American Journal of Hematology最新文献

{"title":"FDA IDE validation of multiple myeloma MRD test by flow cytometry","authors":"Dragan Jevremovic, Min Shi, Pedro Horna, Gregory E. Otteson, Michael M. Timm, Shannon A. Bennett, Linda B. Baughn, Patricia T. Greipp, Wilson I. Gonsalves, Prashant Kapoor, Morie A. Gertz, Moritz Binder, Francis K. Buadi, Angela Dispenzieri, Taxiarchis Kourelis, Eli Muchtar, Jiehao Zhou, S. Vincent Rajkumar, Shaji K. Kumar, Horatiu Olteanu","doi":"10.1002/ajh.27484","DOIUrl":"https://doi.org/10.1002/ajh.27484","url":null,"abstract":"<p>Two recent decisions by the Food and Drug Administration will likely significantly impact testing for multiple myeloma (MM) minimal residual disease (MRD). First, on April 12, 2024, the FDA's Oncologic Drugs Advisory Committee (ODAC) voted to approve the use of MRD as an end point for accelerated approval of new treatments for patients with MM.<span><sup>1</sup></span> This was a result of near 10 years effort by multiple institutions, professional societies, and patient's advocacy groups,<span><sup>2-6</sup></span> and reflects the current state of MM treatment in which new therapeutic options have dramatically improved progression-free and overall survival (PFS and OS),<span><sup>7</sup></span> making them impractical as the only clinical trial endpoints. Second, after many years of deliberations, FDA announced on April 29, 2024 that it will start overseeing laboratory developed tests (LDTs).<span><sup>8</sup></span> LDTs are in vitro diagnostic products (IVDs) intended for clinical use; they are designed and validated for use within individual laboratories certified for performing high complexity testing under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). The FDA's decision is currently being challenged by the American Clinical Laboratory Association.</p>\u0000<p>The most commonly used assays for MRD detection in plasma cell neoplasms are next-generation sequencing (NGS) of the rearranged variable immunoglobulin heavy chain<span><sup>9, 10</sup></span> and high sensitivity flow cytometry immunophenotyping (next-generation flow, NGF).<span><sup>11-14</sup></span> Each type of assay has its advantages and disadvantages. For example, NGS requires knowledge of the diagnostic specimen for sequence comparison, but that knowledge enables higher sensitivity (10<sup>−6</sup>). NGF, as developed by the Euroflow/Spanish flow cytometry experts and commercialized by Cytognos requires no prior diagnostic specimen and can provide information regarding quality of the specimen (hemodilution); the sensitivity of the NGF is between 10<sup>−5</sup> and 2 × 10<sup>−6</sup>, depending on the number of cells (events) collected. In 2016, the International Myeloma Working Group established the minimum sensitivity of 10<sup>−5</sup> for MM MRD testing.<span><sup>4</sup></span></p>\u0000<p>Currently the only FDA-approved test for MM MRD is NGS-based clonoSEQ® by Adaptive Biotechnologies.<span><sup>9</sup></span> For the NGF method to be FDA-approved, it will require a comprehensive package submission to the FDA, either as Premarket Approval (PMA) application or a Premarket Notification 510(k). However, FDA has a category of investigational device exemption (IDE) which allows a test to be used in a clinical study to collect safety and effectiveness data. There is limited data available regarding the requirements for FDA IDE approval of a flow cytometry assay for MRD testing.</p>\u0000<p>In our laboratory, we adopted and validated the NGF method as an LDT, and have, ","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236971","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 importance of autologous stem cell transplantation in improving outcomes in newly diagnosed patients with multiple myeloma","authors":"Morie A. Gertz","doi":"10.1002/ajh.27483","DOIUrl":"https://doi.org/10.1002/ajh.27483","url":null,"abstract":"<h2> CONFLICT OF INTEREST STATEMENT</h2>\u0000<p>The author declares no conflict of interest.