HemaSphere最新文献_第7页

Exciting science from the 16th International Conference on Thalassemia and Hemoglobinopathies 第 16 届地中海贫血和血红蛋白病国际会议的精彩科学成果

IF 7.6 2区医学

HemaSphere Pub Date : 2024-07-19 DOI: 10.1002/hem3.114

Dimitrios Farmakis, Michael Angastiniotis, Androulla Eleftheriou

{"title":"Exciting science from the 16th International Conference on Thalassemia and Hemoglobinopathies","authors":"Dimitrios Farmakis, Michael Angastiniotis, Androulla Eleftheriou","doi":"10.1002/hem3.114","DOIUrl":"https://doi.org/10.1002/hem3.114","url":null,"abstract":"The 16th International Conference on Thalassemia & Hemoglobinopathies was held together with the 18th International Conference for Patients and Parents in Kuala Lumpur, Malaysia, on November 3–5, 2023. Both congresses were organized by the Thalassaemia International Federation (TIF), a patient-oriented, nonprofit, nongovernmental umbrella federation with 231 member associations from 69 countries. TIF works in official relations with the World Health Organization (WHO), the European Council, and the United Nations Economic and Social Council to promote access to quality care for all patients with thalassemia or other hemoglobinopathies worldwide.The scientific program of the conference addressed a broad range of topics concerning thalassemia, sickle cell disease (SCD), and other rare anemias, providing a comprehensive review of the current state of the art, recent advances, and persisting or emerging challenges on diagnosis, management, and prevention of hemoglobinopathies.Impaired maturation of erythroid progenitors to red cells in bone marrow is a key component of β-thalassemia pathophysiology. Luspatercept is a novel drug that promotes erythroid maturation, improving anemia and reducing transfusional requirements. Its efficacy and safety have been documented in transfusion-dependent thalassemia (TDT) and nontransfusion-dependent thalassemia (NTDT) by the randomized trials BELIEVE and BEYOND, respectively,1, 2 resulting in the approval of the drug for TDT in 2020 and for either TDT or NTDT in 2023. Open issues include the efficacy and safety of luspatercept in children, patients with alpha-thalassemia, and in combination with other drugs and the identification of predictors of response and side effects. The high cost of the drug poses a challenge to healthcare systems and creates the need for proper patient selection.Mitapivat is an oral small-molecule activator of red cell-specific pyruvate kinase (PK). PK is crucial for the energetic supply, function, and survival of red cells, which are compromised in patients with PK deficiency, thalassemia, and SCD. A series of clinical trials have addressed the efficacy and safety of mitapivat in these three hemolytic conditions. Two phase 2 studies in NTDT and SCD, respectively, documented improvements in hemoglobin levels, hemolysis, and sickling, with adequate safety.3, 4 Two phase 3 trials in TDT and NTDT and a larger phase 2/3 study in SCD are ongoing.Drugs and interventions promoting hemoglobin F (HbF) synthesis have been tested as potential therapies for β-thalassemia. BCL11A is a transcription factor inhibiting HbF synthesis and its genetic manipulation with the gene-editing technique CRISPR-Cas9, followed by autologous stem cell transplantation with BCL11A-edited cells, is being evaluated in β-thalassemia and SCD.5The TMPRSS6 antisense oligonucleotide (ASO) inhibits the expression of T","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"8 7","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730109","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}

引用次数: 0

Different roles for different bones—Location matters for blood production 不同骨骼的不同作用--位置对造血至关重要

