American Journal of Hematology最新文献

{"title":"Treatment Patterns and Clinical Outcomes After Immunotherapy Failure in Patients With Natural Killer/T-Cell Lymphoma","authors":"Shenrui Bai, Yongping Song, Liang Wang, Fang Liu, Yexiong Li, Shunan Qi, Zhigang Peng, Ying Zhao, Huiqiang Huang, Yi Xia, Bing Bai, Xiaojie Fang, Man Nie, Jun Cai, Yi Cao, Xinna Gao, Qihua Zou, Qingqing Cai, Yuchen Zhang","doi":"10.1002/ajh.70387","DOIUrl":"10.1002/ajh.70387","url":null,"abstract":"<p>Natural killer/T-cell lymphoma (NKTCL) is an aggressive subtype of non-Hodgkin lymphoma (NHL), and predominantly occurs in East Asia and Latin America [<span>1, 2</span>]. NKTCL is closely associated with Epstein–Barr virus (EBV) infection, contributing to a notable pathological feature of the upregulation of programmed death-ligand 1 (PD-L1) on tumor cells [<span>3</span>], which provides a mechanistic rationale for immune checkpoint blockade in NKTCL. Immune checkpoint inhibitors (ICIs) have shown promising activity and mild toxicities in both relapsed/refractory and frontline settings and are now widely incorporated into routine clinical practice [<span>4-7</span>].</p><p>Despite the expanding use of ICIs, a substantial proportion of patients exhibit treatment resistance or experience relapse after an initial response. Real-world evidence defining subsequent treatment approaches and associated clinical outcomes following immunotherapy failure remains limited. In light of these observations, we conducted a multicenter retrospective study to analyze the clinical characteristics, treatment patterns, and outcomes of patients with NKTCL who experienced treatment failure after ICI-based therapy. Our aim was to evaluate the efficacy of different salvage treatment strategies, analyze post-immunotherapy survival outcomes, and identify critical prognostic factors in this group of patients.</p><p>This analysis included patients diagnosed with NKTCL between October 2015 and October 2024 at six hospitals in China. Eligible patients had received ICI-based therapies and subsequently developed refractory disease, relapsed after an initial response, or discontinued immunotherapy due to intolerable toxicity. This study was approved by the institutional review boards of each participating center and was conducted in compliance with the Declaration of Helsinki.</p><p>The post-immunotherapy overall survival (OS-2) was defined as the time from immunotherapy cessation to death from any cause. The post-immunotherapy progression-free survival (PFS-2) was defined as the time from immunotherapy cessation to the first subsequent treatment progression or death. OS-1 was defined as the time from initiation of immunotherapy to death from any cause. PFS-1 was defined as the time from initiation of immunotherapy to progression or death (Figure S1). Responses to the ICI-based regimen and the first post-immunotherapy salvage treatments were determined by the treating physicians in accordance with the 2014 Lugano criteria [<span>8</span>].</p><p>A workflow of the study is shown in Figure 1A. Among 821 screened patients, 186 met inclusion criteria. The baseline characteristics before immunotherapy are summarized in Table S1. The median number of prior treatment lines before immunotherapy was one (range, 0–7). The baseline characteristics following the failure of the ICI-based treatment are summarized in Table 1. The median age was 43 years (interquartile range [IQR], 32–54), a","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 S3","pages":"72-78"},"PeriodicalIF":9.4,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13544475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148101140","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":"Mutation Profiling, Efficacy Monitoring, and Prognosis Evaluation Using Circulating Tumor DNA in Peripheral T-Cell Lymphoma: A Prospective, Multicenter, Observational Study","authors":"Zhao Donglu, Song Yuqin, Qin Jiayue, Tong Hongyan, Ding Kaiyang, Cai Qingqing, Huang Huiqiang, Wu Lili, Jing Hongmei, Zhang Liling, Qian Wenbin, Bai Ou, Cao Shanbo, Jin Jie, Zhu Jun, Ma