American Journal of Hematology最新文献

{"title":"Mitigating HLA Disparity in AML Transplantation: Comparable Outcomes After Haploidentical and 9/10 Mismatched Unrelated Donor Transplantation With Treosulfan and PTCy","authors":"Daniele Avenoso,&nbsp;Mirko Farina,&nbsp;Michele Malagola,&nbsp;Yves Chalandon,&nbsp;Giorgia Saporiti,&nbsp;Annalisa Imovilli,&nbsp;Enrico Derenzini,&nbsp;Peter Remenyi,&nbsp;Massimo Martino,&nbsp;Maija Itala-Remes,&nbsp;Renato Fanin,&nbsp;Didier Blaise,&nbsp;Desiree Kunadt,&nbsp;Arancha Bermudez Rodriguez,&nbsp;Franca Fagioli,&nbsp;Thomas Schroeder,&nbsp;Irene Cavattoni,&nbsp;Maud Ngoya,&nbsp;Mohamed Houhou,&nbsp;Mohamad Mohty,&nbsp;Eolia Brissot,&nbsp;Fabio Ciceri","doi":"10.1002/ajh.70483","DOIUrl":"10.1002/ajh.70483","url":null,"abstract":"<p>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative strategy for acute myeloid leukemia (AML), but the impact of HLA disparity in the era of posttransplant cyclophosphamide (PTCy) and reduced-toxicity conditioning remains unclear. We performed an EBMT registry study including 275 adult AML patients in first complete remission undergoing first allo-HSCT between 2012 and 2023 using a uniform platform of treosulfan-based conditioning and PTCy. Among them, 206 received haploidentical grafts and 69 underwent 9/10 mismatched unrelated donor (MMUD) transplantation. Median follow-up was 2.5 years. At 2 years, overall survival was 73.1% after haploidentical transplantation and 71.6% after MMUD transplantation (<i>p</i> = 0.96). Leukemia-free survival at 1 year was 66.3% and 65.2%, respectively (<i>p</i> = 0.76). Relapse incidence (17.1% vs. 18.7%, <i>p</i> = 0.84) and nonrelapse mortality (16.6% vs. 16.1%, <i>p</i> = 0.86) were comparable between groups. Rates of Grade II–IV and Grade III–IV acute GVHD were similar, whereas chronic GVHD was higher after haploidentical transplantation (36.4% vs. 12.7%, <i>p</i> = 0.001), without differences in extensive forms. In multivariable analyses, donor type was not associated with overall survival, leukemia-free survival, relapse incidence, or nonrelapse mortality. Increasing age adversely affected outcomes, while Karnofsky performance status ≥ 90 and reduced-intensity conditioning were associated with improved survival. These findings suggest that, within a treosulfan–PTCy platform, major transplant outcomes are comparable between donor types, although haploidentical transplantation was associated with a higher incidence of chronic GVHD.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 11","pages":"2736-2745"},"PeriodicalIF":9.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70483","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768630","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":"2026 Update on Clinical Trials in β-Thalassemia","authors":"Khaled M. Musallam,&nbsp;Franco Locatelli,&nbsp;Mattia Algeri,&nbsp;Maria Domenica Cappellini,&nbsp;Ali T. Taher","doi":"10.1002/ajh.70472","DOIUrl":"10.1002/ajh.70472","url":null,"abstract":"<p>The therapeutic landscape of β-thalassemia has evolved rapidly over the past decade, shifting from a historical reliance on transfusion support and iron chelation toward disease-modifying and potentially curative therapies. This review summarizes the clinical development of novel treatments for both non-transfusion-dependent and transfusion-dependent β-thalassemia, including approved therapies, agents in active development, and programs that have been discontinued. Disease-modifying strategies have focused on improving ineffective erythropoiesis, correcting iron dysregulation, and restoring red blood cell metabolism. Luspatercept and mitapivat have demonstrated clinically meaningful improvements in hemoglobin levels and reduction of transfusion burden and are now approved in multiple jurisdictions. Additional pyruvate kinase activators, such as etavopivat, are undergoing clinical evaluation. Curative approaches have advanced substantially through gene addition, gene editing, and base editing technologies. Approved therapies, including betibeglogene autotemcel and exagamglogene autotemcel, have achieved high rates of durable transfusion independence, while emerging platforms aim to further improve efficacy, safety, and accessibility. At the same time, several promising approaches targeting fetal hemoglobin induction, iron metabolism, and ineffective erythropoiesis have failed to demonstrate sufficient clinical benefit despite preclinical proof of concept, highlighting the complexity of therapeutic development in β-thalassemia. Future priorities include refining patient selection, generating real-world and comparative effectiveness data, developing clinically meaningful response criteria, expanding pediatric access, and addressing the substantial cost and accessibility challenges associated with novel therapies.