Bo A Wan, Hamish Nicolson, Heather A Leitch, Ryan J Stubbins, Luke Y C Chen, Timothy Murray, Amy Trottier, Anthony Gador
{"title":"Late Onset Telomere Biology Disorder Presenting With Pancytopenia, Immune Dysregulation, Interstitial Lung Disease and Alopecia.","authors":"Bo A Wan, Hamish Nicolson, Heather A Leitch, Ryan J Stubbins, Luke Y C Chen, Timothy Murray, Amy Trottier, Anthony Gador","doi":"10.1002/ajh.70234","DOIUrl":"https://doi.org/10.1002/ajh.70234","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147281877","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}
Nicolas Dib, David Saadoun, Alexandre Le Joncour, Chloë Dumas de la Roque, Elisabeth Pasquier, Emmanuel Esteve, Isabelle Marie, Gabriel Choukroun, Thomas Quemeneur, Laure Swiader, Catherine Michel, Amandine Perier, Franck Bridoux, Benjamin Thoreau, Matthieu Groh, Benjamin Terrier, Thierry Zenone, David Launay, Patrice Cacoub, Adrien Mirouse
{"title":"Long Term Outcomes in Patients With Non-Infectious Mixed Cryoglobulinemic Vasculitis.","authors":"Nicolas Dib, David Saadoun, Alexandre Le Joncour, Chloë Dumas de la Roque, Elisabeth Pasquier, Emmanuel Esteve, Isabelle Marie, Gabriel Choukroun, Thomas Quemeneur, Laure Swiader, Catherine Michel, Amandine Perier, Franck Bridoux, Benjamin Thoreau, Matthieu Groh, Benjamin Terrier, Thierry Zenone, David Launay, Patrice Cacoub, Adrien Mirouse","doi":"10.1002/ajh.70217","DOIUrl":"https://doi.org/10.1002/ajh.70217","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147275822","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}
Patrizia Chiusolo, Andrea Bacigalupo, Rachel Salit, Thomas Schroeder, Maria Chiara Finazzi, Carmelo Gurnari, Simona Pagliuca, Judith Metzdorf, Christina Rautenberg, Marie Robin, Marie-Thérèse Rubio, Jaroslaw Maciejewski, Uday Popat, Alessandro Rambaldi, Hans Christian Reinhardt, Bart Scott, Nicolaus Kröger, Nico Gagelmann
<p>Allogeneic hematopoietic stem cell transplantation remains the only curative therapy, yet outcomes are tempered by graft failure, relapse, infectious complications, and graft-versus-host disease (GVHD) [<span>1</span>]. Two approaches for GVHD prophylaxis dominate: anti-thymocyte or anti-T-lymphocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy). ATG provides broad in vivo T-cell depletion and reduces GVHD risk and has been shown to improve outcomes in all donor settings [<span>2</span>]. PTCy, primarily used in the haploidentical setting, acts post-transplant to selectively eliminate proliferating alloreactive T cells while preserving regulatory and memory populations, potentially mitigating GVHD while supporting immune reconstitution [<span>3</span>]. Both strategies have shown efficacy [<span>2, 4-7</span>], yet their relative impact in myelofibrosis in the matched donor setting—a disease with unique transplant dynamics—remains unclear. This study aims to evaluate outcomes of HLA-matched transplantation in MF using either ATG or PTCy.