Jun","doi":"10.1002/ajh.70357","DOIUrl":"10.1002/ajh.70357","url":null,"abstract":"<p>Peripheral T-cell lymphoma (PTCL) represents a diverse and aggressive category of hematologic malignancies that significantly affects patient outcome [<span>1</span>]. PTCL is characterized by multiple subtypes, including NK/T-cell lymphoma (NKTCL), angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL), and PTCL, not otherwise specified (PTCL-NOS), and is associated with considerable morbidity and mortality, primarily due to poor response to conventional therapies [<span>2-4</span>]. Recent advancements in molecular diagnostics have highlighted circulating tumor DNA (ctDNA) as a valuable biomarker for various cancers, providing real-time insights into tumor dynamics and treatment responses [<span>5-7</span>]. Previous studies have established the role of ctDNA in assessing tumor burden, prognostication, and monitoring treatment efficacy across several hematological malignancies [<span>8-10</span>]. Moreover, identifying specific ctDNA alterations associated with treatment response may enhance prognostic evaluation and support therapeutic decision-making [<span>11, 12</span>].</p><p>Despite its promising potential, significant gaps remain regarding the clinical applicability of ctDNA in PTCL. In particular, comprehensive and prospective studies examining the association between ctDNA dynamics and treatment outcomes across different PTCL subtypes are lacking. To address these gaps, we conducted a prospective, multicenter, observational cohort design using next-generation sequencing (NGS) to analyze tumor DNA (tDNA) and plasma-derived ctDNA mutation profiles and to evaluate the prognostic significance of ctDNA dynamics in 104 patients with PTCL (Tables S1–S3). The study was approved by the Ethics Committee at the participating centers in accordance with the Declaration of Helsinki.</p><p>Figure 1A,B illustrate the study design flowchart. Thirty-three patients provided baseline, post-four-cycle, and end-staging ctDNA samples, along with paired baseline tDNA samples for concordance, dynamic monitoring, and prognostic analyses. Thirty patients provided baseline and post-four-cycle ctDNA samples with paired baseline tDNA for concordance and dynamic monitoring analysis. Three patients provided baseline and end-staging ctDNA samples with paired baseline tDNA for concordance, dynamic monitoring analysis, and prognostic analyses. Thirty-eight patients contributed baseline tDNA and paired ctDNA samples for concordance analysis only (Figure 1B).</p><p>Baseline tDNA detection identified 161 mutated genes, comprising 529 mutation events. The most frequently mutated genes were <i>TET2</i> (51.0%), followed by <i>RHOA</i> (34.6%), <i>DNMT3A</i> (24.0%), and both <i>STAT3</i> and <i>TP53</i> (13.5%) (Figure 1C), similar to the spectrum of ctDNA mutations (Figure 1D). The percentage of cases detectable via ctDNA in each subtype of PTCL is shown in Table S4.</p><p>Among the 398 concordant mutations detected in both tDNA and ctDNA (Figur","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 S3","pages":"65-71"},"PeriodicalIF":9.4,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13544452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current Treatment Landscape and Advances in Lymphoma in China: A Special Issue","authors":"Yuqin Song","doi":"10.1002/ajh.70471","DOIUrl":"10.1002/ajh.70471","url":null,"abstract":"<p>Lymphoma is a significant and growing health burden in China, with an estimated annual incidence of approximately 6.03 per 100 000 people and an increasing trend over the past 20 years [<span>1</span>]. The high population and rapid economic development of China have created challenges and opportunities for research on lymphoma and clinical care. Over the past decade, there has been considerable progress in research on understanding the biology, improving diagnostic precision, and developing novel therapeutic strategies for lymphoid malignancies in China. From the widespread adoption of immunochemotherapies and targeted agents to the expansion of hematopoietic stem cell transplantation and Chimeric Antigen Receptor T-cell therapy (CAR-T), management of lymphoma in China has transformed. Despite these advances, significant discrepancies remain in access to high-quality medical care, and the unique genetic and epidemiological features of Chinese patients warrant further investigation.