IF 7.6 2区医学

HemaSphere Pub Date : 2024-07-19 DOI: 10.1002/hem3.127

David G. Kent

{"title":"Different roles for different bones—Location matters for blood production","authors":"David G. Kent","doi":"10.1002/hem3.127","DOIUrl":"https://doi.org/10.1002/hem3.127","url":null,"abstract":"Laboratories studying hematopoietic stem cell (HSC) biology from across the world all have their own way of doing things, and this extends not just to the various cell surface marker combinations used to isolate HSCs but also to the more mundane aspects of cell isolation and preparation. At the very beginning of an HSC experiment, all researchers are faced with the question of which bones to obtain their bone marrow sample from. In the mouse, where options are more numerous, researchers commonly obtain marrow samples from the tibia, femur, hip, sternum, or spine. Some researchers then proceed to isolate the marrow by flushing, others by centrifuging bones, and still others by crushing. Yet, the vast majority of studies simply report that mouse bone marrow was isolated, and where it is specified, it is rarely looked at as a major experimental variable (e.g., a study with bone marrow from the tibia and femur is not viewed differently to one that also obtains marrow from spine and hip). Does it really matter which bone (or which part of which bone) cells are isolated from? Recent evidence suggests that the answer is a resounding “yes.”While numerous anecdotes have circulated around various conference circuits and between highly specialized HSC labs, it is rare to see published studies that go into the fine detail of differences in the anatomical location of bone marrow blood cells. That said, studies have been cropping up in various guises over the years, and a major landmark study came out this year from Daniel Lucas' group1 that added fuel to the fire and appears to cement the unique roles of different bones in blood cell production. One of the earliest studies was from Brian Lord in the 1970s where colony-forming cells were isolated from either the central marrow shaft (dubbed “axial”) or the edges of the bone (named “marginal”) and distinct numbers and types of colonies resided in each cell preparation.2 This study preceded a large number of studies that focused on different types of bone and bone matrix, different proposed HSC niches, and different neighboring cell types (reviewed in Comazzetto et al.3).Another provocative study emerged from David Bryder's lab in 20154 that challenged the notion of transplantable HSCs being equally distributed across the skeleton of a repopulated mouse. Following 16 weeks of transplantation and monitoring of overall chimerism in the blood, each of the right and left legs (tibia, femur, and hip) were assessed for donor chimerism, and the differences between bones were substantial, with some animals showing chimerism nearly exclusively in a single bone. Experimentally, this again challenges researchers to not consider that all marrow is equal irrespective of location.Coming back to the Lucas lab study and why it has made such a big impact in the field, they undertook a skeleton-wide imaging stud","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"8 7","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730110","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}

引用次数: 0

Correction to “Influence of donor–recipient sex on engraftment of normal and leukemia stem cells in xenotransplantation” 更正 "异种移植中供体和受体性别对正常干细胞和白血病干细胞移植的影响"

IF 7.6 2区医学

HemaSphere Pub Date : 2024-07-19 DOI: 10.1002/hem3.119

引用次数: 0

Less is more: Depleting myeloid-biased HSCs to restore immune function 少即是多消耗髓系造血干细胞恢复免疫功能

IF 7.6 2区医学

HemaSphere Pub Date : 2024-07-19 DOI: 10.1002/hem3.125

Hansen J. Kosasih, Charles E. de Bock

{"title":"Less is more: Depleting myeloid-biased HSCs to restore immune function","authors":"Hansen J. Kosasih, Charles E. de Bock","doi":"10.1002/hem3.125","DOIUrl":"https://doi.org/10.1002/hem3.125","url":null,"abstract":"The quest to unlock the secrets of eternal youth or extending life span have been described throughout history. This includes ancient texts describing the “fountain of youth” and more recently within the popular fiction series “Harry Potter” where the philosopher's stone provides an “elixir of life.” In reality, our longevity is in part due to the presence of an effective immune system coupled with our ability to pre-emptively manipulate this using vaccinations. Indeed, it could be argued that vaccinations remain one of the most successful health interventions in human history, consigning many of the debilitating illness such as smallpox to the annals of history. Nevertheless, there remains an ongoing need for the rapid development and deployment of new vaccines to protect ourselves against new and emerging threats such as COVID-19. However, whilst we can design new vaccines based on an exquisite understanding of the “enemy,” this needs to be coupled with an individual's ability to mount an effective immune response—which, unfortunately, declines as we age.1It is now established that the hematopoietic stem cell (HSC) population changes over time.2 In youth, the HSCs population has a balanced output of lymphoid and myeloid cells (bal-HSCs), but then changes towards myeloid-biased HSCs (my-HSCs) in older individuals. This in turn results in decreased lymphopoiesis, increased myelopoiesis as well as proinflammation, myeloid-related malignancies and a reduced adaptive immune response in older individuals.3 An elegant new study published in Nature by the Weissman lab4 now provides a tantalising new approach to improve our immune response. They demonstrate that an antibody depletion-based strategy targeting my-HSCs, can push the immune system in favor of a more balanced HSCs, and in essence, reversing time to rejuvenate an old immune system to a more youthful age.Previous studies which have characterised the HSC population (Lin−, SCA1+ KIT+ FLT3− CD34−), found that my-HSCs have higher expression of CD150 (Slamf1) compared to bal-HSCs.3 In this new study, Ross et al.4 sought to extend this by using transcriptional datasets to find the best set of cell surface markers that identify my-HSCs for antibody targeting. They found that the most highly enriched cell-surface markers in my-HSCs were CD41 (Itga2b), CD62p (Selp), and NEO1 (Neo1). These were then validated using flow cytometry on CD150high HSCs (my-HSCs) vs. CD150low HSCs (bal-HSCs) and found that in older mice, the proportion of HSCs that were NEO1+, CD41+, and CD62p+ increased, consistent with the observed increase in my-HSCs associated with aging. These markers were also largely limited to HSCs except for CD41 that was also found on meg","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"8 7","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141730160","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}

