American Journal of Hematology最新文献

{"title":"Improved Transplant Outcomes With Alternative Donors in Myelofibrosis: A 20-Year Japanese Registry Analysis of Donor Sources and the Impact of Ruxolitinib","authors":"Kazuki Sakatoku,&nbsp;Hirohisa Nakamae,&nbsp;Makoto Murata,&nbsp;Yutaka Shimazu,&nbsp;Katsuto Takenaka,&nbsp;Fumihiko Kimura,&nbsp;Naoyuki Uchida,&nbsp;Tetsuya Nishida,&nbsp;Takahiro Fukuda,&nbsp;Noriko Doki,&nbsp;Jun Ishikawa,&nbsp;Emiko Sakaida,&nbsp;Keisuke Kataoka,&nbsp;Shuichi Shirane,&nbsp;Masatsugu Tanaka,&nbsp;Hikaru Kobayashi,&nbsp;Masashi Sawa,&nbsp;Toshio Wakayama,&nbsp;Noboru Asada,&nbsp;Yasufumi Uehara,&nbsp;Makoto Yoshimitsu,&nbsp;Junya Kanda,&nbsp;Marie Ohbiki,&nbsp;Yoshiko Atsuta,&nbsp;Takayoshi Tachibana","doi":"10.1002/ajh.27699","DOIUrl":"10.1002/ajh.27699","url":null,"abstract":"<p>This study of 308 myelofibrosis patients shows that in recent years (2013–2019), alternative donors (mismatched unrelated donors and cord blood) achieved survival rates comparable to HLA-matched donors—a significant improvement compared to earlier years (2000–2012) when outcomes differed substantially. Ruxolitinib showed significant benefits in older patients (≥ 57), particularly with mismatched unrelated donors. Cord blood transplantation outcomes improved with MMF-based GVHD prophylaxis. These findings suggest optimized strategies combining both age-specific and donor-specific approaches can maximize transplant success in myelofibrosis patients.\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 7","pages":"1259-1263"},"PeriodicalIF":10.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27699","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893911","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":"Profound Thrombocytopenia and Dyspnea 11 Days After Cardiac Surgery","authors":"Sebastian Vuong,&nbsp;Menaka Pai,&nbsp;Sarah Patterson,&nbsp;Theodore E. Warkentin","doi":"10.1002/ajh.27691","DOIUrl":"10.1002/ajh.27691","url":null,"abstract":"&lt;p&gt;\u0000 &lt;b&gt;A 59-year-old Caucasian female with hypertension and dyslipidemia presented to the hospital with dyspnea. Her platelet count was 7 × 10&lt;/b&gt;\u0000 &lt;sup&gt;\u0000 &lt;b&gt;9&lt;/b&gt;\u0000 &lt;/sup&gt;\u0000 &lt;b&gt;/L (reference range [RR], 150–400). Eleven days earlier, she had undergone an elective valve-sparing Bentall procedure (replacement of hemi-aortic arch) and ascending aorta repair with cardiopulmonary bypass (CPB) for aortic root aneurysm. Her postoperative course was uneventful, with discharge on postoperative day (POD) 4. The patient reported no bleeding symptoms/signs, and petechiae were not present&lt;/b&gt;.&lt;/p&gt;&lt;p&gt;Platelet count declines are universal post-cardiac surgery, with platelet count recovery to preoperative baseline expected by the seventh POD, and continued platelet count increase that typically peaks by POD14 [&lt;span&gt;1&lt;/span&gt;]; thus, a platelet count of 7 × 10&lt;sup&gt;9&lt;/sup&gt;/L on POD11 is highly abnormal and sufficiently reduced to be classified as “profound” thrombocytopenia (&lt; 20 × 10&lt;sup&gt;9&lt;/sup&gt;/L) [&lt;span&gt;2&lt;/span&gt;]. Yet, this patient presented with dyspnea, not bleeding. The urgent task was to identify promptly the cause of her dyspnea and to address the profound thrombocytopenia with the key question: did a single diagnosis explain both?&lt;/p&gt;&lt;p&gt;\u0000 &lt;b&gt;Vital signs were BP 98/59, HR 102/min, RR 23/min, temperature 38.5°C; oxygen saturation was 95% (room air). Urgent echocardiography showed normal ventricular contractility without valve abnormalities; however, a moderate-to-large pericardial effusion was present; subtle right ventricular diastolic collapse suggested partial or incipient cardiac tamponade. The cardiologists were concerned that the pericardial fluid was blood rather than serous fluid, that is hemorrhagic pericarditis. However, risk of pericardiocentesis was felt to be extremely high due to thrombocytopenia; thus, urgent hematology consultation was requested&lt;/b&gt;.