American Journal of Hematology最新文献

{"title":"Endogenous retroelements in hematological malignancies: From epigenetic dysregulation to therapeutic targeting","authors":"Mohamed Chour,&nbsp;Françoise Porteu,&nbsp;Stéphane Depil,&nbsp;Vincent Alcazer","doi":"10.1002/ajh.27501","DOIUrl":"10.1002/ajh.27501","url":null,"abstract":"<p>Endogenous retroelements (EREs), which comprise half of the human genome, play a pivotal role in genome dynamics. Some EREs retained the ability to encode proteins, although most degenerated or served as a source for novel genes and regulatory elements during evolution. Despite ERE repression mechanisms developed to maintain genome stability, widespread pervasive ERE activation is observed in cancer including hematological malignancies. Challenging the perception of noncoding DNA as “junk,” EREs are underestimated contributors to cancer driver mechanisms as well as antitumoral immunity by providing innate immune ligands and tumor antigens. This review highlights recent progress in understanding ERE co-option events in cancer and focuses on the controversial debate surrounding their causal role in shaping malignant phenotype. We provide insights into the rapidly evolving landscape of ERE research in hematological malignancies and their clinical implications in these cancers.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 1","pages":"116-130"},"PeriodicalIF":10.1,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27501","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405257","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}

{"title":"The invisible lifeline: Intricacies of the global plasma supply","authors":"Jan Hartmann,&nbsp;Sean R. Stowell,&nbsp;Harvey G. Klein","doi":"10.1002/ajh.27499","DOIUrl":"10.1002/ajh.27499","url":null,"abstract":"&lt;p&gt;Like whole blood, plasma is collected from healthy human donors. However, while much is known and has been written about whole blood donations and the worrisome trends that increasingly challenge its safety and global supply,&lt;span&gt;&lt;sup&gt;1-4&lt;/sup&gt;&lt;/span&gt; the complexities of plasma collection and its supply chain—from the donor's arm, through the manufacturing process, to the patient's therapy—have, with few exceptions,&lt;span&gt;&lt;sup&gt;5-8&lt;/sup&gt;&lt;/span&gt; received far less attention. Yet the biological medicines prepared from plasma represent a critical lifeline for an increasing number of patients worldwide.&lt;/p&gt;&lt;p&gt;Human plasma forms the indispensable source material for the drugs that are known as plasma-derived medicinal products (PDMPs). Plasma can be obtained through two processes. “Recovered plasma” is the by-product of separation of whole blood into its component parts. Recovered plasma constitutes a minor fraction of the plasma used to manufacture PDMPs. Most of the plasma intended for fractionation into PDMPs is collected by plasmapheresis and is known as “source plasma.” The frequency and volume of source plasma donations are strictly regulated by national regulatory authorities, for example, by the FDA in the United States, the Paul-Ehrlich Institute in Germany, and the Therapeutic Goods Administration in Australia. Most European blood establishments follow the guidelines of the European Directorate for the Quality of Medicines &amp; HealthCare (EDQM).&lt;/p&gt;&lt;p&gt;More than 30 proteins are currently prepared by fractionating plasma. Many of these PDMPs are deemed sufficiently important to a nation's healthcare system that they have been included in the WHO's Model List of Essential Medicines for Adults and Children. The list of therapies derived from human plasma is long, as is the list of conditions treated by them.&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; The range of indications includes hematological conditions, such as hemophilia, von Willebrand disease, ITP, anti-thrombin III deficiency, HIT, VITT, secondary immunodeficiency in CLL patients and patients undergoing cancer chemotherapy, neurologic, renal, and autoimmune disorders. The list and number of patients continue to grow as does worldwide demand.&lt;span&gt;&lt;sup&gt;9-11&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Many donors and donations are needed to fulfill the current plasma demand. It is estimated that treating one hemophilia A patient for a year requires plasma from approximately 1200 donations (US Department of Health and Human Services, “Why Giving Plasma is So Critical”; retrieved on 9/20/2024 from: https://www.hhs.gov/givingequalsliving/giveplasma/why-give). The World Federation of Hemophilia estimates that 400 000 people are living with hemophilia and only 25% receive adequate treatment.