</p> <p>This was a retrospective, non-randomized comparison in patients undergoing transplantation for myelofibrosis between 2010 and 2024. Additional GVHD prophylaxis in both arms consisted of cyclosporine A together with mycophenolate mofetil or methotrexate, depending on center standards. Patients with accelerated-phase or blast-phase MF were excluded [<span>8</span>]. Dose for PTCy was 50 mg/kg/day on 2 days after transplant. Patients receiving ATG included two different brands: Thymoglobulin (Sanofi, France) 3.5 mg/kg/day on 2 days before transplantation or Grafalon (Neovii, Germany) 30 mg/kg/day for matched siblings and 60 mg/kg/day for matched unrelated donors on 3 days before transplantation.</p> <p>To account for selection bias and potential confounding factors between groups in outcome comparisons, we employed a weighted propensity score analysis to balance baseline characteristics between patients who received ATG versus PTCY. The propensity score model was generated using the inverse probability of treatment weighting (IPTW) approach, where each patient was weighted by the inverse probability of being in the ATG or PTCY group. Weighted Cox proportional hazards models were used to assess survival outcomes, hazard ratios (wHRs), and Fine-Gray regression was used for endpoints with competing risks.</p> <p>A total of 539 patients were included, with 427 receiving ATG and 112 PTCy (Supplemental Table 1), and the median age was comparable between groups (58 vs. 60 years, <i>p</i> = 0.21). Donor type showed a trend toward more matched related donors in the PTCy group compared with ATG (38% vs. 28%, <i>p</i> = 0.06). Conditioning intensity differed significantly between groups: reduced-intensity regimens were predominant in the ATG group (79%), whereas nearly half of patients in the PTCy group received higher-intensity conditioning (47%; <i>p</i> < 0.001). Median follow-up was 4.8 years for
同种异体造血干细胞移植仍然是唯一的治愈性治疗方法，但移植失败、复发、感染性并发症和移植物抗宿主病（GVHD）[1]影响了结果。预防GVHD主要有两种方法：抗胸腺细胞或抗t淋巴细胞球蛋白（ATG）和移植后环磷酰胺（PTCy）。ATG提供了广泛的体内t细胞消耗，降低了GVHD的风险，并已被证明可以改善所有供体环境的预后[10]。PTCy主要用于单倍体相同的情况，在移植后选择性地消除增殖的同种异体反应性T细胞，同时保留调节性和记忆性群体，潜在地减轻GVHD，同时支持免疫重建bb0。这两种策略都显示出疗效[2,4 -7]，但它们对匹配供体骨髓纤维化（一种具有独特移植动力学的疾病）的相对影响尚不清楚。本研究旨在评估ATG或PTCy治疗MF患者hla匹配移植的结果。这是一项回顾性的、非随机的比较，研究对象是2010年至2024年间接受骨髓纤维化移植的患者。另外，根据中心标准，两组的GVHD预防包括环孢素A联合霉酚酸酯或甲氨蝶呤。加速期或爆发期MF患者被排除在外。移植后2天，PTCy剂量为50 mg/kg/天。接受ATG的患者包括两种不同的品牌：胸腺球蛋白（法国赛诺菲）3.5 mg/kg/天，移植前2天，或Grafalon（德国Neovii） 30 mg/kg/天，移植前3天，匹配的非亲属供者60 mg/kg/天。为了在结果比较中考虑组间的选择偏倚和潜在的混杂因素，我们采用加权倾向评分分析来平衡接受ATG和PTCY患者之间的基线特征。倾向评分模型使用治疗加权逆概率（IPTW）方法生成，其中每个患者由ATG或PTCY组的逆概率加权。加权Cox比例风险模型用于评估生存结局、风险比（wHRs），并对具有竞争风险的终点使用细灰色回归。共纳入539例患者，其中427例接受ATG治疗，112例接受PTCy治疗（补充表1），组间中位年龄具有可比性（58岁vs. 60岁，p = 0.21）。与ATG组相比，PTCy组的供体类型有更匹配的相关供体的趋势（38%比28%，p = 0.06）。组间调节强度差异显著：ATG组以低强度方案为主（79%），而PTCy组近一半患者接受高强度调节（47%;p < 0.001）。ATG组的中位随访时间为4.8年，PTCy组为3.7年（p = 0.12）。我们首先对ATG和PTCy进行了未调整的单变量比较（表1）。在移植方面，接受ATG的患者中性粒细胞恢复明显早于接受PTCy的患者（中位14天vs. 23天，p < 0.001；图1），PTCy后原发性移植失败更频繁（7% vs. 1%: p < 0.001）。