American Journal of Hematology最新文献

{"title":"Therapeutic Targeting of the Activin Receptor Signaling Pathway: Proof of Concept in Myeloid Neoplasms","authors":"Ayalew Tefferi, Naseema Gangat","doi":"10.1002/ajh.27638","DOIUrl":"10.1002/ajh.27638","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 5","pages":"755-757"},"PeriodicalIF":10.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27638","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385121","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":"Long-Term Survival After Allogeneic Hematopoietic Stem Cell Transplantation for BCR::ABL1-Negative Atypical Chronic Myeloid Leukemia: A Nationwide Retrospective Study by Adult CML/MPN and MDS Working Groups of the Japanese Society for Transplantation and Cellular Therapy","authors":"Hidehiro Itonaga,&nbsp;Yasushi Miyazaki,&nbsp;Takeshi Kondo,&nbsp;Yutaka Shimazu,&nbsp;Jun Aoki,&nbsp;Shuhei Kurosawa,&nbsp;Takashi Ikeda,&nbsp;Tetsuya Eto,&nbsp;Naoyuki Uchida,&nbsp;Hideyuki Nakazawa,&nbsp;Koji Kawamura,&nbsp;Junya Kanda,&nbsp;Yoshiko Atsuta,&nbsp;Takayoshi Tachibana","doi":"10.1002/ajh.27641","DOIUrl":"10.1002/ajh.27641","url":null,"abstract":"<p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 5","pages":"917-921"},"PeriodicalIF":10.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27641","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385806","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":"Variation Between Imaging and Non-Imaging Transcranial Doppler Systems Versus a Phantom Doppler Generated Velocity","authors":"Mustapha Shu’aibu Hikima,&nbsp;Nura Idris,&nbsp;Muhammad Abba Suwaid,&nbsp;Mark Rodeghier,&nbsp;Ibrahim Musa Idris,&nbsp;Khadija Alkali Bulama,&nbsp;Ahmed Usman,&nbsp;Ted Lynch,&nbsp;Michael R. DeBaun","doi":"10.1002/ajh.27616","DOIUrl":"10.1002/ajh.27616","url":null,"abstract":"&lt;p&gt;Stroke for children with sickle cell disease (SCD) is associated with early mortality and life-long morbidity [&lt;span&gt;1, 2&lt;/span&gt;]. In children with sickle cell anemia (SCA), high blood flow velocity in the distal internal carotid artery or middle cerebral artery, as determined by non-imaging transcranial Doppler sonography, predicts strokes in children with SCD [&lt;span&gt;3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Previous investigators have demonstrated that imaging Doppler sonography produces lower velocity measurements than non-imaging equipment [&lt;span&gt;4, 5&lt;/span&gt;]. At the same time, different non-imaging systems used on the same patient may result in different measurements. The variation of TCD velocity from one machine to another is only one form of variation; the ultrasonographer may also have significant variation on the same child on the same day. Previously, we demonstrated that the intra-observer coefficient of variation for a trainer for TCD velocity exams for our SPIN and SPRING trials, obtained in 21 participants for the right and left MCA, was 7.6% and 12.0% [&lt;span&gt;6&lt;/span&gt;]. These results are consistent with the experience of the STOP Trial group, where the estimate of the coefficient of variation, without a formal analysis, was 10%–15%. We now seek to determine the variation of four commercial non-imaging TCD machines from 3 companies and one imaging TCD machine. With a phantom Doppler, we produced a reference velocity of 191 cm/s, a clinically relevant TCD velocity, and a conditional outcome depicting a significant risk for a stroke in a child with SCA. We employed a CIRS 769 Doppler flow pump and 524 ATS model tissue mimicking Doppler flow phantom to obtain TAMMV from imaging and non-imaging TCD systems. The pump system comprises a validated blood-mimicking fluid, a graduated cylinder, a pulse dampener, a pack of tubing 6/16″ diameter, and control cables. The pump was initially set up and then calibrated to ensure the dispensing of a specific volume of the Doppler fluid into the graduated cylinder. Air bubbles were removed by allowing the pump to circulate the liquid for about 30 min before connection with the phantom and subsequent velocity measurements. Conversion