American Journal of Hematology最新文献

{"title":"Hypomethylating Therapy in VEXAS Syndrome: Disease Modification Beyond Bridging to Transplant","authors":"Emanuele Ammatuna","doi":"10.1002/ajh.70478","DOIUrl":"10.1002/ajh.70478","url":null,"abstract":"<p>I read with great interest the article by Fathima et al. reporting comparative outcomes of allogeneic hematopoietic stem cell transplantation (alloHSCT) and hypomethylating agents (HMA) in VEXAS syndrome [<span>1</span>]. The authors are to be commended for addressing a clinically important question in this rare disorder.</p><p>I would like to offer an additional perspective on the interpretation of the favorable outcomes associated with alloHSCT, particularly in light of the disease-modifying potential of hypomethylating therapy and inherent limitations of retrospective analyses. VEXAS is driven by somatic mutations in the UBA1 gene, most commonly affecting codon Met41, and thus represents a clonal hematopoietic disorder amenable to therapies targeting the malignant clone [<span>2, 3</span>]. In this context, accumulating evidence including data from the present study indicates that azacitidine can reduce the variant allele fraction (VAF) of <i>UBA1</i> mutations and induce molecular remissions in a subset of patients [<span>4-6</span>]. The 22% molecular remission rate observed in the HMA cohort supports prior findings that hypomethylating agents can meaningfully impact clonal burden [<span>4, 6</span>].</p><p>While alloHSCT was associated with higher rates of molecular remission and superior overall survival, this association warrants careful interpretation. Response to HMA therapy appears heterogeneous, and the attenuation of survival differences among patients able to complete prolonged HMA treatment suggests that a subset may achieve durable clinical benefit when therapy is tolerated [<span>4, 6</span>]. In this setting, the intention-to-treat framework, combined with a high rate of early HMA discontinuation, may underestimate the therapeutic potential of HMAs in selected patients.</p><p>A central challenge is residual confounding from selection and survivor effects [<span>7</span>]. Patients undergoing alloHSCT must necessarily survive the interval from diagnosis to transplantation and maintain sufficient fitness to proceed, introducing a survivor effect not fully captured by analyses anchored at treatment initiation. The authors thoughtfully addressed this through 1:1 matching on age and Charlson Comorbidity Index and propensity score based inverse probability treatment weighting, with the association favoring alloHSCT persisting across both analyses. Such adjustments may still leave residual confounding that could contribute to an overestimation of the survival advantage associated with alloHSCT [<span>7, 8</span>]. While these biases are difficult to eliminate entirely in retrospective studies, definitive comparisons between hypomethylating agents and alloHSCT will require prospective evaluation. The interpretation of HMA efficacy in VEXAS remains challenging because of the limitations of the available evidence. The FRENVEX cohort, which is frequently cited as a benchmark for azacitidine activity, was also retrospective and therefore","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 11","pages":"2920-2921"},"PeriodicalIF":9.