血小板植入的累积发生率ATG组为88%，PTCy组为73% （p < 0.001）。ATG组4年复发率（14%）低于PTCy组（33%;p < 0.001）， 4年非复发死亡率组间相似（24%对26%；p = 0.53）。4年总生存率倾向于ATG （71% vs. 64%; p = 0.08）。表1。ATG与PTCY的单因素分析。结果：atgptcypneutrophil移植，中位14天，23天，0.001原发性移植失败，1%7%复发率，4年，14%(11-17),33%(24-42)，0.001无复发死亡率，4年，24%(21-27),26%(17-35)，0.53总生存率，4年，71%(66-75),64%(55-74)，0.08慢性GvHD， 4年，50%(45-55),23%(14-32)，0.001急性GvHD， 180天，30% (26-34),27% (18-36)，0.40GvHD - /无复发生存率，4年，42%(37-47),37%(27-47)，0.14倾向评分匹配复发发生率，4年20% (11-29)33% (24-42)0.15GvHD−/无复发生存率，4年31%(23-41)37%(27-47)0.37图1打开图查看器powerpoint中性粒细胞植入的累积发生率、复发、非复发死亡率和总生存率。在GVHD方面（图2），慢性GVHD在ATG组中更为常见，4年时影响50%，而PTCy组为23% （p < 0.001）。此外，慢性GVHD的严重程度在两组之间也有显著差异，ATG组的中重度慢性GVHD发生率为27%，而PTCy组为10% （p = 0.02）。第180天急性GVHD的发生率具有可比性（30% vs 27%; p = 0.40）， ATG组的严重急性GVHD III-IV级数值高于PTCy组（10%）（5%）。 ATG组4年GRFS为42%，PTCy组为37%，差异无统计学意义（p = 0.14）。图2在图视图中打开powerpoint急性和慢性GvHD累积发病率。精算GvHD和无复发生存率（GRFS）。接下来我们进行匹配分析。在这里，PTCy患者的复发率仍然高于ATG患者（33%对20%，p = 0.15），而GRFS组之间具有可比性（PTCy组37%对ATG组31%，p = 0.37）。在匹配队列的多变量模型中，与ATG相比，PTCy与慢性GVHD的风险显著降低相关（HR 0.60, p = 0.001）， PTCy有增加复发风险的趋势（HR 1.41, p = 0.2）。对于GRFS，我们没有观察到显著差异（HR 0.94; p = 0.7）。总之，这些发现表明，在倾向评分匹配的队列中，没有发现两种预防策略对GRFS的差异影响，GRFS成分的微妙结果表明，与ATG相比，PTCy对慢性GVHD的复发风险更高，但风险更低（支持信息）。GVHD仍然是骨髓纤维化同种异体移植的主要障碍：在最近的一项研究中，据报道，22%的MF患者发生急性GVHD III-IV级，肝脏受累率更高。ATG已被证明可以降低血液恶性肿瘤患者的GVHD，并增加2年后不接受免疫抑制治疗的受体比例[2,7]。移植是同种异体移植后MF患者的另一个关键问题，因为这些患者往往在开始时出现晚期移植、移植物衰竭或移植物功能差的风险更高[10,11]。因此，确定正确的GVHD预防措施对于接受匹配移植的患者至关重要，在这些患者中，移植失败率预计将很低。我们发现PTCy患者移植延迟和移植失败率较高，这与最近的研究结果一致。未来的研究应该探讨PTCy剂量的优化或ATG和PTCy的联合使用是否可以在不影响GVHD保护的情况下降低移植物衰竭风险。移植后复发仍然是一个相关的问题，特别是MF患者。移植领域的关键问题之一是PTCy对GVHD的保护是否与移植物抗白血病效应分离。虽然一些研究表明PTCy不会增加复发[14,15]，但其他研究表明，在MF的特定情况下，GVHD与复发之间存在微妙的关联[9,16]。目前的研究不足以以稳健的方式调查PTCy患者复发和GVHD的潜在关联。值得注意的是，MF与其他髓系疾病的一个特别区别是复发的类型及其评估（分子vs.血液学vs.两者都有）[17]。本组复发率较高的一个原因可能是由于密切的移植后随访和临床评估，而大多数注册研究没有可靠的复发率评估，这可能会影响复发率的解释。然而，PTCy的结果与最近的报告[6]密切相关。本研究具有固有的局限性，其回顾性、非随机设计排除了对未测量混杂因素的完全控
{"title":"PTCy or ATG for Matched Transplantation in Myelofibrosis","authors":"Patrizia Chiusolo, Andrea Bacigalupo, Rachel Salit, Thomas Schroeder, Maria Chiara Finazzi, Carmelo Gurnari, Simona Pagliuca, Judith Metzdorf, Christina Rautenberg, Marie Robin, Marie-Thérèse Rubio, Jaroslaw Maciejewski, Uday Popat, Alessandro Rambaldi, Hans Christian Reinhardt, Bart Scott, Nicolaus Kröger, Nico Gagelmann","doi":"10.1002/ajh.70244","DOIUrl":"https://doi.org/10.1002/ajh.70244","url":null,"abstract":"<p>Allogeneic hematopoietic stem cell transplantation remains the only curative therapy, yet outcomes are tempered by graft failure, relapse, infectious complications, and graft-versus-host disease (GVHD) [<span>1</span>]. Two approaches for GVHD prophylaxis dominate: anti-thymocyte or anti-T-lymphocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy). ATG provides broad in vivo T-cell depletion and reduces GVHD risk and has been shown to improve outcomes in all donor settings [<span>2</span>]. PTCy, primarily used in the haploidentical