Nichola Cooper, A. J. Gerard Jansen, Robert Bird, Jiří Mayer, Michelle Sholzberg, Michael D. Tarantino, Mamta Garg, Paula F. Ypma, Vickie McDonald, Charles Percy, Milan Košťál, Isaac Goncalves, Lachezar H. Bogdanov, Terry B. Gernsheimer, Remco Diab, Mengjie Yao, Ahmed Daak, David J. Kuter
Current treatments for persistent or chronic immune thrombocytopenia (ITP) are limited by inadequate response, toxicity, and impaired quality of life. The Bruton tyrosine kinase inhibitor rilzabrutinib was evaluated to further characterize safety and durability of platelet response. LUNA2 Part B is a multicenter, phase 1/2 study in adults with ITP (≥ 3 months duration, platelet count < 30 × 109/L) who failed ≥ 1 ITP therapy (NCT03395210, EudraCT 2017–004012-19). Oral rilzabrutinib 400 mg bid was given over 24 weeks, with optional long-term extension (LTE). Primary endpoints were safety and platelet counts ≥ 50 × 109/L on ≥ 8 of the last 12 weeks of main treatment without rescue medication. From 22 March2018 to 31 January2023, 26 patients were enrolled. Patients had baseline median platelet count 13 × 109/L, ITP duration 10.3 years, and six prior ITP therapies (46% splenectomized). Nine (35%) patients achieved the primary endpoint. Platelet counts ≥ 50 × 109/L or ≥ 30 × 109/L and doubling from baseline without rescue therapy were sustained for a mean 9.3 weeks. 11 (42%) LTE-eligible patients were ongoing with median LTE platelet > 80 × 109/L. Three (12%) patients received rescue medication during main treatment, none in LTE. Clinically meaningful improvements were observed in fatigue and women's health. With a median treatment duration of 167 days (main treatment), 16 (62%) patients had ≥ 1 treatment-related adverse event (AE), mainly grade 1, including diarrhea (35%), headache (23%), and nausea (15%). There was no treatment-related grade ≥ 2 bleeding/thrombotic events/infections, serious AE, or death. Rilzabrutinib continues to demonstrate durable platelet responses with favorable safety profile in previously treated ITP patients.
{"title":"Efficacy and Safety Results With Rilzabrutinib, an Oral Bruton Tyrosine Kinase Inhibitor, in Patients With Immune Thrombocytopenia: Phase 2 Part B Study","authors":"Nichola Cooper, A. J. Gerard Jansen, Robert Bird, Jiří Mayer, Michelle Sholzberg, Michael D. Tarantino, Mamta Garg, Paula F. Ypma, Vickie McDonald, Charles Percy, Milan Košťál, Isaac Goncalves, Lachezar H. Bogdanov, Terry B. Gernsheimer, Remco Diab, Mengjie Yao, Ahmed Daak, David J. Kuter","doi":"10.1002/ajh.27539","DOIUrl":"https://doi.org/10.1002/ajh.27539","url":null,"abstract":"Current treatments for persistent or chronic immune thrombocytopenia (ITP) are limited by inadequate response, toxicity, and impaired quality of life. The Bruton tyrosine kinase inhibitor rilzabrutinib was evaluated to further characterize safety and durability of platelet response. LUNA2 Part B is a multicenter, phase 1/2 study in adults with ITP (≥ 3 months duration, platelet count < 30 × 10<sup>9</sup>/L) who failed ≥ 1 ITP therapy (NCT03395210, EudraCT 2017–004012-19). Oral rilzabrutinib 400 mg bid was given over 24 weeks, with optional long-term extension (LTE). Primary endpoints were safety and platelet counts ≥ 50 × 10<sup>9</sup>/L on ≥ 8 of the last 12 weeks of main treatment without rescue medication. From 22 March2018 to 31 January2023, 26 patients were enrolled. Patients had baseline median platelet count 13 × 10<sup>9</sup>/L, ITP duration 10.3 years, and six prior ITP therapies (46% splenectomized). Nine (35%) patients achieved the primary endpoint. Platelet counts ≥ 50 × 10<sup>9</sup>/L or ≥ 30 × 10<sup>9</sup>/L and doubling from baseline without rescue therapy were sustained for a mean 9.3 weeks. 11 (42%) LTE-eligible patients were ongoing with median LTE platelet > 80 × 10<sup>9</sup>/L. Three (12%) patients received rescue medication during main treatment, none in LTE. Clinically meaningful improvements were observed in fatigue and women's health. With a median treatment duration of 167 days (main treatment), 16 (62%) patients had ≥ 1 treatment-related adverse event (AE), mainly grade 1, including diarrhea (35%), headache (23%), and nausea (15%). There was no treatment-related grade ≥ 2 bleeding/thrombotic events/infections, serious AE, or death. Rilzabrutinib continues to demonstrate durable platelet responses with favorable safety profile in previously treated ITP patients.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"1 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021097","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}
Amir Mahmoud, Suhong Luo, Brian F. Gage, Amber Afzal, Kenneth Carson, Su-Hsin Chang, Martin Schoen, Tzu-Fei Wang, Kristen M. Sanfilippo
<p>Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in cancer patients. Managing VTE in cancer patients involves balancing elevated risks of VTE recurrence with anticoagulant (AC)-related bleeding. Risk of AC-related bleeding is exacerbated in cancer patients due to older age, thrombocytopenia, frailty, comorbid disease, and tumor invasion [<span>1</span>]. Limited data exist on the association between AC-related bleeding and survival in patients with cancer-associated VTE. In one meta-analysis of patients with cancer, the case fatality rate for AC-related major bleeding was nearly 1 in 10 patients [<span>2</span>]. In another study, patients with cancer-associated VTE had a 2.7-fold increased rate of bleeding-related mortality compared to patients with VTE without cancer [<span>3</span>]. However, fatality in respect to site of bleed was not reported. This study aims to quantify the relationship between clinically significant bleeding events and death in patients with cancer-associated VTE newly initiated on AC therapy, stratified by site of bleeding.</p> <p>Utilizing data from the nationwide US Veterans Affairs (VA) healthcare system between 2012 and 2020, we retrospectively identified patients with solid tumor using international classification of diseases, 9th and 10th Revisions (ICD-9/10) codes. We identified new cancer-associated VTE using a validated algorithm [<span>4</span>] that used the combination of ICD-9/10 codes (from both inpatient and outpatient encounters) and initiation of AC therapy. A VTE was considered as occurring in a patient with active cancer if diagnosed within 3 months prior to cancer diagnosis or 6 months after cancer diagnosis or at any time after a diagnosis of metastatic cancer. Patients with cancer-associated VTE were included if they received a prescription for at least 30 days of direct oral anticoagulants (DOACs), low molecular-weight-heparin (LMWH), or vitamin K antagonists (VKA) within 30 days of VTE diagnosis. To ensure a clear temporal relationship between AC initiation and VTE diagnosis, patients with outpatient AC prescriptions within 6 months preceding the VTE diagnosis were excluded. Using the VA Informatics and Computing Infrastructure platform, data were obtained via the VA Corporate Data Warehouse. We extracted baseline demographic data at the start of AC therapy. All variables considered for the study are defined in the Table S1. We calculated the VA-Frailty Index (FI) as previously described except that we omitted bleeding-related codes.</p> <p>The primary outcome of interest was death within 12-month of AC therapy initiation. We identified date of death using the VA Vital Status File and survival time was calculated as the number of days from the date of initiating AC therapy to the date of death. The primary exposure of interest was clinically significant AC-related bleeding requiring hospitalization within 12-month of AC therapy initiation. Hospitalized bleeding eve
