based bispecific T-cell engaging and activating antibody directed against CD3 on T-cells and CD117, the surface receptor for stem cell factor, expressed by both AML cells and healthy HSPCs. Bispecific CD117xCD3 targeting induced lysis of CD117-positive healthy human HSPCs, AML cell lines and patient-derived AML blasts in the presence of T-cells at subnanomolar concentrations in vitro. Furthermore, in immunocompromised mice, engrafted with human CD117-expressing leukemia cells and human T-cells, the bispecific molecule efficiently prevented leukemia growth in vivo. Additionally, in immunodeficient mice transplanted with healthy human HSPCs, the molecule decreased the number of CD117-positive cells in vivo. Therefore, bispecific CD117xCD3 targeting might be developed clinically in order to reduce CD117-expressing leukemia cells and HSPCs prior to HSCT.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"8 11","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-11-An aging-related cytokine with opportunities for regulating hematopoiesis.","authors":"David G Kent","doi":"10.1002/hem3.70050","DOIUrl":"https://doi.org/10.1002/hem3.70050","url":null,"abstract":"","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"8 11","pages":"e70050"},"PeriodicalIF":7.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical evaluation of the CD38-targeting engineered toxin body MT-0169 against multiple myeloma","authors":"Wassilis S. C. Bruins,&nbsp;Rosa Rentenaar,&nbsp;John Newcomb,&nbsp;Wenrou Zheng,&nbsp;Ruud W. J. Ruiter,&nbsp;Thomas Baardemans,&nbsp;Eric Poma,&nbsp;Chris Moore,&nbsp;Garrett L. Robinson,&nbsp;Anya Lublinsky,&nbsp;Yuhong Zhang,&nbsp;Sakeena Syed,&nbsp;Michael Milhollen,&nbsp;Ajeeta B. Dash,&nbsp;Niels W. C. J. van de Donk,&nbsp;Richard W. J. Groen,&nbsp;Sonja Zweegman,&nbsp;Tuna Mutis","doi":"10.1002/hem3.70039","DOIUrl":"10.1002/hem3.70039","url":null,"abstract":"<p>Despite significant progress in the treatment of multiple myeloma (MM), relapsed/refractory patients urgently require more effective therapies. We here describe the discovery, mechanism of action, and preclinical anti-MM activity of engineered toxin body MT-0169, a next-generation immunotoxin comprising a CD38-specific antibody fragment linked to a de-immunized Shiga-like toxin A subunit (SLTA) payload. We show that specific binding of MT-0169 to CD38 on MM cell lines triggers rapid internalization of SLTA, causing cell death via irreversible ribosome inhibition, protein synthesis blockade, and caspase 3/7 activation. In co-culture experiments, bone marrow mesenchymal stromal cells did not induce drug resistance against MT-0169. In the preclinical setting, MT-0169 effectively lysed primary MM cells from newly diagnosed and heavily pretreated MM patients, including those refractory to daratumumab, with minimal toxicity against nonmalignant hematopoietic cells. MM cell lysis showed a significant correlation with their CD38 expression levels but not with cytogenetic risk, tumor load, or number of prior lines of therapy. Finally, MT-0169 showed efficient in vivo anti-MM activity in various mouse xenograft models, including one in which MM cells are grown in a humanized bone marrow-like niche. These findings support clinical investigation of MT-0169 in relapsed/refractory MM patients, including those refractory to CD38-targeting immunotherapies.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"8 11","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Results of the prospective EORTC Children Leukemia Group study 58081 in precursor B- and T-cell acute lymphoblastic leukemia","authors":"Carine Domenech,&nbsp;Michal Kicinski,&nbsp;Barbara De Moerloose,&nbsp;Caroline Piette,&nbsp;Wadih A. Chahla,&nbsp;Laure Kornreich,&nbsp;Marlène Pasquet,&nbsp;Anne Uyttebroeck,&nbsp;Alexandre Theron,&nbsp;Marilyne Poirée,&nbsp;Chloé Arfeuille,&nbsp;Marleen Bakkus,&nbsp;Nathalie Grardel,&nbsp;Catherine Paillard,&nbsp;Claire Freycon,&nbsp;Frédéric Millot,&nbsp;Pauline Simon,&nbsp;Pierre Philippet,&nbsp;Claire Pluchart,&nbsp;Stefan Suciu,&nbsp;Pierre Rohrlich,&nbsp;Alina Ferster,&nbsp;Yves Bertrand,&nbsp;Hélène Cavé,&nbsp;for the Children's Leukemia Group (CLG) of the European Organization for Research and Treatment of Cancer (EORTC)","doi":"10.1002/hem3.70025","DOIUrl":"10.1002/hem3.70025","url":null,"abstract":"<p>Here, we report the results of the prospective cohort study EORTC-CLG 58081 and compare them to the control arm of the randomized phase 3 trial EORTC-CLG 58951, on which treatment recommendations were built. In both studies, patients aged 1–18 years with <i>BCR::ABL1</i> negative acute lymphoblastic leukemia of the B-lineage (B-ALL) or T-lineage (T-ALL) were treated using a BFM backbone without cranial irradiation. Similarly to the control arm of 58951, prednisolone (PRED) 60 mg/m²/day was used for induction therapy, but a few modifications were made. Dexamethasone (DXM) was used in average-risk 2 (AR2) T-ALL and B-ALL during induction, 10 and 6 mg/m²/day, respectively. Leucovorin rescue was delayed to 42 h instead of 36 h after initiation of high-dose methotrexate, and a postconsolidation MRD time point was added to stratify patients. Between 2011 and 2017, 835 patients were prospectively enrolled in the 58081 study. Overall, the 5-year event-free survival (EFS) was 84.8% versus 83.6% (hazard ratio [HR], 0.96 [95% confidence interval [CI]: 0.76–1.21]) for 58081 versus 58951 considered as a control group, respectively, 84.3% versus 84.9% (HR, 1.06 [99% CI: 0.75–1.49]) in B-ALL but 87.3% versus 76.6% (HR, 0.59 [99% CI: 0.28–1.24]) in T-ALL. The comparison between the two studies regarding EFS differed by risk group (<i>p</i> = 0.012). The HR was 2.15 (99% CI: 0.67–6.85) for very low-risk but 0.34 (99% CI: 0.13–0.89) for AR2. The particularly favorable results observed in the T-ALLs and AR2 subgroups suggest the benefit of using DXM in specific patient groups and highlight the importance of risk stratification.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"8 11","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic risk and survival of asymptomatic IgM monoclonal gammopathy: Results from a Spanish Multicenter Registry","authors":"David F. Moreno,&nbsp;Cristina Jiménez,&nbsp;Fernando Escalante,&nbsp;Elham Askari,&nbsp;Marta Castellanos-Alonso,&nbsp;Mario Arnao,&nbsp;Ángela Heredia,&nbsp;Miguel Á. Canales,&nbsp;Magdalena Alcalá,&nbsp;Arancha Bermúdez,&nbsp;Ana Saus Carreres,&nbsp;María Casanova,&nbsp;Luis Palomera,&nbsp;Cristina Motlló,&nbsp;Ricarda García-Sánchez,&nbsp;Pablo Ríos Rull,&nbsp;Ramón García-Sanz,&nbsp;Carlos Fernández de Larrea","doi":"10.1002/hem3.70029","DOIUrl":"10.1002/hem3.70029","url":null,"abstract":"<p>Asymptomatic IgM gammopathy encompasses IgM monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic Waldenström macroglobulinemia (AWM), both having a risk of progression to symptomatic disease. Here, we assessed the risk of progression and the mortality of 956 patients with asymptomatic IgM gammopathy across 25 Spanish centers. After a median follow-up of 5.7 years, 156 patients progressed, most of them to symptomatic WM (SWM). The cumulative incidence of progression was 13% and 20% at 5 and 10 years, respectively. The serum IgM ≥10 g/L, bone marrow (BM) infiltration ≥20%, β2-microglobulin ≥3 mg/L, and albumin &lt;4 g/dL were the most potent predictors of disease progression in a multivariate Cox regression model, allowing the identification of three risk categories. The probability of progression to symptomatic disease at 5 years was 4.5%, 15.7%, and 42.8% for low-, intermediate-, and high-risk groups, respectively. In patients without a BM evaluation, the presence of none or 1 risk factor and 2 or 3 risk factors conferred a progression risk of 6% and 27% at 5 years, respectively. The model was independent of the presence of <i>MYD88</i> L265P, which conferred a negative impact only in AWM patients. The relative survival (RS) ratio at 5 years of asymptomatic patients was similar to the Spanish population, which contrasted with the 0.76 5-year RS of SWM patients. Overall, the Spanish Multicenter Model comprehensively describes the risk of progression of asymptomatic patients and shows that the excess mortality is increased only in the symptomatic stage of the disease.