setting, acts post-transplant to selectively eliminate proliferating alloreactive T cells while preserving regulatory and memory populations, potentially mitigating GVHD while supporting immune reconstitution [<span>3</span>]. Both strategies have shown efficacy [<span>2, 4-7</span>], yet their relative impact in myelofibrosis in the matched donor setting—a disease with unique transplant dynamics—remains unclear. This study aims to evaluate outcomes of HLA-matched transplantation in MF using either ATG or PTCy.</p>\u0000<p>This was a retrospective, non-randomized comparison in patients undergoing transplantation for myelofibrosis between 2010 and 2024. Additional GVHD prophylaxis in both arms consisted of cyclosporine A together with mycophenolate mofetil or methotrexate, depending on center standards. Patients with accelerated-phase or blast-phase MF were excluded [<span>8</span>]. Dose for PTCy was 50 mg/kg/day on 2 days after transplant. Patients receiving ATG included two different brands: Thymoglobulin (Sanofi, France) 3.5 mg/kg/day on 2 days before transplantation or Grafalon (Neovii, Germany) 30 mg/kg/day for matched siblings and 60 mg/kg/day for matched unrelated donors on 3 days before transplantation.</p>\u0000<p>To account for selection bias and potential confounding factors between groups in outcome comparisons, we employed a weighted propensity score analysis to balance baseline characteristics between patients who received ATG versus PTCY. The propensity score model was generated using the inverse probability of treatment weighting (IPTW) approach, where each patient was weighted by the inverse probability of being in the ATG or PTCY group. Weighted Cox proportional hazards models were used to assess survival outcomes, hazard ratios (wHRs), and Fine-Gray regression was used for endpoints with competing risks.</p>\u0000<p>A total of 539 patients were included, with 427 receiving ATG and 112 PTCy (Supplemental Table 1), and the median age was comparable between groups (58 vs. 60 years, <i>p</i> = 0.21). Donor type showed a trend toward more matched related donors in the PTCy group compared with ATG (38% vs. 28%, <i>p</i> = 0.06). Conditioning intensity differed significantly between groups: reduced-intensity regimens were predominant in the ATG group (79%), whereas nearly half of patients in the PTCy group received higher-intensity conditioning (47%; <i>p</i> < 0.001). Median follow-up was 4.8 years for ","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"336 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146778789","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}
Francesco Pegoraro, Agnese Roveta, Laura Giunti, Maria Fay Cortella, Michele Tanturli, Giulia Simiele, Baldassarre Martire, Marta Pillon, Maria Carla Giarratana, Francesco Saettini, Simone Cesaro, Angela Guarina, Elena Mastrodicasa, Giorgio Costagliola, Maria Licciardello, Giulia Carracchia, Angelica Barone, Sonia Bonanomi, Marinella Veltroni, Carlo Dufour, Francesca Fioredda
