American Journal of Hematology最新文献

{"title":"Thrombosis-Driven Disease Progression in JAK2-Mutant Polycythemia Vera and Essential Thrombocythemia: Reassessing Risk-Based Management","authors":"Tiziano Barbui,&nbsp;Valerio De Stefano,&nbsp;Elena Rossi,&nbsp;Arianna Ghirardi,&nbsp;Alessandra Carobbio,&nbsp;Giuseppe Gaetano Loscocco,&nbsp;Annalisa Condorelli,&nbsp;Paola Guglielmelli","doi":"10.1002/ajh.27657","DOIUrl":"10.1002/ajh.27657","url":null,"abstract":"<div>\u0000 \u0000 <p>This paper explores emerging therapies in polycythemia vera and essential thrombocythemia, focusing on thrombosis as a driver of disease progression leading to myelofibrosis, blast phase, second cancers, and mortality. While the thrombosis rate in high-risk patients has declined, it remains persistently high in low-risk individuals, with most events being arterial. Inflammation driven by JAK2 V617F mutation plays a primary role in pathogenesis, and mounting evidence suggests arterial thrombosis itself can fuel a self-sustaining cycle of inflammation, thereby accelerating hematologic and systemic complications. Early intervention with cytoreductive and anti-inflammatory drugs may not only prevent incidental thrombosis but also disrupt this inflammatory circuit.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 S4","pages":"66-73"},"PeriodicalIF":10.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582814","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":"Depth of Response From Fixed-Duration Treatment Is Associated With Superior Survival in Waldenstrom Macroglobulinemia","authors":"Jonas Paludo,&nbsp;Jithma P. Abeykoon,&nbsp;Nirosha D. Perera,&nbsp;Shayna Sarosiek,&nbsp;Joshua Gustine,&nbsp;Andres Ramirez-Gamero,&nbsp;Marzia Varettoni,&nbsp;Alessandra Tedeschi,&nbsp;Chiara Cavalloni,&nbsp;Anna Maria Frustaci,&nbsp;Levi D. Pederson,&nbsp;Saurabh S. Zanwar,&nbsp;Prashant Kapoor,&nbsp;Thomas M. Habermann,&nbsp;Thomas E. Witzig,&nbsp;Robert A. Kyle,&nbsp;Morie A. Gertz,&nbsp;Susan M. Geyer,&nbsp;Steven P. Treon,&nbsp;Jorge J. Castillo,&nbsp;Stephen M. Ansell","doi":"10.1002/ajh.27663","DOIUrl":"10.1002/ajh.27663","url":null,"abstract":"<div>\u0000 \u0000 <p>As the treatment paradigm for Waldenström macroglobulinemia (WM) continues to evolve, the debate surrounding the prioritization of depth of response versus disease control as therapeutic goals gains significant relevance. However, the impact of depth of response from fixed-duration therapy on overall survival (OS) was unclear. This multicenter study evaluated the prognostic impact of depth of response using a landmark survival analysis. A total of 440 patients with WM treated with frontline fixed-duration regimens were included. Attaining a major response (MaR) was associated with superior outcomes, including significantly longer OS. The estimated 5-year PFS rates for patients with MaR at 6 months versus not were 50% versus 32%, respectively, <i>p</i> &lt; 0.001, and the estimated 5-year OS rates for patients with MaR at 6 months versus not were 89% versus 70%, respectively, <i>p</i> &lt; 0.001. In a multivariable analysis, MaR at 6 months was independently associated with superior PFS (HR 0.66, <i>p</i> = 0.007) and OS (HR 0.28, <i>p</i> &lt; 0.001). Similar results were seen when considering deeper responses (CR + VGPR vs. PR). Depth of response at 6 months is an important prognostic marker in WM and an independent predictor of PFS and OS. These results support its utilization as a suitable endpoint in clinical studies in WM.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 6","pages":"980-986"},"PeriodicalIF":10.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582751","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":"Leukemia Cutis in the Setting of Indolent Chronic Lymphocytic Leukemia","authors":"Kelly S. Chien, Jonathan L. Curry, Naveen Pemmaraju, Nitin Jain","doi":"10.1002/ajh.27654","DOIUrl":"https://doi.org/10.1002/ajh.27654","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":"12 144 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582740","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":"Adverse Impact of Pre-Transplant Liver Dysfunction in Allogeneic Hematopoietic Cell Transplantation","authors":"Yukiko Misaki,&nbsp;Masaharu