of flow rate to average flow velocity was achieved by dividing the flow rate by the cross-sectional area of the tube. The expected average flow velocities were given in a tabular form provided by the pump manufacturers. Readings were obtained in a constant velocity flow format at a flow rate of 180 cm/s, expected to generate a corresponding TAMMV of 191 cm/s., The constant velocity flow is equivalent to peak systolic velocity as shown here: &lt;span&gt;&lt;/span&gt;&lt;math&gt;\u0000 \u0000 &lt;semantics&gt;\u0000 \u0000 &lt;mrow&gt;\u0000 \u0000 &lt;mtext&gt;TAMMV&lt;/mtext&gt;\u0000 \u0000 &lt;mo&gt;=&lt;/mo&gt;\u0000 \u0000 &lt;mfrac&gt;\u0000 \u0000 &lt;mrow&gt;\u0000 ","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 4","pages":"744-746"},"PeriodicalIF":10.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27616","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375648","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":"Treatment of Bleeding Episodes With Efanesoctocog Alfa in Previously Treated Patients With Severe Hemophilia A in the Phase 3 XTEND-1 Study","authors":"Angela C. Weyand,&nbsp;Sandrine Meunier,&nbsp;Nobuaki Suzuki,&nbsp;Linda Bystrická,&nbsp;Graham Neill,&nbsp;Lydia Abad-Franch,&nbsp;Annemieke Willemze,&nbsp;Alberto Tosetto","doi":"10.1002/ajh.27603","DOIUrl":"10.1002/ajh.27603","url":null,"abstract":"<p>Despite therapeutic advances, people with hemophilia experience bleeds. These may be life-threatening, result in permanent joint damage, chronic pain, difficulties with mobility/daily activities, and impact quality of life. In the XTEND-1 study (NCT04161495), once-weekly efanesoctocog alfa (50 IU/kg) prophylaxis provided highly effective bleed prevention and high-sustained factor levels for most of the week and was well-tolerated. We report post hoc analysis of bleeding episodes and their treatment in previously treated patients (≥ 12 years old). Participants received 50 IU/kg efanesoctocog alfa either as once-weekly prophylaxis (Arm A) or on-demand followed by once-weekly prophylaxis (Arm B) in XTEND-1. Endpoints included treatment of bleeding episodes and response to treatment. During XTEND-1, 422 bleeding episodes were reported among 159 participants; 362 were treated. Most treated bleeding episodes (74%; <i>n</i> = 268) occurred during the Arm B on-demand period, of which 197 (74%) were spontaneous. Seventy-five participants had no bleeding episodes in Arm A; all in Arm B had ≥ 1 bleeding episode while on-demand. Most participants (<i>n</i> = 107, 81%) had zero treated spontaneous bleeding episodes and rates of treated bleeding episodes in Arm A (prophylaxis) were low (median [interquartile range] overall ABR: 0.00 [0.00–1.04]). A single injection was sufficient to resolve 97% (350/362) of treated bleeding episodes, no bleeding episodes required &gt; 3 injections, and responses to 95% of evaluable injections were rated excellent/good. Median total dose was 50.9 IU/kg per bleeding episode. Results of this analysis further demonstrated that once-weekly efanesoctocog alfa provides highly effective bleed protection and treatment of bleeding episodes in participants with severe hemophilia A.</p><p>\u0000 <b>Trial Registration:</b> NCT04161495</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 5","pages":"813-820"},"PeriodicalIF":10.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27603","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375650","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":"Clinico-Genomic Interrogation of Secondary-Type Acute Myeloid Leukemia: Response and Outcomes to Contemporary Therapies","authors":"Jayastu Senapati,&nbsp;Sanam Loghavi,&nbsp;Jennifer Marvin-Peek,&nbsp;Guillermo Garcia-Manero,&nbsp;Tapan M. Kadia,&nbsp;Gautam Borthakur,&nbsp;Naval Daver,&nbsp;Nicholas J. Short,&nbsp;Nitin Jain,&nbsp;Ghayas C. Issa,&nbsp;Fadi Haddad,&nbsp;Danielle Hammond,&nbsp;Kelly Chien,&nbsp;Guillin Tang,&nbsp;Beenu Thakral,&nbsp;Guillermo Montalban-Bravo,&nbsp;Naveen Pemmaraju,&nbsp;Alexandre Bazinet,&nbsp;Mahesh Swaminathan,&nbsp;Sherry Pierce,&nbsp;Hussein A. Abbas,&nbsp;Patrick