{"title":"Impact of CSF3R Mutations on Leukemic Transformation in Severe Congenital Neutropenia: A Retrospective Analysis From the Italian Neutropenia Registry.","authors":"Francesco Pegoraro, Agnese Roveta, Laura Giunti, Maria Fay Cortella, Michele Tanturli, Giulia Simiele, Baldassarre Martire, Marta Pillon, Maria Carla Giarratana, Francesco Saettini, Simone Cesaro, Angela Guarina, Elena Mastrodicasa, Giorgio Costagliola, Maria Licciardello, Giulia Carracchia, Angelica Barone, Sonia Bonanomi, Marinella Veltroni, Carlo Dufour, Francesca Fioredda","doi":"10.1002/ajh.70256","DOIUrl":"https://doi.org/10.1002/ajh.70256","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147275817","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}
Meredith E. Fay, Raghav Tandon, Teresa Latham, Albert J. Lee, Angela E. Rankine‐Mullins, Marvin Reid, Cassie S. Mitchell, Russell E. Ware, Wilbur A. Lam
In children with sickle cell anemia (SCA), central nervous system (CNS) complications such as chronic vasculopathy, silent cerebral infarcts, and overt stroke cause significant morbidity and mortality, and remain difficult to predict. Here, we coupled pediatric magnetic resonance angiography (MRA) neuroimaging data from a completed clinical trial with artificial intelligence (AI)–based techniques to investigate associations between vascular morphology and clinical risk groups. Using an automated computer vision workflow, we generated quantitative metrics describing individual vessels, including small vessels not captured by conventional radiologic scoring. We then applied open‐source machine learning algorithms, including: clustering to identify natural groupings within the data, classification to differentiate scans by clinical risk category, and scaled event‐based modeling to order vascular features according to relative changes observed across the cohort. Across these approaches, vessel remodeling at branch points and increased vessel tortuosity consistently emerged as among the earliest observed vascular features distinguishing high‐risk groups, independent of transcranial Doppler ultrasound velocities. These retrospective findings describe associations between MRA‐derived vascular features and clinical groups, but do not establish causality or predict future events. Our results demonstrate that quantitative vascular metrics be extracted from already‐obtained imaging data, without requiring additional patient procedures, and may complement existing risk stratification methods. In addition, as current guidelines recommend neuroimaging in school‐aged children with SCA, and as MRA technologies continue to advance, our results support larger‐scale prospective studies to validate computer vision‐based biomarkers. Ultimately, these approaches may inform future studies aimed at improving SCA‐related CNS complications and support more refined clinical characterization.