总之，我们的研究表明，在实体瘤和癌症相关 VTE 患者中，AC 相关出血与死亡率增加之间存在显著关联，尤其是在 ICH 和消化道出血之后。在缺乏可靠的癌症患者出血风险评估模型的情况下，研究结果强调了个体化风险评估和警惕性监测在管理这类体弱人群的 AC 治疗中的重要性。
{"title":"Association Between Anticoagulant-Related Bleeding and Mortality in Patients With Solid Tumors and Cancer-Associated Venous Thromboembolism","authors":"Amir Mahmoud, Suhong Luo, Brian F. Gage, Amber Afzal, Kenneth Carson, Su-Hsin Chang, Martin Schoen, Tzu-Fei Wang, Kristen M. Sanfilippo","doi":"10.1002/ajh.27588","DOIUrl":"https://doi.org/10.1002/ajh.27588","url":null,"abstract":"<p>Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in cancer patients. Managing VTE in cancer patients involves balancing elevated risks of VTE recurrence with anticoagulant (AC)-related bleeding. Risk of AC-related bleeding is exacerbated in cancer patients due to older age, thrombocytopenia, frailty, comorbid disease, and tumor invasion [<span>1</span>]. Limited data exist on the association between AC-related bleeding and survival in patients with cancer-associated VTE. In one meta-analysis of patients with cancer, the case fatality rate for AC-related major bleeding was nearly 1 in 10 patients [<span>2</span>]. In another study, patients with cancer-associated VTE had a 2.7-fold increased rate of bleeding-related mortality compared to patients with VTE without cancer [<span>3</span>]. However, fatality in respect to site of bleed was not reported. This study aims to quantify the relationship between clinically significant bleeding events and death in patients with cancer-associated VTE newly initiated on AC therapy, stratified by site of bleeding.</p>\u0000<p>Utilizing data from the nationwide US Veterans Affairs (VA) healthcare system between 2012 and 2020, we retrospectively identified patients with solid tumor using international classification of diseases, 9th and 10th Revisions (ICD-9/10) codes. We identified new cancer-associated VTE using a validated algorithm [<span>4</span>] that used the combination of ICD-9/10 codes (from both inpatient and outpatient encounters) and initiation of AC therapy. A VTE was considered as occurring in a patient with active cancer if diagnosed within 3 months prior to cancer diagnosis or 6 months after cancer diagnosis or at any time after a diagnosis of metastatic cancer. Patients with cancer-associated VTE were included if they received a prescription for at least 30 days of direct oral anticoagulants (DOACs), low molecular-weight-heparin (LMWH), or vitamin K antagonists (VKA) within 30 days of VTE diagnosis. To ensure a clear temporal relationship between AC initiation and VTE diagnosis, patients with outpatient AC prescriptions within 6 months preceding the VTE diagnosis were excluded. Using the VA Informatics and Computing Infrastructure platform, data were obtained via the VA Corporate Data Warehouse. We extracted baseline demographic data at the start of AC therapy. All variables considered for the study are defined in the Table S1. We calculated the VA-Frailty Index (FI) as previously described except that we omitted bleeding-related codes.</p>\u0000<p>The primary outcome of interest was death within 12-month of AC therapy initiation. We identified date of death using the VA Vital Status File and survival time was calculated as the number of days from the date of initiating AC therapy to the date of death. The primary exposure of interest was clinically significant AC-related bleeding requiring hospitalization within 12-month of AC therapy initiation. Hospitalized bleeding eve","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"1 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991281","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}
Emma N. Cravo, Hannah L. Hays, Jaahnavi Badeti, Henry A. Spiller, Natalie I. Rine, Motao Zhu, Gary A. Smith
The objective of this study was to investigate the characteristics and trends of therapeutic errors in non-healthcare facility settings associated with antithrombotic medications reported to United States Poison Centers by analyzing data from the National Poison Data System from 2000 to 2021. There were 57 288 reported therapeutic error-related exposures involving antithrombotic medications as the primary substance. The rate of therapeutic errors increased by 590.9% during this 22-year period. Although most (90.1%) therapeutic errors were clinically inconsequential and did not receive treatment at a healthcare facility, 2.3% were medically admitted, and 2.1% experienced a serious medical outcome, including 16 fatalities. Three-fourths (74.9%) of therapeutic errors were among > 59-year-olds, and females represented 58.0% of exposures. Warfarin was the most commonly involved antithrombotic medication (37.5%), followed by direct oral anticoagulants (DOACs, 28.7%) and clopidogrel (23.3%). Therapeutic errors involving warfarin were more likely to be associated with a medical admission (odds ratio [OR] = 2.23; 95% confidence interval [CI]: 1.99–2.49) or a serious medical outcome (OR = 2.99; 95% CI: 2.65–3.37), and DOACs were less likely to be associated with a medical admission (OR = 0.53, 95% CI: 0.46–0.61) or a serious medical outcome (OR = 0.45; 95% CI: 0.38–0.53) than therapeutic errors involving other antithrombotic medications. The rate of therapeutic errors involving warfarin significantly increased by 187.0% during 2000–2011, followed by a 57.6% significant decrease during 2011–2021. The rate of therapeutic errors involving DOACs increased significantly by 1118.2% during 2011–2021. The scenario “inadvertently took/given medication twice” accounted for 56.3% of all therapeutic errors. Increased risk reduction efforts are needed to prevent antithrombotic-related therapeutic errors.