</p><p>In this special issue of the <i>American Journal of Hematology</i>, we present nine outstanding manuscripts that collectively illuminate the current treatment landscape and future directions for lymphomas in China. These articles, authored by leading experts from major academic centers across the country, cover a broad spectrum of disease subtypes, including peripheral T-cell lymphoma (PTCL), extra-nodal natural killer/T-cell lymphoma (NKTCL), primary central nervous system lymphoma (PCNSL), diffuse large B-cell lymphoma, and Hodgkin lymphoma, and address critical topics, including circulating tumor DNA (ctDNA) monitoring, novel targeted and immunotherapeutic approaches, and transplantation strategies. Collectively, they provide a comprehensive snapshot of the advanced Chinese lymphoma research and clinical practice, highlighting the unique challenges and opportunities that lie ahead.</p><p>Peripheral T-cell lymphomas are a heterogeneous group of aggressive malignancies with historically poor outcomes, and several studies have addressed this unmet need from a complementary angle. Zhao et al. [<span>2</span>] reported the first prospective multi-center observational study of Chinese patients with PTCL, demonstrating the utility of ctDNA for mutation profiling, efficacy monitoring, and prognostic evaluation [<span>2</span>]. With a sensitivity of 75.2% for concordant mutations between ctDNA and tumor tissue DNA, this study validated the feasibility of liquid biopsy in this setting and revealed that dynamic changes in ctDNA concentration and variant allele frequency were closely correlated with treatment response and progression-free survival. Notably, the sensitivity of ctDNA varied by subtype, with the highest sensitivity in angioimmunoblastic T-cell lymphoma (AITL) (82.1%) and the lowest in NKTCL (37.1%), highlighting the need for subtype-specific considerations. Similarly, Li et al. [<span>3</span>] presented the RCLARITY trial, a prospective Phase II study ","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 S3","pages":"3-5"},"PeriodicalIF":9.4,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70471","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148729137","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":"Real-World Efficacy and Safety of Glofitamab-Based Salvage Therapy in Chinese Patients With Relapsed or Refractory Aggressive B-Cell Lymphomas","authors":"Jin Zhou,&nbsp;Chenwen Wang,&nbsp;Tao You,&nbsp;Yun Wang,&nbsp;Xiangping Zong,&nbsp;Qian Wang,&nbsp;Wanying Chen,&nbsp;Kaiyu Sheng,&nbsp;Xiao Ma,&nbsp;Jia Chen,&nbsp;Depei Wu,&nbsp;Haiwen Huang","doi":"10.1002/ajh.70359","DOIUrl":"10.1002/ajh.70359","url":null,"abstract":"<p>Glofitamab, a CD20 × CD3 bispecific antibody, has demonstrated significant efficacy in relapsed or refractory (R/R) B-cell lymphomas. However, real-world evidence on its clinical performance and immunologic correlates, particularly in the context of chimeric antigen receptor T-cell (CAR-T) therapy, remains limited. This observational study included 64 patients with R/R aggressive B-cell lymphoma who received glofitamab-based therapy between February 2024 and December 2025 at the First Affiliated Hospital of Soochow University. The primary endpoint was complete response (CR) rate, whereas secondary endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. We also analyzed the impact of prior bispecific antibody (BsAb) exposure on CAR-T cell manufacturing and efficacy and assessed the relationship between peripheral T-cell subsets and treatment outcomes. Among 56 evaluable patients, the CR and ORR were 41.1% and 78.7%, respectively. Median PFS and OS were not reached, with estimated 1-year PFS and OS rates of 61.3% and 67.7%. Patients with non-germinal center B-cell (non-GCB) subtype had significantly higher PFS than those with GCB subtype (<i>p</i> = 0.029), whereas prior CAR-T therapy was associated with poorer PFS (<i>p</i> = 0.022). Prior BsAb exposure did not affect CAR-T manufacture or efficacy. Immunophenotyping revealed that patients achieving CR had higher baseline CD4⁺ effector T-cell counts (<i>p</i> = 0.04) and higher early CD8⁺ T-cell expansion (<i>p</i> = 0.02). Overall, glofitamab demonstrated durable efficacy and a manageable safety profile in R/R aggressive B-cell lymphoma, with treatment outcomes closely associated with T-cell functional status, supporting its potential as an effective bridging strategy before CAR-T therapy.