&lt;span&gt;&lt;sup&gt;12&lt;/sup&gt;&lt;/span&gt; Also, the need for immunoglobulin is growing.&lt;span&gt;&lt;sup&gt;13-15&lt;/sup&gt;&lt;/span&gt; This trend is driven by demographic changes, such as longer life expectancy and increased average weight, by higher diagnostic and treatment ra","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"99 12","pages":"2261-2265"},"PeriodicalIF":10.1,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27499","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379942","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}

{"title":"C-CAR066, a novel fully human anti-CD20 CAR-T therapy for relapsed or refractory large B-cell lymphoma after failure of anti-CD19 CAR-T therapy: A phase I clinical study","authors":"Ping Li,&nbsp;Wei Liu,&nbsp;Lili Zhou,&nbsp;Shiguang Ye,&nbsp;Dan Zhu,&nbsp;Jiaqi Huang,&nbsp;Jing Li,&nbsp;Chengxiao Zheng,&nbsp;Shigui Zhu,&nbsp;Xin Yao,&nbsp;Kevin Zhu,&nbsp;Yihong Yao,&nbsp;Lugui Qiu,&nbsp;Aibin Liang,&nbsp;Dehui Zou","doi":"10.1002/ajh.27488","DOIUrl":"10.1002/ajh.27488","url":null,"abstract":"<p>Managing large B-cell lymphoma (LBCL) that is refractory to or relapsed after chimeric antigen receptor (CAR)-T therapy remains a significant challenge. Here we aimed to investigate the safety and efficacy of C-CAR066, an autologous fully human anti-CD20 specific CAR-T, for relapsed/refractory LBCL after failure of anti-CD19 CAR-T therapy. This first-in-human, single-arm, phase 1 study was conducted at two sites in China. Eligible patients had to be histologically confirmed with CD20-positive LBCL and must have received prior anti-CD19 CAR-T therapy. Patients received a single intravenous infusion of C-CAR066 at a target dose of 2.0 × 10⁶ or 3.0 × 10⁶ CAR-T cells/kg. The primary endpoint was the incidence of adverse events (AEs). As of October 10, 2023, 14 patients had received C-CAR066. The most common AEs of Grade 3 or higher were hematological toxicities. Cytokine release syndrome occurred in 12 (85.7%) patients, with only one was Grade 4 event. No patient experienced immune effector cell-associated neurotoxicity syndrome events. The overall response rate was 92.9% with a complete response rate of 57.1%. With a median follow-up of 27.7 months (range, 3.3–40.9), the median progression-free survival and overall survival were 9.4 months (95% CI, 2.0 to NA) and 34.8 months (95% CI, 7.5 to NA), respectively. C-CAR066 demonstrated a manageable safety profile and promising efficacy in patients in whom prior anti-CD19 CAR-T therapies had failed, providing a promising treatment option for those patients. This trial was registered with ClinicalTrials.gov, NCT04316624 and NCT04036019.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"99 12","pages":"2306-2312"},"PeriodicalIF":10.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27488","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339456","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}

{"title":"The spectrum of sickle cell disease.","authors":"Barbara J Bain","doi":"10.1002/ajh.27494","DOIUrl":"https://doi.org/10.1002/ajh.27494","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339457","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":"Imatinib remains the best frontline therapy in patients with chronic myeloid leukemia: Critical analysis of the ASC4FIRST trial","authors":"Nethra Srinivasan,&nbsp;Timothée Olivier,&nbsp;Alyson Haslam,&nbsp;Vinay Prasad","doi":"10.1002/ajh.27477","DOIUrl":"10.1002/ajh.27477","url":null,"abstract":"&lt;p&gt;A recent study—ASC4FIRST&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;—builds the case that the novel drug, asciminib, a BCR::ABL1 inhibitor, is superior to current tyrosine kinase inhibitors (TKIs) for the treatment of chronic phase (CP) chronic myeloid leukemia (CML). Some have even taken to social media to announce a post-imatinib era.&lt;/p&gt;&lt;p&gt;As the first TKI to be approved in oncology, imatinib has been a transformative oral anti-cancer drug, improving survival for patients with CP CML. Imatinib, and subsequent drugs—dasatinib, bosutinib, and nilotinib—have increased the life expectancy of patients diagnosed with CML to essentially the same length as the general population without CML.