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70478","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768632","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":"SHR-2004, a Humanized Monoclonal Antibody Targeting Factor XI, for Preventing Venous Thromboembolism After Ovarian Cancer Surgery: A Randomized, Active-Controlled Phase 2 Study","authors":"Guangyi Jiang,&nbsp;Jie Tang,&nbsp;Hongwei Zhao,&nbsp;Keqiang Zhang,&nbsp;Jun Gao,&nbsp;Bo Yang,&nbsp;Li Wang,&nbsp;Hongying Yang,&nbsp;Liang Chen,&nbsp;Ruifang An,&nbsp;Hui Zhang,&nbsp;Hualei Bu,&nbsp;Junying Tang,&nbsp;Xizhong Xu,&nbsp;Xiaohong Ruan,&nbsp;Bairong Xia,&nbsp;Ke Wang,&nbsp;Luwei Wei,&nbsp;Xiujie Sheng,&nbsp;Zhe Guo,&nbsp;Lihong Chen,&nbsp;Wei Wang,&nbsp;Jin Li,&nbsp;Danbo Wang,&nbsp;Ping Zhan,&nbsp;Yuhan Guo,&nbsp;Yuqi Wang,&nbsp;Yanli Dong,&nbsp;Jianqing Zhu","doi":"10.1002/ajh.70481","DOIUrl":"10.1002/ajh.70481","url":null,"abstract":"<div>\u0000 \u0000 <p>This multicenter, randomized, open-label, exploratory Phase 2 trial assessed SHR-2004, an anti-FXI antibody, for venous thromboembolism (VTE) prevention in patients undergoing ovarian cancer surgery—a population at particularly high thrombotic risk conducted at 25 sites in China. Patients with newly diagnosed Stage III–IV or recurrent ovarian cancer scheduled for surgery were randomly assigned (1:1) to receive subcutaneous SHR-2004 (180 mg on Day 1 and 120 mg on Day 15) or enoxaparin–rivaroxaban (subcutaneous enoxaparin 40 mg once daily during hospitalization, followed by oral rivaroxaban 10 mg once daily after discharge until Day 28). The primary efficacy outcome was the composite of VTE events within 28 days. The primary safety outcome was major bleeding (MB) or clinically relevant nonmajor bleeding (CRNMB) from first dose to 28 days. Between February 19, 2024 and September 17, 2024, 198 patients received assigned treatment (90 with SHR-2004, 108 with enoxaparin–rivaroxaban) and were included in the safety analysis. Among 181 patients who completed protocol-mandated ultrasonography, VTE occurred in 11 (12.6%) patients in the SHR-2004 group and 19 (20.2%) in the enoxaparin–rivaroxaban group (difference −8.4%, 95% CI −19.9 to 3.1) by Day 28. MB/CRNMB rates were similar between groups (SHR-2004: 2/90 [2.2%]; enoxaparin–rivaroxaban: 2/108 [1.9%]). In this study, SHR-2004 showed comparable efficacy to enoxaparin–rivaroxaban for preventing postoperative VTE in patients undergoing ovarian cancer surgery, with a similar low risk of MB or CRNMB. The twice-monthly dosing schedule offers a potential advantage over daily anticoagulation, supporting further investigation in adequately powered Phase 3 trials.</p>\u0000 <p>\u0000 <b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT06220123</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 11","pages":"2776-2785"},"PeriodicalIF":9.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817219","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":"Chromosome 1q Gain Defines a Plasma Cell–Dominant Adverse-Risk Subtype in AL Amyloidosis With Inferior Long-Term Survival","authors":"Tamer Hellou,&nbsp;Estefania Gauto Mariotti,&nbsp;Ahmed Alnughmush,&nbsp;Linda B. Baughn,&nbsp;Prashant Kapoor,&nbsp;Saurabh Zanwar,&nbsp;Shinichiro Suzuki,&nbsp;Maximilian J. Steinhardt,&nbsp;Daniel G. Packard,&nbsp;Taxiarchis V. Kourelis,&nbsp;Francis K. Buadi,&nbsp;David Dingli,&nbsp;Suzanne R. Hayman,&nbsp;Nelson Leung,&nbsp;Yi Lisa Hwa,&nbsp;Amie Fonder,&nbsp;Miriam Hobbs,&nbsp;Rahma Warsame,&nbsp;Joselle Cook,&nbsp;Moritz Binder,&nbsp;Nadine Abdallah,&nbsp;Yi Lin,&nbsp;Ronald S. Go,&nbsp;Robert A. Kyle,&nbsp;S. Vincent Rajkumar,&nbsp;Wilson I. Gonsalves,&nbsp;Shaji K. Kumar,&nbsp;Morie A. Gertz,&nbsp;Angela Dispenzieri,&nbsp;Eli Muchtar","doi":"10.1002/ajh.70484","DOIUrl":"10.1002/ajh.70484","url":null,"abstract":"<div>\u0000 \u0000 <p>The prognostic relevance of multiple myeloma (MM)-defined high-risk (HR) cytogenetic abnormalities in AL amyloidosis is incompletely defined. We retrospectively evaluated 517 newly diagnosed AL amyloidosis patients seen