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236960","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":"Clearance of pathogenic erythrocytes is maintained despite spleen dysfunction in children with sickle cell disease","authors":"Abdoulaye Sissoko, Astan Cissé, Clémence Duverdier, Mickaël Marin, Lucie Dumas, Sandra Manceau, Blandine Maître, Anita Eckly, Aurélie Fricot-Monsinjon, Camille Roussel, Papa Alioune Ndour, Michael Dussiot, Safi Dokmak, Béatrice Aussilhou, Jeanne Dembinski, Alain Sauvanet, François Paye, Mickaël Lesurtel, Jérôme Cros, Dominique Wendum, Magali Tichit, David Hardy, Carmen Capito, Slimane Allali, Pierre Buffet","doi":"10.1002/ajh.27481","DOIUrl":"https://doi.org/10.1002/ajh.27481","url":null,"abstract":"In children with sickle cell disease (SCD), splenectomy is immediately beneficial for acute sequestration crises and hypersplenism (ASSC/HyS) but portends a long-term risk of asplenia-related complications. We retrieved peripheral and splenic red blood cells (RBCs) from 17 SCD children/teenagers undergoing partial splenectomy for ASSC/HyS, 12 adult subjects without RBC-related disease undergoing splenectomy (controls), five human spleens perfused ex vivo with Hb_SS- and Hb_AA-RBC, and quantified abnormal RBC by microscopy, spleen-mimetic RBC filtration, and adhesion assays. Spleens were analyzed by immunohistochemistry and transmission electron microscopy (TEM). In circulating blood of SCD and control subjects, dysmorphic (elongated/spherocytic) RBCs were &lt;2%, while proportions of pocked-RBC were 4.3-fold higher in SCD children than in controls. Compared to controls, splenic RBCs were more frequently dysmorphic (29.3% vs. 0.4%), stiffer (42.2% vs. 12.4%), and adherent (206 vs. 22 adherent RBC/area) in SCD subjects. By TEM, both polymer-containing and homogenous RBC contributed to spleen congestion, resulting in 3.8-fold higher RBC population density in SCD spleens than in control spleens, predominantly in the cords. Perfused spleens with normal function displayed similar congestion and retention of dysmorphic RBC as SCD spleens. The population density of active macrophages was similar in SCD and control spleens, with a relative deficit in phagocytosis of polymer-containing RBC. Despite the existence of hyposplenism, splenectomy in SCD children removes an organ that still efficiently filters out potentially pathogenic altered RBC. Innovative treatments allowing fine-tuned reduction of RBC retention would alleviate spleen congestion, the major pathogenic process in ASSC/HyS, while preserving spleen protective functions for the future.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142235369","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":"Comparison of prognostic scores according to WHO classification in 170 patients with advanced mastocytosis and C-finding treated with midostaurin","authors":"Maël Heiblig, Clément Gourguechon, Philippe Guilpain, Cristina Bulai-Livideanu, Stéphane Barete, Yannick Chantran, Julie Agopian, Fabienne Brenet, Patrice Dubreuil, Jérémie Lespinasse, Richard Lemal, Olivier Tournilhac, Louis Terriou, David Launay, Laurence Bouillet, Catharina Chatain, Ghandi Damaj, Thomas Ballul, Celine Greco, Laura Polivka, Laurent Frenzel, Cécile Meni, Hassiba Bouktit, Dina Benabou, Caroline Gaudy-Marqueste, Marie Gousseff, Edwige Le Mouel, Antoine Neel, Dana Ranta, Roland Jaussaud, Thierry Jo Molina, Julie Bruneau, Patrick Villarese, Ludovic Lhermitte, Leila Maouche-Chrétien, Marie Temple, Olivier Kosmider, Rose-Marie Javier, Fabien Pelletier, Florence Castelain, Frederique Retornaz, Quentin Cabrera, Patricia Zunic, Marie Pierre Gourin, Ewa Wierzbicka–Hainaut, Jean François Viallard, Christian Lavigne, Cyrille Hoarau, Isabelle Durieu, Sophie Dimicoli-Salazar, Jose Miguel Torregrosa-Diaz, Mathieu Wemeau, Angèle Soria, Michel Arock, Christine Bodemer, Olivier Lortholary, Olivier Hermine, Julien Rossignol","doi":"10.1002/ajh.27478","DOIUrl":"https://doi.org/10.1002/ajh.27478","url":null,"abstract":"Advanced systemic mastocytosis (AdvSM) encompasses heterogeneous mastocytosis subtypes and is associated with poor outcomes. Although