Tamaki,&nbsp;Ryu Yanagisawa,&nbsp;Noriko Doki,&nbsp;Naoyuki Uchida,&nbsp;Masatsugu Tanaka,&nbsp;Tetsuya Nishida,&nbsp;Masashi Sawa,&nbsp;Yuta Hasegawa,&nbsp;Shuichi Ota,&nbsp;Makoto Onizuka,&nbsp;Sakata-Yanagimoto Mamiko,&nbsp;Yuta Katayama,&nbsp;Noboru Asada,&nbsp;Junya Kanda,&nbsp;Takahiro Fukuda,&nbsp;Yoshiko Atsuta,&nbsp;Yoshinobu Kanda,&nbsp;Kimikazu Yakushijin,&nbsp;Hideki Nakasone","doi":"10.1002/ajh.27652","DOIUrl":"10.1002/ajh.27652","url":null,"abstract":"<div>\u0000 \u0000 <p>Although the hematopoietic cell transplantation (HCT)-comorbidity index (HCT-CI) score is associated with an increased risk of mortality after allogeneic HCT, it remains unclear how pre-HCT liver dysfunction affects clinical outcomes. We retrospectively compared clinical HCT outcomes among four groups stratified according to the presence of HCT-CI liver and other organ scores, using a Japan transplant registry database between 2010 and 2020. Of the 14235 recipients, 1527 tested positive for an HCT-CI liver score including HBV or HCV hepatitis (<i>n</i> = 503). The 5-year overall survival (OS) was significantly lower in the HCT-CI liver(+) other(+) and HCT-CI liver(−) other(+) groups compared to the HCT-CI liver(+) other(−) and HCT-CI liver(−) other(−) groups [49.9% vs. 59% vs. 66.5% vs. 68.3%, <i>p</i> &lt; 0.001]. A multivariate analysis showed that both the HCT-CI liver(+) other(+) [HR 1.62, <i>p</i> &lt; 0.001] and HCT-CI liver(−) other(+) groups [HR 1.21, <i>p</i> &lt; 0.001] were significantly associated with inferior OS. Similarly, both the HCT-CI liver(+) other(+) [HR 1.89, <i>p</i> &lt; 0.001] and liver(−) other(+) groups [HR 1.26, <i>p</i> &lt; 0.001] were significantly associated with an increased risk of NRM. On the other hand, the HCT-CI liver(+) other(−) group was not associated with either OS or NRM. Separately analyzing the subcohorts with or without HCT-CI other scores, the presence of an HCT-CI liver score alone did not affect survival, while the co-presence of pretransplant liver dysfunction seemed to synergistically increase the adverse impact on OS and NRM among recipients with other organ comorbidities. Further studies will be needed to identify optimal strategies for recipients with pretransplant liver dysfunction.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 5","pages":"821-829"},"PeriodicalIF":10.1,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575532","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":"Donor Age Matters for Haploidentical HCT Patients Even After Adjusting for HLA Factors: A Machine Learning Approach","authors":"Rohtesh S. Mehta,&nbsp;Rodney Sparapani,&nbsp;Tao Wang,&nbsp;Stephen Spellman,&nbsp;Stephanie J. Lee,&nbsp;Effie W. Petersdorf","doi":"10.1002/ajh.27648","DOIUrl":"10.1002/ajh.27648","url":null,"abstract":"&lt;p&gt;A study by the Center for International Blood and Marrow Transplant Research (CIBMTR) assessed associations between HLA mismatching at individual loci and clinical outcomes after haploidentical donor hematopoietic cell transplantation (HCT) [&lt;span&gt;1&lt;/span&gt;]. The HLA factors associated with superior progression-free survival (PFS) were HLA-B leader match, HLA-DRB1 mismatch, HLA-DQB1 match, and non-permissive T-cell epitope HLA-DPB1 mismatch. Although donor age was noted to be a significant predictor of overall survival, it was not identified as a risk factor for PFS; however, the study was not designed to examine the joint effects of donor age and HLA factors. An online calculator based on the PFS results is available (https://haplodonorselector.b12x.org/v1.0/) to aid in donor selection. The calculator may suggest choosing a much older donor over a younger one, for example, a 65-year-old B leader matched/DRB1 mismatched donor would be recommended over a 30-year-old HLA-B leader-mismatched/DRB1-mismatched donor.