American Journal of Hematology最新文献

{"title":"Peripheral Blood Lymphocytosis Reflecting an Underlying Thymoma","authors":"Léa Ousset,&nbsp;Alban Canali,&nbsp;Barbara J. Bain","doi":"10.1002/ajh.70437","DOIUrl":"10.1002/ajh.70437","url":null,"abstract":"<p>A 36-year-old man with well-controlled asymptomatic myasthenia gravis presented for a biopsy of a 9 cm unresectable anterior mediastinal mass infiltrating the aortopulmonary window (top left, computed tomography). A blood count showed lymphocytosis (lymphocyte count 5.7 × 10⁹/L) and microcytosis without anemia (mean cell volume 74.5 fl), hemoglobin concentration 148 g/L (the patient was known to have α thalassemia trait). The blood film showed target cells and a monomorphic lymphocyte population composed of medium-sized cells with a high nucleocytoplasmic ratio, a somewhat irregular nucleus with delicate chromatin, and weakly basophilic cytoplasm which was sometimes vacuolated; some smudge cells were present and nucleoli were apparent in these (right, composite panel, May-Grünwald-Giemsa, ×100 objective). The findings were suggestive of a low-grade chronic lymphoproliferative neoplasm. Histopathological examination and immunohistochemistry of the biopsy specimen revealed a nodular lymphoid proliferation composed of numerous immature T cells (terminal deoxynucleotidyl transferase +/CD3+), with well-defined medullary areas with clusters of B cells (CD20+/PAX5+), and a network of p40+ epithelial cells within and around the nodules, present either as isolated cells or in clusters of more than three, confirming the diagnosis of thymoma. Flow cytometry immunophenotyping from peripheral blood (bottom left) showed a CD3+ CD8+ lymphocyte subpopulation representing 64% of all lymphoid cells, without activation markers (CD16-/CD56-/CD57-/HLA-DR-) and associated with polytypic expression of T-cell receptor TRBC1 (77%), consistent with a CD8+ peripheral blood T-lymphocytosis. Subsequently, positron emission tomography revealed two pleural masses indicating metastasis of the thymoma.</p><p>Peripheral blood T-cell lymphocytosis is a rare and poorly understood autoimmune/paraneoplastic manifestation of thymoma, with fewer than 25 cases reported to date [<span>1</span>], and may represent the initial clue to this underlying entity. An abnormal peripheral blood film should not limit the differential diagnosis to hematologic malignancies alone and must be interpreted in the context of the clinical presentation. In this setting, assessment of morphological features combined with flow cytometric immunophenotyping is useful for avoiding misdiagnosis of lymphoproliferative neoplasms and establishing this rare but important diagnosis.</p><p>The authors declare no conflicts of interest.</p><p>The data that support the findings of this study are available from the corresponding author upon reasonable request.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 10","pages":"2652-2653"},"PeriodicalIF":9.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70437","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148379904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-Life Study on Gilteritinib-Related Infections (GilteRInf): An Italian SEIFEM Study","authors":"Elisa Buzzatti,&nbsp;Irene Terrenato,&nbsp;Martina Tomassi,&nbsp;Federica Lessi,&nbsp;Sara Pezone,&nbsp;Cristina Papayannidis,&nbsp;Gianluca Martini,&nbsp;Fabio Forghieri,&nbsp;Luana Fianchi,&nbsp;Martina Quattrone,&nbsp;Nicola Fracchiolla,&nbsp;Claudio Fozza,&nbsp;Michela Abbenante,&nbsp;Anna Lina Piccioni,&nbsp;Davide Facchinelli,&nbsp;Claudia Maria Basilico,&nbsp;Caterina Buquicchio,&nbsp;Nicola Di Renzo,&nbsp;Monica Piedimonte,&nbsp;Maria Giovanna Cefalo,&nbsp;Daniele Armiento,&nbsp;Adriano Venditti,&nbsp;Alessandro Busca,&nbsp;Francesco Marchesi,&nbsp;Maria Ilaria Del Principe,&nbsp;Livio Pagano","doi":"10.1002/ajh.70446","DOIUrl":"10.1002/ajh.70446","url":null,"abstract":"&lt;p&gt;Patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) represent an exceedingly fragile population. This vulnerability stems from a combination of factors: prolonged cytopenia secondary to previous intensive chemotherapy and the inherent immunosuppressive nature of the underlying malignancy [&lt;span&gt;1&lt;/span&gt;]. In this context, infectious episodes (IEs) remain a primary cause of morbidity, often delaying the delivery of subsequent treatments. The therapeutic landscape for R/R FLT3+ AML has been significantly transformed by the introduction of gilteritinib, an oral FLT3 inhibitor, which has demonstrated superior efficacy compared to salvage intensive chemotherapy in patients harboring such mutation [&lt;span&gt;2&lt;/span&gt;]. However, most available data regarding IEs during gilteritinib therapy originate from clinical trials, which predominantly report data through the lens of broad categories such as febrile neutropenia or pneumonia. Consequently, there is a scarcity of real-world evidence detailing the specific localization, etiology, timing, and outcomes of IEs in unselected patient populations. Based on these considerations, we conducted a multicenter, cross-sectional, real-world observational study to provide a comprehensive assessment of IEs in 123 consecutive adults with R/R FLT3-mutated AML treated with gilteritinib monotherapy across 18 GIMEMA-SEIFEM centers (April 2020–January 2025). IEs, including fever of unknown origin (FUO) and microbiologically documented infections, were graded per CTCAE v5.0. [&lt;span&gt;3&lt;/span&gt;]. Invasive fungal diseases (IFDs) were categorized according to EORTC criteria [&lt;span&gt;4&lt;/span&gt;]. Baseline variables were collected via standardized electronic CRFs. Statistical analyses utilized Shapiro–Wilk for normality, Mann–Whitney U or &lt;i&gt;t&lt;/i&gt;-tests for continuous variables, and Chi-squared or Fisher's exact tests for categorical data. Survival outcomes were estimated using the Kaplan–Meier method with log-rank tests. Univariate and multivariate logistic regression models identified predictors for IE onset. Analysis was performed using SPSS v30.0. The study was approved by the central Ethics Committee (n°R.S.82.22) and registered on ClinicalTrials.gov (NCT05791890).&lt;/p&gt;&lt;p&gt;The demographic and disease characteristics of the group are described in Table S1. We recorded 82 FUO episodes and 113 microbiologically documented IEs, of which &lt;i&gt;n&lt;/i&gt; = 68 (60%) Grade (G) ≥ 3. Overall, 49% (&lt;i&gt;n&lt;/i&gt; = 60) of patients had ≥ 1 FUO, 60% (&lt;i&gt;n&lt;/i&gt; = 74) ≥ 1 IE, 42% (&lt;i&gt;n&lt;/i&gt; = 52) at least one G ≥ 3 IE. In Table 1, the detailed characteristics and outcomes of the IEs are depicted.&lt;/p&gt;&lt;p&gt;While no primary antibacterial prophylaxis was administered, 35 cases (28%) received antifungal prophylaxis with posaconazole. At the onset of the IEs, the median absolute neutrophil count was 300/mcl (range 0–23 760/mcL). Stratifying the cohort for allogeneic-hematopoietic stem cell transplantation (allo-HSCT) status (yes/no 36/87), the number ","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 10","pages":"2672-2676"},"PeriodicalIF":9.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70446","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148582250","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":"Recombinant Human Thrombopoietin Reduces the Need for Platelet Transfusion in Patients With Chronic Liver Disease and Thrombocytopenia","authors":"Yifan Han,&nbsp;Ning Lin,&nbsp;Jinghang Xu,&nbsp;Sikui Wang,&nbsp;Jinglan Jin,&nbsp;Jia Shang,&nbsp;Yongning Xin,&nbsp;Youwen Tan,&nbsp;Dazhi Zhang,&nbsp;Jinlin Hou,&nbsp;Ping An,&nbsp;Wen Xie,&nbsp;Yujuan Guan,&nbsp;Qingfang Xiong,&nbsp;Hong Wu,&nbsp;Huiguo Ding,&nbsp;Yu Chen,&nbsp;Rongkuan Li,&nbsp;Zhili Wen,&nbsp;Mingqin Lu,&nbsp;Jinhui Yang,&nbsp;Zhongyin Zhou,&nbsp;Yongjian Zhou,&nbsp;Zujiang Yu,&nbsp;Kecan Lin,&nbsp;Wei Wang,&nbsp;Yan Huang,&nbsp;Yuemin Nan,&nbsp;Xinhua Luo,&nbsp;Rongshu Shi,&nbsp;Yi Kang,&nbsp;Tao Han,&nbsp;Shiyan Chen,&nbsp;Kai Wang,&nbsp;Yunfeng Shan,&nbsp;Jiaping Li,&nbsp;Pingguo Liu,&nbsp;Zheng Lu,&nbsp;Jun Chen,&nbsp;Zhen Liu,&nbsp;Liaoyun Zhang,&nbsp;Li Yang,&nbsp;Jifang Sheng,&nbsp;Zhan