引用次数: 0

Oncogenic and immunological targets for matched therapy of pediatric blood cancer patients: Dutch iTHER study experience 儿科血癌患者匹配治疗的致癌和免疫学靶点：荷兰 iTHER 研究经验。

IF 7.6 2区医学

HemaSphere Pub Date : 2024-07-15 DOI: 10.1002/hem3.122

Judith M. Boer, Uri Ilan, Aurélie Boeree, Karin P. S. Langenberg, Jan Koster, Marco J. Koudijs, Jayne Y. Hehir-Kwa, Stefan Nierkens, Corinne Rossi, Jan J. Molenaar, Bianca F. Goemans, Monique L. den Boer, C. Michel Zwaan

{"title":"Oncogenic and immunological targets for matched therapy of pediatric blood cancer patients: Dutch iTHER study experience","authors":"Judith M. Boer, Uri Ilan, Aurélie Boeree, Karin P. S. Langenberg, Jan Koster, Marco J. Koudijs, Jayne Y. Hehir-Kwa, Stefan Nierkens, Corinne Rossi, Jan J. Molenaar, Bianca F. Goemans, Monique L. den Boer, C. Michel Zwaan","doi":"10.1002/hem3.122","DOIUrl":"10.1002/hem3.122","url":null,"abstract":"Over the past 10 years, institutional and national molecular tumor boards have been implemented for relapsed or refractory pediatric cancer to prioritize targeted drugs for individualized treatment based on actionable oncogenic lesions, including the Dutch iTHER platform. Hematological malignancies form a minority in precision medicine studies. Here, we report on 56 iTHER leukemia/lymphoma patients for which we considered cell surface markers and oncogenic aberrations as actionable events, supplemented with ex vivo drug sensitivity for six patients. Prior to iTHER registration, 34% of the patients had received allogeneic hematopoietic cell transplantation (HCT) and 18% CAR-T therapy. For 51 patients (91%), a sample with sufficient tumor percentage (≥20%) required for comprehensive diagnostic testing was obtained. Up to 10 oncogenic actionable events were prioritized in 49/51 patients, and immunotherapy targets were identified in all profiled patients. Targeted treatment(s) based on the iTHER advice was given to 24 of 51 patients (47%), including immunotherapy in 17 patients, a targeted drug matching an oncogenic aberration in 12 patients, and a drug based on ex vivo drug sensitivity in one patient, resulting in objective responses and a bridge to HCT in the majority of the patients. In conclusion, comprehensive profiling of relapsed/refractory hematological malignancies showed multiple oncogenic and immunotherapy targets for a precision medicine approach, which requires multidisciplinary expertise to prioritize the best treatment options for this rare, heavily pretreated pediatric population.","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"8 7","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11247331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619862","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}

引用次数: 0

Refinement of the prognostic impact of somatic CEBPA bZIP domain mutations in acute myeloid leukemia: Results of the AML Study Group (AMLSG) 完善体细胞 CEBPA bZIP 结构域突变对急性髓性白血病预后的影响：急性髓性白血病研究小组（AMLSG）的研究结果。

IF 7.6 2区医学

HemaSphere Pub Date : 2024-07-15 DOI: 10.1002/hem3.123

Frank G. Rücker, Andrea Corbacioglu, Julia Krzykalla, Sibylle Cocciardi, Claudia Lengerke, Ulrich Germing, Gerald Wulf, Maisun A. Samra, Lino L. Teichmann, Michael Lübbert, Michael W. M. Kühn, Martin Bentz, Jörg Westermann, Lars Bullinger, Verena I. Gaidzik, Annika Meid, Sophia Aicher, Frank Stegelmann, Daniela Weber, Anika Schrade, Felicitas Thol, Michael Heuser, Arnold Ganser, Axel Benner, Hartmut Döhner, Konstanze Döhner, for the German-Austrian Acute Myeloid Leukemia Study Group (AMLSG)