{"title":"Therapeutic Errors Associated With Antithrombotic Medications Reported to United States Poison Centers","authors":"Emma N. Cravo, Hannah L. Hays, Jaahnavi Badeti, Henry A. Spiller, Natalie I. Rine, Motao Zhu, Gary A. Smith","doi":"10.1002/ajh.27595","DOIUrl":"https://doi.org/10.1002/ajh.27595","url":null,"abstract":"The objective of this study was to investigate the characteristics and trends of therapeutic errors in non-healthcare facility settings associated with antithrombotic medications reported to United States Poison Centers by analyzing data from the National Poison Data System from 2000 to 2021. There were 57 288 reported therapeutic error-related exposures involving antithrombotic medications as the primary substance. The rate of therapeutic errors increased by 590.9% during this 22-year period. Although most (90.1%) therapeutic errors were clinically inconsequential and did not receive treatment at a healthcare facility, 2.3% were medically admitted, and 2.1% experienced a serious medical outcome, including 16 fatalities. Three-fourths (74.9%) of therapeutic errors were among > 59-year-olds, and females represented 58.0% of exposures. Warfarin was the most commonly involved antithrombotic medication (37.5%), followed by direct oral anticoagulants (DOACs, 28.7%) and clopidogrel (23.3%). Therapeutic errors involving warfarin were more likely to be associated with a medical admission (odds ratio [OR] = 2.23; 95% confidence interval [CI]: 1.99–2.49) or a serious medical outcome (OR = 2.99; 95% CI: 2.65–3.37), and DOACs were less likely to be associated with a medical admission (OR = 0.53, 95% CI: 0.46–0.61) or a serious medical outcome (OR = 0.45; 95% CI: 0.38–0.53) than therapeutic errors involving other antithrombotic medications. The rate of therapeutic errors involving warfarin significantly increased by 187.0% during 2000–2011, followed by a 57.6% significant decrease during 2011–2021. The rate of therapeutic errors involving DOACs increased significantly by 1118.2% during 2011–2021. The scenario “inadvertently took/given medication twice” accounted for 56.3% of all therapeutic errors. Increased risk reduction efforts are needed to prevent antithrombotic-related therapeutic errors.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"42 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987507","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":"Intravenous Iron Associated Hypophosphatemia: Much More Than a Laboratory Curiosity","authors":"Michael Auerbach, Myles Wolf","doi":"10.1002/ajh.27599","DOIUrl":"https://doi.org/10.1002/ajh.27599","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":"94 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987436","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}
<p>Cytogenetic alterations are important in risk stratification for multiple myeloma (MM). Translocations involving the immunoglobulin heavy chain (IGH), such as t(4;14), t(14;16), as well as del(17p) and gain(1q), are recognized as high-risk cytogenetic markers in staging systems [<span>1</span>]. Fluorescence in situ hybridization (FISH) is the primary method for detecting these genetic alterations. However, cytogenetic testing in MM is challenging owing to the lower proportion of plasma cells in bone marrow (BM) aspirates, which may arise from sample variability or suboptimal sample quality. To address these challenges, clinical laboratories employ CD138+ plasma cell enrichment procedures, such as cytoplasmic immunoglobulin FISH or cell sorting using either flow cytometry or magnetic beads. Although these techniques can increase the analytical sensitivity of FISH, they also come with drawbacks, such as the need for additional steps, associated costs, the time required, and the need for larger volumes of BM samples.</p> <p>Optical genome mapping (OGM) is an emerging cytogenetic technology that offers advantages in detecting genome-wide structural variations and copy number variants with high sensitivities in hematologic malignancies [<span>2</span>]. In MM, OGM has revealed promising results compared with the conventional cytogenetic methods, such as karyotyping and FISH [<span>3, 4</span>]. Moreover, with its ability to perform high-resolution, genome-wide analysis, OGM facilitates the classification and detection of genetic alterations not identified by conventional methods, including those involving the <i>MYC</i> gene [<span>3, 5</span>]. Compared with whole-genome sequencing, OGM may be more cost-effective while achieving higher coverage, directly improving the detection of variants with low variant allele frequencies (VAFs). With the 300× coverage, OGM is reported to be capable of detecting VAF ≥ 5%.</p> <p>In this study, we evaluated the clinical application of OGM for detecting cytogenetic alterations, which are routinely performed using FISH. Based on promising results from a pilot study using OGM on BM aspirate samples with a plasma cell percentage > 50% without CD138+ plasma cell enrichment [<span>3</span>], we aimed to evaluate the performance of OGM in samples with varying plasma cell percentages without CD138+ plasma cell enrichment. We also aimed to identify optimal plasma cell percentages to enable routine application of OGM in clinical settings.</p> <p>This study included 25 BM aspirate samples obtained from patients with newly diagnosed MM between January 2023 and June 2024 at the Guro Hospital, Korea University (Table S1). All patients had ≥ 10% plasma cells in BM aspirates. Samples with concurrent results of plasma cell percentages obtained using flow cytometry and FISH results were included. This study was approved by the Institutional Review Board of Korea University (2024GR0240), Guro Hospital, and conducted in accorda
