Angela C Weyand,Jourdan E Triebwasser,Alexander Chaitoff
{"title":"Prevalence of Iron Deficiency and Iron Deficiency Anemia in US Pregnant Individuals, 2003-2023.","authors":"Angela C Weyand,Jourdan E Triebwasser,Alexander Chaitoff","doi":"10.1002/ajh.70207","DOIUrl":"https://doi.org/10.1002/ajh.70207","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"1 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986450","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}
Calreticulin (CALR) mutations are prevalent in 20%-30% of patients with BCR::ABL1-negative myeloproliferative neoplasms (MPN). Mutant calreticulin (mutCALR), presented by the thrombopoietin receptor (MPL, also known as TPOR or CD110) on the surface of the disease-initiating MPN progenitors, represents an ideal target for curative immunotherapies including monoclonal antibodies, bispecific T cell engaging antibodies (TCE), and CAR-T cell therapies. Despite that two clinical TCE candidates have advanced into phase 1 trials in recent 2 years, depletion of mutCALR+ hematopoietic stem cells and normalization of hematopoiesis remained absent in preclinical evaluation. Here, we developed a bispecific T cell engager DX1-2C11 that specifically and efficiently eradicates mutCALR-expressing cells via recruiting polyclonal T cells. DX1-2C11 depleted Ba/F3 cells expressing mutCALR, as well as primary murine myeloid cells in a dose-dependent manner in vitro. In CALRdel52 transgenic mice, a single dose of DX1-2C11 activated CD4+ and CD8+ T cells in the peripheral blood, spleen and bone marrow within 24 h. Furthermore, a single dose of DX1-2C11 reduced platelet counts in the periphery and decreased mutant stem/progenitor cell populations in the spleen and bone marrow by Day 7 posttreatment. Notably, the reduction of mutant burden was durably maintained in secondary recipient mice. In the disseminated NSG model, DX1-2C11 delivered immediate tumor burden reduction and significantly prolonged the overall survival of mice compared to the control group. Taken together, these data suggest that bispecific T cell engaging antibody targeting mutCALR represents a curative strategy that efficiently eliminates mutant MPN stem cells in vivo.
{"title":"A Murine Bispecific Antibody Efficiently Redirects T Cells Against Calr Mutated Stem Cells In Vivo.","authors":"Shengen Xiong,Tamara Wais,Cecilia Varga,Christina Schueller,Sarada Achyutuni,Robert Kralovics","doi":"10.1002/ajh.70206","DOIUrl":"https://doi.org/10.1002/ajh.70206","url":null,"abstract":"Calreticulin (CALR) mutations are prevalent in 20%-30% of patients with BCR::ABL1-negative myeloproliferative neoplasms (MPN). Mutant calreticulin (mutCALR), presented by the thrombopoietin receptor (MPL, also known as TPOR or CD110) on the surface of the disease-initiating MPN progenitors, represents an ideal target for curative immunotherapies including monoclonal antibodies, bispecific T cell engaging antibodies (TCE), and CAR-T cell therapies. Despite that two clinical TCE candidates have advanced into phase 1 trials in recent 2 years, depletion of mutCALR+ hematopoietic stem cells and normalization of hematopoiesis remained absent in preclinical evaluation. Here, we developed a bispecific T cell engager DX1-2C11 that specifically and efficiently eradicates mutCALR-expressing cells via recruiting polyclonal T cells. DX1-2C11 depleted Ba/F3 cells expressing mutCALR, as well as primary murine myeloid cells in a dose-dependent manner in vitro. In CALRdel52 transgenic mice, a single dose of DX1-2C11 activated CD4+ and CD8+ T cells in the peripheral blood, spleen and bone marrow within 24 h. Furthermore, a single dose of DX1-2C11 reduced platelet counts in the periphery and decreased mutant stem/progenitor cell populations in the spleen and bone marrow by Day 7 posttreatment. Notably, the reduction of mutant burden was durably maintained in secondary recipient mice. In the disseminated NSG model, DX1-2C11 delivered immediate tumor burden reduction and significantly prolonged the overall survival of mice compared to the control group. Taken together, these data suggest that bispecific T cell engaging antibody targeting mutCALR represents a curative strategy that efficiently eliminates mutant MPN stem cells in vivo.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"26 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961447","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}
This CME/CE integrates real patient stories, current evidence, evolving guideline recommendations, and expert clinical experience to equip hematology/oncology clinicians with practical strategies for successful asparaginase-based therapy in young adults with acute lymphoblastic leukemia (ALL). The overarching goal is to improve outcomes for young adults with ALL through more consistent application of pediatric-inspired regimens, optimized asparaginase use, and comprehensive, patient-centered care. Leukemia experts synthesize the latest evidence on the efficacy and safety of asparaginase-based ALL treatment for young adults. Using a case-based approach, the curriculum provides structured guidance on mitigation, monitoring, and management of key asparaginase-related toxicities. Practical recommendations include therapeutic drug monitoring of asparaginase activity, detection of clinical and silent hypersensitivity reactions, and timely substitution of Escherichia coli-derived asparaginase with Erwinia-derived asparaginase to preserve therapeutic activity and efficacy after immune-mediated inactivation. Beyond treatment selection and toxicity management, the activity addresses system-level and psychosocial barriers that uniquely affect young adults with ALL, such as distance from specialty centers, employment and family responsibilities, lower rates of clinical trial participation, and survivorship concerns. To view this activity, and obtain CME/CE credit, click here.