at Mayo Clinic between 2012 and 2021 who had baseline plasma cell FISH. HR cytogenetics were defined as <i>t</i>(4;14), <i>t</i>(14;16), <i>t</i>(14;20), del(17p), or 1q gain/amplification (+1q). HR abnormalities were identified in 151 patients (29%); +1q accounted for most HR cases (122/151, 81%). Compared with standard-risk (SR), patients harboring +1q demonstrated a greater clonal disease burden, including higher dFLC and bone marrow plasma cells, greater intact immunoglobulin secretion, higher plasma cell proliferative index, and enrichment for modified SLiM-CRAB features. Hematologic and organ response patterns of +1q patients were generally comparable to SR patients, whereas non-1q HR patients had a higher proportion of early hematologic responses. Patients harboring +1q demonstrated significantly inferior overall survival (OS) compared with both non-1q HR patients and SR patients (median OS 57 months vs. not reached vs. 120 months, <i>p</i> = 0.02). In multivariable piecewise Cox analysis, the adverse prognostic impact of +1q was most evident beyond 24 months from diagnosis (HR 2.89, 95% CI 1.64–5.09, <i>p</i> &lt; 0.001), whereas non-1q HR lesions were not independently prognostic. These findings suggest that +1q identifies a biologically distinct AL amyloidosis subset characterized by plasma cell–dominant features and inferior long-term disease control. In contrast, other MM-defined HR cytogenetic abnormalities appear to have limited prognostic relevance in AL amyloidosis.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 11","pages":"2766-2775"},"PeriodicalIF":9.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148809813","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":"Primary Plasma Cell Leukemia","authors":"Mahin Bhatt,&nbsp;Saurabh Zanwar,&nbsp;Shaji Kumar,&nbsp;S. Vincent Rajkumar","doi":"10.1002/ajh.70487","DOIUrl":"10.1002/ajh.70487","url":null,"abstract":"<div>\u0000 \u0000 <p>Plasma cell leukemia (PCL) is a form of high-risk multiple myeloma comprising 1%–2% of new myeloma diagnoses, and defined by ≥ 5% circulating plasma cells. Classified as primary, de novo or secondary, from relapsed/refractory myeloma, PCL carries worse outcomes than conventional myeloma despite advances. Genomically, PCL demonstrates high-risk abnormalities like del(17p), 1q21 gain/amplification and overrepresentation of t(11;14), marking a distinct biological subgroup. Contemporary management involves quadruplet induction, early autologous stem cell transplantation in eligible patients, and multi-agent consolidation/maintenance. Immune effector therapies, especially BCMA-directed CAR-T, show promise for deeper, more durable responses. This review covers PCL biology, clinical features, prognosis, and treatment, emphasizing emerging therapies.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 11","pages":"2853-2865"},"PeriodicalIF":9.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860840","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":"Targeting B-Cell-Activating Factor and Its Receptor in Immune Thrombocytopenia and Warm Autoimmune Hemolytic Anemia","authors":"Matthieu Mahévas,&nbsp;Nichola Cooper,&nbsp;Vickie McDonald,&nbsp;Karina Yazdanbakhsh,&nbsp;Wilma Barcellini","doi":"10.1002/ajh.70460","DOIUrl":"10.1002/ajh.70460","url":null,"abstract":"<p>Current treatments for immune thrombocytopenia (ITP) and warm autoimmune hemolytic anemia (wAIHA), rare autoimmune diseases in which autoreactive B cells play a major role, can lead to high response rates; however, for many patients these responses are not durable or maintained after treatment discontinuation. Binding of B-cell-activating factor (BAFF) to its receptor (BAFF-R) has been shown to lead to B-cell differentiation, proliferation, and survival, with BAFF levels shown to be elevated in patients with ITP and wAIHA. Targeting the BAFF/BAFF-R pathway could address unmet needs that remain for patients with ITP and wAIHA despite available treatments.