{"title":"Refinement of the prognostic impact of somatic CEBPA bZIP domain mutations in acute myeloid leukemia: Results of the AML Study Group (AMLSG)","authors":"Frank G. Rücker, Andrea Corbacioglu, Julia Krzykalla, Sibylle Cocciardi, Claudia Lengerke, Ulrich Germing, Gerald Wulf, Maisun A. Samra, Lino L. Teichmann, Michael Lübbert, Michael W. M. Kühn, Martin Bentz, Jörg Westermann, Lars Bullinger, Verena I. Gaidzik, Annika Meid, Sophia Aicher, Frank Stegelmann, Daniela Weber, Anika Schrade, Felicitas Thol, Michael Heuser, Arnold Ganser, Axel Benner, Hartmut Döhner, Konstanze Döhner, for the German-Austrian Acute Myeloid Leukemia Study Group (AMLSG)","doi":"10.1002/hem3.123","DOIUrl":"10.1002/hem3.123","url":null,"abstract":"The transcription factor CCAAT/enhancer binding protein alpha (CEBPA) is a key regulator of myelopoiesis and granulocyte differentiation.1, 2 The intronless CEBPA gene on chromosome 19q13.1 encodes two DNA-binding protein isoforms: a full-length 42-kDa protein (p42) and a shorter 30-kDa isoform (p30), initiated from two distinct start sites.2 The p42 isoform contains two N-terminal transactivation domains (TAD1, TAD2), whereas the p30 isoform lacks TAD1. Both isoforms contain the highly conserved C-terminal basic DNA-binding domain and the leucine zipper (bZIP) involved in DNA binding and protein dimerization. In younger adult patients, mutations of CEBPA (CEBPAmut) are present in 5%–10% of newly diagnosed acute myeloid leukemia (AML); the frequency in older patients is considerably lower.2-5 There are two mutational patterns: the first one clusters at the N-terminus involving the two TADs, typically frame-shift mutations; the second one at the C-terminus affecting bZIP, typically in-frame mutations. Out-of-frame TAD mutations result in the truncated p30 isoform that has been shown to act as a dominant negative of the p42 isoform and to be associated with increased proliferation and minimal differentiation of myeloid progenitors.2, 6 Depending on the position, in-frame bZIP mutations cause a p42 isoform defective either in DNA binding or homo- and heterodimerization.3, 7Approximately half of the CEBPAmut AML exhibit biallelic mutations (CEBPAbi), typically consisting of one TAD and one bZIP mutation on separate alleles.3, 4 Based on specific genetic features and its prognostic impact, CEBPAbi was defined as a distinct entity within the 2016 WHO classification and was categorized as favorable in the risk stratification of the 2017 European LeukemiaNet (ELN) recommendations. Recent studies in pediatric and adult AML have demonstrated CEBPAbZIP mutations, and in particular, in-frame mutations (CEBPAbZIP_inf), to be associated with a unique gene-expression profile and favorable outcome, regardless of the mono- or biallelic status.8-10 Based on these data, the former entity of AML with CEBPAbi was expanded by single mutations in bZIP (smbZIP-CEBPA) in the current 2022 WHO classification and replaced by AML with CEBPAbZIP_inf (irrespective of the allelic status) within the 2022 International Consensus Classification (ICC) of myeloid neoplasm and acute leukemias.11, 12 Furthermore, CEBPAbZIP_inf (irrespective of the allelic status) is now categorized as favorable in the 2022 ELN risk stratification.13To evaluate the prognostic impact of CEBPA","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"8 7","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11247273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619864","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}

引用次数: 0

Recommendations for diagnosis, treatment, and prevention of iron deficiency and iron deficiency anemia 诊断、治疗和预防缺铁和缺铁性贫血的建议。

