Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated remarkable clinical efficacy in treating hematological malignancies. Nevertheless, the limited persistence of CAR-T cells in vivo remains a major therapeutic hurdle, leading to disease relapse. This review examines current strategies to enhance CAR-T cell durability, focusing on recent advances in CAR structural design, gene editing techniques, ex vivo culture optimization, clinical management approaches, and in vivo preparation. By integrating insights from preclinical studies and clinical trials, we provide a comprehensive analysis of methods to prolong CAR-T cell persistence from a technical perspective and discuss future directions.
{"title":"Strategies to Enhance CAR-T Cell Persistence in Hematologic Malignancies: From Molecular Design to Clinical Optimization","authors":"Mengqi Yu, Tingting Yang, Shuyi Ding, Yongxian Hu","doi":"10.1002/ajh.70131","DOIUrl":"10.1002/ajh.70131","url":null,"abstract":"<div>\u0000 \u0000 <p>Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated remarkable clinical efficacy in treating hematological malignancies. Nevertheless, the limited persistence of CAR-T cells in vivo remains a major therapeutic hurdle, leading to disease relapse. This review examines current strategies to enhance CAR-T cell durability, focusing on recent advances in CAR structural design, gene editing techniques, ex vivo culture optimization, clinical management approaches, and in vivo preparation. By integrating insights from preclinical studies and clinical trials, we provide a comprehensive analysis of methods to prolong CAR-T cell persistence from a technical perspective and discuss future directions.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 2","pages":"318-336"},"PeriodicalIF":9.9,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145461402","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":"Marked Platelet Clumping and Giant Platelets due to GP Ib/ IX Autoantibodies","authors":"Tatsuya Fukuyama, Tomoko Maruhashi, Makiko Mizuguchi, Kumiko Kagawa, Hironobu Shibata, Shuji Ozaki","doi":"10.1002/ajh.70134","DOIUrl":"https://doi.org/10.1002/ajh.70134","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"53 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145454639","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}
Wei J. Wang, Qiudan Shen, Mehrnoosh Tashakori, Hong Fang, Wen Shuai, Pei Lin, Zhaoxuan Zhang, Guilin Tang, Wei Wang, Michael A. Linden, Elias J. Jabbour, Tapan M. Kadia, Nicholas J. Short, Naval G. Daver, L. Jeffrey Medeiros, Shimin Hu
<p>Mixed-phenotype acute leukemia (MPAL) is classified under the broader category of acute leukemias of ambiguous lineage in the 5th edition of the WHO Classification of Haematolymphoid Tumors (WHO-HAEM5) and 2022 International Consensus Classification (ICC) [<span>1, 2</span>]. MPAL encompasses acute leukemias showing differentiation along more than one lineage, either in a single population of blasts expressing antigens of multiple lineages (biphenotypic), or multiple populations of blasts, each of a different lineage (bilineal).</p><p>Both the WHO-HAEM5 and the ICC Classification recognize myelodysplastic syndrome (MDS) with biallelic <i>TP53</i> inactivation (i.e., multi-hit <i>TP53</i> mutation) as a distinct disease entity. In the ICC classification, <i>TP53</i> mutation is also considered disease-defining for MDS/acute myeloid leukemia (AML) and AML itself [<span>2-5</span>]. However, the clinicopathologic significance of <i>TP53</i> mutation in MPAL remains poorly characterized. A major challenge in the classification of MPAL cases harboring <i>TP53</i> mutations is that these cases frequently harbor complex karyotypes. Some investigators have proposed reclassifying cases of MPAL with complex karyotype as AML, myelodysplasia-related (AML-MR), given that all acute leukemias with complex karyotypes show similarly poor prognoses, regardless of lineage differentiation [<span>6</span>]. The ICC classification stipulates that MPAL with a complex karyotype should be classified as AML, regardless of the tumor burden of the lymphoid component [<span>2, 7</span>]. However, in the final published version of the ICC classification, MPAL is grouped under the broader category of “Lymphoblastic Neoplasms” [<span>8</span>].