{"title":"Patients First: Navigating Asparaginase-Based Treatment in Young Adults With Acute Lymphoblastic Leukemia.","authors":"Ryan D Cassaday,Daniel J DeAngelo","doi":"10.1002/ajh.70195","DOIUrl":"https://doi.org/10.1002/ajh.70195","url":null,"abstract":"This CME/CE integrates real patient stories, current evidence, evolving guideline recommendations, and expert clinical experience to equip hematology/oncology clinicians with practical strategies for successful asparaginase-based therapy in young adults with acute lymphoblastic leukemia (ALL). The overarching goal is to improve outcomes for young adults with ALL through more consistent application of pediatric-inspired regimens, optimized asparaginase use, and comprehensive, patient-centered care. Leukemia experts synthesize the latest evidence on the efficacy and safety of asparaginase-based ALL treatment for young adults. Using a case-based approach, the curriculum provides structured guidance on mitigation, monitoring, and management of key asparaginase-related toxicities. Practical recommendations include therapeutic drug monitoring of asparaginase activity, detection of clinical and silent hypersensitivity reactions, and timely substitution of Escherichia coli-derived asparaginase with Erwinia-derived asparaginase to preserve therapeutic activity and efficacy after immune-mediated inactivation. Beyond treatment selection and toxicity management, the activity addresses system-level and psychosocial barriers that uniquely affect young adults with ALL, such as distance from specialty centers, employment and family responsibilities, lower rates of clinical trial participation, and survivorship concerns. To view this activity, and obtain CME/CE credit, click here.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"82 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961416","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}
Rong Wang,Amy J Davidoff,Martin Schoen,John H Huber,Eric J Feuer,Jennifer Ruhl,Natalia Neparidze,Xiaomei Ma,Su-Hsin Chang,Shi-Yi Wang
{"title":"Trends in Smoldering Myeloma Incidence in the United States From Cancer Registries, 2012-2022.","authors":"Rong Wang,Amy J Davidoff,Martin Schoen,John H Huber,Eric J Feuer,Jennifer Ruhl,Natalia Neparidze,Xiaomei Ma,Su-Hsin Chang,Shi-Yi Wang","doi":"10.1002/ajh.70202","DOIUrl":"https://doi.org/10.1002/ajh.70202","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"29 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145955942","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}
Zaina Inam,Elizabeth Stenger,Tami D John,Katie Liu,Scott Gillespie,Rikin Shah,Deepakbabu Chellapandian,Monica Bhatia,Sonali Chaudhury,Michael J Eckrich,Gregory M T Guilcher,Jeanne E Hendrickson,Monica L Hulbert,Jennifer J Jaroscak,Kimberly A Kasow,Christine Camacho-Bydume,Alexander Ngwube,Timothy S Olson,Hemalatha G Rangarajan,John T Horan,Lakshmanan Krishnamurti,Shalini Shenoy,Allistair Abraham,Robert Sheppard Nickel
Patients with sickle cell disease (SCD) commonly receive red blood cell (RBC) transfusions and can become RBC alloimmunized. This study was designed to investigate if RBC alloimmunization before hematopoietic cell transplant (HCT) was associated with post-HCT outcomes and transfusion support using the multicenter Sickle cell Transplant Advocacy and Research (STAR) retrospective registry. From a cohort of 229 pediatric patients with SCD who underwent human leukocyte antigen (HLA)-matched related donor HCT with myeloablative or reduced intensity conditioning, 40 patients (17%) were RBC alloimmunized pre-HCT. The RBC alloimmunized group had a significantly higher incidence of grade III-IV acute graft-versus-host disease (GVHD) (15% vs. 3.7%, p = 0.013), which remained significant (OR 4.22, 95% CI, 1.19, 14.3; p = 0.027) when controlling for pre-HCT RBC transfusion burden and conditioning intensity. Graft failure occurred in 10% of RBC alloimmunized patients compared with 2.6% of non-alloimmunized patients, p = 0.052. Patients with RBC alloimmunization had lower 5-year severe GVHD-free, rejection-free survival (69% vs. 88%, p = 0.004), which remained significant when controlling for age. Post-HCT patients received a median 3 RBC units (IQR 2, 6) and 11 platelet transfusions (IQR 7, 19). Pre-HCT RBC alloimmunization was associated with a greater requirement for post-HCT platelet transfusions, but not post-HCT RBC units transfused. We postulate that the observed associations of pre-HCT RBC alloimmunization with severe acute GVHD and post-HCT platelet transfusion burden are due to inherent immunologic characteristics that render patients at increased risk of developing multiple immune-mediated complications.