{"title":"Clinical Validation of Optical Genome Mapping in Multiple Myeloma Without Plasma Cell Enrichment","authors":"Jung Yoon, Jung Ah Kwon, Soo-Young Yoon","doi":"10.1002/ajh.27589","DOIUrl":"https://doi.org/10.1002/ajh.27589","url":null,"abstract":"<p>Cytogenetic alterations are important in risk stratification for multiple myeloma (MM). Translocations involving the immunoglobulin heavy chain (IGH), such as t(4;14), t(14;16), as well as del(17p) and gain(1q), are recognized as high-risk cytogenetic markers in staging systems [<span>1</span>]. Fluorescence in situ hybridization (FISH) is the primary method for detecting these genetic alterations. However, cytogenetic testing in MM is challenging owing to the lower proportion of plasma cells in bone marrow (BM) aspirates, which may arise from sample variability or suboptimal sample quality. To address these challenges, clinical laboratories employ CD138+ plasma cell enrichment procedures, such as cytoplasmic immunoglobulin FISH or cell sorting using either flow cytometry or magnetic beads. Although these techniques can increase the analytical sensitivity of FISH, they also come with drawbacks, such as the need for additional steps, associated costs, the time required, and the need for larger volumes of BM samples.</p>\u0000<p>Optical genome mapping (OGM) is an emerging cytogenetic technology that offers advantages in detecting genome-wide structural variations and copy number variants with high sensitivities in hematologic malignancies [<span>2</span>]. In MM, OGM has revealed promising results compared with the conventional cytogenetic methods, such as karyotyping and FISH [<span>3, 4</span>]. Moreover, with its ability to perform high-resolution, genome-wide analysis, OGM facilitates the classification and detection of genetic alterations not identified by conventional methods, including those involving the <i>MYC</i> gene [<span>3, 5</span>]. Compared with whole-genome sequencing, OGM may be more cost-effective while achieving higher coverage, directly improving the detection of variants with low variant allele frequencies (VAFs). With the 300× coverage, OGM is reported to be capable of detecting VAF ≥ 5%.</p>\u0000<p>In this study, we evaluated the clinical application of OGM for detecting cytogenetic alterations, which are routinely performed using FISH. Based on promising results from a pilot study using OGM on BM aspirate samples with a plasma cell percentage > 50% without CD138+ plasma cell enrichment [<span>3</span>], we aimed to evaluate the performance of OGM in samples with varying plasma cell percentages without CD138+ plasma cell enrichment. We also aimed to identify optimal plasma cell percentages to enable routine application of OGM in clinical settings.</p>\u0000<p>This study included 25 BM aspirate samples obtained from patients with newly diagnosed MM between January 2023 and June 2024 at the Guro Hospital, Korea University (Table S1). All patients had ≥ 10% plasma cells in BM aspirates. Samples with concurrent results of plasma cell percentages obtained using flow cytometry and FISH results were included. This study was approved by the Institutional Review Board of Korea University (2024GR0240), Guro Hospital, and conducted in accorda","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"15 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987524","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}
<p>We read with great interest the article by Casella et al. [<span>1</span>] which reported the results of the HU Prevent Trial. Regardless of the limitations acknowledged by the authors, Casella's study suggests that Hydroxyurea (HU) may have neuroprotective effect in very young children with sickle cell disease (SCD) and support a phase III study to encourage the early use of HU in all infants with SCD. While many advances have been made in the understanding of the pathophysiology and the identification of the cornerstones of comprehensive care to reduce mortality in the first years of life, cerebral vasculopathy remains a cause of acute mortality and long-term morbidity with impact on quality of life [<span>2-4</span>].</p> <p>Here, we report on cerebral vasculopathy morbidity in a longitudinal pediatric SCD natural history cohort in a high-income country, showing both the benefit of HU in reducing cerebral vasculopathy but also the need to intensify treatments in young children in order to reduce the serious impact of cerebral complications later in life. We performed a retrospective analysis using data from children with SCD who, at age of diagnosis, were prospectively enrolled in the SCD Natural History Study, which began in December 1, 2007 and is an ongoing, longitudinal follow-up study recording information on the physical examination, laboratory parameters, acute and chronic complications during every outpatient and inpatient visit since diagnosis. The censoring date was December 31, 2020, or the date of death, enrollment in a randomized clinical trial assessing new therapeutic drugs, transfer to a new center, or Hematopoietic Stem Cell Transplantation (HSCT). The study was approved by the Research Ethic Committee of Padua University Hospital, and written informed consent was obtained by each caregiver. The Italian Association of Pediatric Hematology Oncology (AIEOP) guidelines were used to guide acute event treatment, monitoring of chronic organ damage and standardize treatment with Hydroxyurea (HU), red blood cell transfusion and HSCT, as well as management of acute and chronic complications (6–7). HU was indicated in case of more than two vaso-occlusive-crisis (VOC) per year or chronic anemia with hemoglobin < 8 g/dL. Regarding cerebral vasculopathy, the standard care included annual Transcranial doppler (TCD) from age 2 and Magnetic Resonance Imaging/Magnetic Resonance Angiography (MRI/MRA) from 6 years, every 2 years, or earlier in case of abnormal TCD. In this analysis, we evaluated event-free survival (EFS) and cumulative incidence analysis of a composite neurological event defined as the occurrence of at least one of the following: clinical neurological event (transient ischemic attack or stroke), abnormal/conditional TCD, new stenosis at MRA, new silent cerebral infarct (SCI) at MRI.</p> <p>Fisher and chi-square tests were used to compare categorical variables. Kaplan–Meier method was used to estimate survival probabilities