&lt;/p&gt;&lt;p&gt;As donor age is a known predictor of survival after haploidentical donor HCT [&lt;span&gt;2-6&lt;/span&gt;], we hypothesized that the non-significant effect of donor age on PFS in the original study might be related to categorization, not fully capturing its impact. The complexity of haploidentical HCT, where multiple predictors (donor age and relationship) are interrelated and correlated with recipient factors (age), may make it difficult to separate the impact of donor age. Therefore, we reanalyzed the publicly available CIBMTR dataset from the Fuchs et al. study [&lt;span&gt;1&lt;/span&gt;] using gradient boosting machines (GBM), a powerful machine learning regression methodology, with donor age as a continuous variable. As GBM models can capture complex, non-linear relationships and interactions between covariates and survival, this approach is particularly attractive. Additionally, we performed Cox proportional hazard (PH) analysis, again using donor age as a continuous variable, and compared the results of both models.&lt;/p&gt;&lt;p&gt;We used the publicly available CIBMTR dataset from the original publication [&lt;span&gt;1&lt;/span&gt;]. The local Institutional Review Board (FHIRB0020181) approved the study, which was conducted in accordance with the Declaration of Helsinki. Our study population included patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia, or myelodysplastic neoplasm who underwent a haploidentical donor HCT between 2008 and 2017. All patients received posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis.&lt;/p&gt;&lt;p&gt;The primary outcome of interest was PFS. The dataset included 1434 patients. As donor age and HLA factors were key variables of interest, we excluded 1 patient with missing HLA-DRB1 data, 2 patients with missing HLA-DQB1 data, and 2 patients with missing donor age, in addition to excluding 22 patients with missing PFS data. A significant proportion of patients (54%) had missing HLA-DPB1 dat","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 5","pages":"937-940"},"PeriodicalIF":10.1,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27648","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Classification of Myelodysplastic, Myeloproliferative, and Myelodysplastic/Myeloproliferative Neoplasms: The Past, Present, and Future","authors":"Daniel A. Arber,&nbsp;Attilio Orazi","doi":"10.1002/ajh.27656","DOIUrl":"10.1002/ajh.27656","url":null,"abstract":"<p>With the recent publication of new classification systems of hematopoietic neoplasms, understanding how recognition of disease entities has occurred over time and the subsequent development of formal disease classifications is of importance. This review focuses on the early recognition of myeloid disorders, especially chronic myeloid disorders, and how clinical observations became associated with specific cytologic, histologic, immunophenotypic, and eventually genetic features. This combined approach to disease classification is of particular importance in the evaluation of chronic myeloid neoplasms and has resulted in the definition of clinicopathologic disease entities that allow for more customized treatment approaches. The constant incorporation of ever-increasing information related to these disorders illustrates that disease classification is a constantly evolving process that requires constant updates as we strive to better understand the disorders we diagnose and treat.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 S4","pages":"5-15"},"PeriodicalIF":10.1,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27656","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Pathogenetic Mechanisms and New Drugs for Anemia in Myelofibrosis and Myelodysplastic Syndromes","authors":"Naseema Gangat,&nbsp;Ayalew Tefferi","doi":"10.1002/ajh.27659","DOIUrl":"10.1002/ajh.27659","url":null,"abstract":"<div>\u0000 \u0000 <p>Anemia in myeloid neoplasms is multifaceted, with heterogeneous pathogenetic mechanisms that include ineffective erythropoiesis, hepcidin-induced iron-restricted erythropoiesis, and abnormal inflammatory cytokine production. Current management of anemia is challenged by limited approved drugs that specifically treat anemia in myelofibrosis (MF) and myelodysplastic syndrome (MDS). Newer therapies target the transforming growth factor beta (TGF-β)-bone morphogenic protein/sons of mothers against decapentaplegic (BMP-SMAD) signaling pathway, which plays a significant role in ineffective erythropoiesis (SMAD 2/3) and abnormal hepcidin production (SMAD 1/5/8). These include TGF-β ligand traps (luspatercept, elritercept), activin A receptor type 1 (ACVR1)/activin receptor-like kinase 