Reville,&nbsp;Uday Popat,&nbsp;Elizabeth Shpall,&nbsp;Richard Champlin,&nbsp;Elias Jabbour,&nbsp;Farhad Ravandi,&nbsp;Hagop M. Kantarjian,&nbsp;Courtney D. DiNardo","doi":"10.1002/ajh.27628","DOIUrl":"10.1002/ajh.27628","url":null,"abstract":"<div>\u0000 \u0000 <p>Ontogeny of acute myeloid leukemia (AML) provides prognostic information, however closer interrogation with respect to AML characteristics, genomics, and various treatments are warranted. We defined untreated clinical secondary (CS) AML as AML with a diagnosis of antecedent myelodysplastic syndrome (MDS) or MDS/myeloproliferative neoplasm (MDS-MPN) without exposure to hypomethylating agents or chemotherapy; genomic secondary (GS) AML included patients with myelodysplasia related cytogenetics (MRC) or myelodysplasia related mutations (MRM) without a known antecedent myeloid neoplasm or prior chemo-radiotherapy for non-myeloid neoplasms. Among newly diagnosed AML patients classified as untreated CS-AML (<i>n</i> = 133) or GS-AML (<i>n</i> = 389), median relapse-free survival (RFS) (11.9 vs. 12.4 months, <i>p</i> = 0.36) and overall survival (OS) (11.6 vs. 14.4 months, <i>p</i> = 0.75) were similar. No difference in RFS and OS between these groups treated with low-intensity therapy (LIT) and venetoclax regimens was seen, but both were inferior to <i>de novo</i> (DN) AML without secondary-type genomics (pure DN-AML). GS-AML defined by the presence of only MRM had superior OS compared with MRM ± MRC with LIT+ venetoclax therapy (RFS 19.5 vs. 6.8 months [<i>p</i> &lt; 0.01] and OS 29.6 vs. 8.4 [<i>p</i> &lt; 0.01]) and had similar RFS (29.8 months, <i>p</i> = 0.48) and OS (32.0 months, <i>p</i> = 0.48) to pure DN-AML treated with LIT+ venetoclax. On multivariate analysis in patients treated with LIT+ venetoclax, untreated CS-AML (vs. GS-AML), adverse cytogenetics and ELN 2024 adverse-risk disease (mutated <i>TP53</i>) were associated with higher hazard of death. Adverse cytogenetics was the strongest prognostic variable predicting survival. Mutation-driven genomic ontogeny of newly diagnosed AML with MRM appears less prognostic than cytogenetic-driven ontogeny with venetoclax-based therapy.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 5","pages":"758-769"},"PeriodicalIF":10.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371586","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":"It's More Than Complex: Further Insights Into TP53 in MPN","authors":"Nico Gagelmann,&nbsp;Nicolaus Kröger","doi":"10.1002/ajh.27632","DOIUrl":"10.1002/ajh.27632","url":null,"abstract":"<p>TP53 in MPN.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 4","pages":"546-547"},"PeriodicalIF":10.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27632","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371502","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":"A Transfusion Reaction due to Anti-ER5 in a Hyposplenic β0 Thalassemia Major Patient","authors":"Arun Thomas, Kirstin Lund, Viviene Ballon, Barbara J. Bain","doi":"10.1002/ajh.27623","DOIUrl":"https://doi.org/10.1002/ajh.27623","url":null,"abstract":"<div>\u0000<figure>\u0000<div><picture>\u0000<source media=\"(min-width: 1650px)\" srcset=\"/cms/asset/64345587-126f-4f18-a7ea-5159cf375f43/ajh27623-gra-0001-m.jpg\"/><img alt=\"image\" data-lg-src=\"/cms/asset/64345587-126f-4f18-a7ea-5159cf375f43/ajh27623-gra-0001-m.jpg\" loading=\"lazy\" src=\"/cms/asset/7647a287-3036-4ce2-b99b-6c8df39a4ef7/ajh27623-gra-0001-m.png\" title=\"image\"/></picture><p></p>\u0000</div>\u0000</figure>\u0000</div>\u0000<div>\u0000<figure>\u0000<div><picture>\u0000<source media=\"(min-width: 1650px)\" srcset=\"/cms/asset/c47c6691-0665-4106-8ede-5889d765e677/ajh27623-gra-0002-m.jpg\"/><img alt=\"image\" data-lg-src=\"/cms/asset/c47c6691-0665-4106-8ede-5889d765e677/ajh27623-gra-0002-m.jpg\" loading=\"lazy\" src=\"/cms/asset/39c9b4bc-4add-4eab-a443-28a96038c75c/ajh27623-gra-0002-m.png\" title=\"image\"/></picture><p></p>\u0000</div>\u0000</figure>\u0000</div>\u0000<p>A 6-year-old boy of Libyan ethnic origin was referred to pediatric hematology 3 months after entering the United Kingdom