</p><p>To address these challenges, we conducted a comprehensive study of 33 patients diagnosed with <i>TP53</i>-mutated MPAL, focusing on cytogenetic and molecular characteristics, dynamic immunophenotypic changes during treatment, and responses to various chemotherapy regimens. Additionally, we evaluated whether <i>TP53</i>-mutated MPAL should be considered a distinct subtype of MPAL, similar to other genetically defined subtypes such as those with <i>BCR::ABL1</i> or <i>KMT2A</i> rearrangements.</p><p>Cases of <i>TP53</i>-mutated MPAL from three collaborative institutions diagnosed since October 1, 2015, according to the immunophenotypic criteria of the ICC classification [<span>2</span>]. The cohort included 16 men and 17 women, with a median age of 65 years (range, 13–78 years) at diagnosis of MPAL (Table 1). At the time of MPAL diagnosis, 17 (51.5%) cases exhibited a biphenotypic immunophenotype, and 16 (48.5%) cases had a bilineal immunophenotype. Among the biphenotypic MPAL cases, 4 were classified as B/myeloid (B/M) and 13 as T/myeloid (T/M). Among the 16 bilineal MPAL cases, 11 were B/M, 3 T/M, and 2 B/T/M subtypes. Within the bilineal MPAL subgroup, 11 cases exhibited a predominant myeloblast population, whereas 5 cases show
{"title":"Mixed-Phenotype Acute Leukemia With Mutated TP53: Genetic Landscape, Therapeutic Response, and Outcomes","authors":"Wei J. Wang, Qiudan Shen, Mehrnoosh Tashakori, Hong Fang, Wen Shuai, Pei Lin, Zhaoxuan Zhang, Guilin Tang, Wei Wang, Michael A. Linden, Elias J. Jabbour, Tapan M. Kadia, Nicholas J. Short, Naval G. Daver, L. Jeffrey Medeiros, Shimin Hu","doi":"10.1002/ajh.70133","DOIUrl":"10.1002/ajh.70133","url":null,"abstract":"<p>Mixed-phenotype acute leukemia (MPAL) is classified under the broader category of acute leukemias of ambiguous lineage in the 5th edition of the WHO Classification of Haematolymphoid Tumors (WHO-HAEM5) and 2022 International Consensus Classification (ICC) [<span>1, 2</span>]. MPAL encompasses acute leukemias showing differentiation along more than one lineage, either in a single population of blasts expressing antigens of multiple lineages (biphenotypic), or multiple populations of blasts, each of a different lineage (bilineal).</p><p>Both the WHO-HAEM5 and the ICC Classification recognize myelodysplastic syndrome (MDS) with biallelic <i>TP53</i> inactivation (i.e., multi-hit <i>TP53</i> mutation) as a distinct disease entity. In the ICC classification, <i>TP53</i> mutation is also considered disease-defining for MDS/acute myeloid leukemia (AML) and AML itself [<span>2-5</span>]. However, the clinicopathologic significance of <i>TP53</i> mutation in MPAL remains poorly characterized. A major challenge in the classification of MPAL cases harboring <i>TP53</i> mutations is that these cases frequently harbor complex karyotypes. Some investigators have proposed reclassifying cases of MPAL with complex karyotype as AML, myelodysplasia-related (AML-MR), given that all acute leukemias with complex karyotypes show similarly poor prognoses, regardless of lineage differentiation [<span>6</span>]. The ICC classification stipulates that MPAL with a complex karyotype should be classified as AML, regardless of the tumor burden of the lymphoid component [<span>2, 7</span>]. However, in the final published version of the ICC classification, MPAL is grouped under the broader category of “Lymphoblastic Neoplasms” [<span>8</span>].