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 11","pages":"2890-2906"},"PeriodicalIF":9.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70472","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711158","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":"HOPE Kids 2: Phase 3, Randomized Trial of Voxelotor in Children With SCD and Conditional Cerebral Blood Flow Velocities","authors":"Halima Bello-Manga,&nbsp;Shehu Umar Abdullahi,&nbsp;Hoda Hassab,&nbsp;Biobele Brown,&nbsp;Videlis Nduba,&nbsp;Jessie Githanga,&nbsp;Adeseye Michael Akinsete,&nbsp;Amal El-Beshlawy,&nbsp;Diana Hanna,&nbsp;Catherine Segbefia,&nbsp;Iheanyi Okpala,&nbsp;Azza Tantawy,&nbsp;Bernhards Ogutu,&nbsp;Venée N. Tubman,&nbsp;Vivian Paintsil,&nbsp;Yasser Wali,&nbsp;Mohammed Essa,&nbsp;Paul Telfer,&nbsp;Sandy Dixon,&nbsp;Anne Hickman,&nbsp;Jennifer F. Doss,&nbsp;Mark W. Davis,&nbsp;Jeremy Rupon,&nbsp;Fenella J. Kirkham,&nbsp;R. Clark Brown,&nbsp;the HOPE Kids 2 Investigators","doi":"10.1002/ajh.70457","DOIUrl":"10.1002/ajh.70457","url":null,"abstract":"<p>Children with SCD have elevated stroke risk, correlated with cerebral blood flow velocity (CBFV). HOPE Kids 2 was a phase 3, multicenter, double-blind, placebo-controlled trial evaluating the effect of voxelotor on CBFV. Participants aged 2 to &lt; 15 years with SCD (HbSS/HbSβ⁰) and conditional CBFV (170 to &lt; 200 cm/s) were randomized 1:1 to voxelotor (<i>N</i> = 120) or placebo (<i>N</i> = 116) for 96 weeks; 195 (83%) were in sub-Saharan Africa. The primary endpoint, CBFV change from baseline to Week 24, was significantly greater with voxelotor (least-squares mean change: voxelotor [<i>n</i> = 114] −12.06 cm/s, placebo [<i>n</i> = 108] −4.29 cm/s; difference −7.77 cm/s; 95% CI −13.18 to −2.37; <i>p</i> = 0.0048), with significant difference sustained through Week 48. Hemoglobin levels increased at Weeks 24 and 48 with voxelotor. Drug administration was paused in May 2024 when an imbalance of deaths was observed between treatment groups; subsequently, the trial discontinued when all active voxelotor trials were discontinued in September 2024. At study end, median (range) exposure was 84 (3–104) weeks for voxelotor and 84 (3–106) weeks for placebo. The most common SCD-related treatment-emergent adverse event was sickle cell anemia with crisis (voxelotor 59.2%; placebo 37.9%). All deaths (voxelotor <i>n</i> = 8; placebo <i>n</i> = 2) were considered unrelated to study drug by treating investigators. Overall, voxelotor showed CBFV reduction in children with SCD and conditional CBFV, suggesting HbS polymerization inhibition has a potential therapeutic role for this group; nevertheless, additional studies evaluating potential regional risks for sickle cell anemia with crisis or mortality are warranted.</p><p><b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT04218084</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 11","pages":"2799-2811"},"PeriodicalIF":9.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70457","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849664","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":"Navigating Asparaginase Treatment for Patients With Acute Lymphoblastic Leukemia: US Consensus Panel Recommendations on the Role of Multidisciplinary Care","authors":"Amir Ali,&nbsp;Grace Elsey,&nbsp;Kayla Fulginiti,&nbsp;Zanette Kanani-Bradley,&nbsp;Holly R. Kubaney,&nbsp;Sandra Kurtin,&nbsp;Theresa Nguyen,&nbsp;Jennifer Turchina,&nbsp;Charlotte B. Wagner","doi":"10.1002/ajh.70458","DOIUrl":"10.1002/ajh.70458","url":null,"abstract":"<p>Asparaginase is a critical treatment component for patients with acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL). However, the successful delivery of asparaginase-based therapy remains challenging across care settings due to its complex administration, distinct toxicity profile, prolonged treatment duration, and the need for coordinated multidisciplinary care. These challenges are further compounded by variability in institutional infrastructure, provider experience, and access to specialized supportive services. In this article, we describe key operational and clinical barriers to the safe, timely, and complete delivery of asparaginase therapy for patients with ALL/LBL and present recommendations developed using a modified Delphi process