镰状细胞病（SCD）患者通常接受红细胞（RBC）输注，并可成为红细胞异体免疫。本研究旨在通过多中心镰状细胞移植倡导和研究（STAR）回顾性登记，调查造血细胞移植（HCT）前的红细胞异体免疫是否与HCT后的结果和输血支持相关。在229名接受人类白细胞抗原（HLA）匹配相关供体HCT治疗的SCD患儿中，有40名（17%）患者接受了红细胞同种异体免疫前HCT治疗。同种异体红细胞免疫组III-IV级急性移植物抗宿主病（GVHD）发生率显著升高（15% vs. 3.7%, p = 0.013），在控制hct前红细胞输血负担和调节强度时，这一发生率仍然显著（OR 4.22, 95% CI, 1.19, 14.3; p = 0.027）。10%的红细胞同种异体免疫患者发生移植失败，而未进行同种异体免疫的患者为2.6%,p = 0.052。接受同种异体红细胞免疫的患者5年无严重gvhd、无排斥的生存率较低（69% vs. 88%, p = 0.004），在控制年龄的情况下，这一差异仍然显著。hct后患者接受平均3个红细胞单位（IQR 2,6）和11个血小板单位（IQR 7,19）输注。hct前的红细胞同种异体免疫与hct后血小板输注的更高需求相关，但与hct后输注的红细胞单位无关。我们假设，观察到的hct前红细胞异体免疫与严重急性GVHD和hct后血小板输注负担的关联是由于固有的免疫特性，使患者发生多种免疫介导的并发症的风险增加。
{"title":"RBC Alloimmunization Impacts Pediatric Sickle Cell Disease Transplant Outcomes and Transfusion Burden: A STAR Registry Report.","authors":"Zaina Inam,Elizabeth Stenger,Tami D John,Katie Liu,Scott Gillespie,Rikin Shah,Deepakbabu Chellapandian,Monica Bhatia,Sonali Chaudhury,Michael J Eckrich,Gregory M T Guilcher,Jeanne E Hendrickson,Monica L Hulbert,Jennifer J Jaroscak,Kimberly A Kasow,Christine Camacho-Bydume,Alexander Ngwube,Timothy S Olson,Hemalatha G Rangarajan,John T Horan,Lakshmanan Krishnamurti,Shalini Shenoy,Allistair Abraham,Robert Sheppard Nickel","doi":"10.1002/ajh.70200","DOIUrl":"https://doi.org/10.1002/ajh.70200","url":null,"abstract":"Patients with sickle cell disease (SCD) commonly receive red blood cell (RBC) transfusions and can become RBC alloimmunized. This study was designed to investigate if RBC alloimmunization before hematopoietic cell transplant (HCT) was associated with post-HCT outcomes and transfusion support using the multicenter Sickle cell Transplant Advocacy and Research (STAR) retrospective registry. From a cohort of 229 pediatric patients with SCD who underwent human leukocyte antigen (HLA)-matched related donor HCT with myeloablative or reduced intensity conditioning, 40 patients (17%) were RBC alloimmunized pre-HCT. The RBC alloimmunized group had a significantly higher incidence of grade III-IV acute graft-versus-host disease (GVHD) (15% vs. 3.7%, p = 0.013), which remained significant (OR 4.22, 95% CI, 1.19, 14.3; p = 0.027) when controlling for pre-HCT RBC transfusion burden and conditioning intensity. Graft failure occurred in 10% of RBC alloimmunized patients compared with 2.6% of non-alloimmunized patients, p = 0.052. Patients with RBC alloimmunization had lower 5-year severe GVHD-free, rejection-free survival (69% vs. 88%, p = 0.004), which remained significant when controlling for age. Post-HCT patients received a median 3 RBC units (IQR 2, 6) and 11 platelet transfusions (IQR 7, 19). Pre-HCT RBC alloimmunization was associated with a greater requirement for post-HCT platelet transfusions, but not post-HCT RBC units transfused. We postulate that the observed associations of pre-HCT RBC alloimmunization with severe acute GVHD and post-HCT platelet transfusion burden are due to inherent immunologic characteristics that render patients at increased risk of developing multiple immune-mediated complications.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"694 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949712","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}
Lu Zhang, Jia-ying Ge, Si-yuan Li, Hong-yan Tong, Liang-shun You, Jian Li
Idiopathic multicentric Castleman disease (iMCD)-TAFRO (Thrombocytopenia, Anasarca, Fever, Reticulin fibrosis/renal dysfunction, Organomegaly) is the most severe clinical subtype of iMCD characterized by a catastrophic cytokine storm. Currently, iMCD-TAFRO is regarded as incurable which needs “indefinite” treatment. However, long-term data are sparse, and treatment discontinuation may be possible in a subset of patients. This multicenter, retrospective study analyzed 27 patients who discontinued treatment. All patients had biochemical complete response (CR) at the time of drug discontinuation. Most patients were treated with myeloma-like treatment (59.3%) and only 11.1% received anti-IL-6 therapy. With a median follow-up of 31 months (range, 12–108) after treatment discontinuation, only four patients (14.8%) suffered