Zeng,&nbsp;Yanyan Yu,&nbsp;Xiaoyuan Xu","doi":"10.1002/ajh.70444","DOIUrl":"10.1002/ajh.70444","url":null,"abstract":"<p>Chronic liver disease (CLD)-related thrombocytopenia can limit the feasibility of invasive procedures. Recombinant human thrombopoietin (rhTPO) has demonstrated a favorable safety profile without hepatotoxicity. We evaluated the efficacy and safety of rhTPO in patients with CLD-related thrombocytopenia who were undergoing elective invasive procedures. In this multicenter, randomized (2:1), double-blind, placebo-controlled phase III trial, 120 adult Chinese patients with CLD-related thrombocytopenia (platelet count &lt; 50 × 10⁹/L) received rhTPO (<i>n</i> = 80) or placebo (<i>n</i> = 40) once daily for up to 5 or 7 days. The primary endpoint was the proportion of patients with sustained platelet counts ≥ 50 × 10⁹/L from 24 h before invasive procedure to 7 days post-procedure, without requiring emergency bleeding management. The primary endpoint was achieved by 85.0% of patients in the rhTPO group versus 12.5% in the placebo group (<i>p</i> &lt; 0.0001). Preoperatively, platelet counts ≥ 50 × 10⁹/L were achieved in 92.5% and 20.0% of patients in the rhTPO and placebo groups, respectively (<i>p</i> &lt; 0.0001). Platelet transfusion was avoided in 92.5% of rhTPO-treated patients versus 25.0% of placebo-treated patients (<i>p</i> &lt; 0.0001). The median duration of platelet counts ≥ 50 × 10⁹/L was significantly longer with rhTPO than with placebo (21.0 vs. 3.0 days, <i>p</i> = 0.0007). Treatment-related treatment-emergent adverse events (TEAEs) occurred in 12.5% of patients in both the rhTPO and placebo groups. No treatment-related serious adverse events were reported. Overall, rhTPO was effective and well tolerated in patients with CLD-related thrombocytopenia and may represent a viable therapeutic option for those undergoing elective invasive procedures.</p><p>\u0000 <b>Trial Registration:</b> www.chinadrugtrials.org.cn: number CTR20230919.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 10","pages":"2571-2580"},"PeriodicalIF":9.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70444","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148597651","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":"Systemic Bevacizumab for Severe Bleeding From Acquired Gastrointestinal Vascular Malformations","authors":"Nardeen E. Ayad,&nbsp;Jacob R. Anderson,&nbsp;Bimalangshu Dey,&nbsp;Rebecca Karp Leaf,&nbsp;Andrew B. Song,&nbsp;Hanny Al-Samkari","doi":"10.1002/ajh.70464","DOIUrl":"10.1002/ajh.70464","url":null,"abstract":"<p>Acquired gastrointestinal vascular malformations not due to congenital disorders such as hereditary hemorrhagic telangiectasia are a common cause of chronic and acute hemorrhage, particularly in older adults. These lesions cause severe anemia, dependence on intravenous iron and/or red-cell transfusion, and recurring hospitalizations. Hemostatic procedures are temporizing and no standard treatment, including the somatostatin analogs, addresses the underlying angiogenic dysregulation driving vascular malformation formation and recurrence. Therefore, bevacizumab, an anti-VEGF-A monoclonal antibody, is a promising targeted therapeutic. In this observational cohort study, we analyzed 32 patients (median age 75 years, 44% female) with acquired gastrointestinal vascular malformations due to idiopathic angiodysplasia, chronic liver disease, or deficiencies of von Willebrand factor who were treated on a predefined institutional bevacizumab pathway. The median Hematologic Support Score (a composite endpoint integrating red-cell units transfused and elemental iron infused) improved from 15.04 (95% CI, 11.16–21.80) red-cell unit equivalents during 6 months pretreatment to 4.08 (4.00–8.00) during Months 1–6 of bevacizumab treatment (<i>p</i> &lt; 0.001) and further to 0.00 (0.00–5.40) during months 7–12 (<i>p</i> &lt; 0.001). Units of red cells transfused and quantity of elemental iron infused were analyzed independently; both significantly improved after bevacizumab initiation. Annualized hospitalization/ED visit rate improved from 3 (year before bevacizumab) to 1 (year after bevacizumab) (<i>p</i> = 0.01), and median hemoglobin improved by 3.1 g/dL after bevacizumab (<i>p</i> &lt; 0.001). Proteinuria and hypertension occurred in 8 (25%) and 5 (16%) patients, respectively, leading to bevacizumab discontinuation in 3 (9%). In conclusion, bevacizumab is a novel, targeted therapeutic approach for acquired gastrointestinal vascular malformations that may be safe and effective.