American Journal of Hematology最新文献

{"title":"Pseudothrombocytopenia due to Phagocytosis of Platelets by Polymorphonuclear Leukocytes","authors":"Iliana Stamatiou, Zoe Bezirgiannidou, Evangelia Charitaki, Ioannis Kotsianidis, Konstantinos Liapis","doi":"10.1002/ajh.27562","DOIUrl":"https://doi.org/10.1002/ajh.27562","url":null,"abstract":"<p>A 75-year-old woman presented to the emergency department with progressive abdominal pain, fever, and diarrhea after taking levofloxacin for a respiratory tract infection. On evaluation, she was in clinical shock, with blood pressure 88/58 mmHg and heart rate 122 beats per minute. A complete blood count provided by the Sysmex XN-1000 analyzer showed leukocytosis (13.8 × 10<sup>9</sup>/L, 95% neutrophils) and thrombocytopenia (22 × 10<sup>9</sup>/L). She had acidosis, renal impairment, coagulopathy, and elevated C-reactive protein level. Because of the thrombocytopenia, an examination of a peripheral-blood smear was performed in the hematology laboratory, which showed vacuolated neutrophils that contained phagocytized platelets. Of 200 neutrophils examined, 161 (80%) contained between one and six platelets (Figure 1). These findings indicated spurious thrombocytopenia. The emergency department staff were notified by the laboratory that the patient's platelet count was normal. Subsequently, she underwent internal jugular-vein catheterization for fluid resuscitation without oozing or hematoma. Pseudomembranous colitis was diagnosed on the basis of a positive <i>Clostridioides difficile</i> stool test. She was treated with metronidazole and vancomycin, but her course was complicated by renal failure necessitating hemodialysis. Eventually, she made a full recovery. During hospitalization, multiple routinely prepared films from EDTA-anticoagulated blood consistently demonstrated platelet phagocytosis but with the resolution of the colitis, the phenomenon became progressively less pronounced. The automated platelet count became normal within 30 days.</p>\u0000<figure><picture>\u0000<source media=\"(min-width: 1650px)\" srcset=\"/cms/asset/43ba7b26-cdb9-4a52-851b-76e271182229/ajh27562-fig-0001-m.jpg\"/><img alt=\"Details are in the caption following the image\" data-lg-src=\"/cms/asset/43ba7b26-cdb9-4a52-851b-76e271182229/ajh27562-fig-0001-m.jpg\" loading=\"lazy\" src=\"/cms/asset/533e4fe2-c86d-4138-a00c-28ff5b938961/ajh27562-fig-0001-m.png\" title=\"Details are in the caption following the image\"/></picture><figcaption>\u0000<div><strong>FIGURE 1<span style=\"font-weight:normal\"></span></strong><div>Open in figure viewer<i aria-hidden=\"true\"></i><span>PowerPoint</span></div>\u0000</div>\u0000<div>Four fields of the peripheral-blood smear, showing ingestion of platelets by neutrophilic granulocytes (May-Grünwald-Giemsa stain, ×1000).</div>\u0000</figcaption>\u0000</figure>\u0000<p>A peripheral-blood smear should always be examined in new cases of thrombocytopenia or whenever the platelet count is unexpectedly low, in order to confirm the thrombocytopenia. The blood smear may be requested by physicians or initiated by laboratory staff [<span>1</span>]. As seen here, a laboratory-initiated blood smear, is particularly valuable because it may permit earlier recognition of pseudothrombocytopenia. The incidence of pseudothrombocytopenia is 1.9% among hospitalized patients and 0.15% in the outpatient setting [","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"26 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825503","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 Diversity of Spiculated Erythrocytes","authors":"Barbara J. Bain","doi":"10.1002/ajh.27560","DOIUrl":"https://doi.org/10.1002/ajh.27560","url":null,"abstract":"<p><img alt=\"image\" loading=\"lazy\" src=\"/cms/asset/2cd87167-ea76-439c-a36d-dcebdb4994e9/ajh27560-gra-0001.png\"/>Spiculated erythrocytes come in a variety of forms, which are of diagnostic importance. They can be broadly classified as echinocytes, acanthocytes, keratocytes, and schistocytes. However, complexity is added by the superimposition of one abnormality on another. Other spiculated cells can, for example, undergo an echinocytic or acanthocytic change. In addition, other poikilocytes, for example, spherocytes, can also undergo spiculation.