</p><p>To address these challenges, we conducted a comprehensive study of 33 patients diagnosed with <i>TP53</i>-mutated MPAL, focusing on cytogenetic and molecular characteristics, dynamic immunophenotypic changes during treatment, and responses to various chemotherapy regimens. Additionally, we evaluated whether <i>TP53</i>-mutated MPAL should be considered a distinct subtype of MPAL, similar to other genetically defined subtypes such as those with <i>BCR::ABL1</i> or <i>KMT2A</i> rearrangements.</p><p>Cases of <i>TP53</i>-mutated MPAL from three collaborative institutions diagnosed since October 1, 2015, according to the immunophenotypic criteria of the ICC classification [<span>2</span>]. The cohort included 16 men and 17 women, with a median age of 65 years (range, 13–78 years) at diagnosis of MPAL (Table 1). At the time of MPAL diagnosis, 17 (51.5%) cases exhibited a biphenotypic immunophenotype, and 16 (48.5%) cases had a bilineal immunophenotype. Among the biphenotypic MPAL cases, 4 were classified as B/myeloid (B/M) and 13 as T/myeloid (T/M). Among the 16 bilineal MPAL cases, 11 were B/M, 3 T/M, and 2 B/T/M subtypes. Within the bilineal MPAL subgroup, 11 cases exhibited a predominant myeloblast population, whereas 5 cases show","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 1","pages":"133-137"},"PeriodicalIF":9.9,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70133","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145448207","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}
Chris A. Rees, Dunia Hatabah, Rawan Korman, Fahd Ahmad, Gladstone Airewele, Bolanle Akinsola, Noor Alzraikat, Nitya Bakshi, David C. Brousseau, Kathleen Brown, Andrew D. Campbell, T. Charles Casper, Todd P. Chang, Corrie E. Chumpitazi, Daniel Cohen, Keli D. Coleman, Andrea T. Cruz, Christopher Denton, Angela Ellison, Melanie E. Fields, Monica Harding, Sara Leibovich, Allison Remiker, Nidhi V. Singh, Alexis A. Thompson, Elliott Vichinsky, Anthony Villella, Bridget Wynn, Carlton Dampier, Claudia R. Morris, the Pediatric Emergency Care Research Network (PECARN)
Analysis of the placebo cohort in the STArT trial shows that patient characteristics and hospital site strongly influence time-to-crisis-resolution and total opioid use in children and young adults with sickle cell disease, highlighting the need to account for these factors in the design of future clinical trials.
{"title":"Hospital Variations in Time-To-Crisis-Resolution Among Children and Adolescents With Sickle Cell Disease","authors":"Chris A. Rees, Dunia Hatabah, Rawan Korman, Fahd Ahmad, Gladstone Airewele, Bolanle Akinsola, Noor Alzraikat, Nitya Bakshi, David C. Brousseau, Kathleen Brown, Andrew D. Campbell, T. Charles Casper, Todd P. Chang, Corrie E. Chumpitazi, Daniel Cohen, Keli D. Coleman, Andrea T. Cruz, Christopher Denton, Angela Ellison, Melanie E. Fields, Monica Harding, Sara Leibovich, Allison Remiker, Nidhi V. Singh, Alexis A. Thompson, Elliott Vichinsky, Anthony Villella, Bridget Wynn, Carlton Dampier, Claudia R. Morris, the Pediatric Emergency Care Research Network (PECARN)","doi":"10.1002/ajh.70129","DOIUrl":"10.1002/ajh.70129","url":null,"abstract":"<p>Analysis of the placebo cohort in the STArT trial shows that patient characteristics and hospital site strongly influence time-to-crisis-resolution and total opioid use in children and young adults with sickle cell disease, highlighting the need to account for these factors in the design of future clinical trials.\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":"101 1","pages":"206-212"},"PeriodicalIF":9.9,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440602","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}
A. C. Hristov, T. Tejasvi, R. A. Wilcox, and T. Cutaneous, “Cutaneous T-Cell Lymphomas: 2023 Update on Diagnosis, Risk-Stratification, and Management,” American Journal of Hematology 98, no. 1 (2023 Jan): 193–209, https://doi.org/10.1002/ajh.26760.