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 10","pages":"2605-2615"},"PeriodicalIF":9.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70464","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148675055","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 Implications of CD19-Negative Relapse Following CD19-Directed Therapy in B-Cell Acute Lymphoblastic Leukemia","authors":"Tamer Othman,&nbsp;Vaibhav Agrawal,&nbsp;Joo Y. Song,&nbsp;Zhaohui Gu,&nbsp;Paul Koller,&nbsp;Hoda Pourhassan,&nbsp;Yazeed Samara,&nbsp;Julio Alvarenga Thiebaud,&nbsp;Jose Tinajero,&nbsp;Dat Ngo,&nbsp;Rick Lin,&nbsp;Karamjeet Sandhu,&nbsp;Monzr AlMalki,&nbsp;Ahmed Aribi,&nbsp;Salman Otoukesh,&nbsp;Brian Ball,&nbsp;Andrew Artz,&nbsp;Amandeep Salhotra,&nbsp;Samer Khaled,&nbsp;Amanda Blackmon,&nbsp;Idoroenyi Amanam,&nbsp;Haris Ali,&nbsp;Sunmin Park,&nbsp;Pamela Becker,&nbsp;Ryotaro Nakamura,&nbsp;Guido Marcucci,&nbsp;Anthony Stein,&nbsp;Stephen Forman,&nbsp;Vinod Pullarkat,&nbsp;Ibrahim Aldoss","doi":"10.1002/ajh.70450","DOIUrl":"10.1002/ajh.70450","url":null,"abstract":"<div>\u0000 \u0000 <p>CD19-directed therapy remains the mainstay treatment for relapsed/refractory B-cell acute lymphoblastic leukemia (ALL). However, treatment patterns and outcomes following CD19-negative (CD19-) relapse remain poorly defined. We retrospectively analyzed 65 adult patients with ALL who developed CD19-relapse after CD19-directed therapy. TP53 mutations and <i>BCR::ABL1</i>-like ALL were each identified in 27.7% (<i>n</i> = 18) of patients. Forty-six patients (70.8%) received one CD19-targeted therapy, whereas 19 patients (29.2%) received ≥ 2 prior to CD19-relapse. Overall, 60 patients (92.3%) received blinatumomab, and 23 (35.4%) received CAR T-cell therapy. The median time from the initiation of the most recent CD19-targeted therapy to CD19-relapse was 155 days (range, 13–1946). The median follow-up of the entire cohort was 32.7 months (IQR, 15.1–90.3). The median event-free and overall survival (EFS and OS) was 3.1 months (95% CI, 2.5–4.5) and 9.9 months (95% CI, 6.8–24.7), respectively. In multivariate analysis, receipt of ≥ 2 CD19-directed therapies was associated with both inferior EFS and OS, HR 2.17 (95% CI, 1.10–4.29; <i>p</i> = 0.03) and HR 3.05 (95% CI, 1.40–6.62; <i>p</i> = 0.005). The complete remission rate following first salvage therapy was 47.5% and 72.1% any time following CD19-relapse. Sixteen (34.8%) of 46 patients evaluated had subsequent CD19 re-expression, 5 of whom subsequently received CD19-directed therapy, and all 5 patients responded. Patients with ALL who develop CD19-relapse after CD19-directed therapy have poor outcomes and limited therapeutic options. However, since this study lacked a comparator cohort of patients with CD19-positive relapse, the independent prognostic impact of CD19 negativity could not be determined.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 10","pages":"2533-2545"},"PeriodicalIF":9.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148564680","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":"HLA-Haploidentical Anti-CD7 Chimeric Antigen Receptor (CAR) T Cells for Transplant-Naïve Patients With Refractory T-Cell Acute Lymphoblastic Leukemia","authors":"Marco Becilli,&nbsp;Francesca del Bufalo,&nbsp;Pietro Merli,&nbsp;Chiara Rosignoli,&nbsp;Mattia Algeri,&nbsp;Monica Gunetti,&nbsp;Daria Pagliara,&nbsp;Francesco Quagliarella,&nbsp;Emilia Boccieri,&nbsp;Biancamaria Mandelli,&nbsp;Valentina Bertaina,&nbsp;Maria Giuseppina Cefalo,&nbsp;Chiara Agrati,&nbsp;Matilde Sinibaldi,&nbsp;Laura Iaffaldano,&nbsp;Biagio De Angelis,&nbsp;Concetta Quintarelli,&nbsp;Franco Locatelli","doi":"10.1002/ajh.70448","DOIUrl":"10.1002/ajh.70448","url":null,"abstract":"&lt;p&gt;Patients with relapsed/refractory (r/r) T-cell acute lymphoblastic leukemia (T-ALL) still face a dismal prognosis, with survival rates below 30% [&lt;span&gt;1-3&lt;/span&gt;]. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative option provided that a deep complete remission (CR) is achieved [&lt;span&gt;1&lt;/span&gt;]. Progress in T-ALL immunotherapies has been limited by the challenge of identifying targets selectively expressed on leukemic blasts (LB). CD7 represents an attractive target for immunotherapy, being extensively expressed in T-ALL, although it is also present on healthy T and natural killer (NK) cells. Autologous, fratricide-resistant anti-CD7 chimeric antigen receptor (CAR) T cells (auto-PCART7) incorporating an anti-CD7 protein expression blocker (PEBL) have recently proven favorable preliminary outcomes in patients with r/r T-ALL [&lt;span&gt;4&lt;/span&gt;]. The generation of auto-PCART7 from individuals with a high burden of circulating, chemoresistant LB has been hampered by the risk of inadvertent LB transduction during ex vivo manufacturing, and by the difficulty of collecting enough healthy T cells. In this context, allogeneic CAR T cells (allo-CART) might tackle these obstacles. In the absence of suitable matched related or unrelated donors, transplant-naïve patients who receive CAR T cells produced from haploidentical (Haplo) donors might face a theoretical risk of graft-versus-host disease (GvHD), and limited expansion/persistence due to rejection, resulting in insufficient responses.&lt;/p&gt;&lt;p&gt;Between November 2024 and July 2025, at Ospedale Pediatrico Bambino Gesù (OPBG), Rome, we treated two children with highly chemoresistant T-ALL ineligible for our clinical trial investigating auto-PCART7 for r/r T-ALL (NCT06064903), due to a high burden of circulating LB (≥ 5%) and low peripheral T-cell counts (&lt; 300/μL). The authorization for treatment in a Hospital Exemption program (previously described [&lt;span&gt;5&lt;/span&gt;]) was released by the Institutional Ethical Committee and the Italian competent authority (Agenzia Italiana del Farmaco).&lt;/p&gt;&lt;p&gt;Patients' characteristics are reported in Table 1 and prior treatments are summarized in Table S1. Patient 1 (Pt1) had T-ALL with central nervous system involvement (CNS3) and hyperleukocytosis at diagnosis, failed induction therapy according to the ALLTogether protocol and was subsequently treated with Nelarabine achieving CR with measurable residual disease (MRD) positivity (10&lt;sup&gt;−3&lt;/sup&gt;). He was deemed ineligible for allo-HSCT due to disseminated &lt;i&gt;Fusarium&lt;/i&gt; infection (positive cultures from cerebrospinal fluid and bronchoalveolar lavage specimens). Despite following treatment with Nelarabine, 5-Azacytidine, and Venetoclax, the child experienced overt medullary relapse. Salvage therapy with Daratumumab (Delphinus protocol [&lt;span&gt;6&lt;/span&gt;]) failed to re-induce CR. During treatment, he developed severe lower limb peripheral neuropathy resulting in wheelchair dependency. Pati","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 10","pages":"2677-2682"},"PeriodicalIF":9.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70448","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590083","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":"Luspatercept Induces Significant Improvement in Anemia in Dominant Thalassemia Secondary to Heterozygous STEAP3 and Beta-Thalassemia Trait","authors":"Akhila Arcot Vadivelan,&nbsp;Thomas Coates","doi":"10.1002/ajh.70439","DOIUrl":"10.1002/ajh.70439","url":null,"abstract":"&lt;p&gt;We report on a patient who was diagnosed with dominant thalassemia and had chronic, severe, microcytic, hypochromic anemia from the combination of beta thalassemia trait and a &lt;i&gt;STEAP3&lt;/i&gt; mutation and had a significant response to luspatercept.