{"title":"Artificial Intelligence‐Based Analysis of Central Nervous System Vasculopathy in Pediatric Sickle Cell Anemia","authors":"Meredith E. Fay, Raghav Tandon, Teresa Latham, Albert J. Lee, Angela E. Rankine‐Mullins, Marvin Reid, Cassie S. Mitchell, Russell E. Ware, Wilbur A. Lam","doi":"10.1002/ajh.70251","DOIUrl":"https://doi.org/10.1002/ajh.70251","url":null,"abstract":"In children with sickle cell anemia (SCA), central nervous system (CNS) complications such as chronic vasculopathy, silent cerebral infarcts, and overt stroke cause significant morbidity and mortality, and remain difficult to predict. Here, we coupled pediatric magnetic resonance angiography (MRA) neuroimaging data from a completed clinical trial with artificial intelligence (AI)–based techniques to investigate associations between vascular morphology and clinical risk groups. Using an automated computer vision workflow, we generated quantitative metrics describing individual vessels, including small vessels not captured by conventional radiologic scoring. We then applied open‐source machine learning algorithms, including: clustering to identify natural groupings within the data, classification to differentiate scans by clinical risk category, and scaled event‐based modeling to order vascular features according to relative changes observed across the cohort. Across these approaches, vessel remodeling at branch points and increased vessel tortuosity consistently emerged as among the earliest observed vascular features distinguishing high‐risk groups, independent of transcranial Doppler ultrasound velocities. These retrospective findings describe associations between MRA‐derived vascular features and clinical groups, but do not establish causality or predict future events. Our results demonstrate that quantitative vascular metrics be extracted from already‐obtained imaging data, without requiring additional patient procedures, and may complement existing risk stratification methods. In addition, as current guidelines recommend neuroimaging in school‐aged children with SCA, and as MRA technologies continue to advance, our results support larger‐scale prospective studies to validate computer vision‐based biomarkers. Ultimately, these approaches may inform future studies aimed at improving SCA‐related CNS complications and support more refined clinical characterization.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"2 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146778373","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}
Disease Overview AL amyloidosis is a clonal plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include HFpEF, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and “atypical smoldering multiple myeloma or MGUS.” Diagnosis Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple‐green birefringence is required. Organ biopsy is not required in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. Prognosis N‐terminal pro–brain natriuretic peptide (NT‐proBNP or BNP), serum troponin T (or I), and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four stages; 5 year survivals are 82%, 62%, 34%, and 20% respectively. Therapy All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Current first line therapy with the best outcome is daratumumab, bortezomib, cyclophosphamide, and dexamethasone. The goal of therapy is a ≥ VGPR. In patients failing to achieve this depth of response, options for consolidation include pomalidomide, stem cell transplantation, and venetoclax. T‐cell redirecting therapies, both bispecific antibodies and car T, show high level activity and may soon become standard second‐line therapy. Future Challenges Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end‐stage organ failure. An antibody to deplete deposited κ fibrils has reported benefit in patients with cardiomyopathy.