&lt;/p&gt;&lt;p&gt;There is a limited differential diagnosis for profound thrombocytopenia, particularly given the normal platelet count just 11 days earlier. The differential diagnosis includes: pseudothrombocytopenia (spurious thrombocytopenia); consumptive thrombocytopenia (disseminated intravascular coagulation [DIC] secondary to infection/shock, thrombotic microangiopathy [TMA], or immune heparin-induced thrombocytopenia [HIT]); or destructive thrombocytopenia (antibody-mediated platelet clearance by drug-dependent antibodies, autoantibodies, or alloantibodies). A reasonable first diagnostic step is to evaluate the complete blood count (CBC), along with peripheral blood film review.&lt;/p&gt;&lt;p&gt;\u0000 &lt;b&gt;The hemoglobin measured 7.7 g/dL (RR, 13.0–18.0) and the white blood cell (WBC) count was 14.0 × 10&lt;/b&gt;\u0000 &lt;sup&gt;\u0000 &lt;b&gt;9&lt;/b&gt;\u0000 &lt;/sup&gt;\u0000 &lt;b&gt;/L (RR, 4.0–11.0). Repeat CBC confirmed profound thrombocytopenia (8 × 10&lt;/b&gt;\u0000 &lt;sup&gt;\u0000 &lt;b&gt;9&lt;/b&gt;\u0000 &lt;/sup&gt;\u0000 ","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 7","pages":"1234-1239"},"PeriodicalIF":10.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27691","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893910","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":"Integration of Optical Genome Mapping in the Cytogenomic and Molecular Work-Up of Hematological Malignancies: Expert Recommendations From the International Consortium for Optical Genome Mapping","authors":"Rashmi Kanagal-Shamanna,&nbsp;Anna Puiggros,&nbsp;Isabel Granada,&nbsp;Gordana Raca,&nbsp;Katrina Rack,&nbsp;Mar Mallo,&nbsp;Barbara Dewaele,&nbsp;Adam C. Smith,&nbsp;Yassmine Akkari,&nbsp;Brynn Levy,&nbsp;Robert P. Hasserjian,&nbsp;Adela Cisneros,&nbsp;Marta Salido,&nbsp;Guillermo Garcia-Manero,&nbsp;Hui Yang,&nbsp;M. Anwar Iqbal,&nbsp;Ravindra Kolhe,&nbsp;Francesc Solé,&nbsp;Blanca Espinet","doi":"10.1002/ajh.27688","DOIUrl":"10.1002/ajh.27688","url":null,"abstract":"<div>\u0000 \u0000 <p>The latest updates to the classification of hematolymphoid malignancies using the World Health Organization (WHO, 5th ed.) and ICC (International Consensus Classification) criteria highlight the critical need for comprehensive and precise cytogenomic data for diagnosis, prognostication, and treatment. This presents significant challenges for clinical laboratories, requiring a complex workflow using multiple assays to detect different types of structural chromosomal variants (copy number changes, fusions, inversions) across the entire genome. Optical genome mapping (OGM) is an advanced cytogenomic tool for genome-wide detection of structural chromosomal alterations at the gene/exon level. Studies demonstrate that OGM facilitates the identification of novel cytogenomic biomarkers, improves risk stratification, and expands therapeutic targets and personalized treatment strategies. OGM is easy to implement and highly accurate in detecting structural variants (SVs) across various diagnostic entities. Consequently, many centers are integrating OGM into the clinical cytogenetic workflow for hematological malignancies. However, systemic clinical adoption has remained limited due to the lack of expert recommendations on clinical indications, testing algorithms, and result interpretation. To address this, experts from the International Consortium for OGM and relevant multidisciplinary fields developed recommendations for the integration of OGM as a standard-of-care cytogenetic assay for the diagnostic workflow in various clinical settings. These recommendations standardize the use of OGM across laboratories, ensure high-quality cytogenetic data, guide clinical trial design and development, and provide a basis for updates to diagnostic and classification models.