{"title":"Residual Cerebrovascular Morbidity Despite Treatment in Pediatric Sickle Cell Disease Highlights Opportunities for Earlier, Intensified Monitoring and Treatment","authors":"Giulia Reggiani, Beatrice Coppadoro, Maria Paola Boaro, Roberta Trapanese, Ilaria Baido, Alessandra Biffi, Federica Viaro, Alessio Pieroni, Matteo Minerva, Giovanna Barcelos, Renzo Manara, Claudia Baracchini, Raffaella Colombatti","doi":"10.1002/ajh.27596","DOIUrl":"https://doi.org/10.1002/ajh.27596","url":null,"abstract":"<p>We read with great interest the article by Casella et al. [<span>1</span>] which reported the results of the HU Prevent Trial. Regardless of the limitations acknowledged by the authors, Casella's study suggests that Hydroxyurea (HU) may have neuroprotective effect in very young children with sickle cell disease (SCD) and support a phase III study to encourage the early use of HU in all infants with SCD. While many advances have been made in the understanding of the pathophysiology and the identification of the cornerstones of comprehensive care to reduce mortality in the first years of life, cerebral vasculopathy remains a cause of acute mortality and long-term morbidity with impact on quality of life [<span>2-4</span>].</p>\u0000<p>Here, we report on cerebral vasculopathy morbidity in a longitudinal pediatric SCD natural history cohort in a high-income country, showing both the benefit of HU in reducing cerebral vasculopathy but also the need to intensify treatments in young children in order to reduce the serious impact of cerebral complications later in life. We performed a retrospective analysis using data from children with SCD who, at age of diagnosis, were prospectively enrolled in the SCD Natural History Study, which began in December 1, 2007 and is an ongoing, longitudinal follow-up study recording information on the physical examination, laboratory parameters, acute and chronic complications during every outpatient and inpatient visit since diagnosis. The censoring date was December 31, 2020, or the date of death, enrollment in a randomized clinical trial assessing new therapeutic drugs, transfer to a new center, or Hematopoietic Stem Cell Transplantation (HSCT). The study was approved by the Research Ethic Committee of Padua University Hospital, and written informed consent was obtained by each caregiver. The Italian Association of Pediatric Hematology Oncology (AIEOP) guidelines were used to guide acute event treatment, monitoring of chronic organ damage and standardize treatment with Hydroxyurea (HU), red blood cell transfusion and HSCT, as well as management of acute and chronic complications (6–7). HU was indicated in case of more than two vaso-occlusive-crisis (VOC) per year or chronic anemia with hemoglobin < 8 g/dL. Regarding cerebral vasculopathy, the standard care included annual Transcranial doppler (TCD) from age 2 and Magnetic Resonance Imaging/Magnetic Resonance Angiography (MRI/MRA) from 6 years, every 2 years, or earlier in case of abnormal TCD. In this analysis, we evaluated event-free survival (EFS) and cumulative incidence analysis of a composite neurological event defined as the occurrence of at least one of the following: clinical neurological event (transient ischemic attack or stroke), abnormal/conditional TCD, new stenosis at MRA, new silent cerebral infarct (SCI) at MRI.</p>\u0000<p>Fisher and chi-square tests were used to compare categorical variables. Kaplan–Meier method was used to estimate survival probabilities","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"20 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987121","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}
Kathryn Lurain, Ramya Ramaswami, Eric Oksenhendler, David Boutboul, Alessia Dalla Pria, Lara Ulrich, Krithika Shanmugasundaram, Thomas S. Uldrick, Mark Bower, Robert Yarchoan, Laurence Gérard, Seth M. Steinberg
Primary effusion lymphoma (PEL) is an HIV-associated B-cell non-Hodgkin lymphoma (NHL) caused by Kaposi sarcoma herpesvirus (KSHV). There is no validated prognostic model in PEL, and prognosis is thought to be poor compared to other HIV-associated NHL. We derived the PEL-Prognostic score (PEL-PS) from an international real-world training set of 59 patients with HIV-associated PEL who received first-line anthracycline-containing chemotherapy from the HIV and AIDS Malignancy Branch at the National Cancer Institute (NCI) in the United States and the National Center for HIV Malignancy at the Chelsea and Westminster Hospital (CWH) in England from 2000 to 2022. We identified prognostic factors associated with overall survival (OS). In a multivariable Cox model, ECOG ≥ 3 (p = 0.007; hazard ratio [HR] = 4.0 [95% CI: 1.5–11.1]) and hemoglobin < 8 g/dL (p = 0.006; HR = 3.8 [95% CI: 1.5–9.7]) were jointly associated with lower survival probability. The resulting PEL-PS separated patients with no negative prognostic factors (score 0: hemoglobin ≥ 8 g/dL and ECOG ≤ 2, 48.1% of patients) with median OS of 10.6 years versus patients with 1–2 negative prognostic factors (score 1–2: hemoglobin < 8 g/dL and/or ECOG ≥ 3, 51.9% of patients) with median OS of 0.8 years (p < 0.0001). The PEL-PS was then validated in 58 patients with HIV-associated PEL treated with first-line anthracycline-containing chemotherapy at Hôpital Saint-Louis in France over the same period: median OS in patients with PEL-PS 0 was 16.9 years versus 0.6 years in patients with PEL-PS score of 1–2 (p < 0.0001). The PEL-PS identifies patients with good and poor prognosis. Patients with poor prognosis may benefit from novel therapies.