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 11","pages":"2836-2852"},"PeriodicalIF":9.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70460","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148836232","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":"Impact of Response to Hypomethylating Agent-Based Therapy on Survival Outcomes in the Context of Baseline Clinical-Molecular Risk and Transplant Status in Patients With Higher-Risk Myelodysplastic Syndromes/Neoplasms: An analysis From the International Consortium for MDS (icMDS)","authors":"Benjamin Rolles,&nbsp;Jan Philipp Bewersdorf,&nbsp;Tariq Kewan,&nbsp;Ondrej Blaha,&nbsp;Jessica M. Stempel,&nbsp;Luca Lanino,&nbsp;Najla H. Al Ali,&nbsp;Amy E. DeZern,&nbsp;Mikkael A. Sekeres,&nbsp;Geoffrey L. Uy,&nbsp;Samuel Urrutia,&nbsp;Hetty E. Carraway,&nbsp;Pinkal Desai,&nbsp;Elizabeth A. Griffiths,&nbsp;Eytan M. Stein,&nbsp;Andrew M. Brunner,&nbsp;Christine McMahon,&nbsp;Rory M. Shallis,&nbsp;Joshua F. Zeidner,&nbsp;Michael R. Savona,&nbsp;Shougat Barua,&nbsp;Namrata Sonia Chandhok,&nbsp;Constantine Logothetis,&nbsp;Aram Bidikian,&nbsp;Ted M. Getz,&nbsp;Gail J. Roboz,&nbsp;Eunice S. Wang,&nbsp;Amyah C. Harris,&nbsp;Maria L. Amaya,&nbsp;Hayley Hawkins,&nbsp;Somedeb Ball,&nbsp;Justin Grenet,&nbsp;Parisa Abedi,&nbsp;Shai Shimony,&nbsp;R. Coleman Lindsley,&nbsp;Zhuoer Xie,&nbsp;Yazan F. Madanat,&nbsp;Yasmin Abaza,&nbsp;Talha Badar,&nbsp;Torsten Haferlach,&nbsp;Jaroslaw P. Maciejewski,&nbsp;David Sallman,&nbsp;Anoop Enjeti,&nbsp;Kamal Al-Rabi,&nbsp;Khalid Halahleh,&nbsp;Devendra Hiwase,&nbsp;Maria Diez-Campelo,&nbsp;David Valcarcel,&nbsp;Claudia Haferlach,&nbsp;Lisa Pleyer,&nbsp;Ioannis Kotsianidis,&nbsp;Vasiliki Pappa,&nbsp;Valeria Santini,&nbsp;Angela Consagra,&nbsp;Aref Al-Kali,&nbsp;Seishi Ogawa,&nbsp;Yasuhito Nannya,&nbsp;Matteo Giovanni Della Porta,&nbsp;Rami S. Komrokji,&nbsp;Amer M. Zeidan,&nbsp;Maximilian Stahl","doi":"10.1002/ajh.70474","DOIUrl":"10.1002/ajh.70474","url":null,"abstract":"<div>\u0000 \u0000 <p>Baseline IPSS-M risk, response to hypomethylating agent (HMA) therapy, and receipt of allogeneic stem cell transplant (allo-HCT) have all been individually shown to impact overall survival (OS) in patients with myelodysplastic syndromes (MDS). However, the prognostic impact of response when adjusting for IPSS-M risk and treatment strategy remains unclear. Hence, we used the VALIDATE database of the International Consortium for MDS (icMDS) to evaluate the impact of International Working Group (IWG) 2023 best response on OS in 715 HMA-treated, higher-risk MDS patients stratified by baseline IPSS-M risk and their treatment strategy (subsequent allo-HCT vs. medical therapy alone) treating both best response and allo-HCT as time-dependent variables. Baseline IPSS-M risk (hazard ratio (HR): 0.5, <i>p</i> &lt; 0.001) and receipt of allo-HCT (HR: 0.5, <i>p</i> &lt; 0.001) were the strongest independent predictors of OS, whereas achievement of composite complete response (cCR) had a more modest impact on OS (HR: 0.8, <i>p</i> = 0.004). Among patients treated with medical therapy alone, achieving cCR improved OS significantly (HR: 0.7, <i>p</i> = 0.006). In contrast, among transplanted patients, cCR did not retain independent prognostic value for post-transplant survival after adjusting for baseline IPSS-M (HR: 0.9, <i>p</i> = 0.634). Achieving cCR did not fully overcome adverse disease biology as OS continued to segregate according to baseline IPSS-M risk. In summary, achieving cCR improves outcomes in non-transplanted patients, but it does not significantly impact post-transplant OS, suggesting that failure to achieve cCR with HMA may not warrant delay or preclude allo-HCT. Clinical trials should consider response in the context of IPSS-M risk distribution and treatment strategy (subsequent allo-HCT vs. medical therapy alone) to avoid overinterpretation of high response rates.