&lt;/p&gt;&lt;p&gt;Dominant thalassemia refers to patients who are heterozygous for beta thalassemia trait and may have other characteristics suggestive of thalassemia intermedia such as hemoglobin less than 10 g%, splenomegaly, and iron overload. Beta thalassemia trait by itself can cause a hemoglobin as low as 10 g% but does not cause ineffective erythropoiesis or hyper absorption of iron [&lt;span&gt;1&lt;/span&gt;]. Previously, dominant thalassemia was considered to be a very severe beta thalassemia trait; however, with the availability of more thorough genetic testing, we now understand that dominant thalassemia is a combination of beta thalassemia trait and an additional mutation related to anemia. Likely, the most recognized combination is the alpha triplication and beta thalassemia trait leading to ineffective erythropoiesis [&lt;span&gt;2&lt;/span&gt;]. There are now several genetic abnormalities which, in combination with beta thalassemia trait, can lead to anemia and ineffective erythropoiesis [&lt;span&gt;3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;\u0000 &lt;i&gt;STEAP3&lt;/i&gt; is a ferrireductase that reduces ferric iron (Fe&lt;sup&gt;3+&lt;/sup&gt;) to ferrous iron (Fe&lt;sup&gt;2+&lt;/sup&gt;) in the endosomes, which is important for mobilizing iron to the erythroid precursors [&lt;span&gt;4&lt;/span&gt;] &lt;i&gt;STEAP3&lt;/i&gt; mutations have been seen in population studies in humans with no phenotypic red cell changes [&lt;span&gt;5&lt;/span&gt;]; however, there is one reported family of Pakistan origin with chronic microcytic hypochromic anemia [&lt;span&gt;6&lt;/span&gt;]. Mouse models also show severe anemia [&lt;span&gt;7&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;We encountered a 27-year-old Caucasian female who had been diagnosed as dominant thalassemia at age 5, had a hemoglobin 6.9 g% and otherwise normal electrophoresis, was placed on the luspatercept study, and had a dramatic response with improved anemia. Subsequent genetic evaluation showed that she has a &lt;i&gt;STEAP3&lt;/i&gt; mutation. We report here her clinical evaluation and outcomes.&lt;/p&gt;&lt;p&gt;A 27-year-old female of northern European descent diagnosed with dominant thalassemia presented to us with a lifetime history of anemia, with hemoglobin ~6.9 g%. The patient experienced fatigue, dizziness, and lightheadedness most of her life. Family history is significant for the patient's father who had also been diagnosed with dominant thalassemia, with hemoglobin in the 9–10 g/dL range, splenomegaly (20 cm) and had cholecystectomy done. Besides the father, there are two sisters, one of whom required blood transfusions and splenectomy. At presentation, the patient had Hemoglobin 5.9 g/dL, RBC 2.65 × 10&lt;sup&gt;6&lt;/sup&gt;/microliter, MCV 79.2 fL, MCH 22.3 pg, MCHC 28.1%, serum iron 356 mcg/dL, transferrin saturation 70%, total iron binding capacity 509 mcg/dL and ferritin 220 ng/mL. Peripheral blood smear showed anisop","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 10","pages":"2659-2661"},"PeriodicalIF":9.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70439","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148393519","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":"POEMS Syndrome: 2026 Update on Diagnosis, Risk-Stratification, and Management","authors":"Angela Dispenzieri","doi":"10.1002/ajh.70438","DOIUrl":"10.1002/ajh.70438","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Disease Overview</h3>\u0000 \u0000 <p>POEMS syndrome is a life-threatening syndrome due to an underlying plasma cell neoplasm. The major criteria for the syndrome are polyneuropathy, clonal plasma cell disorder (PCD), sclerotic bone lesions, elevated vascular endothelial growth factor, and the presence of Castleman disease. Minor features include organomegaly, endocrinopathy, characteristic skin changes, papilledema, extravascular volume overload, and thrombocytosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Diagnosis</h3>\u0000 \u0000 <p>The diagnosis of POEMS syndrome is made with three of the major criteria, two of which must include polyneuropathy and clonal plasma cell disorder, and at least one of the minor