{"title":"Immunoglobulin Light Chain Amyloidosis: 2026 Update on Diagnosis, Prognosis, and Treatment","authors":"Morie A. Gertz","doi":"10.1002/ajh.70246","DOIUrl":"https://doi.org/10.1002/ajh.70246","url":null,"abstract":"Disease Overview AL amyloidosis is a clonal plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include HFpEF, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and “atypical smoldering multiple myeloma or MGUS.” Diagnosis Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple‐green birefringence is required. Organ biopsy is not required in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. Prognosis N‐terminal pro–brain natriuretic peptide (NT‐proBNP or BNP), serum troponin T (or I), and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four stages; 5 year survivals are 82%, 62%, 34%, and 20% respectively. Therapy All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Current first line therapy with the best outcome is daratumumab, bortezomib, cyclophosphamide, and dexamethasone. The goal of therapy is a ≥ VGPR. In patients failing to achieve this depth of response, options for consolidation include pomalidomide, stem cell transplantation, and venetoclax. T‐cell redirecting therapies, both bispecific antibodies and car T, show high level activity and may soon become standard second‐line therapy. Future Challenges Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end‐stage organ failure. An antibody to deplete deposited κ fibrils has reported benefit in patients with cardiomyopathy.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"8 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260716","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}
Hans C Lee, Melody R Becnel, Lei Feng, Oren Pasvolsky, Astrid Murga, Ralph J Johnson, Sheeba K Thomas, Qaiser Bashir, Muzaffar H Qazilbash, Raphael Steiner, Swaminathan P Iyer, Donna M Weber, Krina K Patel, Gregory P Kaufman, Elisabet E Manasanch, Robert Z Orlowski
{"title":"A Phase 1 Study of Daratumumab, Ixazomib, and Dexamethasone in AL Amyloidosis.","authors":"Hans C Lee, Melody R Becnel, Lei Feng, Oren Pasvolsky, Astrid Murga, Ralph J Johnson, Sheeba K Thomas, Qaiser Bashir, Muzaffar H Qazilbash, Raphael Steiner, Swaminathan P Iyer, Donna M Weber, Krina K Patel, Gregory P Kaufman, Elisabet E Manasanch, Robert Z Orlowski","doi":"10.1002/ajh.70239","DOIUrl":"https://doi.org/10.1002/ajh.70239","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146224754","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}
Naseema Gangat, Momna Warraich, Sudhesh Kumar, Mahnoor Fatima, Kristen McCullough, Kebede H. Begna, Aref Al‐Kali, Mrinal M. Patnaik, William J. Hogan, Abhishek Mangaonkar, Antoine N. Saliba, Mehrdad Hefazi Torghabeh, Hassan Alkhateeb, Mithun V. Shah, James M. Foran, Talha Badar, Jeanne M. Palmer, Cecilia Arana Yi, Animesh Pardanani, Ayalew Tefferi
{"title":" TP53 Mutations and Circulating Blasts ≥ 20% Are the Primary Determinants of Survival in Accelerated/Blast‐Phase Myeloproliferative Neoplasms Treated With Frontline Venetoclax Plus Hypomethylating Agent","authors":"Naseema Gangat, Momna Warraich, Sudhesh Kumar, Mahnoor Fatima, Kristen McCullough, Kebede H. Begna, Aref Al‐Kali, Mrinal M. Patnaik, William J. Hogan, Abhishek Mangaonkar, Antoine N. Saliba, Mehrdad Hefazi Torghabeh, Hassan Alkhateeb, Mithun V. Shah, James M. Foran, Talha Badar, Jeanne M. Palmer, Cecilia Arana Yi, Animesh Pardanani, Ayalew Tefferi","doi":"10.1002/ajh.70248","DOIUrl":"https://doi.org/10.1002/ajh.70248","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"413 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215607","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}
Ashik Zala, Ahmed Sadek, Ahmed Elsaid, Ketan C. Patel, Maximiliano Ramia De Cap, Barbara J. Bain
{"title":"Hemophagocytic Macrophages in the Peripheral Blood of a Critically Ill Patient With COVID ‐19 and RSV Infection","authors":"Ashik Zala, Ahmed Sadek, Ahmed Elsaid, Ketan C. Patel, Maximiliano Ramia De Cap, Barbara J. Bain","doi":"10.1002/ajh.70243","DOIUrl":"https://doi.org/10.1002/ajh.70243","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"18 2 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215823","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}
Barbara Mora, Valentina Bellani, Daniela Pietra, Elena Tagliaferri, Daniele Cattaneo, Oscar Borsani, Alessandra Iurlo, Elisa Fermo, Paola Bianchi, Elisa Rumi, Francesco Passamonti
{"title":"Characterization of a Newly Discovered Non‐Coding Variant in the EPO Gene Identified in Two Unrelated Italian Pedigrees With Erythrocytosis","authors":"Barbara Mora, Valentina Bellani, Daniela Pietra, Elena Tagliaferri, Daniele Cattaneo, Oscar Borsani, Alessandra Iurlo, Elisa Fermo, Paola Bianchi, Elisa Rumi, Francesco Passamonti","doi":"10.1002/ajh.70238","DOIUrl":"https://doi.org/10.1002/ajh.70238","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"107 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：