</p>\u0000<p>An acanthocyte is an erythrocyte with a small number of irregularly shaped and irregularly disposed projections on its surface. The name comes from the Greek, <i>άκανθα</i>, meaning thorn. These cells are most often a feature of hyposplenism but also occur in liver failure, when the term “spur cell hemolytic anemia” has been used. The upper images show acanthocytosis in a patient with drug-induced acute liver failure (all images May–Grunwald–Giemsa, ×100 objective). Acanthocytes also occur in rare inherited disorders such as the McLeod phenotype and choreo-acanthocytosis [<span>1</span>]. The lower images show a more complex situation. Here we have spheroacanthocytes in a patient with hereditary spherocytosis who has had a splenectomy. The formation of the spicules has been constrained by the spherical form of the cell.</p>\u0000<p>An echinocyte is a cell with numerous short regular spicules. The name comes from the Greek, <i>εχĩνος</i> meaning sea-urchin. Echinocytosis is most often seen as a storage artifact, when it is referred to as crenation. It is a feature of pyruvate kinase deficiency, particularly post-splenectomy when the defective cells persist in the circulation [<span>2</span>].</p>\u0000<p>A keratocyte is a cell with two or four paired spicules, from the Greek, <i>κέρα</i>ς, for horn, while a schistocyte is a jagged red cell fragment, from the Greek, <i>σχίζω</i>, for split or divide. Both are features of microangiopathic and mechanical hemolytic anemias [<span>3</span>]. Keratocytes are also seen in Heinz body hemolytic anemia, as in acute hemolysis in glucose-6-phosphate dehydrogenase deficiency.</p>\u0000<p>An appreciation of these diverse spiculated cells can be important in diagnosis.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"22 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816211","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":"Mayo Genetic Risk Models for Newly Diagnosed Acute Myeloid Leukemia Treated With Venetoclax + Hypomethylating Agent","authors":"Naseema Gangat, Azeem Elbeih, Nour Ghosoun, Kristen McCullough, Fnu Aperna, Isla M. Johnson, Maymona Abdelmagid, Aref Al-Kali, Hassan B. Alkhateeb, Kebede H. Begna, Michelle Elliott, Abhishek Mangaonkar, Aasiya Matin, Antoine N. Saliba, Mehrdad Hefazi Torghabeh, Mark R. Litzow, William Hogan, Mithun Shah, Mrinal M. Patnaik, Animesh Pardanani, Talha Badar, Hemant Murthy, James Foran, Jeanne Palmer, Lisa Sproat, Nandita Khera, Cecilia Arana Yi, Samuel Yates, Abigail Sneider, Emily Dworkin, Anand A. Patel, Alexandre Bazinet, Jayastu Senapati, Alex Bataller, Courtney DiNardo, Tapan Kadia, Ayalew Tefferi","doi":"10.1002/ajh.27564","DOIUrl":"https://doi.org/10.1002/ajh.27564","url":null,"abstract":"Patients with newly diagnosed acute myeloid leukemia (ND-AML) derive variable survival benefit from venetoclax + hypomethylating agent (Ven-HMA) therapy. The primary objective in the current study was to develop genetic risk models that are predictive of survival and are applicable at the time of diagnosis and after establishing treatment response. Among 400 ND-AML patients treated with Ven-HMA at the Mayo Clinic, 247 (62%) achieved complete remission with (CR) or without (CRi) count recovery. Multivariable analysis–derived hazard ratios (HR), including 1.8 for European LeukemiaNet (ELN) adverse karyotype, 4.7 for <i>KMT2Ar</i>, 1.7 for <i>TP53</i>^MUT, 2.6 for <i>KRAS</i> ^MUT, and 2.1 for <i>IDH2</i>^WT were applied to develop an HR-weighted risk model: low, intermediate, and high; respective median survival censored for allogeneic stem cell transplant (ASCT) (3-year survival) were “not reached” (67%), 19.1 (33%), and 7.1 months (0%). In patients achieving CR/CRi, adverse karyotype, <i>KMT2Ar</i>, <i>KRAS</i>^MUT, <i>IDH2</i>^WT predicted inferior survival, allowing for a complementary response-stratified risk model. The model was externally validated and was shown to be superior to the ELN 2024 risk model (AIC 179 vs. 195 and AUC 0.77 vs. 0.69). Survival was inferior with failure to achieve CR/CRi or not receiving ASCT; 3-year survival for high-risk with or without ASCT was 42% versus 0% (<i>p</i> &lt; 0.01); intermediate 72% versus 43% (<i>p</i> = 0.06); and low-risk 88% versus 78% (<i>p</i> = 0.53). The Mayo genetic risk models offer pre-treatment and response-based prognostic tools for ND-AML treated with Ven-HMA. The current study underscores the prognostically indispensable role of achieving CR/CRi and ASCT.