from progression of disease (PD) and the others (85.2%) maintained biochemical CR. Patients who suffered from PD had a significantly lower pretreatment CRP level than patients maintaining responses (43.7 ± 39.3 vs. 126.4 ± 62.5 mg/L, p = 0.018). No significant impacts of different treatment approaches or duration of treatment on the likelihood of achieving long-term remission were observed. The median time between drug discontinuation to PD (n = 4) was 9.5 months (range, 5–12). These patients all achieved treatment responses again with the same or similar treatment approaches. The estimated PFS at 6 months, 1 year, and 3 years were 96.3%, 85.2%, and 85.2%, respectively. All patients remained alive with a median of 31 months follow-up after drug discontinuation. This study suggests that some iMCD-TAFRO patients might maintain long-term remission after treatment discontinuation. For patients who achieved biochemical CR, an attempt at treatment discontinuation could be considered.
特发性多中心Castleman病(iMCD) - TAFRO（血小板减少、贫血、发热、网状蛋白纤维化/肾功能障碍、器官肿大）是iMCD最严重的临床亚型，其特征是灾难性的细胞因子风暴。目前，iMCD - TAFRO被认为是无法治愈的，需要“无限期”治疗。然而，长期数据很少，并且在一部分患者中可能会停止治疗。这项多中心回顾性研究分析了27例停止治疗的患者。所有患者停药时生化完全缓解（CR）。大多数患者接受骨髓瘤样治疗（59.3%），只有11.1%接受抗IL - 6治疗。停药后中位随访31个月（12-108个月），只有4例患者（14.8%）出现疾病进展（PD），其余患者（85.2%）维持生化CR， PD患者的预处理CRP水平明显低于维持反应的患者（43.7±39.3 vs 126.4±62.5 mg/L, p = 0.018）。未观察到不同治疗方法或治疗持续时间对实现长期缓解的可能性有显著影响。从停药到PD （n = 4）的中位时间为9.5个月（范围5-12）。这些患者都通过相同或类似的治疗方法再次获得了治疗反应。估计6个月、1年和3年的PFS分别为96.3%、85.2%和85.2%。所有患者在停药后的中位随访时间为31个月。这项研究表明，一些iMCD - TAFRO患者在停止治疗后可能保持长期缓解。对于达到生化CR的患者，可以考虑尝试停止治疗。
{"title":"Idiopathic Multicentric Castleman Disease—TAFRO: A Potentially Curable Disease?","authors":"Lu Zhang, Jia-ying Ge, Si-yuan Li, Hong-yan Tong, Liang-shun You, Jian Li","doi":"10.1002/ajh.70199","DOIUrl":"10.1002/ajh.70199","url":null,"abstract":"<div>\u0000 \u0000 <p>Idiopathic multicentric Castleman disease (iMCD)-TAFRO (Thrombocytopenia, Anasarca, Fever, Reticulin fibrosis/renal dysfunction, Organomegaly) is the most severe clinical subtype of iMCD characterized by a catastrophic cytokine storm. Currently, iMCD-TAFRO is regarded as incurable which needs “indefinite” treatment. However, long-term data are sparse, and treatment discontinuation may be possible in a subset of patients. This multicenter, retrospective study analyzed 27 patients who discontinued treatment. All patients had biochemical complete response (CR) at the time of drug discontinuation. Most patients were treated with myeloma-like treatment (59.3%) and only 11.1% received anti-IL-6 therapy. With a median follow-up of 31 months (range, 12–108) after treatment discontinuation, only four patients (14.8%) suffered from progression of disease (PD) and the others (85.2%) maintained biochemical CR. Patients who suffered from PD had a significantly lower pretreatment CRP level than patients maintaining responses (43.7 ± 39.3 vs. 126.4 ± 62.5 mg/L, <i>p</i> = 0.018). No significant impacts of different treatment approaches or duration of treatment on the likelihood of achieving long-term remission were observed. The median time between drug discontinuation to PD (<i>n</i> = 4) was 9.5 months (range, 5–12). These patients all achieved treatment responses again with the same or similar treatment approaches. The estimated PFS at 6 months, 1 year, and 3 years were 96.3%, 85.2%, and 85.2%, respectively. All patients remained alive with a median of 31 months follow-up after drug discontinuation. This study suggests that some iMCD-TAFRO patients might maintain long-term remission after treatment discontinuation. For patients who achieved biochemical CR, an attempt at treatment discontinuation could be considered.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 3","pages":"447-455"},"PeriodicalIF":9.9,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938021","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}
Alexandre-Raphael Wery, Fabio Andreozzi, Hussein Farhat, Sebastian Wittnebel, Philippe Lewalle, Aspasia Georgala
Conflicts of Interest
The authors declare no conflicts of interest.