as a refugee. The child was known to have thalassemia major. His parents were first cousins. He had previously been transfused every 4 weeks, received chelation therapy and had been splenectomized. More recently, transfusion requirement had increased to every 2 weeks and he had developed post-transfusion hemoglobinuria, which was not ameliorated by corticosteroids. He had not been transfused since arriving in the United Kingdom and his hemoglobin concentration (Hb) was 72 g/L. Anti-c and anti-E were present together with a panagglutinating antibody directed at the high frequency antigen, ER5. It was not possible to source ER5-negative blood and he was therefore transfused with Rh-typed red cells under cover of intravenous immunoglobulin, methylprednisolone, and eculizumab. Transfusion led to an initial rise of Hb to 96 g/L but, despite the precautions taken, by 3 days the Hb had fallen to 65 g/L. His mother reported that following the transfusion his urine had again become red.</p>\u0000<p>Post-transfusion his blood film (both images, ×100 objective) showed hypochromic red cells, target cells, Howell–Jolly bodies, Pappenheimer bodies, schistocytes, alpha chain inclusions within hypochromic erythrocytes (upper image), and nucleated red blood cells. In addition to the evidence of thalassemia and hyposplenism, there were also considerable numbers of spherocytes, indicating a transfusion reaction. The direct antiglobulin test was positive for immunoglobulin G (+). Molecular analysis showed homozygosity for β⁰ thalassemia, specifically NM_000518.4: c93-22_95del p.? In addition, there was homozygosity for the Xmn1 (−158) polymorphism of the <i>HBG2</i> gene, which leads to some increase in hemoglobin F synthesis.</p>\u0000<p>ER5 is a recently recognized, high incidence antigen, antibodies to which can cause hemolytic disease of the fetus and newborn [<span>1</span>]. Future management of the child will be fraught with problems.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"123 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257965","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":"Outcomes of Relapsed or Refractory Diffuse Large B-Cell Lymphoma Treated With R-GemOx: A Multicenter Cohort Study","authors":"Samuel Yamshon,&nbsp;Jean L. Koff,&nbsp;Melissa C. Larson,&nbsp;Brad S. Kahl,&nbsp;Carla Casulo,&nbsp;Izidore S. Lossos,&nbsp;Sara Haddadi,&nbsp;Michele Stanchina,&nbsp;Dai Chihara,&nbsp;Amy Ayers,&nbsp;Thomas M. Habermann,&nbsp;Yucai Wang,&nbsp;Arushi Khurana,&nbsp;Grzegorz S. Nowakowski,&nbsp;Tanner W. Reicks,&nbsp;Umar Farooq,&nbsp;Brian K. Link,&nbsp;Jonathon B. Cohen,&nbsp;Peter Martin,&nbsp;Jia Li,&nbsp;Ashwini Shewade,&nbsp;Connie Lee Batlevi,&nbsp;Andrea Lo-Rossi,&nbsp;David Fox,&nbsp;Anthony Masaquel,&nbsp;Yong Mun,&nbsp;James R. Cerhan,&nbsp;Christopher R. Flowers,&nbsp;Matthew J. Maurer,&nbsp;Loretta J. Nastoupil","doi":"10.1002/ajh.27630","DOIUrl":"10.1002/ajh.27630","url":null,"abstract":"<div>\u0000 \u0000 <p>Rituximab, gemcitabine, and oxaliplatin (R-GemOx) is a commonly used chemoimmunotherapy regimen for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), but there are limited real-world data. In a multicenter retrospective study from a cohort of eight US academic centers (LEO CReWE), we evaluated 183 patients with R/R DLBCL and high-grade B cell lymphoma treated with R-GemOx, including subgroups treated without intent for consolidation with autologous stem cell transplant (ASCT) or chimeric antigen receptor (CAR) T cell therapy (<i>n</i> = 100), those utilizing R-GemOx as a bridge to ASCT or CAR T (<i>n</i> = 83), and those aged 70 and older (<i>n</i> = 71). Overall response rates (ORRs) for all patients treated with R-GemOx were 45% with a complete response (CR) rate of 29%. The median event-free survival (EFS) was 2.3 months, and the median overall survival (OS) was 13.5 months. Patients receiving R-GemOx without intent for ASCT or CAR T had ORR and CR rates of 33% and 18%, respectively, with median EFS and OS of 2.0 and 9.5 months, respectively. Patients receiving R-GemOx as a bridge to ASCT or CAR T had ORR and CR rates of 57% and 36%, respectively, with median EFS and OS of 3.5 and 17.4 months, respectively. Patients receiving R-GemOx aged 70 and older had ORR and CR rates of 53% and 33%, respectively, with median EFS and OS of 2.2 and 13.9 months, respectively. These data provide a benchmark for R-GemOx in the rapidly evolving landscape of R/R DLBCL therapies.