IF 7.6 2区医学

HemaSphere Pub Date : 2024-07-15 DOI: 10.1002/hem3.108

Achille Iolascon, Immacolata Andolfo, Roberta Russo, Mayka Sanchez, Fabiana Busti, Dorine Swinkels, Patricia Aguilar Martinez, Rayan Bou-Fakhredin, Martina U. Muckenthaler, Sule Unal, Graça Porto, Tomas Ganz, Antonis Kattamis, Lucia De Franceschi, Maria Domenica Cappellini, Malcolm G. Munro, Ali Taher, from EHA-SWG Red Cell and Iron

{"title":"Recommendations for diagnosis, treatment, and prevention of iron deficiency and iron deficiency anemia","authors":"Achille Iolascon, Immacolata Andolfo, Roberta Russo, Mayka Sanchez, Fabiana Busti, Dorine Swinkels, Patricia Aguilar Martinez, Rayan Bou-Fakhredin, Martina U. Muckenthaler, Sule Unal, Graça Porto, Tomas Ganz, Antonis Kattamis, Lucia De Franceschi, Maria Domenica Cappellini, Malcolm G. Munro, Ali Taher, from EHA-SWG Red Cell and Iron","doi":"10.1002/hem3.108","DOIUrl":"10.1002/hem3.108","url":null,"abstract":"Iron is an essential nutrient and a constituent of ferroproteins and enzymes crucial for human life. Generally, nonmenstruating individuals preserve iron very efficiently, losing less than 0.1% of their body iron content each day, an amount that is replaced through dietary iron absorption. Most of the iron is in the hemoglobin (Hb) of red blood cells (RBCs); thus, blood loss is the most common cause of acute iron depletion and anemia worldwide, and reduced hemoglobin synthesis and anemia are the most common consequences of low plasma iron concentrations. The term iron deficiency (ID) refers to the reduction of total body iron stores due to impaired nutrition, reduced absorption secondary to gastrointestinal conditions, increased blood loss, and increased needs as in pregnancy. Iron deficiency anemia (IDA) is defined as low Hb or hematocrit associated with microcytic and hypochromic erythrocytes and low RBC count due to iron deficiency. IDA most commonly affects women of reproductive age, the developing fetus, children, patients with chronic and inflammatory diseases, and the elderly. IDA is the most frequent hematological disorder in children, with an incidence in industrialized countries of 20.1% between 0 and 4 years of age and 5.9% between 5 and 14 years (39% and 48.1% in developing countries). The diagnosis, management, and treatment of patients with ID and IDA change depending on age and gender and during pregnancy. We herein summarize what is known about the diagnosis, treatment, and prevention of ID and IDA and formulate a specific set of recommendations on this topic.","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"8 7","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11247274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619863","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}

引用次数: 0

Prospective genetic germline evaluation in a consecutive group of adult patients aged <60 years with myelodysplastic syndromes 对一组年龄小于 60 岁的骨髓增生异常综合征成年患者进行前瞻性基因种系评估。

IF 7.6 2区医学

HemaSphere Pub Date : 2024-07-15 DOI: 10.1002/hem3.112

Enrico Attardi, Lucia Tiberi, Giorgio Mattiuz, Daniela Formicola, Elia Dirupo, Marco G. Raddi, Angela Consagra, Debora Vergani, Rosangela Artuso, Valeria Santini

{"title":"Prospective genetic germline evaluation in a consecutive group of adult patients aged <60 years with myelodysplastic syndromes","authors":"Enrico Attardi, Lucia Tiberi, Giorgio Mattiuz, Daniela Formicola, Elia Dirupo, Marco G. Raddi, Angela Consagra, Debora Vergani, Rosangela Artuso, Valeria Santini","doi":"10.1002/hem3.112","DOIUrl":"10.1002/hem3.112","url":null,"abstract":"Relevance of germline (GL) predisposition in myelodysplastic syndromes (MDSs) was stressed in both 2022 WHO and International Consensus classifications, but its incidence is probably underestimated, especially in young adult patients. We selected a cohort of 31 consecutive de novo MDS patients with unusual young age (<60 years). We performed exome sequencing (ES) on DNA extracted from noninvasive sources (peripheral blood and saliva), filtering for a panel of 344 genes specifically tailored for detecting GL variants related to clonal and nonclonal cytopenia. We observed at least one high- or low-confidence GL MDS variant in 7/31 (22.6%) and 9/31 (29.0%) of cases, respectively. Four of 31 patients (12.9%) confirmed having established MDS/AML predisposing disorders. We found heterozygous variants in genes involved in DNA repair/cancer predisposition (ATM, ATR, FANCM, PARN, BRCA1, BRCA2, CHEK2, MSH2) in 9/31 (29.0%) cases and variants affecting ribosome biogenesis (SBDS), hematopoietic stem cell (GATA2), and megakaryocyte (ANKRD26) differentiation in single cases. Two cases had variants in RBBP6, a gene previously described exclusively in familial myeloproliferative neoplasms. Lastly, four cases had variants in genes related to inherited anemias (CUBN and PIEZO1 genes). Our results showed that “young” MDS patients aged 40–60 years carried reported and unreported GL variants with an unexpectedly high proportion, and these events co-occurred with somatic mutations recurrent in myeloid neoplasms. We explored the “no man's land” of the young adult MDS cases adopting a practical and scalable diagnostic tool, capable to detect GL variants avoiding invasive methods.","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"8 7","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11250510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626550","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}