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"12 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816212","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":"Effect of Ferric Derisomaltose on Fatigue in Iron Deficiency Anemia Associated With Abnormal Uterine Bleeding","authors":"Petra Stute, Imo J. Akpan, Christian Breymann, Ally Murji, Sarah H. O'Brien, Jacquelyn M. Powers, Malcolm G. Munro","doi":"10.1002/ajh.27555","DOIUrl":"https://doi.org/10.1002/ajh.27555","url":null,"abstract":"&lt;p&gt;Anemia is prevalent among women of reproductive age, with iron deficiency (ID) being the primary etiology. ID can lead to fatigue and reduced quality of life, particularly in the context of abnormal menstrual bleeding [&lt;span&gt;1&lt;/span&gt;]. Abnormal menstrual bleeding refers to a set of symptoms collectively known as abnormal uterine bleeding (AUB), and includes heavy menstrual bleeding (HMB), experienced by up to around 50% of reproductive-aged women [&lt;span&gt;1, 2&lt;/span&gt;]. Notably, as many as 63% of women with HMB have been reported to have ID or iron deficiency anemia (IDA) [&lt;span&gt;1&lt;/span&gt;]. Despite symptoms of IDA being common alongside AUB, there is a paucity of data on response to intravenous (IV) iron treatment in such a population.&lt;/p&gt;\u0000&lt;p&gt;This &lt;i&gt;post hoc&lt;/i&gt; analysis evaluated pooled data from IV iron-treated participants with AUB-associated IDA from two Phase III trials, PROVIDE and FERWON-IDA (ClinicalTrials.gov identifiers: NCT02130063 and NCT02940886, respectively). The detailed study designs and results of these trials have been published previously [&lt;span&gt;3, 4&lt;/span&gt;]. While the trials compared the efficacy and safety of ferric derisomaltose (FDI; a high-dose formulation) to a low-dose IV iron, iron sucrose (IS), the main focus of this analysis was the effect of FDI – the newer IV iron associated with increased convenience through its high-dose regimen – on fatigue, a symptom frequently experienced by women with ID or IDA [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;\u0000&lt;p&gt;Female participants from the FDI treatment arms of PROVIDE and FERWON-IDA were included in this &lt;i&gt;post hoc&lt;/i&gt; analysis if they had received treatment, were aged 18–55 years, and had AUB-associated IDA (defined as hemoglobin [Hb] &lt; 12 g/dL, serum ferritin &lt; 100 ng/mL, and transferrin saturation &lt; 20% at baseline). The underlying cause of IDA was recorded in the trials, but AUB was not a term specified in the case report form; instead, a range of terms were used, including menorrhagia, metrorrhagia, and uterine hemorrhage, which were categorized under AUB in this &lt;i&gt;post hoc&lt;/i&gt; analysis. Participants with uterine leiomyoma listed as the cause of their IDA were also included in the analysis, as it was assumed that they experienced AUB.&lt;/p&gt;\u0000&lt;p&gt;The primary outcome was the change from Week 0 (baseline) to Week 8 (last study visit in FERWON-IDA) in the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale score, a 13-item patient-reported measure of fatigue and its impact on daily functioning over the past 7 days [&lt;span&gt;5&lt;/span&gt;]. Each item is marked from 0 (“not at all”) to 4 (“very much”) on a 5-point Likert scale [&lt;span&gt;5&lt;/span&gt;]. The data are then transformed according to scoring guidelines [&lt;span&gt;5&lt;/span&gt;]. The resulting total score falls within the range of 0–52, with a lower score indicating greater fatigue [&lt;span&gt;5&lt;/span&gt;]. Fatigue data were collected by both trials.