利益冲突作者声明无利益冲突。
{"title":"Rare and Deadly Complication of Disseminated Toxoplasma gondii Infection After Allogeneic Hematopoietic Stem Cell Transplantation: Hemophagocytic Lymphohistiocytosis","authors":"Alexandre-Raphael Wery, Fabio Andreozzi, Hussein Farhat, Sebastian Wittnebel, Philippe Lewalle, Aspasia Georgala","doi":"10.1002/ajh.70180","DOIUrl":"https://doi.org/10.1002/ajh.70180","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":"42 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920325","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}
Charalampos Filippatos, Ioanna Kanteli, Dafni Georgia Pasipoularidou, Maria Gavriatopoulou, Anastasios Tentolouris, Panagiotis Malandrakis, Theodoros N. Sergentanis, Evangelos Terpos, Ioannis Ntanasis-Stathopoulos
This meta-analysis examined the safety and efficacy of CAR T-cell therapy in 3281 patients with hematological malignancies enrolled in phase 1/2, 2 and 3 clinical trials, published until July 23, 2025 according to the PRISMA guidelines. All trials involved relapsed/refractory, pretreated individuals. In 11 multiple myeloma trials, CAR T-cell therapy showed significant efficacy, with pooled ORR and ≥CR rates of 89% and 53%, respectively. These responses translated into important survival benefits, with 1-year OS and PFS rates of 84% and 60%, respectively. However, AEs including any-grade CRS, infections and grade ≥ 3 neutropenia emerged in pooled rates of 89%, 46% and 88%, respectively. In 23 trials on high-grade lymphomas, the pooled ORR was 76% and the pooled ≥CR rate 55%. The pooled 1-year OS and PFS rates were 65% and 46%, respectively. Any-grade CRS was prevalent in a pooled rate of 46% and grade ≥ 3 neutropenia in 56%. Data from 16 records investigating CAR T-cells for leukemia yielded pooled ORR and ≥CR rates of 78% and 70%, respectively, with pooled 1-year OS and PFS rates being 61% and 40%, respectively. Similarly to myeloma and lymphoma, any-grade CRS was very common at a pooled rate of 85% and any-grade infections occurred at a pooled rate of 29%. Apart from grade ≥ 3 neutropenia (70%), grade ≥ 3 anemia emerged as an equally common serious hematological AE (69%). In conclusion, CAR T-cells constitute a highly effective therapeutic option for patients with hematological cancer at relapse, but close patient monitoring is essential to address treatment-related toxicities.
{"title":"Chimeric Antigen Receptor T-Cells (CAR T-Cells) in Hematological Malignancies: A Systematic Review and Meta-Analysis of Proportions From Clinical Trials","authors":"Charalampos Filippatos, Ioanna Kanteli, Dafni Georgia Pasipoularidou, Maria Gavriatopoulou, Anastasios Tentolouris, Panagiotis Malandrakis, Theodoros N. Sergentanis, Evangelos Terpos, Ioannis Ntanasis-Stathopoulos","doi":"10.1002/ajh.70201","DOIUrl":"10.1002/ajh.70201","url":null,"abstract":"<div>\u0000 \u0000 <p>This meta-analysis examined the safety and efficacy of CAR T-cell therapy in 3281 patients with hematological malignancies enrolled in phase 1/2, 2 and 3 clinical trials, published until July 23, 2025 according to the PRISMA guidelines. All trials involved relapsed/refractory, pretreated individuals. In 11 multiple myeloma trials, CAR T-cell therapy showed significant efficacy, with pooled ORR and ≥CR rates of 89% and 53%, respectively. These responses translated into important survival benefits, with 1-year OS and PFS rates of 84% and 60%, respectively. However, AEs including any-grade CRS, infections and grade ≥ 3 neutropenia emerged in pooled rates of 89%, 46% and 88%, respectively. In 23 trials on high-grade lymphomas, the pooled ORR was 76% and the pooled ≥CR rate 55%. The pooled 1-year OS and PFS rates were 65% and 46%, respectively. Any-grade CRS was prevalent in a pooled rate of 46% and grade ≥ 3 neutropenia in 56%. Data from 16 records investigating CAR T-cells for leukemia yielded pooled ORR and ≥CR rates of 78% and 70%, respectively, with pooled 1-year OS and PFS rates being 61% and 40%, respectively. Similarly to myeloma and lymphoma, any-grade CRS was very common at a pooled rate of 85% and any-grade infections occurred at a pooled rate of 29%. Apart from grade ≥ 3 neutropenia (70%), grade ≥ 3 anemia emerged as an equally common serious hematological AE (69%). In conclusion, CAR T-cells constitute a highly effective therapeutic option for patients with hematological cancer at relapse, but close patient monitoring is essential to address treatment-related toxicities.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 3","pages":"497-511"},"PeriodicalIF":9.9,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145931467","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}