2 (ALK2) inhibitors (momelotinib, zilurgisertib), and anti-hemojuvelin antibody-based therapies (DISC-0974). Luspatercept and momelotinib are approved for anemia related to lower-risk MDS and MF, respectively, and represent an important addition to the treatment armamentarium, along with imetelstat, a telomerase inhibitor, recently ratified for anemia in lower-risk MDS. A promising strategy to overcome the limitations of existing anemia-directed therapies includes the use of drug combinations with complementary mechanisms (luspatercept + erythropoiesis stimulating agents, luspatercept + momelotinib, DISC-0974 + momelotinib), and harnessing the erythropoietic potential of sodium-glucose co-transporter-2 inhibitors (SGLT-2I). Future research should address the complex pathophysiology of anemia, standardize definitions for anemia with gender-specified cutoffs, implement uniform erythroid response criteria, and consider early therapeutic intervention in clinical trials for anemia-directed therapies.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 S4","pages":"51-65"},"PeriodicalIF":10.1,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27659","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the Phenotype of DNA Ligase 1 Deficiency: First Report of Macrocytic Sideroblastic Anemia","authors":"Debbie Jiang,&nbsp;Emily Vistica Sampino,&nbsp;Kira Rosenlind,&nbsp;Dean R. Campagna,&nbsp;Stephanie DiTroia,&nbsp;Mark D. Fleming,&nbsp;Siobán B. Keel","doi":"10.1002/ajh.27649","DOIUrl":"10.1002/ajh.27649","url":null,"abstract":"&lt;p&gt;DNA Ligase 1 (LIG1) is 1 of 3 ATP-dependent DNA ligases expressed in vertebrates that play a key role in DNA replication by joining Okazaki fragments [&lt;span&gt;1&lt;/span&gt;]. LIG1 also mediates single-strand DNA repair by catalyzing the final step of the base excision repair pathway and has a redundant function alongside LIG3 in mediating alternative end-joining of double-strand DNA breaks. LIG1 deficiency is a rare inborn error of immunity reported in 8 cases to date that is typically characterized by recurrent infections, early-onset hypogammaglobulinemia, and erythrocyte macrocytosis [&lt;span&gt;2-4&lt;/span&gt;]. Seven of the 8 prior cases feature variants affecting coding regions that result in impaired LIG1 catalytic activity [&lt;span&gt;2&lt;/span&gt;]. The remaining patient presented with severe combined immunodeficiency and Omenn-like erythematous-exfoliative skin lesions and was found to have a novel splice variant (c.776+5G&gt;T) leading to a shift in reading frame and a premature stop codon [&lt;span&gt;4&lt;/span&gt;]. Here, we report on 2 cases of LIG1 deficiency that presented with macrocytic sideroblastic anemia, a phenotype not previously recognized in this disease. Additionally, Patient 1 is the first reported case of LIG1 deficiency diagnosed in adulthood.&lt;/p&gt;&lt;p&gt;Patient 1 is a 37-year-old female of Northern European ancestry who was referred to adult hematologic care with a long-standing history of a mild underproduction macrocytic anemia (hemoglobin [Hb] 11.6 g/L; mean corpuscular volume [MCV] 125 fL) with normal vitamin B12 and folate levels. She had a history of recurrent sinopulmonary infections as a child, including several hospitalizations for community-acquired pneumonias, seizure disorder, moderate-persistent asthma, mild obstructive sleep apnea, and attention-deficit/hyperactivity disorder. Her mother died at age 64 from complications related to transverse myelitis; a full brother and 2 maternal half-sisters are healthy (Figure 1A). Bone marrow aspirate and biopsy showed a normocellular marrow for age with a relative erythroid hyperplasia (myeloid to erythroid ratio of 0.6:1) associated with dyserythropoiesis in a subset of erythroids, including nuclear irregularities, binucleation, and budding, as well as megaloblastic maturation. Iron stain revealed &gt; 15% ring sideroblasts (Figure 1C). Flow cytometry on the marrow identified no abnormal myeloid, B, or T cell populations, and routine karyotype was 46, XX. Clinical &lt;i&gt;ALAS2&lt;/i&gt; sequencing was negative. She had hypogammaglobulinemia (Table S1). Immunophenotyping showed mildly reduced CD19+ B cells, normal numbers of CD27+ memory B cells, and reduced immunoglobulin (Ig) class-switching with low IgM/IgD memory cells and virtual absence of IgA+ and IgG+ class-switched memory B cells. Vaccination titers were protective for only 3 of 23 pneumococcal serotypes. T and NK cell numbers were normal, and response to mitogen stimulation with phytohemagglutinin and CD3 was normal. The patient was started on replaceme","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 5","pages":"941-943"},"PeriodicalIF":10.1,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27649","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TP53 Mutations Detected by NGS Are a Major Clinical Risk Factor for Stratifying Mantle Cell Lymphoma","authors":"Grégory Lazarian,&nbsp;Lotfi Chemali,&nbsp;Merieme Bensalah,&nbsp;Carla Zindel,&nbsp;Valérie Lefebvre,&nbsp;Catherine Thieblemont,&nbsp;Antoine Martin,&nbsp;Giulia Tueur,&nbsp;Rémi Letestu,&nbsp;Carole Fleury,&nbsp;Vincent Leymarie,&nbsp;Valérie Vidal,&nbsp;Audrey Bidet,&nbsp;Elsa Maitre,&nbsp;Florence Cymbalista,&nbsp;Vincent Levy,&nbsp;Thierry Soussi,&nbsp;Fanny Baran-Marszak","doi":"10.1002/ajh.27650","DOIUrl":"10.1002/ajh.27650","url":null,"abstract":"<p>\u0000 \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":"100 5","pages":"933-936"},"PeriodicalIF":10.1,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27650","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Outcomes and Treatment Strategies of Adult Transplant-Associated Thrombotic Microangiopathy: External Validation of Harmonizing Definitions and High-Risk Criteria","authors":"Aldo A. Acosta-Medina,&nbsp;Meera Sridharan,&nbsp;Ronald S. Go,&nbsp;Ann M. Moyer,&nbsp;Nelson Leung,&nbsp;Maria Alice V. Willrich,&nbsp;Robert Wolf,&nbsp;Rabee Kassis,&nbsp;Almothana Manasrah,&nbsp;Mira A. Kohorst,&nbsp;Urshila Durani,&nbsp;Aasiya Matin,&nbsp;Mehrdad Hefazi,&nbsp;Saad J. Kenderian,&nbsp;Abhishek A. Mangaonkar,&nbsp;Mithun V. Shah,&nbsp;Mark R. Litzow,&nbsp;William J. Hogan,&nbsp;David Dingli,&nbsp;Hassan B. Alkhateeb","doi":"10.1002/ajh.27651","DOIUrl":"10.1002/ajh.27651","url":null,"abstract":"<p>Transplant-associated thrombotic microangiopathy (TA-TMA) is an endothelial dysfunction syndrome observed after allogeneic hematopoietic cell transplant (alloHCT). Our aim was to externally validate the impact of high-risk features on the clinical outcomes of adult patients meeting the updated TA-TMA harmonizing criteria. Between 2005 and 2022, 99 patients were diagnosed with TA-TMA at Mayo Clinic Rochester (incidence 6.2%) after a median of 137 days post alloHCT (IQR: 34–283 days). The development of TA-TMA was associated with an inferior overall survival posttransplant (HR: 3.8, 95% CI: 2.97–4.72). High-risk features, including concomitant infection, acute graft-versus-host disease (GVHD), and organ dysfunction, were associated with poor survival, while LDH elevation was not associated with inferior outcomes. The most common treatment strategy for TA-TMA was discontinuation of calcineurin or mTOR inhibitors in 80 (81%) patients. Thirty (37.5%) patients experienced worsening of GVHD with this strategy, of which 26 (86.7%) patients had died at last follow-up. The most common cause of death among these patients was worsening GVHD (69%; <i>n</i> = 18), followed by infection (11%; <i>n</i> = 3), disease relapse (8%; <i>n</i> = 2), other/unknown causes (8%; <i>n</i> = 2), or TA-TMA (4%; <i>n</i> = 1). Objective response rate (ORR) to initial treatment for the cohort was 56.6%. Eculizumab was used in 11 patients with an observed ORR of 70%, including 5 complete responses. In conclusion, TA-TMA remains a significant contributor to non-relapse mortality and is associated with worse survival following alloHCT. Not all high-risk features, particularly LDH elevation, have consistently demonstrated a negative impact in adult cohorts. Patients with TA-TMA may benefit from immune suppression dose adjustment, rather than a discontinuation, and the addition of complement-directed therapy, particularly among high-risk patients.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"100 5","pages":"830-839"},"PeriodicalIF":10.1,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.27651","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560784","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}