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 6","pages":"1029-1048"},"PeriodicalIF":10.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase II Trial of Geriatric Assessment-Guided Selection of Treatment Intensity in Older Adults With AML","authors":"Vijaya R. Bhatt,&nbsp;Christopher S. Wichman,&nbsp;Thuy T. Koll,&nbsp;Alfred L. Fisher,&nbsp;Tanya M. Wildes,&nbsp;Michael Haddadin,&nbsp;Ann M. Berger,&nbsp;James O. Armitage,&nbsp;Sarah A. Holstein,&nbsp;Lori J. Maness,&nbsp;Krishna Gundabolu","doi":"10.1002/ajh.27694","DOIUrl":"10.1002/ajh.27694","url":null,"abstract":"<p>How to select the appropriate intensity of chemotherapy in older adults with acute myeloid leukemia (AML) remains an unanswered question. In a phase II trial of older adults ≥ 60 years with AML (<i>n</i> = 73), we used geriatric assessment (measures of comorbidity burden, physical and cognitive function) to determine fitness for intensive chemotherapy. We integrated the geriatric assessment and genetic test results to personalize the selection of chemotherapy intensity with a goal to reduce early mortality (NCT03226418). Broad eligibility criteria allowed enrolling patients representative of those treated in real-world practices: 45% of patients were ≥ 70 years, 57% had ≥ 2 comorbidities, 27% had a history of solid malignancies, and 74% had impairments in ≥ 2 geriatric assessment domains used to assign treatment intensity. Thirty-two percent of patients resided in rural areas, and 45% were comanaged with community oncologists. The median time from enrollment to therapy initiation was 1 day (range 0–13). Eight patients (11%) received intensive chemotherapy; others received low-intensity chemotherapy. Mortality at 30 days from diagnosis was 6.8% (95% confidence interval, CI 3.0%–15.1%) and at 90 days was 21.9% (95% CI 14.0%–32.7%). One-year survival was 45.9% (95% CI 35.6%–59.3%). Our study demonstrates that pre-treatment geriatric assessment in older adults with AML is feasible, can identify several functional impairments, and guide the selection of treatment intensity. A randomized trial is necessary to confirm the survival benefit of this approach over the traditional approach of treatment selection.</p><p>\u0000 <b>Trial Registration:</b> NCT03226418</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 7","pages":"1163-1172"},"PeriodicalIF":10.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27694","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885068","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 Synthetic Image Crisis in Science","authors":"Enrico M. Bucci,&nbsp;Angelo Parini","doi":"10.1002/ajh.27697","DOIUrl":"10.1002/ajh.27697","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 7","pages":"1114-1117"},"PeriodicalIF":10.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27697","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880210","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":"Acute Megakaryoblastic Leukemia Masquerading as a Germ Cell Tumor","authors":"Lindsay M. Olson, Mark Gurney, Marissa Li, Yuan Yao, Tucker Johnson, Horatiu Olteanu, Naseema Gangat","doi":"10.1002/ajh.27698","DOIUrl":"https://doi.org/10.1002/ajh.27698","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":"79 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880227","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":"Rocky