In the manuscript, on Page 196, Lines 33–37, it is remarked that “recent consensus recommendations support of the use of peripheral blood flow cytometry in specific patient groups: those with advanced stage (≥ IIB) disease, intractable pruritis, generalize patches/plaques, erythroderma, lymphocytosis, an elevated LDH, or a lack of response to skin-directed therapies.” However, upon review of the primary research (Citation 81) this line references, it appears this statement is misleading. In the article referenced, Vermeer MH, Moins-Teisserenc H, Bagot M, Quaglino P, Whittaker S. Flow cytometry for the assessment of blood tumour burden in cutaneous T-cell lymphoma: towards a standardized approach. Br J Dermatol. 2022 Jul;187(1):21-28. doi: https://doi.org/10.1111/bjd.21053. Epub 2022 May 3. PMID: 35157307; PMCID: PMC9541328., the populations listed on Page 24, Table 2 are listed for “for minimum use of flow cytometry for mycosis fungoides and Sézary syndrome when not performed at all stages” meaning if it is not practical to perform flow cytometry on all patients, these populations at a minimum need to have the testing performed. In your review article as it is currently written, it implies that those are the only groups that flow cytometry should be performed in. This is an important distinction as some patients with a clinically perceived limited stage disease can in fact have a large blood burden making the use of flow cytometry if possible important in all patients as it has significant implications on prognosis and treatment.
A. C. Hristov， T. Tejasvi， R. A. Wilcox，和T. skin，“皮肤t细胞淋巴瘤：2023年诊断、风险分层和管理的最新进展”，《美国血液学杂志》，第98期。1（2023年1月）：193-209,https://doi.org/10.1002/ajh.26760.In手稿，第196页，第33-37行，指出“最近的共识建议支持在特定患者群体中使用外周血流式细胞术：晚期（≥IIB）疾病、顽固性瘙痒、广泛性斑块/斑块、红皮病、淋巴细胞增多、LDH升高或对皮肤定向治疗缺乏反应的患者。”然而，在回顾这一行参考文献的主要研究（引文81）后，这种说法似乎具有误导性。文中引用了Vermeer MH， Moins-Teisserenc H, Bagot M, Quaglino P, Whittaker S.流式细胞术评估皮肤t细胞淋巴瘤血液肿瘤负荷：走向标准化的方法。中华皮肤科杂志，2016,32(1):1- 4。doi: https://doi.org/10.1111/bjd.21053。2022年5月3日。PMID: 35157307;PMCID: PMC9541328。在第24页，表2中列出的人群是“在没有在所有阶段进行流式细胞术的情况下，最少使用流式细胞术治疗蕈样真菌病和sims综合征”，这意味着如果对所有患者进行流式细胞术是不切实际的，这些人群至少需要进行检测。在您目前撰写的综述文章中，它暗示这些是唯一应该进行流式细胞术的组。这是一个重要的区别，因为一些临床认为有限期疾病的患者实际上可能有很大的血液负担，因此，如果可能的话，流式细胞术的使用对所有患者都很重要，因为它对预后和治疗具有重要意义。
{"title":"Erratum to: “Cutaneous T-Cell Lymphomas: 2023 Update on Diagnosis, Risk-Stratification, and Management”","authors":"","doi":"10.1002/ajh.70135","DOIUrl":"10.1002/ajh.70135","url":null,"abstract":"<p>A. C. Hristov, T. Tejasvi, R. A. Wilcox, and T. Cutaneous, “Cutaneous T-Cell Lymphomas: 2023 Update on Diagnosis, Risk-Stratification, and Management,” <i>American Journal of Hematology</i> 98, no. 1 (2023 Jan): 193–209, https://doi.org/10.1002/ajh.26760.</p><p>In the manuscript, on Page 196, Lines 33–37, it is remarked that “recent consensus recommendations support of the use of peripheral blood flow cytometry in specific patient groups: those with advanced stage (≥ IIB) disease, intractable pruritis, generalize patches/plaques, erythroderma, lymphocytosis, an elevated LDH, or a lack of response to skin-directed therapies.” However, upon review of the primary research (Citation 81) this line references, it appears this statement is misleading. In the article referenced, Vermeer MH, Moins-Teisserenc H, Bagot M, Quaglino P, Whittaker S. Flow cytometry for the assessment of blood tumour burden in cutaneous T-cell lymphoma: towards a standardized approach. Br J Dermatol. 2022 Jul;187(1):21-28. doi: https://doi.org/10.1111/bjd.21053. Epub 2022 May 3. PMID: 35157307; PMCID: PMC9541328., the populations listed on Page 24, Table 2 are listed for “for minimum use of flow cytometry for mycosis fungoides and Sézary syndrome when not performed at all stages” meaning if it is not practical to perform flow cytometry on all patients, these populations at a minimum need to have the testing performed. In your review article as it is currently written, it implies that those are the only groups that flow cytometry should be performed in. This is an important distinction as some patients with a clinically perceived limited stage disease can in fact have a large blood burden making the use of flow cytometry if possible important in all patients as it has significant implications on prognosis and treatment.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 1","pages":""},"PeriodicalIF":9.9,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70135","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145433890","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}
Ruah Alyamany, Ahmed Alnughmush, Oleksandr Klymenko, Mohammad Alhousani, Animesh Pardanani, Paul L. Ollila, David S. Viswanatha, Naseema Gangat, Rong He, Ayalew Tefferi
Diagnostic correlates and clonal progression patterns among 91 patients with low (< 1% VAF) or very low (< 0.1% VAF) JAK2 V617F allele burden encountered in routine clinical practice.