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Will asciminib further improve upon existing TKIs? We consider this alongside three questions raised by the ASC4FIRST trial: does it establish superiority over second-generation TKIs (dasatinib, bosutinib, and nilotinib), does the improvement in major molecular milestones mean the drug will improve survival or quality of life, and what can we conclude about adverse effects in this open-label study?&lt;/p&gt;&lt;p&gt;A primary concern with the ASC4FIRST trial is its approach to comparing asciminib with other TKIs, as a combined entity. The trial's design included two primary comparisons: asciminib versus all TKIs (a combined group of imatinib and second-generation TKIs) and asciminib versus imatinib alone. However, a direct comparison between asciminib and second-generation TKIs was relegated to a “secondary objective” and “not compared […] as a primary objective.” This design choice raises critical questions about the validity and clinical relevance of the findings.&lt;/p&gt;&lt;p&gt;Combining imatinib and second-generation TKIs into a single control group undermines the distinct therapeutic profiles and efficacy of these drugs. It is well-established that second-generation TKIs, such as dasatinib and nilotinib, outperform imatinib in achieving significant molecular responses in CML patients.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; By lumping these agents together, the trial essentially sets up a comparison that is guaranteed to favor asciminib. This strategy, which we have called the use of “nested groups” as opposed to “adjacent groups,” is a common tactic in clinical trials which creates confusion about precisely which groups benefit or which comparisons are significant.&lt;span&gt;&lt;sup&gt;4, 5&lt;/sup&gt;&lt;/span&gt; In this case it lacks clinical justification and can mislead stakeholders about the true efficacy of the investigational drug.&lt;/p&gt;&lt;p&gt;In the ASC4FIRST trial, the difference in the 48-week major molecular response (MMR) between asciminib and the combined TKI group (a nested group) was significant. Yet, the more relevant comparison—asciminib versus second-generation TKIs (omitting imatinib, an adjacent subgroup)—revealed no significant difference (66.0% vs. 57.8%, respectively).&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; This finding is crucial because it highlights that asciminib may not offer a substantial im","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"99 12","pages":"2392-2394"},"PeriodicalIF":10.1,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27477","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142329107","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}

{"title":"Peripheral blood smear reveals human granulocytic anaplasmosis, a rare cause of hemophagocytic lymphohistiocytosis","authors":"Charlotte M. Story, Shruti Chaturvedi","doi":"10.1002/ajh.27485","DOIUrl":"https://doi.org/10.1002/ajh.27485","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"46 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142325544","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":"PHF6 mutations in chronic myelomonocytic leukemia identify a unique subset of patients with distinct phenotype and superior prognosis","authors":"Ayalew Tefferi,&nbsp;Saubia Fathima,&nbsp;Ali Khalid A. Alsugair,&nbsp;Fnu Aperna,&nbsp;Anuya Natu,&nbsp;Maymona G. Abdelmagid,&nbsp;Clifford M. Csizmar,&nbsp;Mark Gurney,&nbsp;Terra L. Lasho,&nbsp;Christy M. Finke,&nbsp;Abhishek A. Mangaonkar,&nbsp;Aref Al-Kali,&nbsp;Animesh Pardanani,&nbsp;Kaaren K. Reichard,&nbsp;Rong He,&nbsp;Naseema Gangat,&nbsp;Mrinal M. Patnaik","doi":"10.1002/ajh.27492","DOIUrl":"10.1002/ajh.27492","url":null,"abstract":"<p>The current study was inspired by observations from exploratory analyses of an institutional cohort with chronic myelomonocytic leukemia (CMML; <i>N</i> = 398) that revealed no instances of blast transformation in the seven patients with plant homeodomain finger protein 6 (<i>PHF6</i>) mutation (<i>PHF6</i>^MUT). A subsequent Mayo Clinic enterprise-wide database search identified 28 more cases with <i>PHF6</i>^MUT. Compared with their wild-type <i>PHF6</i> counterparts (<i>PHF6</i>^WT; <i>N</i> = 391), <i>PHF6</i>^MUT cases (<i>N</i> = 35) were more likely to co-express <i>TET2</i> (89% vs. 45%; <i>p</i> &lt; .01), <i>RUNX1</i> (29% vs. 14%; <i>p</i> = .03), <i>CBL</i> (14% vs. 