Mountain Spotted Fever, a Lymphoma Mimic on Peripheral Blood Smear","authors":"Patricia Lupu, Linnea Banker, Richard D. Hammer","doi":"10.1002/ajh.27695","DOIUrl":"https://doi.org/10.1002/ajh.27695","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":"25 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880209","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":"Elotuzumab in Combination With Dose Reduced IMiDs and Dexamethasone for AL Amyloidosis Patients With Relapsed/Refractory Plasma Cell Dyscrasia and Advanced Organ Involvement","authors":"Tobias Dittrich,&nbsp;Timon Hansen,&nbsp;Christoph R. Kimmich,&nbsp;Kaya Veelken,&nbsp;Anna Jauch,&nbsp;Marc S. Raab,&nbsp;Carsten Müller-Tidow,&nbsp;Ute Hegenbart,&nbsp;Stefan O. Schönland","doi":"10.1002/ajh.27684","DOIUrl":"10.1002/ajh.27684","url":null,"abstract":"&lt;p&gt;Systemic light chain (AL) amyloidosis is a rare, life-threatening disorder characterized by toxic light chain deposition and multiorgan dysfunction [&lt;span&gt;1, 2&lt;/span&gt;]. Standard treatment targets the clonal plasma cells, and daratumumab-based regimens have demonstrated rapid hematologic responses with significant organ recovery [&lt;span&gt;3&lt;/span&gt;]. However, with the increasing use of daratumumab in early treatment regimens, there is a growing need for effective therapies for AL patients with double or triple refractory plasma cell disorders. Elotuzumab, a humanized IgG1 monoclonal antibody targeting SLAMF7 on plasma cells and natural killer cells, has been proposed as a promising option in case of daratumumab failure in multiple myeloma, particularly when used in combination with pomalidomide [&lt;span&gt;3&lt;/span&gt;]. Although its combination with immunomodulatory drugs (IMiDs) appears promising for AL amyloidosis, data remain scarce, highlighting the need for further investigation to better define its role in patients with advanced organ involvement.&lt;/p&gt;&lt;p&gt;We retrospectively evaluated 33 AL patients with relapsed/refractory plasma cell disorder who were initiated with elotuzumab, dexamethasone, and an IMiD (pomalidomide in 25 patients) between January 2017 and October 2022. Table S1 displays the patient characteristics at initial diagnosis of the AL amyloidosis. All patients had the baseline visit prior to therapy start with elotuzumab and at least one follow-up visit at one of the two institutions, Heidelberg Amyloidosis Center or Hamburg Amyloidosis outpatient clinic (at Onkologicum HOPA). Elotuzumab was administered intravenously according to the manufacturer's prescribing guidelines along with standard premedication including antihistamines and dexamethasone. The initial dexamethasone dose was 20 mg, followed by 8 mg in subsequent treatments, with dose reductions considered in response to toxicity. The initial elotuzumab dose was 10 mg/kg total body weight administered weekly for the first 2 cycles, followed by 10 mg/kg total body weight every 2 weeks (combination with lenalidomide) or 20 mg/kg total body weight every 4 weeks (combination witch pomalidomide) until disease progression or unacceptable toxicities emerged. Additionally, patients orally received pomalidomide and lenalidomide on days 1–21 of each cycle, with median doses of 3 mg (range: 2–4 mg) and 7.5 mg (range: 2.5–15 mg), respectively. As of the data-cutoff date on August 4, 2024, a median of five elotuzumab cycles were administered (range: 2–46). Data acquisition, response evaluation, evaluation of tolerability and adverse events as well as statistical methods are detailed in the supplemental information.