{"title":"Low (0.1% to ≤ 1%) or Very Low (0.06% to < 0.1%) JAK2V617F Allele Burden in Routine Testing: Clinical Correlates and Clonal Trajectory","authors":"Ruah Alyamany, Ahmed Alnughmush, Oleksandr Klymenko, Mohammad Alhousani, Animesh Pardanani, Paul L. Ollila, David S. Viswanatha, Naseema Gangat, Rong He, Ayalew Tefferi","doi":"10.1002/ajh.70128","DOIUrl":"10.1002/ajh.70128","url":null,"abstract":"<p>Diagnostic correlates and clonal progression patterns among 91 patients with low (< 1% VAF) or very low (< 0.1% VAF) JAK2 V617F allele burden encountered in routine clinical practice.\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":"101 1","pages":"213-217"},"PeriodicalIF":9.9,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427424","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}
Giovanni Leone, Mattia D'Antiga, Michela Pelloso, Andrea Serafin, Nicolò Danesin, Arianna Bevilacqua, Alessandro Cellini, Francesco Angotzi, Valentina Trimarco, Chiara Briani, Enrico Tiacci, Francesco Piazza, Livio Trentin, Andrea Visentin
<p>Hairy cell leukemia (HCL) is an indolent, rare B-cell lymphoproliferative disorder that accounts for approximately 2% of all leukemias. The disease is characterized by abnormal lymphocytes showing distinctive cytoplasmic projections (“hairy cells”). The hallmark genetic alteration in classic HCL is the <i>BRAF V600E</i> mutation, which promotes malignant proliferation via constitutive MAPK pathway activation [<span>1, 2</span>].</p><p>While HCL primarily involves the bone marrow and spleen, extranodal manifestations, including central nervous system (CNS) involvement, are rare and determine significant diagnostic and therapeutic challenges [<span>3</span>].</p><p>In March 2023, a 75-year-old man with a 30-year history of HCL was admitted to the emergency department (ED) with acute-onset confusion, episodic verbal aggression, and amnesia. Initial management included vortioxetine, with minimal symptomatic improvement. Due to progressive cognitive decline, aphasia, and emesis, he presented again to the ED where he underwent neuroimaging to rule out stroke. Brain computed tomography (CT) and intracranial CT angiography were negative, and neurological evaluation (including NIHSS scoring) excluded acute cerebrovascular pathology. The patient was admitted to the internal medicine unit for further investigation. He had been diagnosed with HCL in 1986 and received multiple lines of therapy: recombinant α-interferon (1986, 1989), splenectomy (1991), pentostatin (11 cycles, 1992) achieved complete remission (CR), cladribine (1999, CR), rituximab-pentostatin (8 cycles, 2009, CR), cladribine (2013; CR), rituximab-pentostatin (8 cycles, 2015, partial response [PR]), rituximab-fludarabine (4 cycles, 2016, PR), and experimental vemurafenib-cobimetinib-obinutuzumab within a clinical trial (2017–2018). The remainder of the medical history was unremarkable aside from HCL. Admission labs revealed a normal blood count except for monocytopenia (Hb 141 g/L, MCV 107.7 fL, PLTs 124 × 10<sup>9</sup>/L, WBC 6.80 × 10<sup>9</sup>/L—N 4.41, Ly 2.15, Mo 0.19), mildly elevated bilirubin (total 24.6 μmol/L, conjugated 7.7 μol/L), and hyperferritinemia (1.734 μg/L). Peripheral blood flow cytometry identified an immunoglobulin light chain kappa-restricted B-lymphocyte population (25% of lymphocytes) co-expressing CD20, CD11c, CD25, CD103, CD123, and CD200.