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 11","pages":"2786-2798"},"PeriodicalIF":9.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823458","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":"Myeloma Progression Without Osteolysis: Rethinking Whole-Body Low-Dose CT Criteria for Bone Disease","authors":"Vassilis Koutoulidis,&nbsp;Lia A. Moulopoulos,&nbsp;Ioannis Ntanasis-Stathopoulos,&nbsp;Maria Douka,&nbsp;Maria Gavriatopoulou,&nbsp;Meletios A. Dimopoulos,&nbsp;Evangelos Terpos","doi":"10.1002/ajh.70477","DOIUrl":"10.1002/ajh.70477","url":null,"abstract":"&lt;p&gt;Whole-body low-dose CT (WBLDCT) is recommended as the first-line modality for assessing osteolytic bone disease in multiple myeloma [&lt;span&gt;1&lt;/span&gt;]. Under current criteria, myeloma-related bone disease requires at least one osteolytic lesion of 5 mm or more; focal hyperattenuating medullary lesions in the appendicular skeleton, however large or numerous, do not satisfy this criterion [&lt;span&gt;2&lt;/span&gt;]. MRI and PET/CT apply a different standard, in which focal bone marrow lesions meeting modality-specific criteria are considered positive for myeloma activity, irrespective of location [&lt;span&gt;3, 4&lt;/span&gt;]. We report a patient in whom progressive hyperattenuating femoral medullary lesions were visible on two consecutive annual WBLDCT examinations, neither of which fulfilled the criteria for myeloma-related bone disease in the absence of osteolysis; symptomatic myeloma was established on subsequent MRI.&lt;/p&gt;&lt;p&gt;A 46-year-old man with smoldering multiple myeloma underwent WBLDCT at initial diagnosis, which showed no osteolytic lesions; whole-body MRI, performed per current recommendations, showed no focal lesions. He entered annual WBLDCT surveillance per institutional practice. Two years later, in his third annual WBLDCT, no osteolytic lesions were identified, whereas a single 5 mm hyperattenuating lesion was present in the mid-diaphyseal medullary cavity of the left femur (Figure 1). The finding did not fulfill the criteria for myeloma-related bone disease, and surveillance was continued. At the next annual examination, osteolytic lesions were again absent, whereas the left femoral lesion had enlarged to approximately 3.1 cm, and multiple new focal hyperattenuating lesions had developed in both femoral medullary cavities (Figure 2); the examination again did not establish myeloma bone disease under current criteria, despite clear interval progression of the imaging findings. Subsequently, whole-body MRI was performed. It confirmed the femoral focal lesions and showed additional focal lesions in the axial skeleton (Figure 3a). Retrospective review of the WBLDCT showed no osteolysis at the sites of the MRI focal lesions in the axial skeleton (Figure 3b,c). The patient was reclassified to symptomatic myeloma on the basis of the presence of more than one focal lesion greater than 5 mm on MRI. No other CRAB-SLiM criteria were met during the 2-year surveillance period. The patient initiated treatment with daratumumab, bortezomib, lenalidomide, and dexamethasone, and underwent autologous transplantation, achieving an MRD-negative complete response.