incorporating literature review and expert consensus. We provide practical recommendations organized across three core areas: (1) defining essential members of the specialized care team and outlining the necessary infrastructure for safe and effective asparaginase administration; (2) identifying key steps in the asparaginase treatment journey for ALL/LBL patients and providing recommendations for successful patient navigation and improved outcomes; and (3) sharing practical resources and solutions used by pharmacists, advanced practice providers, and nurses to optimize asparaginase delivery and ensure treatment completion. These recommendations are intended to provide actionable guidance to harmonize multidisciplinary efforts, minimize avoidable treatment interruptions, and support completion of planned asparaginase therapy. Broad implementation across specialized and nonspecialized centers may improve treatment adherence, mitigate toxicity-related discontinuation, and ultimately optimize outcomes for patients with ALL/LBL receiving asparaginase.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 11","pages":"2713-2725"},"PeriodicalIF":9.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70458","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148729155","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 Venetoclax-Based Therapy in Treatment-Naïve and Relapsed/Refractory CLL/SLL: Interim Results From the Prospective REVEAL Study","authors":"Yair Herishanu,&nbsp;Neta Goldschmidt,&nbsp;Gilad Itchaki,&nbsp;Liron Hofstetter,&nbsp;Osnat Bairey,&nbsp;Yotam Bronstein,&nbsp;Itai Levi,&nbsp;Ariel Aviv,&nbsp;Riva Fineman,&nbsp;Najib Dally,&nbsp;Tamar Tadmor,&nbsp;Aaron Ronson,&nbsp;Uri Abadi,&nbsp;Lev Shvidel,&nbsp;Galia Stemer,&nbsp;Chen Glait Santar,&nbsp;Tara Weinstein,&nbsp;Alex Bleterman,&nbsp;Brit Vidmayer,&nbsp;Ohad Benjamini","doi":"10.1002/ajh.70470","DOIUrl":"10.1002/ajh.70470","url":null,"abstract":"&lt;p&gt;Venetoclax-based regimens have transformed the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with pivotal trials such as CLL13, CLL14, and MURANO demonstrating superior progression-free survival (PFS), high rates of undetectable minimal residual disease (uMRD), and the feasibility of fixed-duration therapy [&lt;span&gt;1-6&lt;/span&gt;]. However, real-world data remain essential for understanding treatment effectiveness and tolerability in broader patient populations, including those with comorbidities or advanced age who are underrepresented in clinical trials [&lt;span&gt;7, 8&lt;/span&gt;]. Herein, we report interim results from the REVEAL study, a prospective, multicenter, observational study evaluating venetoclax-based therapy in a national Israeli cohort of patients with CLL/SLL.&lt;/p&gt;&lt;p&gt;REVEAL is an ongoing study initiated in February 2019 across 13 medical centers in Israel. Eligible patients were aged ≥ 18 years with confirmed CLL/SLL and deemed candidates for venetoclax treatment in either the first-line (treatment-naïve [TN]) or relapsed/refractory (R/R) setting. Patients with active Richter transformation or concurrent enrollment in interventional trials were excluded. Treatment was administered per standard clinical practice and participants were followed for up to 48 months. This interim analysis includes data collected through September 2024. Study endpoints included physician-assessed clinical overall response rate (ORR), complete response (CR), PFS, overall survival (OS), time to next treatment (TTNT), MRD negativity measured at 10&lt;sup&gt;−4&lt;/sup&gt; (uMRD4) and 10&lt;sup&gt;−5&lt;/sup&gt; (uMRD5) thresholds in peripheral blood at 12 and 24 months by centralized flow cytometry per the ERIC protocol [&lt;span&gt;9&lt;/span&gt;], and safety analyses. Dose intensity was defined as the ratio of administered to planned dose (400 mg/day) for patients who did not discontinue treatment due to disease progression or death. Full dose was defined as ≥ 80% of the recommended daily dose [&lt;span&gt;10&lt;/span&gt;]. Statistical analyses included Kaplan–Meier survival estimates, log-rank tests, and univariable and multivariable Cox proportional hazards models, as detailed in the Supporting Information Methods. The study was approved by each center's Institutional Review Board and all patients provided written informed consent.