American Journal of Hematology最新文献

{"title":"High‐grade B‐cell lymphoma not otherwise specified, with diffuse large B‐cell lymphoma gene expression signatures: Genomic analysis and potential therapeutics","authors":"Waseem Lone, Alyssa Bouska, Tyler A. Herek, Catalina Amador, Joo Song, Alexander M. Xu, Dylan Jochum, Issa Ismail Issa, Dennis D. Weisenburger, Xuan Zhang, Sharath Kumar Bhagavathi, Tayla B. Heavican‐Foral, Sunandini Sharma, Ab Rauf Shah, Abdul Rouf Mir, Aisha Ahmad Alkhinji, Dalia El‐Gamal, Bhavana J. Dave, Keenan Hartert, Jiayu Yu, Mallick Saumyaranjan, Timothy C. Greiner, Julie Vose, Timothy W. McKeithan, Kai Fu, Michael Green, Chengfeng Bi, Akil Merchant, Wing C. Chan, Javeed Iqbal","doi":"10.1002/ajh.27513","DOIUrl":"https://doi.org/10.1002/ajh.27513","url":null,"abstract":"High‐grade B‐cell lymphoma not otherwise specified (HGBCL, NOS) has overlapping morphological and genetic features with diffuse large B‐cell lymphoma (DLBCL) and Burkitt lymphoma (BL), leading to uncertainty in its diagnosis and clinical management. Using functional genomic approaches, we previously characterized HGBCL and NOS, that demonstrate gene expression profiling (GEP), and genetic signatures similar to BL. Herein, we characterize distinct HGBCL, NOS, cohort (<jats:italic>n</jats:italic> = 55) in adults (<jats:italic>n</jats:italic> = 45) and in children (<jats:italic>n</jats:italic> = 10), and compared the GEP, genomic DNA copy number (CN), and mutational spectrum with <jats:italic>de novo</jats:italic> DLBCL (<jats:italic>n</jats:italic> = 85) and BL (<jats:italic>n</jats:italic> = 52). This subgroup, representing ~60% of HGBCL, NOS, lack gene‐expression signature of BL and double hit/dark zone lymphoma, but express DLBCL like signatures and are characterized by either GCB‐ or ABC‐like mRNA signatures and exhibit higher genomic complexity, similar to <jats:italic>de novo</jats:italic> DLBCL, and show alteration in genes regulating B‐cell activation (<jats:italic>CD79B</jats:italic>, <jats:italic>MYD88</jats:italic>, <jats:italic>PRDM1</jats:italic>, <jats:italic>TBLIXR1</jats:italic>, <jats:italic>CARD11</jats:italic>), epigenome (<jats:italic>KMT2D</jats:italic>, <jats:italic>TET2</jats:italic>) and cell cycle transition (<jats:italic>TP53</jats:italic>, <jats:italic>ASPM</jats:italic>). However, recurrent mutations in genes often mutated in BL (DDX3X, GNA13, CCND3), but rare in DLBCL, are also present in HGBCL‐NOS, highlighting genetic heterogeneity. Consistent with mutation spectrum, frequent genomic CN alterations in genes regulating B‐cell activation (del‐<jats:italic>PRDM1</jats:italic>, gain‐<jats:italic>BCL6</jats:italic>, ‐<jats:italic>REL</jats:italic>, ‐<jats:italic>STAT3</jats:italic>) and cell cycle regulators (del‐<jats:italic>TP53</jats:italic>, del‐<jats:italic>CDKN2A</jats:italic>, del‐<jats:italic>RB1</jats:italic>, gain‐<jats:italic>CCND3</jats:italic>) were observed. Pediatric cases showed GCB‐DLBCL‐like mRNA signatures, but also featured hallmark mutations of pediatric BL. Frequent oncogenic <jats:italic>PIM1</jats:italic> mutations were present in adult HGBCL, NOS. <jats:italic>In vitro</jats:italic> analyses with pharmacologic or genetic inhibition of <jats:italic>PIM1 expression</jats:italic> triggered B‐cell activation and NF‐κB‐induced apoptosis, suggesting that <jats:italic>PIM1</jats:italic> is a rational therapeutic target.