&lt;/p&gt;&lt;p&gt;This case illustrates several points regarding the imaging criteria for myeloma-related bone disease. Although myelomatous involvement predominates in the axial skeleton, a minority of patients harbor focal lesions confined to the appendicular skeleton. The precise frequency of truly appendicular-confined disease is unknown, and existing figures are both dated and methodologically non-comparable; they depe","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 11","pages":"2917-2919"},"PeriodicalIF":9.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70477","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768633","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":"Older Age, STAG2, and DNMT3A Mutations Predict Superior Posttransplant Survival in Newly Diagnosed Acute Myeloid Leukemia Treated With Venetoclax Plus Hypomethylating Agents","authors":"Momna Warraich,&nbsp;Sudhesh Kumar,&nbsp;Mahnoor Fatima,&nbsp;Kristen McCullough,&nbsp;Aref Al-Kali,&nbsp;Hassan B. Alkhateeb,&nbsp;Kebede H. Begna,&nbsp;Abhishek Mangaonkar,&nbsp;Antoine N. Saliba,&nbsp;Aasiya Matin,&nbsp;Mark R. Litzow,&nbsp;William Hogan,&nbsp;Mithun V. Shah,&nbsp;Mrinal M. Patnaik,&nbsp;Animesh Pardanani,&nbsp;James Foran,&nbsp;Lisa Sproat,&nbsp;Nandita Khera,&nbsp;Ayalew Tefferi,&nbsp;Naseema Gangat","doi":"10.1002/ajh.70480","DOIUrl":"10.1002/ajh.70480","url":null,"abstract":"<div>\u0000 \u0000 <p>Venetoclax (Ven) plus hypomethylating agents (HMA) is standard frontline therapy for newly diagnosed AML (ND-AML) patients unfit for intensive chemotherapy and is also considered in younger, fit patients. However, consolidation with allogeneic stem cell transplant (ASCT) is often required to secure durable remission. The current study examines posttransplant outcomes in patients with ND-AML treated with frontline Ven-HMA who subsequently underwent ASCT. A total of 111 ND-AML patients (58% male, 60% secondary/therapy-related, median age 70 years [range, 37–80]) received a median of 3 cycles of Ven-HMA. Mutations at the time of diagnosis included <i>RUNX1</i> (18%), <i>SRSF2</i> (17%), <i>TP53</i> (16%), <i>ASXL1</i>, <i>IDH2</i>, <i>K/NRAS</i>, <i>TET2</i> (14% each), <i>STAG2</i> (11%), <i>DNMT3A</i> (8%). All patients were in CR/CRi at the time of transplant including 88% after Ven-HMA. Measurable residual disease (MRD) by flow cytometry was detectable in 18/76 (24%) patients. Donors were mostly HLA-matched unrelated (75%); 51% receiving fludarabine/melphalan conditioning and 67% posttransplant cyclophosphamide. At a median follow-up of 15 months, 42 (38%) of patients have died and 18 (16%) experienced posttransplant relapse. Median posttransplant survival was not reached (NR), with 1-, 2-, 3-year survival rates of 69%/60%/57%, respectively. On multivariate analysis, age ≥ 65 years, <i>STAG2</i> mutation (<i>STAG2</i>\u0000 ^{\u0000 <i>MUT</i>\u0000}\u0000 <i>)</i>, and <i>DNMT3A</i>\u0000 ^{\u0000 <i>MUT</i>\u0000} were associated with superior posttransplant survival. Patients were stratified into low- (0–1 point), intermediate- (2 points), and high-risk (3 points); age &lt; 65 years, <i>STAG2</i> wild type, and <i>DNMT3A</i> wild type, with 3-year survival rates of 89%, 59%, and 19%, respectively (<i>p</i> &lt; 0.01). Taken together, age, <i>STAG2</i>\u0000 ^{\u0000 <i>MUT</i>\u0000} and <i>DNMT3A</i>\u0000 ^{\u0000 <i>MUT</i>\u0000} stratified posttransplant survival in Ven-HMA treated patients with ND-AML.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 11","pages":"2746-2757"},"PeriodicalIF":9.