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 S3","pages":"6-17"},"PeriodicalIF":9.4,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13544502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147866345","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":"Development and Validation of a Novel Geriatric Risk Score for Prognostication in Older Patients With Hodgkin Lymphoma: A Multicenter Retrospective Study","authors":"Peiqi Zhao,&nbsp;Yihan Wang,&nbsp;Min Bai,&nbsp;Chen Huang,&nbsp;Jiesong Wang,&nbsp;Yajun Li,&nbsp;Yanan Jiang,&nbsp;Ganggang Wang,&nbsp;Feng Zhu,&nbsp;Shu Zhao,&nbsp;Wei Guo,&nbsp;Shukai Qiao,&nbsp;Jianxia He,&nbsp;Ji Ma,&nbsp;Yanyan Zhang,&nbsp;Lei Zhu,&nbsp;Li Li,&nbsp;Wenyue Yu,&nbsp;Shaozhen Chen,&nbsp;Junqing Xu,&nbsp;Ou Bai,&nbsp;Hui Zhou,&nbsp;Qingyuan Zhang,&nbsp;Liping Su,&nbsp;Yuanlin Xu,&nbsp;Huilai Zhang","doi":"10.1002/ajh.70456","DOIUrl":"10.1002/ajh.70456","url":null,"abstract":"<p>Outcomes in older patients with Hodgkin lymphoma (HL) are compromised by the interplay of patient frailty and disease aggressiveness; however, current stratification tools, including the International Prognostic Score (IPS) and Comprehensive Geriatric Assessment (CGA), lack sufficient prognostic discrimination in the older HL population. We developed and validated a prognostic model integrating metabolic tumor burden and geriatric assessment. In this retrospective study across 14 centers in China between 2006 and 2024, we enrolled 306 patients aged ≥ 60 years with histologically confirmed HL. Patients were randomly partitioned into training (<i>n</i> = 250) and validation (<i>n</i> = 56) cohorts. Among the 306 patients, 98 deaths and 130 progression events were recorded during follow-up. We analyzed 21 candidate variables. The least absolute shrinkage and selection operator (LASSO) analysis and multivariable Cox regression identified five independent predictors for 5-year overall survival (OS): age &gt; 73 years, baseline 18F-FDG PET/CT-derived total lesion glycolysis (TLG) &gt; 200, hemoglobin ≤ 101 g/L, activities of daily living (ADL) dependence, and lymphocyte-depleted classical Hodgkin lymphoma (LDCHL). A weighted Geriatric Risk Score stratified patients into low-, intermediate-, and high-risk groups. In the validation cohort, the Geriatric Risk Score showed higher discriminatory accuracy than the CGA for both OS (C-index, 0.770 [95% CI, 0.674–0.867] vs. 0.671 [0.581–0.762]) and PFS (0.761 [0.668–0.853] vs. 0.635 [0.535–0.735]). Among advanced-stage (Ann Arbor stage III–IV) patients, it also outperformed the IPS-7 and IPS-3. By integrating metabolic tumor burden and geriatric assessment, the Geriatric Risk Score improves risk stratification over existing tools in older patients with HL.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 S3","pages":"50-64"},"PeriodicalIF":9.4,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70456","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148717279","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":"Integrated Genomic and Tumor Microenvironment Subtyping Improved Risk Stratification in Primary Central Nervous System Lymphoma","authors":"Xianggui Yuan,&nbsp;Qian Luo,&nbsp;Yurong Huang,&nbsp;Chaoyi Li,&nbsp;Teng Yu,&nbsp;Shanshan Guo,&nbsp;Qunyi Guo,&nbsp;Xueli Jin,&nbsp;Jiefeng Tong,&nbsp;Aiqi Zhao,&nbsp;Wen Lei,&nbsp;Xian Li,&nbsp;Baizhou Li,&nbsp;Shumei Wei,&nbsp;Wenbin Qian,&nbsp;Yun Liang","doi":"10.1002/ajh.70396","DOIUrl":"10.1002/ajh.70396","url":null,"abstract":"<p>Current