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 4","pages":"606-615"},"PeriodicalIF":10.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143258064","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":"Multicenter Prospective First-Line Helicobacter Pylori Eradication for Localized Gastric “Pure” Diffuse Large B-Cell Lymphoma","authors":"Li-Tzong Chen, Kun-Huei Yeh, Chung-Wu Lin, Tsang-En Wang, Ming-Chung Wang, Chin-Fu Hsiao, Chieh-Chang Chen, Jyh-Ming Liou, Hsiu-Po Wang, Ming-Feng Wei, Hsiao-Wei Lee, Chia-Tung Shun, Tsang-Wu Liu, Hwei-Fang Tien, Ming-Shiang Wu, Sung-Hsin Kuo, Ann-Lii Cheng","doi":"10.1002/ajh.27624","DOIUrl":"https://doi.org/10.1002/ajh.27624","url":null,"abstract":"&lt;p&gt;Our exploratory study evaluated the efficacy of first-line &lt;i&gt;Helicobacter pylori&lt;/i&gt; eradication (HPE) therapy on early-stage (stage IE/IIE1) &lt;i&gt;Helicobacter pylori&lt;/i&gt; (HP)-positive gastric diffuse large B-cell lymphomas (DLBCLs) without histological evidence of mucosa-associated lymphoid tissue (MALT) (“pure” DLBCLs). The study showed that 11 of 16 (68.8%) patients achieved complete remission (CR) after successful HPE and remained lymphoma-free after a median follow-up of 7.7 years [&lt;span&gt;1&lt;/span&gt;]. Another study by Tari et al. demonstrated that 4 of 15 (26.7%) patients with gastric “pure” DLBCLs who received first-line antibiotic treatment achieved CR and remained lymphoma-free after a median follow-up of 7–100 months [&lt;span&gt;2&lt;/span&gt;]. Additionally, Ferrieri et al. studied 16 patients with gastric DLBCLs, of whom, 11 had “pure” DLBCLs and five had DLBCLs with histological evidence of MALT (DLBCL[MALT]), who were administered HPE (including clarithromycin, tinidazole or metronidazole, and omeprazole) [&lt;span&gt;3&lt;/span&gt;]. Of these, eight patients achieved CR and three achieved partial remission (PR), with an overall response rate (ORR) of 68.8% after HPE [&lt;span&gt;3&lt;/span&gt;]. Cumulatively, these findings indicate that certain patients with gastric “pure” DLBCLs are responsive to first-line antibiotic therapy and might have a better quality of life because they are not exposed to the conventional immunochemotherapy-related adverse effects. However, prospective studies evaluating patients whose tumors are not limited to the stomach but extend to the perigastric lymph node area are warranted.&lt;/p&gt;\u0000&lt;p&gt;Considering that “pure” DLBCLs of the stomach grow rapidly when the tumors do not respond to first-line HPE, identifying molecular markers that can predict HP independence (the lack of CR of tumors after completing HPE) is necessary. Our previous study showed that in in vitro DLBCL cell lines, B cell activating factor (BAFF) triggered the activation of NF-κB. Furthermore, it caused nuclear translocation of BCL10 by inducing AKT phosphorylation and disrupting the interaction of BCL10 with MALT1 and subsequent complex formation of BCL10 and BCL3 (nuclei translation-related genes) [&lt;span&gt;4&lt;/span&gt;]. Furthermore, in tumor samples from patients with gastric DLBCL(MALT)s who received first-line HPE, BAFF overexpression was significantly associated with the nuclear translocation of BCL10 or NF-κB (p65), and the aforementioned molecules (including BAFF, nuclear BCL10, and nuclear NF-κB (p65)) were significantly correlated with HP independence of the tumor [&lt;span&gt;4&lt;/span&gt;]. In contrast to HP-independent biomarkers, we detected HP-encoded protein cytotoxin-associated gene A (CagA) in tumor samples of patients with gastric MALT lymphomas and DLBCL(MALT)s [&lt;span&gt;5, 6&lt;/span&gt;]. The expression of CagA was more frequent in HP-dependent tumors than in HP-independent tumors of gastric lymphomas [&lt;span&gt;5, 6&lt;/span&gt;].