&lt;/p&gt;&lt;p&gt;At the start of elotuzumab (Table S2), the cohort exhibited significant organ dysfunction (27% on dialysis; 50% with NT-proBNP &gt; 8500 ng/L) and extensive pretreatment (median of three prior lines, with 79% refractory to proteasome inhibitors, 55% to IMiDs, and 85% to daratum","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 6","pages":"1098-1101"},"PeriodicalIF":10.1,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27684","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872818","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":"Integrating Optical Genome Mapping With TP53 FISH: A Synergistic Approach for Cytogenomic Analysis in Chronic Lymphocytic Leukemia","authors":"Joanna Kamaso,&nbsp;Rocío García-Serra,&nbsp;Marina Munné,&nbsp;María Rodríguez-Rivera,&nbsp;Carme Melero,&nbsp;Sílvia Ramos-Campoy,&nbsp;Marta Salido,&nbsp;Marta Lorenzo,&nbsp;Eva Gimeno,&nbsp;Joan Gibert,&nbsp;Peter Vandenberghe,&nbsp;Katrina Rack,&nbsp;Anna Puiggros,&nbsp;Barbara Dewaele,&nbsp;Blanca Espinet","doi":"10.1002/ajh.27690","DOIUrl":"10.1002/ajh.27690","url":null,"abstract":"&lt;p&gt;Fluorescence in situ hybridization (FISH) is the gold standard technique for cytogenetic assessment in chronic lymphocytic leukemia (CLL). In addition, chromosome banding analysis (CBA) is recommended as part of testing to detect complex karyotypes (CK, ≥ 3 abnormalities in the same cell clone), especially as those with a high-CK (≥ 5 abnormalities) have a known worst outcome [&lt;span&gt;1, 2&lt;/span&gt;]. Optical genome mapping (OGM) has emerged as a high-resolution technique to detect genome-wide balanced and unbalanced abnormalities, overcoming some disadvantages associated with current cytogenomic methods [&lt;span&gt;3&lt;/span&gt;]. This study aimed to compare the effectiveness of OGM against CBA and FISH techniques in detecting poor prognostic cytogenomic biomarkers in CLL within a cohort of 102 CLL patients from two European centers, thus assessing the potential of OGM as a future routine diagnostic test.&lt;/p&gt;&lt;p&gt;Patients were selected to represent all the risk categories of the FISH-based Döhner hierarchical model: isolated del(13q) (&lt;i&gt;n&lt;/i&gt; = 19), normal FISH (&lt;i&gt;n&lt;/i&gt; = 18), trisomy 12 (&lt;i&gt;n&lt;/i&gt; = 17), del(11q)(&lt;i&gt;ATM&lt;/i&gt;) (&lt;i&gt;n&lt;/i&gt; = 28), and del(17p)(&lt;i&gt;TP53&lt;/i&gt;) (&lt;i&gt;n&lt;/i&gt; = 20) (Table S1). OGM experiments were performed following the manufacturer's protocols, analyzed using the rare variant analysis pipeline (GRCh38/hg38 as a reference) and results visualized with the Bionano Access software (v1.7.2) (Bionano Genomics, San Diego, CA, USA). The detected structural variants (SVs) and copy number alterations (CNAs; gains and losses) were filtered out in different steps by discarding artifacts and polymorphisms, and applying filter settings based on confidence scores and size for the remaining alterations. The filtering strategy was based on criteria used in chromosomal microarrays analyses [&lt;span&gt;4&lt;/span&gt;], and aimed to identify translocations, clinically relevant abnormalities in CLL independent of the size, and other abnormalities ≥ 5 Mb. Additionally, non-CLL abnormalities, sized between 200Kb and 5 Mb, were exclusively retained if they were part of a chromoanagenesis event or associated with other retained SV. First, we evaluated OGM's ability to detect abnormalities identified by the FISH panel and CBA. Next, we analyzed genomic complexity in patients stratified by CK status to determine a potential threshold for defining complexity by OGM. Statistical analyses were performed using SPSS v.23 software (SPSS Inc., Chicago, IL, USA). &lt;i&gt;p&lt;/i&gt; values &lt; 0.05 were considered statistically significant. Further details on methodology are described in Supporting Information.