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"8 11","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causes of death among patients diagnosed with chronic lymphocytic leukemia: A population-based study in the Netherlands, 1996–2020","authors":"Lina van der Straten,&nbsp;Mark-David Levin,&nbsp;Manette A. W. Dinnessen,&nbsp;Otto Visser,&nbsp;Eduardus F. M. Posthuma,&nbsp;Jeanette K. Doorduijn,&nbsp;Anton W. Langerak,&nbsp;Arnon P. Kater,&nbsp;Avinash G. Dinmohamed","doi":"10.1002/hem3.70015","DOIUrl":"10.1002/hem3.70015","url":null,"abstract":"<p>Chronic lymphocytic leukemia (CLL) manifests heterogeneously with varying outcomes. This population-based study examined causes of death (CODs), as registered by the physician who established the death, among 20,588 CLL patients diagnosed in the Netherlands between 1996 and 2020. Utilizing cause-specific flexible parametric survival models, we estimated cause-specific hazard ratios (HRs) and cumulative incidences of death due to CLL, solid malignancies, other hematological malignancies, infections, and other causes. Our findings reveal CLL as the predominant COD, contributing to around 40% of relative mortality, with a declining 5-year death probability from 16.8% in 1996–2002 to 7.6% in 2010–2020. Also, deaths attributed to solid malignancies, other hematological malignancies, and other COD diminished over time, as evidenced by respective HRs (95% confidence interval) of 0.68 (0.60%–0.77%), 0.45 (0.38%–0.53%), and 0.77 (0.66%–0.90%). In summary, our comprehensive, population-based analysis underscores a noticeable reduction in CLL-attributed deaths and other competing causes over the studied period. Nonetheless, CLL is registered as the most prevalent cause of mortality among contemporary diagnosed patients with CLL, emphasizing the continued relevance of CLL-centric clinical strategies and research.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"8 11","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibiotic-associated neutropenia is marked by the depletion of intestinal Lachnospiraceae and associated metabolites in pediatric patients","authors":"Josaura Fernandez-Sanchez,&nbsp;Rachel Rodgers,&nbsp;Arushana A. Maknojia,&nbsp;Nusrat Shaikh,&nbsp;Hannah Yan,&nbsp;Marlyd E. Mejia,&nbsp;Hope Hendricks,&nbsp;Robert R. Jenq,&nbsp;Pavan Reddy,&nbsp;Ritu Banerjee,&nbsp;Jeremy M. Schraw,&nbsp;Megan T. Baldridge,&nbsp;Katherine Y. King","doi":"10.1002/hem3.70038","DOIUrl":"10.1002/hem3.70038","url":null,"abstract":"<p>Prolonged antibiotic exposure causes dangerous hematologic side effects, including neutropenia, in up to 34% of patients. Murine studies established a link between the intestinal microbiota and hematopoiesis. To identify factors that predispose to neutropenia in pediatric patients, we evaluated changes in microbiota-derived metabolites and intestinal microbiota composition after prolonged courses of antibiotics. In this multi-center study, patients with infections requiring anticipated antibiotic treatment of two or more weeks were enrolled. Stool samples were obtained at the start and completion of antibiotics or at neutropenia onset (prospective arm). Some patients were enrolled in a retrospective arm in which a stool sample was collected at the time of neutropenia during antibiotic therapy and 2–4 weeks after completion of antibiotics with recovery of blood counts. We identified 10 patients who developed neutropenia on antibiotics and 29 controls matched for age, sex, race, and ethnicity. Clinical data demonstrated no association between neutropenia and the type of infection or antibiotic used; however, patients with neutropenia were admitted to the intensive care unit more often and received longer courses of antibiotics. Reduced intestinal microbiome richness and, specifically, decreased abundance of <i>Lachnospiraceae</i> family members correlated with neutropenia. Untargeted stool metabolomic profiling revealed several metabolites that were depleted exclusively in patients with neutropenia, including members of the urea cycle pathway, pyrimidine metabolism, and fatty acid metabolism that are known to be produced by <i>Lachnospiraceae</i>. Our study shows a relationship between intestinal microbiota disruption and abnormal hematopoiesis and identifies taxa and metabolites likely to contribute to microbiota-sustained hematopoiesis.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"8 11","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}