引用次数: 0

CD49d expression is included in a revised 4-factor model predicting outcome in patients with chronic lymphocytic leukemia treated with ibrutinib: A multicenter real-world experience CD49d表达被纳入预测伊布替尼治疗慢性淋巴细胞白血病患者预后的修订4因素模型：多中心真实世界经验。

IF 7.6 2区医学

HemaSphere Pub Date : 2024-07-15 DOI: 10.1002/hem3.128

Riccardo Bomben, Antonella Zucchetto, Roberta Laureana, Annalisa Chiarenza, Jacopo Olivieri, Erika Tissino, Francesca M. Rossi, Filippo Vit, Tamara Bittolo, Robel Papotti, Federico Pozzo, Annalisa Gaglio, Massimo Degan, Jerry Polesel, Roberto Marasca, Andrea Visentin, Riccardo Moia, Idanna Innocenti, Candida Vitale, Roberta Murru, Marzia Varettoni, Agostino Tafuri, Francesco Zaja, Massimiliano Postorino, Enrica A. Martino, Adalgisa Condoluci, Davide Rossi, Antonio Cuneo, Francesco Di Raimondo, Paolo Sportoletti, Ilaria Del Giudice, Robin Foà, Francesca R. Mauro, Marta Coscia, Luca Laurenti, Gianluca Gaidano, Livio Trentin, Maria I. Del Principe, Massimo Gentile, Valter Gattei

{"title":"CD49d expression is included in a revised 4-factor model predicting outcome in patients with chronic lymphocytic leukemia treated with ibrutinib: A multicenter real-world experience","authors":"Riccardo Bomben, Antonella Zucchetto, Roberta Laureana, Annalisa Chiarenza, Jacopo Olivieri, Erika Tissino, Francesca M. Rossi, Filippo Vit, Tamara Bittolo, Robel Papotti, Federico Pozzo, Annalisa Gaglio, Massimo Degan, Jerry Polesel, Roberto Marasca, Andrea Visentin, Riccardo Moia, Idanna Innocenti, Candida Vitale, Roberta Murru, Marzia Varettoni, Agostino Tafuri, Francesco Zaja, Massimiliano Postorino, Enrica A. Martino, Adalgisa Condoluci, Davide Rossi, Antonio Cuneo, Francesco Di Raimondo, Paolo Sportoletti, Ilaria Del Giudice, Robin Foà, Francesca R. Mauro, Marta Coscia, Luca Laurenti, Gianluca Gaidano, Livio Trentin, Maria I. Del Principe, Massimo Gentile, Valter Gattei","doi":"10.1002/hem3.128","DOIUrl":"10.1002/hem3.128","url":null,"abstract":"Chronic lymphocytic leukemia (CLL) is a malignancy of mature clonal B lymphocytes that accumulate in blood, bone marrow, and lymphoid tissues.1 One of the most important key players in the pathobiology and progression of CLL is the B-cell receptor (BCR) whose activation supports growth and survival of CLL cells.2 For this reason, the use of Bruton's tyrosine kinase inhibitors (BTKi) including ibrutinib emerged as one of the most effective treatment options for both naïve (TN) and relapsed/refractory (RR) CLL.2 Treatment with BTKi often results in an increase blood lymphocytosis driven by the release of cells from lymph nodes due to impaired interaction with the microenvironment.2-4 One of the key molecules of these interactions is the integrin VLA-4 which mediates both cell–cell and cell–matrix interactions playing a crucial role in the retention of CLL cells in tissue-sites thus protecting them from proapoptotic signal.3, 5-7 In keeping with these observations, high expression of the VLA-4 integrin alpha chain CD49d (≥30% positive cells), or expression of CD49d according to a bimodal pattern (i.e., concurrent CD49d-positive and CD49d-negative subpopulations, irrespective of the 30% cutoff) identifies CLL cases with reduced recirculation lymphocytosis, inferior nodal response, and shorter progression-free survival (PFS) in the ibrutinib setting.4, 5In addition to CD49d evaluation, a 4-factor model has been proposed to identify patients at high risk of treatment failure and death during ibrutinib therapy, afterward validated in real-world, which included the TN/RR status, the levels of β2-microglobulin (β2M) and lactate dehydrogenase (LDH) serum concentration, and the TP53 disruption status.8, 9 In this context, as well as in other clinical studies on CLL, the TP53 disruption category includes CLL cases with either concurrent TP53 mutation and deletion, or only one of the lesions.1, 8, 9 Recently, the prognostic impact of TP53 disruption in ibrutinib-treated CLL has been refined by demonstrating that only cases with the concomitant presence of TP53 deletion and mutations, did not gain maximum benefit from this therapy.10, 11The aim of this study is to integrate these observations in a comprehensive scoring system for a better management of ibrutinib-treated patients.The study is a retrospective/multicenter analysis of 401 CLL patients treated with ibrutinib in the current clinical practice (12/2013–03/2022; approvals IRB-05-2010/IRB-05-2015; CRO Aviano). All CLL cases were characterized for CD49d expression, as reported previously.4-7, 12 TP53 disruption was simultaneously evaluated by FISH (17p deletion, del17p) and next-generation sequencing (TP53 mutations), as reported.<s","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"8 7","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11247362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619861","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}