midostaurin was the first tyrosine kinase inhibitor to be approved for AdvSM patients, long-lasting responses are limited. The mutation-Adjusted Risk Score (MARS), the International Prognostic Scoring System for mastocytosis (IPSM) and the Global Prognostic Score for Systemic Mastocytosis (GPSM) have been established to characterize the outcomes of patients with overall AdvSM. However, given the outcome's dependency on the AdvSM subtype, prognostic characterization within each subtype is critical. We aimed to study the predictive ability using Harrell's concordance index of prognostic scores according to the AdvSM subtype. We conducted a nationwide retrospective study using the French mastocytosis reference center's registry and included all midostaurin-treated patients with C finding. Overall, 170 patients were identified: 46 aggressive SM (ASM), 11 mast cell leukemia (MCL), and 113 SM with associated hematological neoplasm (SM-AHN). All risk scores improved their discriminative value for overall survival (OS) when combined with the AdvSM subtype. The best predictive value was for adjusted MARS (C-index = 0.689), followed by GPSM (C-index = 0.677) and IPSM (C-index = 0.618). In a multivariable analysis, MARS stratification and the AdvSM subtype were both prognostic for OS. Accordingly, five subgroups of patients with AdvSM and a different median OS were identified: 9.9 months for MCL, 24 months for intermediate/high-risk SM-AHN, 33 months for intermediate/high-risk ASM, 58 months for low-risk SM-AHN and was not reached for low-risk ASM (<i>p</i> &lt; 0.001). The AdvSM subtype and the MARS are the most predictive of OS and should prompt specific management.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142235429","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":"Thrombotic thrombocytopenic purpura masquerading as Evans syndrome","authors":"Sarah E. Mudra, Kaleb Ardoin, Vanya Aggarwal, Garrett Diltz, Pedro E. Alcedo Andrade, Catherine M. Broome","doi":"10.1002/ajh.27476","DOIUrl":"https://doi.org/10.1002/ajh.27476","url":null,"abstract":"&lt;h2&gt;1 CASE PRESENTATION&lt;/h2&gt;\u0000&lt;p&gt;A 26-year-old female with a history of chronic urticaria (treated with omalizumab in the past) and recently treated chlamydia trachomatis infection presented to an outside emergency department after a syncopal episode. She endorsed a three-day history of nausea, vomiting, fatigue, and ecchymoses. Initial laboratory analysis revealed macrocytic anemia (hemoglobin 4.6 g/dL) with a mean corpuscular volume (MCV) of 100.7 fL, thrombocytopenia (2000 plts/μL), indirect hyperbilirubinemia (indirect bilirubin 3.7 mg/dL), lactate dehydrogenase (LDH) 1245 units/L, absolute reticulocyte count of 0.237 million/μL, haptoglobin 1 mg/dL, international normalized ratio (INR) 1.2 and creatinine 0.75 mg/dL. Peripheral blood smear identified numerous spherocytes and microspherocytes, true thrombocytopenia, and increased reticulocytes without evidence of erythrocyte fragmentation (Figure 1). Direct antiglobulin testing (DAT) was positive for IgG (2+) and C3 (2+) at 37°C, although quantitative analysis was not performed. She received one unit of packed red blood cells and one unit of platelets and was transferred to our institution for further evaluation.&lt;/p&gt;\u0000&lt;figure&gt;&lt;picture&gt;\u0000&lt;source media=\"(min-width: 1650px)\" srcset=\"/cms/asset/45e8172d-9a99-40bc-b833-1714ce08081d/ajh27476-fig-0001-m.jpg\"/&gt;&lt;img alt=\"Details are in the caption following the image\" data-lg-src=\"/cms/asset/45e8172d-9a99-40bc-b833-1714ce08081d/ajh27476-fig-0001-m.jpg\" loading=\"lazy\" src=\"/cms/asset/39a9c16a-ac16-4f5a-98f6-9b6266075274/ajh27476-fig-0001-m.png\" title=\"Details are in the caption following the image\"/&gt;&lt;/picture&gt;&lt;figcaption&gt;\u0000&lt;div&gt;&lt;strong&gt;FIGURE 1&lt;span style=\"font-weight:normal\"&gt;&lt;/span&gt;&lt;/strong&gt;&lt;div&gt;Open in figure viewer&lt;i aria-hidden=\"true\"&gt;&lt;/i&gt;&lt;span&gt;PowerPoint&lt;/span&gt;&lt;/div&gt;\u0000&lt;/div&gt;\u0000&lt;div&gt;Peripheral smear on admission (two sections) which showed spherocytes and microspherocytes, but no increased schistocytes.