prognostic models fail to capture the biological complexity of primary central nervous system lymphoma (PCNSL). We integrated whole-genome sequencing and multiplex immunofluorescence in 68 treatment-naïve patients to define four genomic subtypes (C1, C2, C3, and C4) with divergent survival (C4 worst: median overall survival [OS], 26 months). In parallel, a novel tumor microenvironment (TME) classification based on CD8⁺T/M2 macrophage ratio stratified patients into High (&gt; 1.5), Intermediate (0.8–1.5), and Low (&lt; 0.8) groups. Unexpectedly, the Intermediate TME group showed the poorest outcomes (5-year OS: 10%). Integration revealed a lethal subgroup (C4 + Intermediate TME; 9.8% of cohort) with a median OS of 3.0 months (hazard ratio = 7.24, <i>p</i> = 0.006). Prognostic nomograms incorporating these subtypes showed promising discriminative performance in internal validation (C-index &gt; 0.78), but external validation is needed. Together, these findings identify a high-risk biological subset and provide a hypothesis-generating framework for future biomarker-driven risk stratification and therapeutic discovery in PCNSL.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 S3","pages":"27-41"},"PeriodicalIF":9.4,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13544481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148196883","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":"Upfront Autologous Stem Cell Transplantation in First Complete Remission for Advanced-Stage Extra-Nodal NK/T-Cell Lymphoma: A Multicenter Retrospective Study","authors":"Shaoxuan Hu,&nbsp;Weiping Liu,&nbsp;Linjun Zhao,&nbsp;Wenrong Huang,&nbsp;Zhenyang Gu,&nbsp;Huiqiang Huang,&nbsp;Liping Su,&nbsp;Hui Zhou,&nbsp;Haisheng Liu,&nbsp;Tao Wu,&nbsp;Liling Zhang,&nbsp;Xia He,&nbsp;Mei Shi,&nbsp;Hua Wang,&nbsp;Xiaopei Wang,&nbsp;Jun Zhu,&nbsp;Yexiong Li,&nbsp;Shunan Qi,&nbsp;Yuqin Song","doi":"10.1002/ajh.70415","DOIUrl":"10.1002/ajh.70415","url":null,"abstract":"<p>The aim of this study was to evaluate the effect of upfront autologous stem cell transplantation (ASCT) on the prognosis in patients with advanced-stage extra-nodal NK/T-cell lymphoma (NKTCL) achieving first complete remission (CR1) after frontline therapy. To this end, we retrospectively reviewed data from patients diagnosed with stage III or IV NKTCL who achieved CR1 after frontline treatment between 2006 and 2023 at 14 medical centers in China. A total of 107 patients were included in this study. The majority of patients (87%) received non-anthracycline-based first-line chemotherapy, and 38 (36%) received upfront ASCT consolidation at the time of CR1. With a median follow-up time of 39.8 months, progression-free survival (PFS) and overall survival (OS) rates were significantly better in the ASCT group than in the non-ASCT group (3-year PFS: 78.2% vs. 54.6%, <i>p</i> = 0.005; 3-year OS: 86.0% vs. 68.9%, <i>p</i> = 0.04). However, in the subgroup of patients receiving non-anthracycline-based chemotherapy (<i>N</i> = 93), ASCT was significantly associated with better PFS (3-year PFS: 77.6% vs. 59.3%, <i>p</i> = 0.025) but not with OS (3-year OS: 85.6% vs. 74.8%, <i>p</i> = 0.164). In multivariate analyzes, upfront ASCT was an independent predictor of better PFS (hazard ratio [HR] = 0.37, 95% confidence interval [CI]: 0.15–0.88, <i>p</i> = 0.025) but not OS after adjusting for baseline prognostic index of NK-cell lymphoma (PINK), types of first-line chemotherapy, and local radiotherapy. After propensity score matched analyzes, upfront ASCT remained significantly associated with better PFS but not with OS. These real-world data suggest upfront ASCT prolongs PFS in patients with advanced-stage NKTCL in CR1, yet its impact on OS remains unclear.