2%; <i>p</i> &lt; .01), and <i>U2AF1</i> (17% vs. 6%; <i>p</i> = .04) and less likely <i>SRSF2</i> (23% vs. 45%; <i>p</i> &lt; .01) mutation. They were also more likely to display loss of Y chromosome (LoY; 21% vs. 2%; <i>p</i> &lt; .01) and platelets &lt;100 × 10⁹/L (83% vs. 51%; <i>p</i> &lt; .01). Multivariable analysis identified <i>PHF6</i>^MUT (HR 0.28, 95% CI 0.15–0.50) and <i>DNMT3A</i>^MUT (HR 5.8, 95% CI 3.3–10.5) as the strongest molecular predictors of overall survival. The same was true for blast transformation-free survival with corresponding HR (95% CI) of 0.08 (0.01–0.6) and 9.5 (3.8–23.5). At median 20 months follow-up, blast transformation was documented in none of the 33 patients with <i>PHF6</i>^MUT/<i>DNMT3A</i>^WT but in 6 (32%) of 19 with <i>DNMT3A</i>^MUT and 74 (20%) of 374 with <i>PHF6</i>^WT/<i>DNMT3A</i>^WT (<i>p</i> &lt; .01). The specific molecular signatures sustained their significant predictive performance in the context of the CMML-specific molecular prognostic model (CPSS-mol). <i>PHF6</i>^MUT identifies a unique subset of patients with CMML characterized by thrombocytopenia, higher prevalence of LoY, and superior prognosis.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"99 12","pages":"2321-2327"},"PeriodicalIF":10.1,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27492","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142325773","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}

{"title":"Three-generation female cohort with macrocytic anemia and iron overload","authors":"Alexander A. Boucher,&nbsp;Vanessa J. Dayton,&nbsp;Annaliisa R. Pratt,&nbsp;Nicolas N. Nassar,&nbsp;Yasmin Elgammal,&nbsp;Theodosia A. Kalfa","doi":"10.1002/ajh.27489","DOIUrl":"10.1002/ajh.27489","url":null,"abstract":"&lt;p&gt;&lt;b&gt;A 16-year-old female (P-IIIA) with a past medical history of asthma presented to the hematology clinic with mild macrocytic anemia (hemoglobin 10 g/dL, red blood cells [RBC] 3.19 × 10&lt;/b&gt;&lt;sup&gt;&lt;b&gt;6&lt;/b&gt;&lt;/sup&gt;&lt;b&gt;/μL, mean corpuscular volume [MCV] 103 femtoliters [fL], and red cell distribution width [RDW] of 12.9%). Platelet and white blood cell counts were normal. Two complete blood counts (CBC) tested within the previous 3 years on two occasions, once for a syncopal episode and the other for abdominal pain, had demonstrated similar findings. She was referred to hematology after her macrocytic anemia was noted during an attempted blood donation. At the hematology clinic, along with the CBC results noted above, she was found to have a negative direct antiglobulin test, a mildly elevated ferritin (158 ng/mL), with normal renal function, iron, total iron binding capacity (TIBC, 322 μg/dL), and iron saturation (30%). She reported mild occasional fatigue and intermittent thoracic back pain but was otherwise asymptomatic. She denied bleeding symptoms. Her examination was unremarkable, and she did not have evidence of splenomegaly. At the time of evaluation, she had transitioned to a pescatarian diet for 7 months, eating also vegetables and dairy. Her grandmother (P-I), mother (P-II), and younger sister (P-IIIB) were also noted to have mild macrocytic anemia, while P-II had also been found to have elevated ferritin of unclear etiology (reaching 646 ng/mL, but improved after phlebotomy every 6 weeks for a year).&lt;/b&gt;&lt;/p&gt;&lt;p&gt;Macrocytosis is defined as an MCV above the upper limit of normal for age, which varies from infants to adults. Increased MCV in an automatic complete blood count (CBC) may be artifactual, such as with a marked compensatory reticulocytosis in response to anemia; reticulocytes are normally larger than mature circulating red cells (up to 126 fL for healthy adults), while they can be even larger in conditions of stress erythropoiesis, raising the perceived MCV of the total erythrocytes (mature and non-mature) in automated CBC measurements.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Cold agglutinins may also cause spurious macrocytosis due to cell counting errors of red cell aggregates.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Obtaining the reticulocyte count and evaluating the blood smear are always valuable first steps to confirm a true macrocytosis and start the diagnostic evaluation.