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"17 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142642568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A prophylactic tyrosine kinase inhibitor strategy based on measurable residual disease pre-transplantation for Ph+ acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation: A prospective multicenter cohort study","authors":"Hui Liu, Hui Xu, Peiru Chi, Zinan Feng, Xiaojun Xu, Danian Nie, Xudong Li, Xinquan Liang, Zhiping Fan, Na Xu, Fen Huang, Ren Lin, Zhixiang Wang, Hua Jin, Hongsheng Zhou, Xutao Guo, Dongjun Lin, Jing Sun, Qifa Liu, Li Xuan","doi":"10.1002/ajh.27516","DOIUrl":"https://doi.org/10.1002/ajh.27516","url":null,"abstract":"Relapse is the major cause of treatment failure in Philadelphia chromosome-positive (Ph⁺) acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to evaluate the effect of a prophylactic tyrosine kinase inhibitor (TKI) strategy on relapse in this population. Patients were assigned to prophylactic or control groups based on measurable residual disease (MRD) pre-transplantation. The primary endpoint was the cumulative incidence of relapse. A total of 110 patients with Ph⁺ ALL undergoing allo-HSCT were enrolled in this prospective study. Thirty-eight patients with positive MRD pre-transplantation were included in the prophylactic group, and 72 with negative MRD pre-transplantation were included in the control group. The 4-year cumulative incidence of relapse was 25.3% (95% CI: 12.1%–41.0%) and 20.3% (11.6%–30.7%; HR = 1.272, 95% CI: 0.551–2.940, <i>p</i> = .549), and non-relapse mortality was 10.5% (3.3%–22.7%) and 9.7% (4.2%–17.9%; HR = 1.094, 95% CI: 0.320–3.738, <i>p</i> = .928) in the prophylactic and control groups. The 4-year overall survival was 71.8% (53.2%–84.1%) and 84.1% (72.9%–90.9%; HR = 1.746, 95% CI: 0.741–4.112, <i>p</i> = .196), and leukemia-free survival was 64.1% (45.8%–77.7%) and 70.0% (57.6%–79.4%; HR = 1.212, 95% CI: 0.607–2.421, <i>p</i> = .585) in the prophylactic and control groups. Our results suggest that prophylactic TKI post-HSCT in patients with positive MRD pre-transplantation can produce outcomes comparable to negative MRD pre-transplantation without TKI post-HSCT.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"76 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical significance of complete remission and measurable residual disease in relapsed/refractory multiple myeloma patients treated with T-cell redirecting immunotherapy","authors":"Aintzane Zabaleta, Noemi Puig, Maria-Teresa Cedena, Aina Oliver-Caldes, José J. Perez, Cristina Moreno, Luis-Esteban Tamariz-Amador, Paula Rodriguez-Otero, Felipe Prosper, Veronica Gonzalez-Calle, Lucía López-Corral, Beatriz Rey-Búa, Borja Puertas, Fátima Mirás, José María Sánchez-Pina, Nieves López-Muñoz, Manel Juan, E. Azucena González-Navarro, Álvaro Urbano, Carlos Fernández de Larrea, Joan Blade, Juan-José Lahuerta, Joaquín Martinez-Lopez, Maria-Victoria Mateos, Jesús F. San Miguel, Bruno Paiva","doi":"10.1002/ajh.27526","DOIUrl":"https://doi.org/10.1002/ajh.27526","url":null,"abstract":"The impact of measurable residual disease (MRD) in relapse/refractory multiple myeloma (RRMM) patients treated with T-cell redirecting immunotherapy is uncertain. We analyzed MRD dynamics using next-generation flow in 201 patients treated in clinical trials with chimeric antigen receptor (CAR) T cells and T-cell engagers (TCE). Achieving MRD negativity at 10⁻⁶ was associated with 89% reduction in the risk of progression and/or death. Survival outcomes were improved in patients with sustained versus transient MRD negativity and were dismal in those who remained MRD positive. The intent-to-treat MRD negative rates were higher in patients treated with CAR T cells versus TCE. However, among patients achieving MRD negativity, there were no differences in survival outcomes when stratified according to treatment with CAR T cells versus TCE. In multivariate analysis including the number of prior lines of treatment, International Staging System, cytogenetic risk, extramedullary disease and type of T-cell redirecting immunotherapy, only the complete remission (CR) and MRD statuses showed independent prognostic value for progression-free and overall survival. In conclusion, our study shows that deep and sustained MRD negative CR is the most relevant prognostic factor and should be considered as the treatment endpoint in RRMM patients treated with CAR T cells and TCE.