&lt;/div&gt;\u0000&lt;/figcaption&gt;\u0000&lt;/figure&gt;\u0000&lt;p&gt;This patient presented with profound thrombocytopenia and hemolytic anemia as evidenced by elevated LDH, elevated reticulocyte count, decreased haptoglobin, and indirect hyperbilirubinemia. The lack of schistocytes or evidence of erythrocyte fragmentation on peripheral smear as well as positive DAT was consistent with Evans syndrome—warm autoimmune hemolytic anemia (AIHA) with concomitant immune thrombocytopenia (ITP). Evans syndrome can arise spontaneously (primary) or secondary to diseases that generate autoantibodies. Etiologies may include infections, autoimmune disorders, lymphoproliferative disorders, or pregnancy.&lt;/p&gt;\u0000&lt;p&gt;On physical exam, the patient was well-appearing. She was afebrile with the remainder of her vital signs within normal limits. Physical examination was only notable for mild gingival bleeding. No rashes, petechiae, purpura, or ecchymoses were identified. She conversed appropriately and was oriented to person, location, and time. She had not received a blood product transfusion prior to this admission.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234099","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 cognitive age in medicine: Artificial intelligence, large language models, and iterative intelligence","authors":"John Nosta","doi":"10.1002/ajh.27480","DOIUrl":"https://doi.org/10.1002/ajh.27480","url":null,"abstract":"<h2> CONFLICT OF INTEREST STATEMENT</h2>\u0000<p>The author declares no conflicts of interest.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234104","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":"White blood cell count levels are associated with inflammatory response and constitute independent outcome predictors in adult patients with acute myeloid leukemia aged <60 years","authors":"Michael Ozga, Deedra Nicolet, Krzysztof Mrózek, Christopher J. Walker, James S. Blachly, Jessica Kohlschmidt, Shelley Orwick, Andrew J. Carroll, Richard A. Larson, Jonathan E. Kolitz, Bayard L. Powell, Richard M. Stone, John C. Byrd, Ann-Kathrin Eisfeld, Alice S. Mims","doi":"10.1002/ajh.27465","DOIUrl":"https://doi.org/10.1002/ajh.27465","url":null,"abstract":"&lt;p&gt;Acute myeloid leukemia (AML) is a biologically and clinically heterogenous disease with diverse genetic abnormalities&lt;span&gt;&lt;sup&gt;1-6&lt;/sup&gt;&lt;/span&gt; and a wide-ranging white blood cell counts (WBC) at diagnosis.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The 2022 European LeukemiaNet (ELN) genetic-risk classification incorporates cytogenetic and selected molecular alterations to define Favorable, Intermediate, and Adverse genetic-risk groups providing valuable prognostic information.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Pretreatment WBC levels are also a main prognostic factor for patients with AML;&lt;span&gt;&lt;sup&gt;7, 8&lt;/sup&gt;&lt;/span&gt; however, there are no standardized WBC-associated groups that improve prognostication for younger patients. de Jonge et al.&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt; first investigated the impact of WBC on outcome of AML patients harboring &lt;i&gt;NPM1&lt;/i&gt; mutations and &lt;i&gt;FLT&lt;/i&gt;3 internal tandem duplications (&lt;i&gt;FLT3&lt;/i&gt;-ITD) that were divided into three WBC groups: &lt;20 000/μL, WBC 20 000/μL–100 000/μL, and ≥100 000/μL. We decided to build upon this previous work by analyzing a larger, clinically and molecularly well-characterized cohort of 1121 younger (aged &lt;60 years) adults with de novo AML to define clinically relevant WBC level groups and determine their potential independent prognostic impact and associations with gene-expression profiles.