{"title":"Primary Effusion Lymphoma Prognostic Score (PEL-PS): A Validated International Prognostic Score in HIV-Associated Primary Effusion Lymphoma","authors":"Kathryn Lurain, Ramya Ramaswami, Eric Oksenhendler, David Boutboul, Alessia Dalla Pria, Lara Ulrich, Krithika Shanmugasundaram, Thomas S. Uldrick, Mark Bower, Robert Yarchoan, Laurence Gérard, Seth M. Steinberg","doi":"10.1002/ajh.27580","DOIUrl":"https://doi.org/10.1002/ajh.27580","url":null,"abstract":"Primary effusion lymphoma (PEL) is an HIV-associated B-cell non-Hodgkin lymphoma (NHL) caused by Kaposi sarcoma herpesvirus (KSHV). There is no validated prognostic model in PEL, and prognosis is thought to be poor compared to other HIV-associated NHL. We derived the PEL-Prognostic score (PEL-PS) from an international real-world training set of 59 patients with HIV-associated PEL who received first-line anthracycline-containing chemotherapy from the HIV and AIDS Malignancy Branch at the National Cancer Institute (NCI) in the United States and the National Center for HIV Malignancy at the Chelsea and Westminster Hospital (CWH) in England from 2000 to 2022. We identified prognostic factors associated with overall survival (OS). In a multivariable Cox model, ECOG ≥ 3 (<i>p</i> = 0.007; hazard ratio [HR] = 4.0 [95% CI: 1.5–11.1]) and hemoglobin < 8 g/dL (<i>p</i> = 0.006; HR = 3.8 [95% CI: 1.5–9.7]) were jointly associated with lower survival probability. The resulting PEL-PS separated patients with no negative prognostic factors (score 0: hemoglobin ≥ 8 g/dL and ECOG ≤ 2, 48.1% of patients) with median OS of 10.6 years versus patients with 1–2 negative prognostic factors (score 1–2: hemoglobin < 8 g/dL and/or ECOG ≥ 3, 51.9% of patients) with median OS of 0.8 years (<i>p</i> < 0.0001). The PEL-PS was then validated in 58 patients with HIV-associated PEL treated with first-line anthracycline-containing chemotherapy at Hôpital Saint-Louis in France over the same period: median OS in patients with PEL-PS 0 was 16.9 years versus 0.6 years in patients with PEL-PS score of 1–2 (<i>p</i> < 0.0001). The PEL-PS identifies patients with good and poor prognosis. Patients with poor prognosis may benefit from novel therapies.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"36 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981660","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}
Ondrej Venglar, Eva Radova, David Zihala, Ivana Tvrda, Viktor Kubala, Kamila Kutejova, Ludmila Muronova, Veronika Kapustova, Lucie Broskevicova, Jan Vrana, Tereza Popkova, Jana Mihalyova, Hana Plonkova, Tereza Sevcikova, Michal Kascak, Milan Navratil, Zdenek Koristek, Roman Hajek, Tomas Jelinek
<p>High-dose melphalan followed by autologous stem cell transplantation (ASCT) remains the standard of care for multiple myeloma (MM) patients. However, hematopoietic cell autografts are often contaminated with aberrant plasma cells (aPC) following CD34+ cell mobilization [<span>1</span>], making graft MRD (gMRD) assessment potentially valuable. Nevertheless, the clinical significance of gMRD was not fully leveraged so far. It was demonstrated that the gMRD positivity is associated with worse progression-free survival (PFS) and overall survival (OS) [<span>1, 2</span>]. Recent studies utilizing next generation flow cytometry (NGF) with the limit of detection (LOD) 0.0002% (2 × 10<sup>−6</sup>) provided similar results, together with predicting worse post-induction response in gMRD positive patients [<span>3-5</span>]. Therefore, gMRD evaluation holds significant potential for patient benefit. However, there is currently virtually no knowledge about the relationship between gMRD status and pre-ASCT MRD levels in the bone marrow (BM), despite the invasive MRD assessment is increasingly common at this timepoint due to improved first-line therapeutic regimens that induce rapid and deep responses [<span>6</span>].</p> <p>To enhance the understanding of gMRD clinical significance, we performed a single-center study involving 99 transplant-eligible MM patients diagnosed between 2019 and 2023. All patients were treated with standard induction therapy, followed by CD34+ cell mobilization, leukapheresis of hematopoietic cell graft, high-dose melphalan, and ASCT (Methods S1–S3). MRD was evaluated in grafts on a day of the first apheresis (gMRD), in BMs one day prior to ASCT (pre-ASCT), and in BMs day +100 after ASCT (post-ASCT) using NGF by EuroFlow protocol (Methods S4, Figure S1).</p> <p>In total, 44% (44/99) of patients in our cohort were gMRD+ and 56% (55/99) were gMRD-. Both groups were well balanced without any significant differences in terms of age, gender, cytogenetic risk, induction regimens used or number of their cycles (median number of cycles = 4), mobilization regimen, or maintenance status. Notably, patients in the gMRD- group more frequently received anti-CD38 therapy (22% vs. 6.8%), whereas VTd was more common in the gMRD+ group (64% vs. 49%); however, the difference was not statistically significant. ISS I stage was more prevalent in gMRD- group (ISS I, II, III frequency: 47%, 31%, 22%), while ISS II and III were more frequent in gMRD+ cohort (18%, 43%, 39%; <i>p</i> = 0.009). R-ISS comparison showed similar results (R ISS I, II, III frequency: gMRD- 44%, 51%, 5.5%, gMRD+ 19%, 69%, 12%; <i>p</i> = 0.033). CD34+ cell yields were significantly higher in gMRD+ group (median, range CD34+ cells × 10<sup>6</sup>/kg: 13, 9–24 vs. 10, 6–14, <i>p</i> = 0.013), which might be partially attributed to higher rates of AraC + G-CSF administered in this group (30% vs. 13%), although the difference was not significant (<i>p</i> = 0.11). Tandem ASCT was m