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"76 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperparathyroidism and the Hematologist","authors":"Hajer Oun, Kirsteen Harper, Mike Leach, Barbara J. Bain","doi":"10.1002/ajh.27527","DOIUrl":"https://doi.org/10.1002/ajh.27527","url":null,"abstract":"<div>\u0000<figure>\u0000<div><picture>\u0000<source media=\"(min-width: 1650px)\" srcset=\"/cms/asset/b04baa4a-6e9e-4b9c-9c1d-6db3d8f072e6/ajh27527-gra-0001-m.jpg\"/><img alt=\"image\" data-lg-src=\"/cms/asset/b04baa4a-6e9e-4b9c-9c1d-6db3d8f072e6/ajh27527-gra-0001-m.jpg\" loading=\"lazy\" src=\"/cms/asset/596227e9-704e-4d09-a9bc-5ecba0f0acec/ajh27527-gra-0001-m.png\" title=\"image\"/></picture><p></p>\u0000</div>\u0000</figure>\u0000</div>\u0000<p>A 76-year-old man with a history of chronic obstructive pulmonary disease with lung fibrosis, type 2 diabetes mellitus, and chronic kidney disease underwent computed tomography imaging of the chest due to increasing dyspnea. The bones appeared sclerotic, and a bone scan showed diffuse tracer uptake throughout the axial and appendicular skeleton. The prostate showed no features of malignancy on magnetic resonance imaging and prostate-specific antigen was 6.6 μg/L (normal range (NR) 0–5). Serum tryptase levels were mildly elevated at 16 μg/L (NR 2–14) on two occasions. Biochemical investigations showed vitamin D &lt; 14 nmol/L (NR &gt; 50), alkaline phosphatase 665 U/L (NR 30–130), parathyroid hormone 52.8 pmol/L (NR 1.6–7.5), calcium 2.43 mmol/L (NR 2.2–2.6) and phosphate 1.07 mmol/L (NR 0.8–1.5), in keeping with hyperparathyroidism secondary to vitamin D deficiency and chronic kidney disease (creatinine 169 μmol/L and estimated glomerular filtration rate 34 mL/min).</p>\u0000<p>Bone marrow trephine biopsy sections showed areas of active bone resorption by multinucleate osteoclasts forming recesses known as Howship's lacunae (top and bottom left, all histological images hematoxylin and eosin, ×50 objective). In other areas, lamellar bone was being actively laid down by rows of osteoblasts (top center). There was patchy fibrosis at sites of previous bone resorption (bottom center). Notably, there were osteoclasts also visible in the marrow aspirate (top and bottom right, May–Grünwald–Giemsa, ×100 objective). There was no abnormal mast cell population.</p>\u0000<p>These features are typical of hyperparathyroidism where osteoclasts strive to release calcium whilst osteoblasts attempt to repair the trabecular damage. This active bone remodeling with the associated trabecular changes generates the sclerotic radiological appearance of the affected bones. Osteoblasts and osteoclasts normally work together in bone repair, remodeling, and growth but this process is exaggerated under the influence of increased parathyroid hormone whether primary, due to a parathyroid adenoma, or secondary, as a result of vitamin D deficiency or chronic kidney disease. The recognition of the features of bone disorders with associated bone marrow fibrosis is important so that they are not confused with myeloproliferative neoplasms.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"19 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Globalization in clinical drug development for sickle cell disease","authors":"Enrico Costa, Russell E. Ware, Léon Tshilolo, Julie Makani, Hubert G. M. Leufkens, Lucio Luzzatto","doi":"10.1002/ajh.27525","DOIUrl":"https://doi.org/10.1002/ajh.27525","url":null,"abstract":"&lt;h2&gt;1 BACKGROUND&lt;/h2&gt;\u0000&lt;p&gt;Globalization of clinical trials, defined operationally as conduct in the international arena, has grown over the past few decades. The pharmaceutical industry is expanding its activities not only in High-Income countries but also in Low- and Middle-Income countries (LMICs).