&lt;/p&gt;\u0000&lt;p&gt;We defined three WBC groups: &lt;i&gt;low&lt;/i&gt; (&lt;10 000/μL, &lt;i&gt;n&lt;/i&gt; = 298 patients), &lt;i&gt;intermediate&lt;/i&gt; (10 000–49 999/μL, &lt;i&gt;n&lt;/i&gt; = 488), and &lt;i&gt;high&lt;/i&gt; (≥50 000/μL, &lt;i&gt;n&lt;/i&gt; = 335). These groups were chosen because there was no correlation with an observable steady decrease in any analyzed outcome endpoint, including disease-free (DFS), event-free (EFS), or overall (OS) survival, with WBC increasing above 50 000/μL by 10 000/μL increments, nor were there any linear changes in endpoints associated with WBC decreasing below 10 000/μL in 1000/μL increments across the entire cohort (Figure S1A,B). All patients were similarly treated with a cytarabine/anthracycline based induction on frontline Cancer and Leukemia Group B (CALGB)/Alliance for Clinical Trials in Oncology (Alliance) protocols, with details of CALGB treatment protocols provided in the Data S1. No patient included in the analysis received an allogeneic hematopoietic stem-cell transplantation (HSCT) in first complete remission (CR), and patients who underwent an allogeneic HSCT off-study were not included because of incomplete or missing follow-up information. All patients were enrolled on CALGB 8461 (cytogenetic studies), CALGB 9665 (leukemia tissue bank), and CALGB 20202 (molecular studies) companion protocols, with further treatment details provided in the Data S1. The mutational status of 80 total protein-coding genes was determined centrally at The Ohio State University by targeted amplicon sequencing using the MiSeq platform (Illumina)&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; and further detailed in the Data S1. Analysis of differentially expressed genes within each WBC g","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234113","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":"Real-world efficacy and safety of luspatercept and predictive factors of response in patients with transfusion-dependent β-thalassemia","authors":"Daniele Lello Panzieri, Dario Consonni, Natalia Scaramellini, Guido Ausenda, Francesca Granata, Nancy Caponio, Lorena Duca, Simona Leoni, Silvia Elli, Marta Ferraresi, Vittorio Bolis, Cristina Curcio, Milena Agata Irrera, Diletta Maira, Giovanna Graziadei, Elena Cassinerio, Maria Domenica Cappellini, Rayan Bou-Fakhredin, Valentina Brancaleoni, Irene Motta","doi":"10.1002/ajh.27474","DOIUrl":"https://doi.org/10.1002/ajh.27474","url":null,"abstract":"&lt;p&gt;Luspatercept is the first erythropoiesis-modulating agent approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for treating anemia in adult transfusion-dependent β-thalassemia (TDT) patients. As observed in clinical trials&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; and real-life experience,&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; response to luspatercept in TDT is heterogeneous. It can range from patients who do not respond to those who become transfusion-independent. So far, no predictors of response have been identified. However, the definition of the different profiles and predictors of response is necessary for optimizing treatment allocation, limiting costs, and increasing sustainability. The ELEMENT study is an observational prospective cohort study that enrolled adult TDT patients regularly followed at Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico in Milan (Italy) treated with luspatercept. Luspatercept was administered, according to the indications of the Italian Regulatory Agency, subcutaneously at a starting dose of 1.0 mg/kg every 3 weeks and was increased to 1.25 mg/kg after dose 3 if a clinical response was not achieved.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; The drug was discontinued according to the Italian Regulatory Agency indications, namely, if the patient does not achieve transfusion reduction (amount not specified) after three doses at the maximum dosage or in the presence of unacceptable toxicity. Treatment response was assessed by comparing the transfusion burden (TB) during any 12-week treatment period with that in the 24 weeks before treatment. Responders (RSP) were defined as individuals who have a reduction of the TB ≥33% in any 12 weeks of treatment, while those with a TB reduction &lt;33% were considered “non-responders” (NR). Moreover, as in the phase 3 trial, transfusion independence was defined as a transfusion-free period of at least 8 weeks.