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 S3","pages":"42-49"},"PeriodicalIF":9.4,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70415","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148499001","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":"Autoantibodies to Extracellular Erythrocyte Band 3 Epitopes Are Associated With Anemia in Plasmodium vivax Infection","authors":"Aline Marzano-Miranda,&nbsp;Vanessa G. Fraga,&nbsp;Cor Jésus F. Fontes,&nbsp;Simone Ladeia-Andrade,&nbsp;Marcelo U. Ferreira,&nbsp;Daniella C. Bartholomeu,&nbsp;Érika M. Braga","doi":"10.1002/ajh.70463","DOIUrl":"10.1002/ajh.70463","url":null,"abstract":"<p>\u0000 <i>Plasmodium vivax</i>-associated anemia is a multifactorial clinical outcome, in which the destruction of uninfected red blood cells (uRBCs) plays a major role in disease development and severity. Here, we identified autoantibody targets within the extracellular loops of Band 3 (B3), a major erythrocyte transmembrane protein. <i>In silico</i> epitope prediction identified six of the seven potentially immunogenic extracellular domains of B3. Patients with \u0000 <i>P. vivax</i>\u0000 infection who were anemic (<i>n</i> = 79) and non-anemic (<i>n</i> = 95), and 40 healthy donors from a non-endemic area were included as negative controls. In addition, 15 anemic and 15 non-anemic infected individuals were also analyzed immediately before treatment (D0) and on Days 7, 14, and 28 after antimalarial therapy. Synthetic peptides corresponding to the six B3 domains were robustly recognized by autoantibodies from \u0000 <i>P. vivax</i>\u0000 -infected patients. Anemic individuals exhibited prominent autoantibody responses, particularly against loops 4 and 6. IgG3 was the predominant subclass targeting these loops and remained detectable up to 28 days post-treatment, suggesting a possible role in the persistence of anemia even after parasite clearance. In contrast, IgG1 was the principal subclass recognizing the peptides corresponding to loops 1, 2, and 3, indicating a significant response to senescent domains during \u0000 <i>P. vivax</i>\u0000 infection. Analysis of IgG subclass against full-length B3 confirmed the presence of both IgG1 and IgG3 responses. The pro-inflammatory properties of these IgG subclasses support the hypothesis that anti-B3 autoantibodies contribute to the immunopathogenesis of \u0000 <i>P. vivax</i>\u0000 -related anemia. Collectively, these findings identify potential targets for future mechanistic investigations and therapeutic intervention strategies.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 10","pages":"2592-2604"},"PeriodicalIF":9.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70463","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618178","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":"Eltrombopag Added to Standard Immunosuppressive Treatment as Front-Line Therapy for Severe Aplastic Anemia: Long-Term Outcomes of the Phase-3 Randomized Superiority EBMT-SAAWP RACE Study","authors":"Antonio M. Risitano,&nbsp;Simona Iacobelli,&nbsp;Austin Kulasekararaj,&nbsp;Marleen van Os,&nbsp;Sofie R. Terwel,&nbsp;Joe Tuffnell,&nbsp;Brian Piepenbroek,&nbsp;Morag Griffin,&nbsp;Constantijn J. M. Halkes,&nbsp;Christian Recher,&nbsp;Fiorenza Barraco,&nbsp;Edouard Forcade,&nbsp;Juan Carlos Vallejo,&nbsp;Beatrice Drexler,&nbsp;Jean-Baptiste Mear,&nbsp;Roochi Trikha,&nbsp;Shreyans Gandhi,&nbsp;Anna Maria Raiola,&nbsp;L. G. M. Daenen,&nbsp;Marco R. de Groot,&nbsp;Etienne Daguindau,&nbsp;Erfan Nur,&nbsp;Wilma Barcellini,&nbsp;Nigel H. Russell,&nbsp;Louis Terriou,&nbsp;Anna Paola Iori,&nbsp;Walter Barberi,&nbsp;Anna Sureda,&nbsp;Isabel Sánchez-Ortega,&nbsp;Blanca Xicoy,&nbsp;Isidro Jarque,&nbsp;James Cavenagh,&nbsp;Flore Sicre de Fontbrune,&nbsp;Camilla Frieri,&nbsp;Talha Munir,&nbsp;Jennifer M. L. Tjon,&nbsp;Suzanne Tavitian,&nbsp;Aline Praire,&nbsp;Laurence Clement,&nbsp;Florence Rabian,&nbsp;Luana Marano,&nbsp;Anita Hill,&nbsp;Elena Palmisani,&nbsp;Petra Muus,&nbsp;Serena Marotta,&nbsp;Fabiana Cacace,&nbsp;Marica Laurino,&nbsp;Jakob R. Passweg,&nbsp;Gérard Socié,&nbsp;Ghulam J. Mufti,&nbsp;Carlo Dufour,&nbsp;Régis Peffault de Latour,&nbsp;Severe Aplastic Anaemia Working Party of the EBMT","doi":"10.1002/ajh.70445","DOIUrl":"10.1002/ajh.70445","url":null,"abstract":"<p>The RACE study (NCT02009747) compared horse antithymocyte globulin (hATG) plus cyclosporine A (CsA) ± eltrombopag as initial immunosuppressive treatment (IST) for severe aplastic anemia. Here we