&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;\u0000&lt;p&gt;For pharmaceutical companies, this shift can be associated with several benefits: a larger pool of potential participants, faster enrollment in trials, and substantial cost savings.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; At the same time, there may be advantages also for LMICs in terms of capacity building, gaining experience, and access to innovation.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;\u0000&lt;p&gt;Drug development and access to medicines in LMICs is certainly a challenge for patients with sickle cell disease (SCD), a condition that is most highly prevalent in malaria-endemic countries in the global South, but that, through the tragedy of the transatlantic slave trade and subsequent migrations, is also prominent in the global North.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;\u0000&lt;p&gt;The prevalence of SCD outside Africa has accelerated the development of new medicinal products, enhanced by a conducive regulatory framework. The orphan drug legislation in the United States (US) and the European Union (EU) have provided pharmaceutical developers with special incentives (e.g., periods of market exclusivity) to counterbalance the limited market size. In addition, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have implemented special pathways to expedite the review and approval of treatments for serious and life-threatening diseases. Accordingly, in both the US and the EU, treatments for SCD can be approved based on surrogate endpoints or more flexible evidence.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;\u0000&lt;p&gt;To assess the trends and impact of globalization on the development of SCD drugs, we analyzed data from industry-sponsored studies initiated in the time interval from 1 January 1990 through 30 June 2024 (see Appendix S1). In the study period, a total of 79 pharmaceutical active substances were tested in 156 clinical trials.&lt;/p&gt;\u0000&lt;p&gt;Overall, 56.4% of enrolling centers were in North America, 20.5% in Europe, 7.9% in Africa, 5.7% in Latin America, 9.1% in Asia and Middle East, and 0.4% in Australia. Temporal trends from the early 2000s to the last 5 years showed a relative decrease of enrolling centers in North America from 63.1% to 44.0%, and in Europe from 28.5% to 22.2%. By contrast, in African centers there was an increase from 0.5% to 13.2%, in Latin America from 1.1% to 9.0%, and in Asia and the Middle East from 5.7% to 11.4%. The number of Australian centers remained low over time.&lt;/p&gt;\u0000&lt;p&gt;Similar trends were mirrored in the drug development phases: for instance, enrolling centers in Africa increased from 2.8% in Phase 1 trials to 4.2% in Phase 2, and to 10.6% in Phase 3 and 11.9% in Phase 4 trials. Similar increases were observed in Latin America","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"32 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of zanubrutinib monotherapy for chronic lymphocytic leukemia/small lymphocytic lymphoma: A multicenter, real-world study in China.","authors":"Jing Luo, Jiaojiao Zhang, Ligen Liu, Rong Wei, Yonghua Yao, Min Xu, Jumei Shi, Jianmin Yang, Jian Hou, Jin Wang, Jian-Qing Mi","doi":"10.1002/ajh.27519","DOIUrl":"https://doi.org/10.1002/ajh.27519","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of post-remission granulocyte colony-stimulating factor use in the phase 3 studies of venetoclax combination treatments in patients with newly diagnosed acute myeloid leukemia","authors":"Courtney D. DiNardo, Keith W. Pratz, Panayiotis Panayiotidis, Xudong Wei, Vladimir Vorobyev, Árpád Illés, Inho Kim, Vladimir Ivanov, Grace Ku, Catherine L. Miller, Meng Zhang, Fernando Tatsch, Jalaja Potluri, Xenia Schmidt, Christian Récher","doi":"10.1002/ajh.27515","DOIUrl":"https://doi.org/10.1002/ajh.27515","url":null,"abstract":"&lt;p&gt;Based on results from the randomized, placebo-controlled phase 3 VIALE-A (NCT02993523) and VIALE-C (NCT03069352) trials,&lt;span&gt;&lt;sup&gt;1-4&lt;/sup&gt;&lt;/span&gt; venetoclax in combination with hypomethylating agents or low-dose cytarabine (LDAC) has become standard of care in patients with newly diagnosed acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy. Cytopenias are common adverse events with venetoclax and are primarily managed with protocol-mandated dose modifications, including dose interruptions and cycle delays.