</p><p>Lumbar puncture excluded active infections, autoimmune and paraneoplastic etiologies but showed elevated cerebrospinal fluid (CSF) protein levels (2.33 g/L), lactate (6.2 mmol/L), and pleocytosis (178 cells/μL; 97% mononuclear). Flow cytometry confirmed CNS involvement by HCL, describing a kappa restricted B cell population expressing CD11c, CD19, CD25, and CD103 surface antigens. Morphologic evaluation of CSF demonstrated the presence of a population of cells with large cytoplasm with surface projections and oval nuclei, consistent with hairy cells (Figure 1 A). Further investigations revealed elevated lev
{"title":"An Uncommon Localization of Hairy Cell Leukemia: Central Nervous System Involvement and Response to Ibrutinib—A Case Report and a Review of the Literature","authors":"Giovanni Leone, Mattia D'Antiga, Michela Pelloso, Andrea Serafin, Nicolò Danesin, Arianna Bevilacqua, Alessandro Cellini, Francesco Angotzi, Valentina Trimarco, Chiara Briani, Enrico Tiacci, Francesco Piazza, Livio Trentin, Andrea Visentin","doi":"10.1002/ajh.70126","DOIUrl":"10.1002/ajh.70126","url":null,"abstract":"<p>Hairy cell leukemia (HCL) is an indolent, rare B-cell lymphoproliferative disorder that accounts for approximately 2% of all leukemias. The disease is characterized by abnormal lymphocytes showing distinctive cytoplasmic projections (“hairy cells”). The hallmark genetic alteration in classic HCL is the <i>BRAF V600E</i> mutation, which promotes malignant proliferation via constitutive MAPK pathway activation [<span>1, 2</span>].</p><p>While HCL primarily involves the bone marrow and spleen, extranodal manifestations, including central nervous system (CNS) involvement, are rare and determine significant diagnostic and therapeutic challenges [<span>3</span>].</p><p>In March 2023, a 75-year-old man with a 30-year history of HCL was admitted to the emergency department (ED) with acute-onset confusion, episodic verbal aggression, and amnesia. Initial management included vortioxetine, with minimal symptomatic improvement. Due to progressive cognitive decline, aphasia, and emesis, he presented again to the ED where he underwent neuroimaging to rule out stroke. Brain computed tomography (CT) and intracranial CT angiography were negative, and neurological evaluation (including NIHSS scoring) excluded acute cerebrovascular pathology. The patient was admitted to the internal medicine unit for further investigation. He had been diagnosed with HCL in 1986 and received multiple lines of therapy: recombinant α-interferon (1986, 1989), splenectomy (1991), pentostatin (11 cycles, 1992) achieved complete remission (CR), cladribine (1999, CR), rituximab-pentostatin (8 cycles, 2009, CR), cladribine (2013; CR), rituximab-pentostatin (8 cycles, 2015, partial response [PR]), rituximab-fludarabine (4 cycles, 2016, PR), and experimental vemurafenib-cobimetinib-obinutuzumab within a clinical trial (2017–2018). The remainder of the medical history was unremarkable aside from HCL. Admission labs revealed a normal blood count except for monocytopenia (Hb 141 g/L, MCV 107.7 fL, PLTs 124 × 10<sup>9</sup>/L, WBC 6.80 × 10<sup>9</sup>/L—N 4.41, Ly 2.15, Mo 0.19), mildly elevated bilirubin (total 24.6 μmol/L, conjugated 7.7 μol/L), and hyperferritinemia (1.734 μg/L). Peripheral blood flow cytometry identified an immunoglobulin light chain kappa-restricted B-lymphocyte population (25% of lymphocytes) co-expressing CD20, CD11c, CD25, CD103, CD123, and CD200.