&lt;/p&gt;&lt;p&gt;True macrocytosis, typically associated with anemia, can have numerous causes based on clinical context, encompassing both acquired and congenital disorders. The most common pathophysiologic mechanisms involved are (1) impaired DNA synthesis in the erythroblast nuclei during terminal erythropoiesis causing megaloblastic bone marrow changes because of nuclear-cytoplasmic asynchrony, (2) altered red cell hydration increasing cell volume, or (3) altered composition of the lipid bilayer of the RBC membrane.&lt;/p&gt;&lt;p&gt;Impaired DNA synthesis in megaloblastic anemia is caused by vitamin B12 ","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 1","pages":"133-138"},"PeriodicalIF":10.1,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27489","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142325775","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}

{"title":"Current state and potential applications of neonatal Fc receptor (FcRn) inhibitors in hematologic conditions","authors":"Jeremy W. Jacobs,&nbsp;Garrett S. Booth,&nbsp;Sheharyar Raza,&nbsp;Landon M. Clark,&nbsp;Ross M. Fasano,&nbsp;Eleni Gavriilaki,&nbsp;Elizabeth A. Abels,&nbsp;Thomas C. Binns,&nbsp;Miriam Andrea Duque,&nbsp;Zoe K. McQuilten,&nbsp;María Eva Mingot-Castellano,&nbsp;Bipin N. Savani,&nbsp;Deva Sharma,&nbsp;Minh-Ha Tran,&nbsp;Christopher A. Tormey,&nbsp;Kenneth J. Moise Jr,&nbsp;Evan M. Bloch,&nbsp;Brian D. Adkins","doi":"10.1002/ajh.27487","DOIUrl":"10.1002/ajh.27487","url":null,"abstract":"<p>The neonatal fragment crystallizable (Fc) receptor (FcRn) transports IgG across mucosal surfaces and the placenta and protects IgG from degradation. Numerous clinical trials are investigating therapeutic FcRn inhibition for various immune-mediated neuromuscular and rheumatologic conditions; however, FcRn inhibition also represents a potential therapy for IgG-mediated hematologic conditions (e.g., immune thrombocytopenia, autoimmune hemolytic anemia, immune thrombotic thrombocytopenic purpura, acquired hemophilia, red blood cell/platelet alloimmunization). Current evidence derived from both in vitro and in vivo studies suggests that FcRn inhibitors effectively reduce total IgG levels without impacting its production or altering the levels of other immunoglobulin isotypes. Moreover, the risk of serious adverse events, including serious infections, appears to be lower than that seen with other commonly used immunomodulatory/immunosuppressive therapies, albeit in the setting of limited clinical trial data. Ultimately, additional clinical trials that include varied patient populations are required prior to incorporating these agents into standard treatment algorithms for most hematologic conditions. However, based on the pathophysiology of IgG-mediated hematologic disorders and the mechanism of action of FcRn inhibitors, these agents may represent a future novel therapeutic strategy for patients with hematologic conditions caused by IgG antibodies.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"99 12","pages":"2351-2366"},"PeriodicalIF":10.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27487","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324863","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}

{"title":"Measurable residual disease monitoring in AML: Prospects for therapeutic decision-making and new drug development","authors":"Nicholas J. Short, Richard Dillon","doi":"10.1002/ajh.27482","DOIUrl":"https://doi.org/10.1002/ajh.27482","url":null,"abstract":"Measurable residual disease (MRD) is strongly associated with risk of relapse and long-term survival outcomes in patients with acute myeloid leukemia (AML). Apart from its clear prognostic impact, MRD information is also increasingly used to guide therapeutic decision-making, including selection of appropriate patients for stem cell transplant, use of post-transplant maintenance, and candidacy for non-transplant maintenance therapies or MRD-directed clinical trials. While much progress has been made in accurately assessing MRD and understanding its clinical importance, many questions remain about how to optimize MRD testing and guide treatment decisions for individual patients. In this review, we discuss the common methods to assess MRD in AML and the prognostic impact of MRD across common clinical scenarios. We also review emerging and investigational strategies to target MRD and discuss some of the important unanswered questions and challenges in the field.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"31 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317789","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}