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; In this study, TB was also expressed as the number of units of packed red blood cells (pRBC) per week (unit/week) by dividing the number of units transfused in a period by the number of weeks evaluated.&lt;/p&gt;\u0000&lt;p&gt;Between January 1, 2021, and May 31, 2024, 56 TDT patients received at least one dose of luspatercept after drug authorization. At the start of the study, treatment was offered to TDT patients with high TB, iron overload demonstrated by T2* magnetic resonance imaging (MRI), or other clinically relevant conditions that might benefit from TB reduction. Subsequently, the treatment was made available to all the patients who met the Italian regulatory agency criteria and were willing to receive the drug. The decision to initiate treatment was always discussed between the physician and the patient.&lt;/p&gt;\u0000&lt;p&gt;Seven patients discontinued the drug before completing at least 12 weeks. The reasons for discontinuation are detailed in Table S1 (early drug discontinuation group). At the time of the analysis, one patient had not yet completed 12 weeks of tr","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142171324","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":"Cybersecurity and the blood supply: The vulnerabilities of the technological revolution","authors":"Jeremy W. Jacobs, Nicole De Simone, Miriam Andrea Duque, Yanyun Wu, Dawn C. Ward, Jennifer S. Woo, Laura D. Stephens, Elizabeth S. Allen, Mandy F. O'Leary, Sheharyar Raza, Garrett S. Booth, Brian D. Adkins","doi":"10.1002/ajh.27479","DOIUrl":"https://doi.org/10.1002/ajh.27479","url":null,"abstract":"<h2> CONFLICT OF INTEREST STATEMENT</h2>\u0000<p>The authors declare no conflicts of interest.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142171329","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":"Machine-learning based subgroups of AL amyloidosis and cumulative incidence of mortality and end stage kidney disease","authors":"Shankara K. Anand, Andrew Staron, Lisa M. Mendelson, Tracy Joshi, Natasha Burke, Vaishali Sanchorawala, Ashish Verma","doi":"10.1002/ajh.27472","DOIUrl":"https://doi.org/10.1002/ajh.27472","url":null,"abstract":"Immunoglobulin light chain (AL) amyloidosis is a multisystem disease with varied treatment options and disease-related outcomes. Current staging systems rely on a limited number of cardiac, renal, and plasma cell dyscrasia biomarkers. To improve prognostication for all-cause mortality and end-stage kidney disease (ESKD), we applied unsupervised machine learning using a comprehensive set of clinical and laboratory parameters. Our study cohort comprised 2067 patients with newly diagnosed, biopsy-proven AL amyloidosis from the Boston University Amyloidosis Center. Variables included 31 clinical symptoms and 28 baseline laboratory values. Our clustering algorithm identified three subgroups of AL amyloidosis (low-risk, intermediate-risk, and high-risk) with distinct clinical phenotypes and median overall survival (OS) estimates of 6.1, 3.7, and 1.2 years, respectively. The 10-year adjusted cumulative incidences of all-cause mortality were 66.8% (95% CI 63.4–70.1), 75.4% (95% CI 72.1–78.6), and 90.6% (95% CI 87.4–93.3) for low, intermediate, and high-risk subgroups. The 10-year adjusted cumulative incidences of end-stage kidney disease (ESKD) were 20.4% (95% CI 6.1–24.5), 37.6% (95% CI 31.8–43.8), and 6.7% (95% CI 2.8–11.3) for low-risk, intermediate-risk, and high-risk subgroups. Finally, we trained a classifier for external validation with high cross-validation accuracy (85% [95% CI 83–86]) using a subset of easily obtainable clinical parameters. This marks an initial stride toward integrating precision medicine into risk stratification of AL amyloidosis for both all-cause mortality and ESKD.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166203","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}