</p><p>Lumbar puncture excluded active infections, autoimmune and paraneoplastic etiologies but showed elevated cerebrospinal fluid (CSF) protein levels (2.33 g/L), lactate (6.2 mmol/L), and pleocytosis (178 cells/μL; 97% mononuclear). Flow cytometry confirmed CNS involvement by HCL, describing a kappa restricted B cell population expressing CD11c, CD19, CD25, and CD103 surface antigens. Morphologic evaluation of CSF demonstrated the presence of a population of cells with large cytoplasm with surface projections and oval nuclei, consistent with hairy cells (Figure 1\u0000 A). Further investigations revealed elevated lev","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 1","pages":"160-164"},"PeriodicalIF":9.9,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145404662","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}
Iman Sarami, Jeremy S. Haley, Diane T. Smelser, Adam M. Cook, Joseph J. Vadakara, Yi Ding, David J. Carey
Analysis of whole-exome sequencing data from 92,434 MyCode EHR-linked biobank participants characterizes the spectrum and co-mutation architecture of clonal hematopoiesis and myelodysplastic syndromes (MDS). Age-related increases in variants affecting DNMT3A, TET2, ASXL1, SRSF2, SF3B1, and RUNX1 are observed, with co-mutation patterns distinguishing MDS-associated clonal evolution. Allele balance patterns suggest predominantly somatic origins for most MDS-related variants, while RUNX1 variants show enrichment consistent with germline origin. MDS is associated with elevated cardiovascular risk, whereas CHIP demonstrates no significant cardiovascular association after adjustment for demographic factors.
{"title":"Genetic Landscape of Myelodysplastic Syndrome and Clonal Hematopoiesis: Insights From Whole Exome Sequencing of 90 000 Individuals","authors":"Iman Sarami, Jeremy S. Haley, Diane T. Smelser, Adam M. Cook, Joseph J. Vadakara, Yi Ding, David J. Carey","doi":"10.1002/ajh.70113","DOIUrl":"10.1002/ajh.70113","url":null,"abstract":"<p>Analysis of whole-exome sequencing data from 92,434 MyCode EHR-linked biobank participants characterizes the spectrum and co-mutation architecture of clonal hematopoiesis and myelodysplastic syndromes (MDS). Age-related increases in variants affecting <i>DNMT3A</i>, <i>TET2</i>, <i>ASXL1</i>, <i>SRSF2</i>, <i>SF3B1</i>, and <i>RUNX1</i> are observed, with co-mutation patterns distinguishing MDS-associated clonal evolution. Allele balance patterns suggest predominantly somatic origins for most MDS-related variants, while RUNX1 variants show enrichment consistent with germline origin. MDS is associated with elevated cardiovascular risk, whereas CHIP demonstrates no significant cardiovascular association after adjustment for demographic factors.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 12","pages":"2448-2451"},"PeriodicalIF":9.9,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145397488","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}
Lucas Kühne, Linus A. Völker, Ulf Schönermarck, Christian Pfrepper, Asterios Tzalavras, Ralph Wendt, Vedat Schwenger, Lena Schulte-Kemna, Thomas Osterholt, Boris Böll, Alexander Shimabukuro-Vornhagen, Felix Eisinger, Anja Mühlfeld, Lars Graßhoff, Martin Nitschke, Tobias Liebregts, Sirak Petros, Anke von Bergwelt-Baildon, Matthias Kochanek, Paul T. Brinkkoetter, Dennis A. Eichenauer
Symptoms, management and outcomes of patients with immune TTP admitted to the intensive care unit.