&lt;/p&gt;\u0000&lt;p&gt;In March 2015, the National Taiwan University and the","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"42 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192495","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":"Recipient Cells Are the Source of Hematologic Malignancies After Graft Failure and Mixed Chimerism in Adults With SCD","authors":"Mohamed A. E. Ali,&nbsp;Emily M. Limerick,&nbsp;Matthew M. Hsieh,&nbsp;Kalpana Upadhyaya,&nbsp;Xin Xu,&nbsp;Oswald Phang,&nbsp;Jean Pierre Kambala Mukendi,&nbsp;Katherine R. Calvo,&nbsp;Maria Lopez-Ocasio,&nbsp;Pradeep Dagur,&nbsp;Courtney D. Fitzhugh","doi":"10.1002/ajh.27627","DOIUrl":"10.1002/ajh.27627","url":null,"abstract":"&lt;p&gt;Hematopoietic cell transplant (HCT) is the only curative option for individuals with sickle cell disease (SCD). Traditionally, young patients with a human leukocyte antigen (HLA)-matched donor received myeloablative conditioning followed by HCT to completely replace recipient hematopoietic cells with healthy donor cells (full donor chimerism). Unfortunately, less than 15% of patients have an HLA-matched sibling donor (MSD). Conversely, haploidentical (haplo) HCT greatly expands the donor pool. Moreover, adults with SCD and overt organ damage cannot tolerate myeloablative conditioning. Therefore, we developed a non-myeloablative approach that could be applied to such patients. This approach initially aimed at achieving a state of mixed donor and recipient chimerism, where the hematopoietic system is constituted by both the donor's and recipient's cells. Indeed, we have reported that 20% donor myeloid chimerism is sufficient to reverse the SCD phenotype because of a significant difference in the life span of healthy versus sickled red blood cells [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;In 2023, the FDA approved two additional potentially curative therapies. First, Lyfgenia, by Bluebird Bio, uses a lentiviral vector to genetically modify hematopoietic stem and progenitor cells (HSPCs) to produce HbA&lt;sup&gt;T87Q&lt;/sup&gt;, which functions similarly to HbA. Second, Casgevy, a clustered, regularly interspaced palindromic repeats-associated protein-9 nuclease (CRISPR-Cas9) gene-edited therapy, reactivates the production of fetal hemoglobin. Both therapies would still require myeloablative conditioning, which limits its application to younger patients with no significant organ damage.&lt;/p&gt;&lt;p&gt;Two studies have reported an increased relative risk of leukemia development in patients with SCD, though the absolute risk is low [&lt;span&gt;2&lt;/span&gt;]. Moreover, several groups have reported an increased risk of leukemia development after curative therapies, mainly after graft failure in SCD patients [&lt;span&gt;2&lt;/span&gt;]. We have recently reported that eight out of 120 patients who received nonmyeloablative allogeneic HCT developed hematologic malignancies (HMs) between 4 months and 9 years post-HCT: five developed aggressive therapy-related myeloid neoplasms (myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)), one T-cell acute lymphoblastic leukemia (ALL), one chronic myeloid leukemia, and one mantle cell lymphoma [&lt;span&gt;2&lt;/span&gt;]. In addition, two adult Group A patients from the bluebird bio study subsequently developed AML [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Leukemia development has been associated with the acquisition of somatic mutations, which accumulate with aging in a condition known as clonal hematopoiesis (CH). Somatic mutations in genes involved in stem cell self-renewal or cellular differentiation pathways bestow a considerable survival advantage or fitness upon the mutant hemopoietic clone, resulting in its significant expansion compared with nonmutant cells [&lt;span&gt;3&lt;/span&gt;]. Whol","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 5","pages":"903-905"},"PeriodicalIF":10.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27627","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192277","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}