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768948","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":"Hematopoietic Stem Cell Transplantation in Children With Transfusion Dependent β-Thalassemia: A Two-Decade Single-Center Experience","authors":"Abdullah Al-Jefri,&nbsp;Khawar Siddiqui,&nbsp;Murtada Al-Sultan,&nbsp;Sami Al-Otaibi,&nbsp;Saadiya Khan,&nbsp;Awatif Al-Anazi,&nbsp;Mouhab Ayas,&nbsp;Hawazen AlSaedi,&nbsp;Abdulrahman Al-Musa,&nbsp;Mahasen Al-Saleh,&nbsp;Ali Al-Ahmari,&nbsp;Ibrahim Ghemlas","doi":"10.1002/ajh.70455","DOIUrl":"10.1002/ajh.70455","url":null,"abstract":"&lt;p&gt;Allogeneic hematopoietic stem cell transplantation (HCT) remains the only established curative treatment for transfusion-dependent β-thalassemia (TDT). Although regular transfusions and iron chelation have improved survival, many patients still develop progressive organ damage, endocrine complications, and impaired quality of life. Early studies from the Pesaro group demonstrated long-term thalassemia-free survival exceeding 70% in carefully selected recipients of HLA-identical sibling donor transplants [&lt;span&gt;1&lt;/span&gt;]. Over the past two decades, advances in donor selection, conditioning regimens, and supportive care have further improved transplant outcomes, with recent studies reporting overall survival exceeding 90% and thalassemia-free survival ranging between 70% and 90% [&lt;span&gt;2-5&lt;/span&gt;]. Despite these improvements, graft failure, mixed chimerism, graft-versus-host disease (GvHD), and late transplant-related complications remain important challenges [&lt;span&gt;6, 7&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;β-thalassemia is highly prevalent in the Middle East; however, long-term transplant outcome data from the region remain limited. Most published HCT experiences originate from European or East Asian centers, and data describing long-term graft durability and survivorship in Middle Eastern pediatric populations are scarce. Here, we report one of the largest single-center Middle Eastern experiences of pediatric TDT, evaluating transplant outcomes and post-transplant transfusion dependency over a two-decade period.&lt;/p&gt;&lt;p&gt;A total of 205 pediatric patients with TDT who underwent allogeneic HCT at our institution between January 1998 and September 2024 were enrolled in this retrospective study. Clinical and transplant-related data were obtained from prospectively curated institutional databases. All parents and/or guardians signed institutional review board–approved parental informed consent prior to the transplant. Median age at transplant was 5.1 years (range, 1.0–15.8) and 109 (53.2%) patients were male. Donors included HLA-identical siblings in 158 (77.1%) transplants, HLA-identical other relatives in 42 (20.5%), related one-antigen mismatch donors in 4 (2.0%), and one HLA-identical unrelated donor (0.5%). All patients were conditioned with a myeloablative chemotherapy regimen. Bone marrow (BM) was the primary stem cell source in 199 (97.1%) transplants while peripheral blood stem cells (PBSC) were used in six cases (3.0%). Patient characteristics and transplant-related parameters are summarized in Table S1. Acute GvHD (grades I and II) was seen in 37 patients (18.0%), while grades III–IV acute GvHD was noted in 16 (7.8%) transplants. Chronic GvHD was observed in eight patients (4.1%) (Table 1).&lt;/p&gt;&lt;p&gt;Neutrophil engraftment was achieved in 202 of 205 patients (98.5%) at a median of 17 days (range, 9–42 days) while platelet recovery was observed in 193 patients (94.1%) at a median of 33 days (range 17–103) (Table 1). Post–HCT graft failure occurred in 20 patients (9.8","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 11","pages":"2913-2916"},"PeriodicalIF":9.