&lt;/p&gt;\u0000&lt;p&gt;Other outcomes included change from baseline to Week 8 in Hb, and the proportions of partici","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"62 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142810172","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":"Correction to “Benefit of Axicabtagene Ciloleucel Versus Chemoimmunotherapy in Older Patients and/or Patients With Poor ECOG Performance Status With Relapsed or Refractory Large B-Cell Lymphoma After 2 or More Lines of Prior Therapy”","authors":"","doi":"10.1002/ajh.27551","DOIUrl":"https://doi.org/10.1002/ajh.27551","url":null,"abstract":"<p>Lunning MA, Wang HL, Hu ZH, et al., “Benefit of Axicabtagene Ciloleucel Versus Chemoimmunotherapy in Older Patients and/or Patients With Poor ECOG Performance Status With Relapsed or Refractory Large B-Cell Lymphoma After 2 or More Lines of Prior Therapy,” <i>American Journal of Hematology</i> 99, no. 5 (2024): 880–889.</p>\u0000<p>In Figure 1C, a typographical error was made reporting incorrect median overall survival (OS) values for the axi-cel and chemoimmunotherapy (CIT) arms by Eastern Cooperative Oncology Group performance status (ECOG PS). The correct values are reported in Table S2 and are reproduced here:</p>\u0000<p>Median OS (95% CI).</p>\u0000<p>Axi-cel, ECOG PS &lt; 2 (<i>n</i> = 526): 28.0 months (20.8-NE).</p>\u0000<p>CIT, ECOG PS &lt; 2 (<i>n</i> = 296): 6.4 months (5.7–7.6).</p>\u0000<p>Axi-cel, ECOG PS = 2 (<i>n</i> = 33): 3.6 months (2.3–8.1).</p>\u0000<p>CIT, ECOG PS = 2 (<i>n</i> = 27): 2.7 months (1.4–5.1).</p>\u0000<p>We apologize for this error.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"88 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142810170","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 Obinutuzumab in Immune-Mediated Thrombotic Thrombocytopenic Purpura","authors":"Julia Weisinger, Raïda Bouzid, Jehane Fadlallah, Christelle Barbet, Francois Provot, Pascale Poullin, Antoine Neel, Manon Marie, Virginie Rieu, Tarik Kanouni, Olivier Moranne, Elie Azoulay, Zora Marjanovic, Elise Corre, Anne-Christine Joly, Minh-Tam Baylatry, Bérangère S. Joly, Agnes Veyradier, Paul Coppo","doi":"10.1002/ajh.27550","DOIUrl":"https://doi.org/10.1002/ajh.27550","url":null,"abstract":"&lt;p&gt;Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare form of thrombotic microangiopathy (TMA) caused by an autoantibody-mediated deficiency of the von Willebrand factor (vWF) cleaving protease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin-1 motifs, 13th Member) [&lt;span&gt;1&lt;/span&gt;]. Without treatment, the disease is almost always fatal. In the last decades, the combination of therapeutic plasma exchange (TPE), corticosteroids, the chimeric anti-CD20 B-cell depleting monoclonal antibody rituximab and the anti-vWF nanobody caplacizumab, resulted in an improvement of survival rate, now exceeding 90% in the acute phase [&lt;span&gt;2, 3&lt;/span&gt;]. However, relapses may occur during follow-up, exposing patients to death and treatment-related complications while increasing the burden of care. To circumvent these issues, a regular monitoring of ADAMTS13 activity during follow up, and the use of preemptive rituximab treatment in patients experiencing a severe ADAMTS13 deficiency (ADAMTS13 relapse) became a standard of care [&lt;span&gt;3-5&lt;/span&gt;]. However, up to 15% of patients fail to improve ADAMTS13 activity following rituximab treatment; moreover, patients can develop adverse events, including immediate infusion intolerance or later serum sickness. In this context, alternative therapeutic options are needed, while evidence-based experience or direct comparisons of possible agents are scarce.