重症监护室免疫TTP患者的症状、管理和结局
{"title":"Characteristics and Management of Patients With Immune Thrombotic Thrombocytopenic Purpura Admitted to the Intensive Care Unit: A Multicenter Retrospective Analysis","authors":"Lucas Kühne, Linus A. Völker, Ulf Schönermarck, Christian Pfrepper, Asterios Tzalavras, Ralph Wendt, Vedat Schwenger, Lena Schulte-Kemna, Thomas Osterholt, Boris Böll, Alexander Shimabukuro-Vornhagen, Felix Eisinger, Anja Mühlfeld, Lars Graßhoff, Martin Nitschke, Tobias Liebregts, Sirak Petros, Anke von Bergwelt-Baildon, Matthias Kochanek, Paul T. Brinkkoetter, Dennis A. Eichenauer","doi":"10.1002/ajh.70125","DOIUrl":"10.1002/ajh.70125","url":null,"abstract":"<p>Symptoms, management and outcomes of patients with immune TTP admitted to the intensive care unit.\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":"101 1","pages":"198-205"},"PeriodicalIF":9.9,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145381080","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}
Naoki Kurita, Kazushi Maruo, Fumihiko Kimura, Yachiyo Kuwatsuka, Toshihiro Matsukawa, Takaaki Konuma, Shinichi Kobayashi, Mamiko Sakata-Yanagimoto, Noriko Doki, Masatsugu Tanaka, Naoyuki Uchida, Tetsuya Nishida, Masashi Sawa, Yuta Hasegawa, Hirohisa Nakamae, Shuichi Ota, Makoto Onizuka, Takahiro Fukuda, Nobuhiro Hiramoto, Toshiro Kawakita, Noboru Asada, Fumihiko Ishimaru, Junya Kanda, Ken Tabuchi, Yoshiko Atsuta, Hideki Nakasone, Donor/Source and Transplant Complications Working Groups of the Japanese Society for Transplantation and Cellular Therapy
In this Japanese registry-based analysis of 9105 adult patients with acute leukemia undergoing allogeneic hematopoietic stem cell transplantation, a marked difference in survival was observed based on platelet levels: ≤ 20 × 109/L, 20–50 × 109/L, and > 50 × 109/L. The number of patients with thrombocytopenia receiving cord blood (CB, 39%) was significantly larger than those receiving unrelated bone marrow (uBM, 17%) on Day 50 (p < 0.001); however, this difference disappeared on Day 100 posttransplantation (both 11%, p = 0.4).
{"title":"Platelet Recovery and Its Impact on Outcomes After Allogeneic Hematopoietic Stem Cell Transplantation: A Japanese Nationwide Retrospective Study","authors":"Naoki Kurita, Kazushi Maruo, Fumihiko Kimura, Yachiyo Kuwatsuka, Toshihiro Matsukawa, Takaaki Konuma, Shinichi Kobayashi, Mamiko Sakata-Yanagimoto, Noriko Doki, Masatsugu Tanaka, Naoyuki Uchida, Tetsuya Nishida, Masashi Sawa, Yuta Hasegawa, Hirohisa Nakamae, Shuichi Ota, Makoto Onizuka, Takahiro Fukuda, Nobuhiro Hiramoto, Toshiro Kawakita, Noboru Asada, Fumihiko Ishimaru, Junya Kanda, Ken Tabuchi, Yoshiko Atsuta, Hideki Nakasone, Donor/Source and Transplant Complications Working Groups of the Japanese Society for Transplantation and Cellular Therapy","doi":"10.1002/ajh.70124","DOIUrl":"10.1002/ajh.70124","url":null,"abstract":"<p>In this Japanese registry-based analysis of 9105 adult patients with acute leukemia undergoing allogeneic hematopoietic stem cell transplantation, a marked difference in survival was observed based on platelet levels: ≤ 20 × 10<sup>9</sup>/L, 20–50 × 10<sup>9</sup>/L, and > 50 × 10<sup>9</sup>/L. The number of patients with thrombocytopenia receiving cord blood (CB, 39%) was significantly larger than those receiving unrelated bone marrow (uBM, 17%) on Day 50 (<i>p</i> < 0.001); however, this difference disappeared on Day 100 posttransplantation (both 11%, <i>p</i> = 0.4).\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":"101 1","pages":"193-197"},"PeriodicalIF":9.9,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70124","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145381079","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}
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