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70455","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148717280","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-World Outcomes of Midostaurin Plus Intensive Chemotherapy in FLT3-Mutated AML: The PETHRATIFY Study","authors":"Mónica Alejandra Romero Riquelme,&nbsp;Gaspar Aspas Requena,&nbsp;Pilar Lloret-Madrid,&nbsp;Cristina Gil,&nbsp;Eliana Aguiar,&nbsp;Mar Tormo,&nbsp;Teresa del Bernal del Castillo,&nbsp;Eduardo Rodríguez Arbolí,&nbsp;Josefina Serrano,&nbsp;Joaquín Sánchez-García,&nbsp;Carlos Rodríguez-Medina,&nbsp;José Mário Mariz,&nbsp;Rosa Ayala,&nbsp;Joaquín Martínez-López,&nbsp;María Luz Amigo,&nbsp;Susana Vives,&nbsp;Lorenzo Algarra Algarra,&nbsp;Raimundo García Boyero,&nbsp;Joana Brioso,&nbsp;Tamara Castaño,&nbsp;Juan M. Bergua Burgués,&nbsp;Olga Salamero,&nbsp;María Francisca Bass Maturana,&nbsp;Mercedes Colorado,&nbsp;María García Fortes,&nbsp;María José Sayas Lloris,&nbsp;Belén Vidriales Vicente,&nbsp;Carmen Chillón,&nbsp;Esther Pérez Santaolalla,&nbsp;María Dolores Madrigal,&nbsp;Jorge Labrador Gómez,&nbsp;María José García Pérez,&nbsp;Soledad Casado Calderón,&nbsp;Manuel Pérez Encinas,&nbsp;Amaia Balerdi Malcorra,&nbsp;María Solé Rodríguez,&nbsp;Lara María Gómez García,&nbsp;Pilar Herrera Puente,&nbsp;Olga Arce Fernández,&nbsp;Manuel Barrios García,&nbsp;Víctor Noriega,&nbsp;Rosa Fernández,&nbsp;Mamen Mateos,&nbsp;Carolina Lacalzada,&nbsp;Ágata Almela Gallego,&nbsp;María Carmen García Garay,&nbsp;Carmen Couto,&nbsp;José Antonio Pérez-Simón,&nbsp;Eva Barragán González,&nbsp;Pau Montesinos","doi":"10.1002/ajh.70488","DOIUrl":"10.1002/ajh.70488","url":null,"abstract":"<p>Mutations in <i>FLT3</i> are present in approximately 30% of patients with AML. The addition of midostaurin (MIDO) to intensive chemotherapy (IC) became standard of care following the RATIFY trial, but comprehensive real-world data spanning the full adult age spectrum and including both <i>FLT3</i>-ITD and <i>FLT3</i>-TKD mutations remain limited. We retrospectively analyzed 1658 adults aged 14–85 years with newly diagnosed <i>FLT3</i>-mutated AML from 129 PETHEMA registry centers: 469 received IC + MIDO and 1189 IC alone. Composite complete remission was higher with IC + MIDO than IC (81.4% vs. 71.7%; <i>p</i> &lt; 0.001) and Day 30 mortality was substantially lower (2.1% vs. 7.1%; <i>p</i> &lt; 0.001). Median overall survival was 47.2 versus 19.3 months (HR 0.64; 95% CI, 0.53–0.76; <i>p</i> &lt; 0.001), and the benefit was sustained after multivariable adjustment (HR 0.73; <i>p</i> = 0.017). In 261 propensity score–matched pairs, the effect was attenuated, remaining significant for event-free survival (HR 0.77; <i>p</i> = 0.029) and showing a nonsignificant trend for OS (HR 0.77; <i>p</i> = 0.06). Allogeneic hematopoietic stem cell transplantation in first remission was more frequent in the IC + MIDO cohort (48.9% vs. 41.3%; <i>p</i> = 0.023). Time-dependent analyses showed the largest MIDO effect among autologous and non-transplanted patients (OS HR 0.45; <i>p</i> = 0.138, and HR 0.69; <i>p</i> = 0.014, respectively). The benefit of MIDO was consistent irrespective of <i>FLT3</i> mutation type, <i>FLT3</i>-ITD allelic burden, cytogenetic risk, and gender, while less improvement occurred among <i>NPM1</i> wild type and secondary AML patients. This large real-world cohort confirms the survival benefit of MIDO plus IC across the full adult age spectrum, supporting its standard-of-care status in <i>FLT3</i>-mutated AML.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 11","pages":"2812-2826"},"PeriodicalIF":9.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70488","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860856","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}