criteria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Risk Stratification</h3>\u0000 \u0000 <p>Because the pathogenesis of the syndrome is not well understood, risk stratification is limited to clinical phenotype rather than specific molecular markers. Risk factors include low serum albumin, age, pleural effusion, pulmonary hypertension, and reduced eGFR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Risk-Adapted Therapy</h3>\u0000 \u0000 <p>For those patients with a dominant plasmacytoma, first line therapy is irradiation. Patients with diffuse sclerotic lesions or disseminated bone marrow involvement should receive systemic therapy. Corticosteroids are temporizing, but alkylators and lenalidomide are the mainstays of treatment, the former either in the form of low dose conventional therapy or as high-dose conditioning for stem cell transplantation. Thalidomide and bortezomib also have activity, but their benefit needs to be weighed against their risk of exacerbating the peripheral neuropathy. Daratumumab combinations also appear promising based on case series. Prompt recognition and institution of both supportive care measures and therapy directed against the plasma cell result in the best outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 10","pages":"2632-2651"},"PeriodicalIF":9.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70438","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148395535","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":"Risk-Adjusted Comparison of Survival in Chronic Myelomonocytic Leukemia With and Without Allogeneic Stem Cell Transplant: Mayo Clinic Experience in 775 Consecutive Patients","authors":"Ali Alsugair,&nbsp;Saubia Fathima,&nbsp;Mohammad M. Alhousani,&nbsp;Estefania Gauto Mariotti,&nbsp;Abiola Bolarinwa,&nbsp;Priyansh Faldu,&nbsp;Muhammad Yousuf,&nbsp;Clifford M. Csizmar,&nbsp;James Foran,&nbsp;Abishek A. Mangaonkar,&nbsp;Mark Litzow,&nbsp;Hemant Murthy,&nbsp;Lisa Sproat,&nbsp;Jeanne Palmer,&nbsp;Aasiya Matin,&nbsp;Ernesto Ayala,&nbsp;James Slack,&nbsp;Luis Porrata,&nbsp;Madiha Iqbal,&nbsp;Nandita Khera,&nbsp;Nathan Punwani,&nbsp;Saad Kenderian,&nbsp;Saurabh Chhabra,&nbsp;Kebede H. Begna,&nbsp;Animesh Pardanani,&nbsp;William J. Hogan,&nbsp;Mithun Vinod Shah,&nbsp;Hassan B. Alkhateeb,&nbsp;Naseema Gangat,&nbsp;Mrinal Patnaik,&nbsp;Ayalew Tefferi","doi":"10.1002/ajh.70453","DOIUrl":"10.1002/ajh.70453","url":null,"abstract":"<div>\u0000 \u0000 <p>The recently published BLAST clinical risk model for chronic myelomonocytic leukemia (CMML) and its molecular version (BLAST-Mol) differentiate low, intermediate, and high-risk groups. The objective of the current retrospective study was to examine the survival impact of allogeneic stem cell transplant (ASCT) in a consecutive series of Mayo Clinic patients (<i>n</i> = 775; 68% males, median age 71 years) with CMML, overall and adjusted for baseline BLAST/BLAST-Mol risk categories. At a median follow-up of 77 months, 151 (20%) patients underwent ASCT. Overall survival (OS) was longer in the ASCT compared to the non-ASCT cohorts (median 77 vs. 28 months; <i>p</i> &lt; 0.01). The significant difference in OS between the ASCT and non-ASCT cohorts was retained after adjusting for BLAST clinical risk groups: high-risk (median 50 vs. 14 months; <i>p</i> &lt; 0.01), intermediate-risk (81 vs. 28 months; <i>p</i> &lt; 0.01), and low-risk (111 vs. 65 months; <i>p</i> = 0.04), respectively. The same was mostly the case when OS comparison was adjusted for BLAST-Mol with respective <i>p</i> values of &lt; 0.01, &lt; 0.01, and 0.08, respectively. Time-dependent cox models confirmed the favorable survival impact of ASCT in the BLAST/BLAST-Mol high- and intermediate-risk groups. The current study highlights the benefit of ASCT for BLAST/BLAST-Mol high- and intermediate-risk groups in CMML and its potential to overcome the adverse impact of some high risk cytogenetic or molecular abnormalities. These observations support the early use of ASCT in CMML, ideally before BT and regardless of genetic characteristics.