&lt;/p&gt;\u0000&lt;p&gt;Obinutuzumab (Gazyvaro, Roche) is a type 2 humanized anti-CD20 monoclonal antibody, glyco-engineered to potently induce direct death of CD20-positive cells. Obinutuzumab proved to be efficient in various B-cell malignancies even following previous rituximab treatments, as well as in autoimmune diseases, where rituximab was contraindicated due to either resistance or intolerance. In iTTP, case reports and small series of patients suggested an efficacy for obinutuzumab in patients with intolerance or refractoriness to rituximab [&lt;span&gt;6&lt;/span&gt;]. Here, we report from a large series of patients more definitive evidence that obinutuzumab is efficient and safe in preventing relapses in iTTP patients experiencing refractoriness or intolerance to rituximab.&lt;/p&gt;\u0000&lt;p&gt;Data on patients with a diagnosis of iTTP treated with obinutuzumab in the registry of the French Thrombotic Microangiopathies Reference Center (www.cnr-mat.fr) have been collected according to a predefined computerized dataset. Treatment of iTTP in the acute phase was based on current national and international guidelines [&lt;span&gt;2-5&lt;/span&gt;]. Obinutuzumab was used as a compassionate off-label therapy; it was considered in patients with a persistent severe ADAMTS13 deficiency despite the use of rituximab, combined or not with other immunomodulators, or in patients with an ADAMTS13 relapse and intolerance to rituximab. Persistent severe ADAMTS13 deficiency was defined by an ADAMTS13 activity &lt; 20% on at least two consecutive time points, on patients usually assessed for ADAMTS13 ac","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"14 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816213","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":"Peri-Transplant Management of JAK Inhibitor Therapy in Myelofibrosis","authors":"Ayalew Tefferi, Vincent T. Ho","doi":"10.1002/ajh.27559","DOIUrl":"https://doi.org/10.1002/ajh.27559","url":null,"abstract":"<h2> Conflicts of Interest</h2>\u0000<p>The authors declare no conflicts of interest.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"42 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816214","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 of Midostaurin Combined With Intensive Chemotherapy in Core Binding Factor Leukemia: A Phase II Clinical Trial","authors":"Roberto Cairoli, Arianna Gatti, Giovanni Grillo, Marta Rachele Stefanucci, Barbara Di Camillo, Monica Fumagalli, Mauro Krampera, Gianpaolo Nadali, Patrizia Zappasodi, Erika Borlenghi, Elisabetta Todisco, Marta Ubezio, Massimo Bernardi, Alfredo Molteni, Claudia Basilico, Mauro Turrini, Rosa Greco, Valentina Mancini, Marta Riva, Davide Paolo Bernasconi, Bruno Brando, Silvio Marco Veronese, Alessandro Beghini","doi":"10.1002/ajh.27547","DOIUrl":"https://doi.org/10.1002/ajh.27547","url":null,"abstract":"Samples from 34 adult patients newly diagnosed with core binding factor leukemia (CBFL) were collected both at the time of diagnosis and at relapse and were centrally analyzed. Eligible patients received either standard induction CT known as “3 + 7” or an equivalent regimen, according to the recruiting center's policy. Patients who achieved CR or CRi received 3 courses of high-dose ARA-C (Cytarabine) 3000 mg/m² every 12 h on days 1, 3, and 5, along with midostaurin at the dose of 50 mg b.i.d from Day 8 to Day 21 as part of consolidation therapy. Following the completion of the consolidation phase, patients received midostaurin as a monotherapy at the dose of 50 mg b.i.d. for 1 year as continuation therapy. The CR rate was 97%; we recorded an OS rate of 73.52% and a DFS rate of 48.4% for the entire cohort. The RI was 38.8% in the <i>CBFB::MYH11</i> and 66.6% in the <i>RUNX1::RUNX1T1</i> group. MRD (Measurable Residual Disease) was assessed by RQ-PCR at 10 time points throughout the study, as indicated by arrows.