{"title":"Level of Clonal Plasma Cells in Hematopoietic Cell Autografts Reflects the Pre-Transplant Bone Marrow Minimal Residual Disease in Multiple Myeloma Patients","authors":"Ondrej Venglar, Eva Radova, David Zihala, Ivana Tvrda, Viktor Kubala, Kamila Kutejova, Ludmila Muronova, Veronika Kapustova, Lucie Broskevicova, Jan Vrana, Tereza Popkova, Jana Mihalyova, Hana Plonkova, Tereza Sevcikova, Michal Kascak, Milan Navratil, Zdenek Koristek, Roman Hajek, Tomas Jelinek","doi":"10.1002/ajh.27590","DOIUrl":"https://doi.org/10.1002/ajh.27590","url":null,"abstract":"<p>High-dose melphalan followed by autologous stem cell transplantation (ASCT) remains the standard of care for multiple myeloma (MM) patients. However, hematopoietic cell autografts are often contaminated with aberrant plasma cells (aPC) following CD34+ cell mobilization [<span>1</span>], making graft MRD (gMRD) assessment potentially valuable. Nevertheless, the clinical significance of gMRD was not fully leveraged so far. It was demonstrated that the gMRD positivity is associated with worse progression-free survival (PFS) and overall survival (OS) [<span>1, 2</span>]. Recent studies utilizing next generation flow cytometry (NGF) with the limit of detection (LOD) 0.0002% (2 × 10<sup>−6</sup>) provided similar results, together with predicting worse post-induction response in gMRD positive patients [<span>3-5</span>]. Therefore, gMRD evaluation holds significant potential for patient benefit. However, there is currently virtually no knowledge about the relationship between gMRD status and pre-ASCT MRD levels in the bone marrow (BM), despite the invasive MRD assessment is increasingly common at this timepoint due to improved first-line therapeutic regimens that induce rapid and deep responses [<span>6</span>].</p>\u0000<p>To enhance the understanding of gMRD clinical significance, we performed a single-center study involving 99 transplant-eligible MM patients diagnosed between 2019 and 2023. All patients were treated with standard induction therapy, followed by CD34+ cell mobilization, leukapheresis of hematopoietic cell graft, high-dose melphalan, and ASCT (Methods S1–S3). MRD was evaluated in grafts on a day of the first apheresis (gMRD), in BMs one day prior to ASCT (pre-ASCT), and in BMs day +100 after ASCT (post-ASCT) using NGF by EuroFlow protocol (Methods S4, Figure S1).</p>\u0000<p>In total, 44% (44/99) of patients in our cohort were gMRD+ and 56% (55/99) were gMRD-. Both groups were well balanced without any significant differences in terms of age, gender, cytogenetic risk, induction regimens used or number of their cycles (median number of cycles = 4), mobilization regimen, or maintenance status. Notably, patients in the gMRD- group more frequently received anti-CD38 therapy (22% vs. 6.8%), whereas VTd was more common in the gMRD+ group (64% vs. 49%); however, the difference was not statistically significant. ISS I stage was more prevalent in gMRD- group (ISS I, II, III frequency: 47%, 31%, 22%), while ISS II and III were more frequent in gMRD+ cohort (18%, 43%, 39%; <i>p</i> = 0.009). R-ISS comparison showed similar results (R ISS I, II, III frequency: gMRD- 44%, 51%, 5.5%, gMRD+ 19%, 69%, 12%; <i>p</i> = 0.033). CD34+ cell yields were significantly higher in gMRD+ group (median, range CD34+ cells × 10<sup>6</sup>/kg: 13, 9–24 vs. 10, 6–14, <i>p</i> = 0.013), which might be partially attributed to higher rates of AraC + G-CSF administered in this group (30% vs. 13%), although the difference was not significant (<i>p</i> = 0.11). Tandem ASCT was m","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"18 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981754","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}
Natalia Scaramellini, Marta Canzi, Elena Cassinerio, Margherita Migone De Amicis, Loredana Pettine, Bruno Fattizzo, Francesca Gaia Rossi, Giorgio Croci, Irene Motta
<p>A 35-year-old man came to our attention for the suspicion of Gaucher disease (GD). The patient had undergone a bone marrow aspirate and biopsy because of massive splenomegaly (30 cm), severe thrombocytopenia (platelet count 30 000/mm<sup>3</sup>), and mild anemia [hemoglobin (Hb) 12.1 g/dL] observed in the emergency department, where he presented for acute abdominal pain. Bone marrow biopsy (BMB) revealed foci of fibrosis accompanied by aggregates of CD163+/CD1a− epithelioid histiocytes, featuring a fibrillary, dimly eosinophilic, PASD+ cytoplasm, accounting for 60% of the cellularity. These histological findings were consistent with lysosomal storage disease. GD was then confirmed by beta-glucocerebrosidase activity on dried blood spot (GBA activity 0.4 μmol/L/h, n.v. > 3.5 μmol/L/h) and molecular analysis of the <i>GBA</i> gene that showed compound heterozygosity c.475C>T/c.1226A>G [p.(Arg159Trp)/p.(Asn409Ser)] mutations. At the time of diagnosis, he also had hyperferritinemia (serum ferritin 1300 ng/mL) with normal transferrin saturation (25%). Substrate reduction therapy with eliglustat was started with hematologic improvement at 1 year: platelet counts 55 000/mm<sup>3</sup>, Hb 14.1 g/dL, and reduction in the spleen volume (22 cm).