引用次数: 0

Parents' perception of treatment-related toxicity in children treated according to the NOPHO ALL2008 protocol for acute lymphoblastic leukemia 按照 NOPHO ALL2008 方案治疗急性淋巴细胞白血病的儿童家长对治疗相关毒性的看法

IF 7.6 2区医学

HemaSphere Pub Date : 2024-07-12 DOI: 10.1002/hem3.124

Nina Mogensen, Ulrika Kreicbergs, Birgitte K. Albertsen, Päivi M. Lähteenmäki, Mats Heyman, Arja Harila

{"title":"Parents' perception of treatment-related toxicity in children treated according to the NOPHO ALL2008 protocol for acute lymphoblastic leukemia","authors":"Nina Mogensen, Ulrika Kreicbergs, Birgitte K. Albertsen, Päivi M. Lähteenmäki, Mats Heyman, Arja Harila","doi":"10.1002/hem3.124","DOIUrl":"https://doi.org/10.1002/hem3.124","url":null,"abstract":"This study aimed to assess how parents perceived treatment-related side effects during acute lymphoblastic leukemia (ALL) treatment. Parents of children 1–17.9 years at diagnosis in Sweden, Finland, and Denmark who were alive and in first remission ≥6 months after end of ALL treatment were asked to respond on specific items regarding how their child was affected by side effects related to vincristine (VCR), corticosteroids, peg-asparaginase (ASP), and maintenance therapy, as well as overall impact of these treatments, complications in general, and their perception of impact on their child in comparison with other children with ALL. Parents of 307 children responded. More than a third reported that their child had been affected to a high extent by VCR (39.7%) and corticosteroids (35.8%), with walking difficulties, muscular weakness, pain, changes in appetite, and mood swings as the most common and severe symptoms. Reporting of these toxicities was lacking from the NOPHO ALL2008 database, except for peripheral paralysis (12.1%). For distinct toxicities reported in the NOPHO ALL2008 database, for example, thrombosis and pancreatitis, parent reports were similar to the database. Although a high overall negative impact during treatment was reported, parents generally rated the impact on their child as less, or similar, to other children with ALL. Parents perceived VCR and corticosteroid therapy, in particular, to have a negative impact on their child during ALL treatment, which was not captured in the NOPHO ALL2008 toxicity reporting. Our results highlight the importance of including patient/parent-reported outcomes in toxicity reporting.","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"8 7","pages":""},"PeriodicalIF":7.6,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141597148","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}

引用次数: 0