Keith W. Pratz, Courtney D. DiNardo, Martha Arellano, Michael J. Thirman, Vinod Pullarkat, Pamela S. Becker, B. Douglas Smith, Meng Zhang, Kaylee Miu, Jalaja Potluri, Daniel A. Pollyea
<p>Allogeneic hematopoietic stem cell transplantation (SCT) remains the most effective curative treatment for patients with intermediate- and poor-risk acute myeloid leukemia (AML). Patients ineligible for intensive chemotherapy due to age or comorbidities have historically not been candidates for SCT. Venetoclax in combination with hypomethylating agents (HMA) decitabine or azacitidine demonstrated rapid and durable remission in newly diagnosed AML patients ineligible for intensive chemotherapy and is approved globally for this indication [<span>1, 2</span>]. An increase in patients achieving remission with alternative induction therapies could allow more patients to proceed to SCT, since reduced intensity conditioning regimens used for older patients have similar post-SCT outcomes compared with myeloablative conditioning [<span>3</span>]. This analysis evaluates long-term clinical outcomes of patients receiving SCT after venetoclax plus HMA therapy.</p> <p>A combined cohort of patients enrolled to the randomized phase 3 trial VIALE-A (NCT02993523) and open-label phase 1b dose-escalation and expansion trial M14-358 (NCT02203773) was included. Study designs have been reported previously [<span>1, 2</span>]. Briefly, enrolled patients were ineligible for intensive chemotherapy due to age (≥ 75 years old) or comorbidities and had no prior AML-related therapy. Patients enrolled in VIALE-A were administered 400 mg oral venetoclax daily plus azacitidine, while patients in M14-358 were administered oral venetoclax at either 400 or 800 mg daily in combination with either azacitidine (75 mg/m<sup>2</sup> subcutaneously or intravenously on Days 1–7) or decitabine (20 mg/m<sup>2</sup> intravenously on Days 1–5) in 28-day cycles. The data cutoff was July 19, 2019, for M14-358 and December 1, 2021, for VIALE-A.</p> <p>Outcomes were assessed before and after allogeneic SCT. Overall survival (OS) was assessed from randomization or first dose of venetoclax. Best response was assessed per modified International Working Group criteria for AML [<span>4</span>]. A measurable residual disease (MRD)-negative response was defined as < 10<sup>−3</sup> leukemia cells/leukocyte. MRD was assessed by flow cytometry [<span>1, 2</span>]. Additional outcomes included time to best response, 2-year post-SCT remission, and 2-year post-SCT OS. Results are reported using descriptive statistics unless otherwise specified. Survival analyses and estimates were calculated using the Kaplan–Meier method. Patients who were lost to follow-up were censored at the date of the last study visit or the last known date alive, whichever was later.</p> <p>In total, 33 patients from VIALE-A (<i>n</i> = 2) and M14-358 (<i>n</i> = 31) received SCT after venetoclax plus HMA therapy. Patients were a median age of 69 years (range, 63–76). Most had <i>de novo</i> AML (69.7%) and adverse risk disease (54.5%) based on 2022 European LeukemiaNet categories (Table S1). Baseline mutations were identified w
{"title":"Long-Term Outcomes of Stem Cell Transplant in Older Patients With Acute Myeloid Leukemia Treated With Venetoclax-Based Therapies","authors":"Keith W. Pratz, Courtney D. DiNardo, Martha Arellano, Michael J. Thirman, Vinod Pullarkat, Pamela S. Becker, B. Douglas Smith, Meng Zhang, Kaylee Miu, Jalaja Potluri, Daniel A. Pollyea","doi":"10.1002/ajh.70204","DOIUrl":"https://doi.org/10.1002/ajh.70204","url":null,"abstract":"<p>Allogeneic hematopoietic stem cell transplantation (SCT) remains the most effective curative treatment for patients with intermediate- and poor-risk acute myeloid leukemia (AML). Patients ineligible for intensive chemotherapy due to age or comorbidities have historically not been candidates for SCT. Venetoclax in combination with hypomethylating agents (HMA) decitabine or azacitidine demonstrated rapid and durable remission in newly diagnosed AML patients ineligible for intensive chemotherapy and is approved globally for this indication [<span>1, 2</span>]. An increase in patients achieving remission with alternative induction therapies could allow more patients to proceed to SCT, since reduced intensity conditioning regimens used for older patients have similar post-SCT outcomes compared with myeloablative conditioning [<span>3</span>]. This analysis evaluates long-term clinical outcomes of patients receiving SCT after venetoclax plus HMA therapy.