&lt;span&gt;&lt;sup&gt;2, 5&lt;/sup&gt;&lt;/span&gt; Neutropenia and febrile neutropenia may be mitigated with granulocyte-colony stimulating factor (G-CSF)&lt;span&gt;&lt;sup&gt;4, 6&lt;/sup&gt;&lt;/span&gt;; however, limited evidence exists on G-CSF use and impact on safety and efficacy in patients receiving low-intensity therapies. The present analysis assessed outcomes by G-CSF use post-remission (i.e., following blast clearance) among patients with newly diagnosed, intensive-chemotherapy–ineligible AML who received venetoclax-azacitidine or venetoclax-LDAC in the VIALE-A and VIALE-C trials, respectively.&lt;/p&gt;\u0000&lt;p&gt;VIALE-A and VIALE-C study designs have been previously described.&lt;span&gt;&lt;sup&gt;1, 3&lt;/sup&gt;&lt;/span&gt; Both trials enrolled patients aged ≥18 years with newly diagnosed AML who were ineligible for induction chemotherapy (aged ≥75 years or with comorbid conditions precluding intensive chemotherapy treatment). In VIALE-A, patients received venetoclax-azacitidine or placebo-azacitidine; in VIALE-C, patients received venetoclax-LDAC or placebo-LDAC. Both trial protocols allowed G-CSF use with administration for cytopenia management as per institutional practice. In this exploratory post hoc analysis, patients treated with venetoclax combinations who had achieved a best response of complete remission (CR)/CR with incomplete hematologic recovery (CRi) were assessed for outcomes by G-CSF use, including overall survival (OS), duration of CR/CRi (DOR), and safety. G-CSF use was analyzed from the time of remission achievement (post-remission), defined as blast clearance (&lt;5% bone marrow blasts) for this analysis. Clinical data cutoff was December 1, 2021 for VIALE-A and February 15, 2021 for VIALE-C.&lt;span&gt;&lt;sup&gt;2, 3&lt;/sup&gt;&lt;/span&gt; The analysis populations included patients who achieved best response of CR/CRi, unless otherwise specified.&lt;span&gt;&lt;sup&gt;1, 3&lt;/sup&gt;&lt;/span&gt; Data presentation is descriptive in nature, and formal statistical comparisons were not performed due to the post hoc nature of this analysis. Additional details are in the Data S1.&lt;/p&gt;\u0000&lt;p&gt;Approximately half of patients treated with venetoclax combinations in VIALE-A and VIALE-C received G-CSF post-remission. In VIALE-A, 50% (95/191) of CR/CRi responders in the venetoclax-azacitidine arm and 26% (11/42) in the placebo-azacitidine arm received G-CSF post-remission (Tables S1 and S2). In VIALE-C, 46% (32/69) of CR/CRi responders in the venetoclax-LDAC arm and 22% (2/9) in the placebo-LDAC arm received G-CSF post","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"213 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ibrutinib-related stellar hematomas of the palms and soles.","authors":"Naia Oillarburu, Loic Ysebaert, Caroline Protin, Ariadna Ortiz-Brugues, Sarah Baali, Estelle Parriel, Vincent Sibaud","doi":"10.1002/ajh.27514","DOIUrl":"https://doi.org/10.1002/ajh.27514","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic significance of early acute splenic sequestration in children with severe sickle cell genotypes: A comprehensive longitudinal neonatal cohort study","authors":"Alizée Soulié, Cécile Arnaud, Serge Pissard, Isabelle Hau, Mickaël Shum, Fouad Madhi, Céline Delestrain, Sandra Biscardi, Sabine Blary, Bassem Khazem, Ekaterina Belozertsteva, Eric Guemas, Ralph Epaud, Annie Kamdem, Corinne Pondarré","doi":"10.1002/ajh.27517","DOIUrl":"https://doi.org/10.1002/ajh.27517","url":null,"abstract":"&lt;p&gt;Acute splenic sequestration crisis (ASSC) is one of the earliest acute clinical manifestations of sickle cell anemia (SCA), with a median age at first episode of 1.8 years [range: 0.4–12.9] as reported for our recently published regional longitudinal newborn cohort, beginning with the introduction of newborn screening (1986) and ending just before the introduction of preventive intensification with hydroxyurea (HU) in 2015.