</p> <p>A year and a half later, he complained of night sweats, weight loss of 3 kg over 3 weeks, and fatigue. Blood tests showed slightly microcytic anemia (Hb 10.5 g/dL, mean corpuscular volume 78.7 fL), platelet count three times the previous value (176 000/mm<sup>3</sup>), even higher values of ferritin (2756 ng/mL), and serologies negative for active infections (HIV CMV, EBV, and Toxoplasma). A total body CT scan showed cervical and thoracic lymphadenopathies up to 4.5 cm and an increase in spleen volume (25 cm). Bone marrow aspirate was negative, while BMB showed foci of Gaucher-type histiocytes, with scattered iron-laden cells, alternated with foci of sclerosis (Figure 1a), with admixed histiocytes, small lymphocytes, eosinophilic granulocytes, and rare scattered, CD30-positive Hodgkin and Reed-Sternberg (HRS) cells (Figure 1b), confirming the clinical suspicion of classical Hodgkin lymphoma (cHL). Interestingly, the diffused and massive macrophage infiltration, which initially masked the rare HRS cells, displayed a double functional phenotype, highlighted through immunohistochemical PD-L1 expression. On the one hand, we observed Gaucher cells with extremely dim PDL-1 intensity [<span>1</span>]; on the other hand, the tumor microenvironment (TME) of cHL expressed abundant PD-L1 (Figure 1c) [<span>2, 3</span>].</p> <figure><picture> <source media="(min-width: 1650px)" srcset="/cms/asset/68d98e5f-7e31-462c-8af3-b2fa991436b1/ajh27587-fig-0001-m.jpg"/><img alt="Details are in the caption following the image" data-lg-src="/cms/asset/68d98e5f-7e31-462c-8af3-b2fa991436b1/ajh27587-fig-0001-m.jpg" loading="lazy" src="/cms/asset/80ef25d5-f23d-4eb6-86e8-b16c43ebd7bb/ajh27587-fig-0001-m.png" title="Details a
{"title":"A Case of Hodgkin Lymphoma in a Gaucher Disease Patient: Distinguishing Gaucher and Pseudo-Gaucher Cells","authors":"Natalia Scaramellini, Marta Canzi, Elena Cassinerio, Margherita Migone De Amicis, Loredana Pettine, Bruno Fattizzo, Francesca Gaia Rossi, Giorgio Croci, Irene Motta","doi":"10.1002/ajh.27587","DOIUrl":"https://doi.org/10.1002/ajh.27587","url":null,"abstract":"<p>A 35-year-old man came to our attention for the suspicion of Gaucher disease (GD). The patient had undergone a bone marrow aspirate and biopsy because of massive splenomegaly (30 cm), severe thrombocytopenia (platelet count 30 000/mm<sup>3</sup>), and mild anemia [hemoglobin (Hb) 12.1 g/dL] observed in the emergency department, where he presented for acute abdominal pain. Bone marrow biopsy (BMB) revealed foci of fibrosis accompanied by aggregates of CD163+/CD1a− epithelioid histiocytes, featuring a fibrillary, dimly eosinophilic, PASD+ cytoplasm, accounting for 60% of the cellularity. These histological findings were consistent with lysosomal storage disease. GD was then confirmed by beta-glucocerebrosidase activity on dried blood spot (GBA activity 0.4 μmol/L/h, n.v. > 3.5 μmol/L/h) and molecular analysis of the <i>GBA</i> gene that showed compound heterozygosity c.475C>T/c.1226A>G [p.(Arg159Trp)/p.(Asn409Ser)] mutations. At the time of diagnosis, he also had hyperferritinemia (serum ferritin 1300 ng/mL) with normal transferrin saturation (25%). Substrate reduction therapy with eliglustat was started with hematologic improvement at 1 year: platelet counts 55 000/mm<sup>3</sup>, Hb 14.1 g/dL, and reduction in the spleen volume (22 cm).</p>\u0000<p>A year and a half later, he complained of night sweats, weight loss of 3 kg over 3 weeks, and fatigue. Blood tests showed slightly microcytic anemia (Hb 10.5 g/dL, mean corpuscular volume 78.7 fL), platelet count three times the previous value (176 000/mm<sup>3</sup>), even higher values of ferritin (2756 ng/mL), and serologies negative for active infections (HIV CMV, EBV, and Toxoplasma). A total body CT scan showed cervical and thoracic lymphadenopathies up to 4.5 cm and an increase in spleen volume (25 cm). Bone marrow aspirate was negative, while BMB showed foci of Gaucher-type histiocytes, with scattered iron-laden cells, alternated with foci of sclerosis (Figure 1a), with admixed histiocytes, small lymphocytes, eosinophilic granulocytes, and rare scattered, CD30-positive Hodgkin and Reed-Sternberg (HRS) cells (Figure 1b), confirming the clinical suspicion of classical Hodgkin lymphoma (cHL). Interestingly, the diffused and massive macrophage infiltration, which initially masked the rare HRS cells, displayed a double functional phenotype, highlighted through immunohistochemical PD-L1 expression. On the one hand, we observed Gaucher cells with extremely dim PDL-1 intensity [<span>1</span>]; on the other hand, the tumor microenvironment (TME) of cHL expressed abundant PD-L1 (Figure 1c) [<span>2, 3</span>].</p>\u0000<figure><picture>\u0000<source media=\"(min-width: 1650px)\" srcset=\"/cms/asset/68d98e5f-7e31-462c-8af3-b2fa991436b1/ajh27587-fig-0001-m.jpg\"/><img alt=\"Details are in the caption following the image\" data-lg-src=\"/cms/asset/68d98e5f-7e31-462c-8af3-b2fa991436b1/ajh27587-fig-0001-m.jpg\" loading=\"lazy\" src=\"/cms/asset/80ef25d5-f23d-4eb6-86e8-b16c43ebd7bb/ajh27587-fig-0001-m.png\" title=\"Details a","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"87 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968303","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：