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 10","pages":"2557-2570"},"PeriodicalIF":9.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148582251","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":"A Multicenter, Open-Label, Phase 2 Trial Comparing Crizanlizumab Combined With Standard Therapy to Standard Therapy Alone on Renal Function in Patients With Sickle Cell Nephropathy (STEADFAST)","authors":"Kenneth I. Ataga,&nbsp;Pablo Bartolucci,&nbsp;Santosh L. Saraf,&nbsp;Vimal K. Derebail,&nbsp;Adlette Inati,&nbsp;Jeffrey D. Lebensburger,&nbsp;Laurie DeBonnett,&nbsp;Rodolfo D. Cancado,&nbsp;Claire C. Sharpe","doi":"10.1002/ajh.70447","DOIUrl":"10.1002/ajh.70447","url":null,"abstract":"&lt;p&gt;Sickle cell nephropathy (SCN) represents one of the most serious chronic complications of sickle cell disease (SCD), contributing substantially to morbidity and premature mortality [&lt;span&gt;1, 2&lt;/span&gt;]. SCN manifests as hyperfiltration, albuminuria, and progressive loss of kidney function [&lt;span&gt;3&lt;/span&gt;], with an estimated 12% of adults with SCD progressing to end-stage kidney disease (ESKD) over 10 years [&lt;span&gt;4-6&lt;/span&gt;]. Albuminuria, especially urine albumin-to-creatinine ratio (ACR) ≥ 100 mg/g, is among the strongest predictors of rapid estimated glomerular filtration rate (eGFR) decline and future kidney failure [&lt;span&gt;7-10&lt;/span&gt;]. Despite this burden, no therapies are approved specifically for SCN. The recommended standard of care (SoC) includes use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) and/or hydroxyurea/hydroxycarbamide (HU/HC), although the supporting evidence is modest, largely from small or short-term studies not powered for renal outcomes [&lt;span&gt;11-13&lt;/span&gt;]. This underscores the need to evaluate new therapeutic strategies that target the mechanisms driving SCN progression.&lt;/p&gt;&lt;p&gt;P-selectin mediates vaso-occlusion by promoting interactions among sickled erythrocytes, leukocytes, and activated endothelium [&lt;span&gt;14&lt;/span&gt;]. In preclinical studies, P-selectin is upregulated after kidney ischemia–reperfusion injury, and blockade reduces neutrophil infiltration and glomerular injury [&lt;span&gt;14-16&lt;/span&gt;]. Crizanlizumab, a humanized anti-P-selectin monoclonal antibody, reduced annualized vaso-occlusive crises (VOCs) in the Phase 2 SUSTAIN trial and was initially approved to reduce VOC frequency in SCD [&lt;span&gt;17, 18&lt;/span&gt;]. However, its role in mitigating kidney injury due to SCD has not been evaluated in a dedicated clinical trial.&lt;/p&gt;&lt;p&gt;We report STEADFAST, a multicenter, open-label, randomized Phase 2 trial (NCT04053764) evaluating crizanlizumab plus SoC versus SoC alone for kidney outcomes in patients with SCN at moderate-to-very high risk of CKD progression.&lt;/p&gt;&lt;p&gt;Patients aged ≥ 16 years with confirmed HbSS or HbSβ&lt;sup&gt;0&lt;/sup&gt; thalassemia (six HbSβ&lt;sup&gt;+&lt;/sup&gt; genotype patients were enrolled in protocol deviations) were eligible if they had: eGFR 45–140 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt; and ACR ≥ 100 and &lt; 2000 mg/g, on stable SoC (ACE inhibitor and/or ARB ≥ 3 months and/or HU/HC ≥ 6 months). Patients with recent acute kidney injury, kidney replacement therapy, uncontrolled hypertension, or recent voxelotor use were excluded. Patients were stratified by CKD risk category (moderate vs. high/very high, based on ACR and eGFR Table S1) and HU/HC use, and randomized 1:1 to crizanlizumab 5 mg/kg intravenously (Weeks 1 and 3, then every 4 weeks for 12 months) plus SoC, or SoC alone (Figure 1).&lt;/p&gt;&lt;p&gt;The primary endpoint was the proportion of patients achieving ≥ 30% reduction in urine ACR at Month 12. Secondary endpoints included changes in ACR and eGFR over time, protein-to-creatinine rat","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 10","pages":"2666-2671"},"PeriodicalIF":9.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70447","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148459555","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}