&lt;/p&gt;&lt;p&gt;Concerning cytogenomic abnormalities included in Döhner's model, OGM identified 90% (112/125) of those previously detected by FISH. Additionally, OGM detected two small deletions [one del(11q) and one del(13q)] undetectable by the standard FISH probes used in routine practice due to their small size (Figure 1A). Although OGM failed to identify 13 CNAs present in 6.5% to 17% of nu","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 7","pages":"1242-1245"},"PeriodicalIF":10.1,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27690","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872817","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":"Arginine Therapy for Pain in Sickle Cell Disease: A Phase-2 Randomized, Placebo-Controlled Trial","authors":"Claudia R. Morris,&nbsp;Dunia Hatabah,&nbsp;Rawan Korman,&nbsp;Scott Gillespie,&nbsp;Nitya Bakshi,&nbsp;Lou Ann Brown,&nbsp;Frank Harris,&nbsp;Deborah Leake,&nbsp;Chris A. Rees,&nbsp;Kirshma Khemani,&nbsp;Elliott P. Vichinsky,&nbsp;Alexus Locke,&nbsp;Bridget Wynn,&nbsp;Mark A. Griffiths,&nbsp;Hagar Wilkinson,&nbsp;Polly Kumari,&nbsp;Lisa Sudmeier,&nbsp;Sruti Shiva,&nbsp;Carlton D. Dampier","doi":"10.1002/ajh.27692","DOIUrl":"10.1002/ajh.27692","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>We present a prospective randomized, placebo-controlled trial of intravenous arginine in patients 3–21 years hospitalized with sickle cell disease vaso-occlusive pain episodes (SCD-VOE) at two tertiary-care children's hospitals. Participants were randomized into 1 of 3 arms: <i>Standard-dose</i> (SD; 100 mg/kg/dose) every 8 h, <i>Loading-dose</i> (200 mg/kg followed by SD), or <i>Placebo</i>. The primary outcome was total parenteral opioid use (TPO). Secondary outcomes included time-to-crisis-resolution, pain scores, patient-reported outcomes (PROs), arginine bioavailability, and biomarkers of oxidative stress/mitochondrial function. Of 1548 patients screened, 108 were randomized (36 per study-arm; mean 12.6 ± 3.8 years, 52% female, and 65% hemoglobin-SS). This study did not meet its primary endpoint. TPO, time-to-crisis-resolution, pain scores, and PROs at discharge were similar across arms. <i>Post hoc</i> sensitivity analyses of children 5–16 years old demonstrated nearly double TPO utilization in those receiving placebo versus arginine (<i>n</i> = 87, <i>p</i> = 0.056), achieving significance in patients with plasma arginine &lt; 60 μM. Arginine was low at presentation in 79% of patients (mean 50 ± 28 μM), and increased with arginine therapy (<i>p</i> &lt; 0.001). Arginine bioavailability at VOE presentation inversely correlated with time-to-crisis-resolution (<i>r</i> = −0.39, <i>p</i> = 0.01) after placebo, an association eliminated by arginine supplementation (<i>r</i> = −0.04, <i>p</i> = 0.70). A dose-dependent increase in platelet-mitochondrial activity occurred after arginine versus no change after placebo (<i>p</i> &lt; 0.001); plasma protein-carbonyl levels, a measure of oxidative stress, decreased after arginine therapy (<i>p</i> &lt; 0.001) but increased in the placebo group (<i>p</i> = 0.02). SCD-VOE is associated with an acquired arginine deficiency that correlates with worse clinical outcomes. Arginine improved mitochondrial function and decreased oxidative stress compared to placebo, with clinically relevant opioid-sparing becoming significant in children with the lowest arginine concentration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>Registered with ClinicalTrials.gov (NCT02536170) in August 2015</p>\u0000 </section>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 7","pages":"1119-1131"},"PeriodicalIF":10.1,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866820","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}