</p>\u0000<p>A combined cohort of patients enrolled to the randomized phase 3 trial VIALE-A (NCT02993523) and open-label phase 1b dose-escalation and expansion trial M14-358 (NCT02203773) was included. Study designs have been reported previously [<span>1, 2</span>]. Briefly, enrolled patients were ineligible for intensive chemotherapy due to age (≥ 75 years old) or comorbidities and had no prior AML-related therapy. Patients enrolled in VIALE-A were administered 400 mg oral venetoclax daily plus azacitidine, while patients in M14-358 were administered oral venetoclax at either 400 or 800 mg daily in combination with either azacitidine (75 mg/m<sup>2</sup> subcutaneously or intravenously on Days 1–7) or decitabine (20 mg/m<sup>2</sup> intravenously on Days 1–5) in 28-day cycles. The data cutoff was July 19, 2019, for M14-358 and December 1, 2021, for VIALE-A.</p>\u0000<p>Outcomes were assessed before and after allogeneic SCT. Overall survival (OS) was assessed from randomization or first dose of venetoclax. Best response was assessed per modified International Working Group criteria for AML [<span>4</span>]. A measurable residual disease (MRD)-negative response was defined as < 10<sup>−3</sup> leukemia cells/leukocyte. MRD was assessed by flow cytometry [<span>1, 2</span>]. Additional outcomes included time to best response, 2-year post-SCT remission, and 2-year post-SCT OS. Results are reported using descriptive statistics unless otherwise specified. Survival analyses and estimates were calculated using the Kaplan–Meier method. Patients who were lost to follow-up were censored at the date of the last study visit or the last known date alive, whichever was later.</p>\u0000<p>In total, 33 patients from VIALE-A (<i>n</i> = 2) and M14-358 (<i>n</i> = 31) received SCT after venetoclax plus HMA therapy. Patients were a median age of 69 years (range, 63–76). Most had <i>de novo</i> AML (69.7%) and adverse risk disease (54.5%) based on 2022 European LeukemiaNet categories (Table S1). Baseline mutations were identified w","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"186 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920326","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}
Asya Makhro, Rick Huisjes, Elena Seiler, Min Qiao, Marije Bartels, Inga Hegemann, Patrick Eppenberger, Nicole Bender, Isabel Dorn, Anna Bogdanova, Richard van Wijk, Lars Kaestner
<p>Hereditary xerocytosis (HX), also known as dehydrated hereditary stomatocytosis (DHS), is a rare red blood cell (RBC) disorder caused by gain-of-function (GOF) mutations in the <i>PIEZO1</i> gene [<span>1-3</span>], which encodes a mechanosensitive, nonselective cation channel. Activation of Piezo1 leads to, i.a., Ca<sup>2+</sup> influx, opening of the Gárdos-channel, K<sup>+</sup> efflux, and subsequent RBC dehydration [<span>4, 5</span>]. Patients with HX typically exhibit compensated hemolysis, elevated reticulocyte counts, and iron overload. Mechanistic links—such as the relationship between Piezo1 activity and altered RBC lifespan, or between reticulocyte counts and erythropoiesis rate—are hypothesized but remain unconfirmed [<span>6, 7</span>].</p> <p>We investigated a cohort of 12 genetically confirmed HX patients (see Table S1 and Figure S1 for details). Our objective was to determine how GOF variants in <i>PIEZO1</i> affect RBC physiology and erythropoietic regulation in HX. In contrast to sickle cell disease (SCD), where RBC lifespan is markedly shortened and highly variable (10–60 days) [<span>8</span>], much less is known about RBC survival in HX. Therefore, we first assessed the average lifespan of HX RBCs using the protein 4.1a/4.1b ratio, which functions as a molecular clock [<span>9</span>] and scales linearly with RBC age. Figure 1A,B depict this ratio for healthy controls, SCD patients, and HX patients, plotted against reticulocyte counts. HX patients exhibit elevated reticulocyte counts despite having a comparable RBC age to SCD patients, suggesting delayed reticulocyte maturation [<span>10</span>]. This “uncoupling” of reticulocyte count from RBC age accounts for its weak correlation with erythropoietin (EPO) levels (Figure 1C), indicating that here the reticulocyte count is not a reliable marker of erythropoiesis rate. Based on the established lifespan of SCD RBCs [<span>8</span>], HX RBCs appear to have similarly shortened lifespans (0.66 ± 0.16 vs. 0.62 ± 0.11 days; <i>p</i> = 0.5).