report the final 2-year analysis of this prospective randomized phase III study. One hundred ninety-seven treatment-naive patients were randomized to standard IST (hATG 40 mg/kg × 4 days and CsA 5 mg/kg/day; arm A; <i>n</i> = 101) or standard IST + eltrombopag at the dose of 150 mg/day (arm B; <i>n</i> = 96) from day +14 until 6 months (or 3 months, in case of complete response). The median follow-up was 23.2 months. The 2-year cumulative incidence of complete response was significantly superior in arm B (62.4% vs. 35.3%; <i>p</i> &lt; 0.001). The 2-year overall survival (OS) was 86% in arm A and 91% in arm B (<i>p</i> = 0.081), with hazard ratio (HR), adjusted for age and disease severity, of 0.54 (<i>p</i> = 0.064). The 2-year disease-free survival (DFS) was 56% vs. 37% (adjusted HR = 0.49; <i>p</i> &lt; 0.001), while event-free survival (EFS) was 48% vs. 32% (<i>p</i> &lt; 0.001), with adjusted HR = 0.54 (<i>p</i> &lt; 0.001), both significantly superior for arm B. The cumulative incidence of relapse was comparable in the two arms, while evolution to clinical paroxysmal nocturnal hemoglobinuria was 8% in arm A and 1% in arm B (<i>p</i> = 0.041). The risk of clonal evolution remained negligible, with one patient in arm A and two in arm B developing karyotypic abnormalities. The initial hematological response benefit of eltrombopag added to IST as front-line treatment of AA is associated with better 2-year OS, DFS, and EFS without increased risk of secondary myeloid malignancies.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 10","pages":"2520-2532"},"PeriodicalIF":9.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70445","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148498996","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":"Monoclonal Gammopathy of Thrombotic Significance","authors":"Matthew Ho,&nbsp;Saurabh Zanwar,&nbsp;Shaji Kumar,&nbsp;S. Vincent Rajkumar","doi":"10.1002/ajh.70467","DOIUrl":"10.1002/ajh.70467","url":null,"abstract":"<div>\u0000 \u0000 <p>Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant precursor to multiple myeloma (MM). While development of end-organ damage in MM largely reflects increasing clonal burden, emerging evidence indicates that qualitative properties of the monoclonal immunoglobulins in MGUS can be directly pathogenic, leading to serious organ injury independent of disease burden. This has led to the recognition of a broader spectrum of disorders collectively termed monoclonal gammopathy of clinical significance (MGCS). MGCS can be further subclassified based on the organ system involved; for example, monoclonal gammopathy of renal significance specifically refers to monoclonal immunoglobulin-driven renal injury. Along these lines, we propose monoclonal gammopathy of thrombotic significance (MGTS) as encompassing thrombotic disorders in which there is definitive, mechanistically supported evidence that a monoclonal (M)-protein associated with a clonal plasma or B-cell disorder directly contributes to thrombosis. Based on current evidence, monoclonal protein–induced immune thrombocytopenia and thrombosis is the only disorder that meets our criteria for MGTS. Other thrombotic disorders, such as thrombotic microangiopathy and antiphospholipid syndrome, may occur in the setting of a monoclonal protein and have biologically plausible M-protein-mediated mechanisms; however, direct evidence implicating the M-protein in thrombosis is currently lacking. Accordingly, we provisionally classify these disorders as thrombotic syndromes associated with M-proteins, pending causal validation. We also highlight thrombotic disease associations with multifactorial pathogenesis that should not be classified as MGTS. Broader recognition of MGTS is essential to advance consensus definitions, establish diagnostic criteria, and develop evidence-based management strategies for this clinically important group of disorders.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 10","pages":"2616-2631"},"PeriodicalIF":9.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700519","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}