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Early predictive biomarkers have been identified for ASSC, but little is known about the impact of early ASSC on disease severity.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Unlike early dactylitis, early ASSC was not found to be associated with an increase in the risk of adverse outcomes, including death, stroke, frequent vaso-occlusive crisis (VOC), and recurrent acute chest syndrome (ACS), in a cohort of newborns with SCA.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;\u0000&lt;p&gt;Our main objective here was to determine, from our SCA birth cohort, whether children experiencing early ASSC have a higher disease burden. In addition, we aimed to update clinical information on ASSC and confirm the prognostic factors identified in previous studies. Consistent with the French standards of care, for the whole cohort, disease-modifying therapies (DMT) were started only after the occurrence of complications: transfusion program (TP) was mainly implemented for stroke prevention, and HU was prescribed only to children over the age of 3 years for low hemoglobin (Hb) levels and/or recurrence of VOC/ACS. Specifically at our center, TP was offered for frequent VOC/ACS or anemia despite HU, or in children younger than 3 years, and hematopoietic stem cell transplantation (HSCT) to patients with cerebral vasculopathy or frequent VOC/ACS with a human leukocyte antigen-identical sibling. In our cohort-study, the use of DMT was thus considered a surrogate for disease severity.&lt;/p&gt;\u0000&lt;p&gt;ASSC was defined as splenic enlargement (increase of at least 2 cm from baseline) measured below the costal margin and associated with acute anemia (decrease in Hb concentration &gt;2 g/dL relative to the previous measurement). Early and late ASSC were defined as a first episode of ASSC occurring before or after the age of 2 years respectively. During ASSC, standard management was prompt transfusion to restore effective circulating volume. After the resolution of a first ASSC, local guidelines recommended watchful waiting, unless children had another reason for receiving TP or HU. After the second or third episode, then either splenectomy or a temporary prophylactic TP were considered, to prevent ASSC recurrence. The age at which splenectomy was considered (usually after 3 years of age) and the indication for splenectomy after TP (only if persistent splenomegaly during TP or systematic) varied over time.&lt;/p&gt;\u0000&lt;p&gt;Children were classified into two groups on the basis of the timing of the first ASSC: before 2 years (early ASSC group), or after 2 years or no ASSC (other group). Descript","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"214 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of myelodysplasia-related mutations on 2022 European LeukemiaNet genetic risk classification in de novo acute myeloid leukemia with normal karyotype.","authors":"Srija Shanker, Robert P Hasserjian, Yazan Madanat, Olga K Weinberg, Miguel D Cantu","doi":"10.1002/ajh.27518","DOIUrl":"https://doi.org/10.1002/ajh.27518","url":null,"abstract":"<p><p>De novo normal karyotype AML 2017ELN and 2022ELN Genetic Risk Category Changes and Overall Survival in Induction Treated Patients.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}