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"19 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804733","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":"Mutation of Epigenetic Regulators at Diagnosis Is an Independent Predictor of Tyrosine Kinase Inhibitor Treatment Failure in Chronic Myeloid Leukemia: A Report From the RESIDIAG Study","authors":"Hippolyte Guerineau, Jean-Michel Cayuela, Stéphanie Dulucq, Violaine Tran Quang, Sihem Tarfi, Guillaume Gricourt, Quentin Barathon, Corine Joy, Orianne Wagner-Ballon, Stéphane Morisset, Frank-Emmanuel Nicolini, Erika Brunet, Sébastien Maury, Lydia Roy, Gabriel Etienne, Delphine Réa, Ivan Sloma","doi":"10.1002/ajh.27553","DOIUrl":"https://doi.org/10.1002/ajh.27553","url":null,"abstract":"&lt;p&gt;Additional mutations at chronic myeloid leukemia (CML) diagnosis have been shown to variably affect tyrosine kinase inhibitor (TKI) response [&lt;span&gt;1&lt;/span&gt;], and were inconstantly detected at loss of response [&lt;span&gt;2&lt;/span&gt;]. Contradictory observations may have resulted from difficulties in reliably inferring CML clonal architecture from mutations quantified by NGS, &lt;i&gt;BCR::ABL1 by qRT-PCR&lt;/i&gt;, and ABL1-tyrosine kinase domain (&lt;i&gt;ABL1&lt;/i&gt;-TKD) mutations by RNA-Seq. In the RESIDIAG (RESistance molecular markers at DIAGnosis) study, the mutational profile of 117 CML patients (&lt;i&gt;n&lt;/i&gt; = 60 responders and &lt;i&gt;n&lt;/i&gt; = 57 nonresponders) (Table S1) was analyzed at diagnosis (both groups) and at relapse (nonresponders only) by asymmetric capture sequencing (aCAP-Seq, Table S2) [&lt;span&gt;3&lt;/span&gt;] to identify molecular events that predict TKI failure and decipher the clonal architecture and the order of acquisition of mutations relative to &lt;i&gt;BCR&lt;/i&gt; and &lt;i&gt;ABL1&lt;/i&gt; fusion. This study complied with French regulations and was approved (no. 2019_048) by the Henri Mondor Institutional Review Board (No. 00011558). The study methodologies conformed to the standards set by the Declaration of Helsinki. All patient data were anonymized and de-identified before analysis. Informed consent was obtained from all participants.&lt;/p&gt;\u0000&lt;p&gt;The median time follow-up of responders was 7.1 years. There were no significant differences in terms of age, sex, CML stage, first-line treatment, additional chromosomal abnormalities (ACA), or first-line therapy between the two groups, while the proportions of patients with high Sokal or The EUTOS long-term survival (ELTS) scores were significantly increased among nonresponders (&lt;i&gt;p&lt;/i&gt; &lt; 0.001, Pearson's chi-square test, Table S3). Both ELTS and Sokal scores predicted failure-free survival (&lt;i&gt;p&lt;/i&gt; &lt; 0.001, Log-rank test, Figure S1). Patients in both groups were mainly treated first-line with Imatinib (61.5%), Nilotinib (25.6%), or Dasatinib (10.3%). TKI switch before failure analysis was mostly due to first-line intolerance. Blast crisis (BC) progression occurred in eight nonresponders, including four myeloid and four lymphoid BC, with a median time of transformation from diagnosis at 15 months [8.6–24.3 months].&lt;/p&gt;\u0000&lt;p&gt;At diagnosis, the number of additional mutations per patient was higher in nonresponders (&lt;i&gt;p&lt;/i&gt; &lt; 0.001, Pearson's chi-squared test, Table S4), especially in &lt;i&gt;ASXL1, DNMT3A&lt;/i&gt;, and &lt;i&gt;TET2&lt;/i&gt; referred to as epigenetic genes hereafter (&lt;i&gt;p&lt;/i&gt; &lt; 0.001, &lt;i&gt;p&lt;/i&gt; = 0.02, &lt;i&gt;p&lt;/i&gt; = 0.02, respectively, Pearson's chi-squared test, Figure 1A, Figure S2A,B and Table S4). The average A&lt;i&gt;SXL1&lt;/i&gt; mutation VAF in nonresponders (23.6% ± 3.6%, &lt;i&gt;n&lt;/i&gt; = 21) were significantly different from the &lt;i&gt;BCR::ABL1&lt;/i&gt; frequency (47.9% ± 0.8%, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001, Dunnett's multiple comparison test, Figure S2C) suggesting that &lt;i&gt;ASXL1&lt;/i&gt; mutant were either CML subclones or clones driving an independent clonal ","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"141 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797739","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":"THSNA 2024 Abstracts","authors":"","doi":"10.1002/ajh.27535","DOIUrl":"10.1002/ajh.27535","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 S1","pages":"3-137"},"PeriodicalIF":10.1,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27535","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}