</p> <figure><picture> <source media="(min-width: 1650px)" srcset="/cms/asset/f2557b40-e805-481c-88a7-167763d85bce/ajh70188-fig-0001-m.jpg"/><img alt="Details are in the caption following the image" data-lg-src="/cms/asset/f2557b40-e805-481c-88a7-167763d85bce/ajh70188-fig-0001-m.jpg" loading="lazy" src="/cms/asset/970e0275-9fa0-4097-b695-93c3ee28a88f/ajh70188-fig-0001-m.png" title="Details are in the caption following the image"/></picture><figcaption> <div><strong>FIGURE 1<span style="font-weight:normal"></span></strong><div>Open in figure viewer<i aria-hidden="true"></i><span>PowerPoint</span></div> </div> <div>Red blood cell age, oxygen binding, and erythropoietin levels in hereditary xerocytosis (HX) patients. Panel A shows a representative example of gel electrophoresis to determine the protein Band 4.1a to 4.1b ratio, which is known to be a molecular clock for RBC age. Both bands just differ by the deamidation of the Band 4.1 protein. Pa
{"title":"Mechanistic Consequences of Piezo1 Gain-of-Function Variants for Decreased Red Cell Survival in Hereditary Xerocytosis","authors":"Asya Makhro, Rick Huisjes, Elena Seiler, Min Qiao, Marije Bartels, Inga Hegemann, Patrick Eppenberger, Nicole Bender, Isabel Dorn, Anna Bogdanova, Richard van Wijk, Lars Kaestner","doi":"10.1002/ajh.70188","DOIUrl":"https://doi.org/10.1002/ajh.70188","url":null,"abstract":"<p>Hereditary xerocytosis (HX), also known as dehydrated hereditary stomatocytosis (DHS), is a rare red blood cell (RBC) disorder caused by gain-of-function (GOF) mutations in the <i>PIEZO1</i> gene [<span>1-3</span>], which encodes a mechanosensitive, nonselective cation channel. Activation of Piezo1 leads to, i.a., Ca<sup>2+</sup> influx, opening of the Gárdos-channel, K<sup>+</sup> efflux, and subsequent RBC dehydration [<span>4, 5</span>]. Patients with HX typically exhibit compensated hemolysis, elevated reticulocyte counts, and iron overload. Mechanistic links—such as the relationship between Piezo1 activity and altered RBC lifespan, or between reticulocyte counts and erythropoiesis rate—are hypothesized but remain unconfirmed [<span>6, 7</span>].</p>\u0000<p>We investigated a cohort of 12 genetically confirmed HX patients (see Table S1 and Figure S1 for details). Our objective was to determine how GOF variants in <i>PIEZO1</i> affect RBC physiology and erythropoietic regulation in HX. In contrast to sickle cell disease (SCD), where RBC lifespan is markedly shortened and highly variable (10–60 days) [<span>8</span>], much less is known about RBC survival in HX. Therefore, we first assessed the average lifespan of HX RBCs using the protein 4.1a/4.1b ratio, which functions as a molecular clock [<span>9</span>] and scales linearly with RBC age. Figure 1A,B depict this ratio for healthy controls, SCD patients, and HX patients, plotted against reticulocyte counts. HX patients exhibit elevated reticulocyte counts despite having a comparable RBC age to SCD patients, suggesting delayed reticulocyte maturation [<span>10</span>]. This “uncoupling” of reticulocyte count from RBC age accounts for its weak correlation with erythropoietin (EPO) levels (Figure 1C), indicating that here the reticulocyte count is not a reliable marker of erythropoiesis rate. Based on the established lifespan of SCD RBCs [<span>8</span>], HX RBCs appear to have similarly shortened lifespans (0.66 ± 0.16 vs. 0.62 ± 0.11 days; <i>p</i> = 0.5).</p>\u0000<figure><picture>\u0000<source media=\"(min-width: 1650px)\" srcset=\"/cms/asset/f2557b40-e805-481c-88a7-167763d85bce/ajh70188-fig-0001-m.jpg\"/><img alt=\"Details are in the caption following the image\" data-lg-src=\"/cms/asset/f2557b40-e805-481c-88a7-167763d85bce/ajh70188-fig-0001-m.jpg\" loading=\"lazy\" src=\"/cms/asset/970e0275-9fa0-4097-b695-93c3ee28a88f/ajh70188-fig-0001-m.png\" title=\"Details are in the caption following the image\"/></picture><figcaption>\u0000<div><strong>FIGURE 1<span style=\"font-weight:normal\"></span></strong><div>Open in figure viewer<i aria-hidden=\"true\"></i><span>PowerPoint</span></div>\u0000</div>\u0000<div>Red blood cell age, oxygen binding, and erythropoietin levels in hereditary xerocytosis (HX) patients. Panel A shows a representative example of gel electrophoresis to determine the protein Band 4.1a to 4.1b ratio, which is known to be a molecular clock for RBC age. Both bands just differ by the deamidation of the Band 4.1 protein. Pa","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"167 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919789","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}
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