&lt;/p&gt;&lt;p&gt;A total of 304 patients were enrolled, including 154 TN and 150 R/R patients. Baseline characteristics are summarized in Table 1; the CONSORT flow diagram is provided in Figure S1. Median age at treatment initiation was 68 years (range 34–85) for TN and 70 years (range 25–91) for R/R patients. Most patients were male (66% TN; 65% R/R) with good performance status (ECOG 0–1: 94% TN; 91% R/R). High-risk cytogenetic and molecular features were more prevalent in the R/R cohort: del(17p)/TP53 aberrations were present in 28% of R/R versus 11% of TN patients, and unmutated IGHV in 80% versus 64%, respectively. Among R/R patients, 52% had received one p","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 11","pages":"2907-2912"},"PeriodicalIF":9.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70470","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700542","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":"Phase II Study of Posttransplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis After HLA-Mismatched Unrelated Donor Reduced Intensity Transplantation: Results From the ACCESS Trial Expansion Cohort","authors":"Brian C. Shaffer,&nbsp;Monzr M. Al Malki,&nbsp;Antonio Martin Jimenez Jimenez,&nbsp;Joseph Stanek,&nbsp;Stephanie Bo-Subait,&nbsp;Brent R. Logan,&nbsp;Jianqun Kou,&nbsp;Erin Leckrone,&nbsp;Heather E. Stefanski,&nbsp;Stephen R. Spellman,&nbsp;Craig Malmberg,&nbsp;Medhat Askar,&nbsp;Rachel Cusatis,&nbsp;Dipenkumar Modi,&nbsp;Farhad Khimani,&nbsp;Mehdi Hamadani,&nbsp;Martin Maiers,&nbsp;Rachel Cook,&nbsp;Karen Ballen,&nbsp;Javier Bolaños-Meade,&nbsp;Uttam Rao,&nbsp;Jordan Milner,&nbsp;Ramzi Abboud,&nbsp;Katarzyna Jamieson,&nbsp;George Carrum,&nbsp;Bhagirathbhai Dholaria,&nbsp;William J. Hogan,&nbsp;Ran Reshef,&nbsp;Satyajit Kosuri,&nbsp;Alison Loren,&nbsp;Karilyn Larkin,&nbsp;Sally Arai,&nbsp;Muna Qayed,&nbsp;Sung Won Choi,&nbsp;Larisa Broglie,&nbsp;Jeffery J. Auletta,&nbsp;Bronwen E. Shaw,&nbsp;Steven M. Devine,&nbsp;Mahasweta Gooptu","doi":"10.1002/ajh.70489","DOIUrl":"10.1002/ajh.70489","url":null,"abstract":"<p>Posttransplant cyclophosphamide (PTCy) to prevent graft-versus-host disease (GVHD) improves outcomes in recipients of HLA mismatched unrelated donor (MMUD) allogeneic hematopoietic cell transplantation (allo HCT). Outcomes of MMUD HCT using PTCy in patients requiring reduced intensity or non-myeloablative conditioning (RIC/NMA) are not well described. The Phase II, prospective, ACCESS trial sought to evaluate PTCy-based GVHD prophylaxis in adult recipients of MMUD using peripheral blood stem cell allografts. Here, we report combined results of RIC/NMA recipients treated in the initial study (<i>N</i> = 70) and a planned expansion cohort (<i>N</i> = 123). The number of centers participating in the expansion protocol was 33 compared to 13 in the initial study. Median participant age was 65.0 (range: 22.9–78.9) and the HCT comorbidity index was high-risk (≥ 3) in 65 (33.7%). Donor HLA matching was &lt; 7/8 in 62 (32.1%) participants. One-year survival was 79.6% (95% confidence interval: 73.2–84.7) and was similar between HLA 7/8- and HLA &lt; 7/8-matched donor recipients. Survival was similar between participants in the initial study (78.6%) and the expansion cohort (80.3%) indicating generalizability of this strategy. One-year incidence of severe infection (Grade 3–5) was 39% (32%–46.9%). The 1-year incidence of non-relapse mortality and relapse estimates were 12.5% (8.3%–17.6%) and 17.3% (12.3%–23%), respectively. MMUD with PTCy-based GVHD prophylaxis and RIC/NMA conditioning was safe and effective to facilitate HCT. Outcomes were similar in the expansion cohort that enrolled from a greater number of centers. Post-HCT infections were prevalent.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 11","pages":"2827-2835"},"PeriodicalIF":9.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70489","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860987","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":"Myeloma Elderly Prognostic Score (MEPS): A Proposed Prognostic Score Integrating Age, Renal Function, Performance Status, and Ultra-High-Risk Cytogenetics","authors":"Eirini Katodritou,&nbsp;Bruna Velosa Ferreira,&nbsp;Efstathios Kastritis,&nbsp;Dimitra Dalampira,&nbsp;Emmanouil Spanoudakis,&nbsp;Joana Vieira,&nbsp;Sosana Delimpasi,&nbsp;Ioannis Ntanasis-Stathopoulos,&nbsp;Aikaterini Daiou,&nbsp;Helena Martins,&nbsp;Elpiniki Rentzeperi,&nbsp;Foteini Theodorakakou,&nbsp;Elisabeth Karadrakonti,&nbsp;Graca Luiza O. P. Neto Vasconcelos Esteves,&nbsp;Vasiliki Tara,&nbsp;Vasiliki Douka,&nbsp;Dionysios Stoumpos,&nbsp;Xanthippi Dimitriadou,&nbsp;Catarina Isabel Batista Geraldes Santos,&nbsp;Vasiliki Palaska,&nbsp;Maria Tsirogianni,&nbsp;Maria Kotsopoulou,&nbsp;Rui Bergantim,&nbsp;Maria Gavriatopoulou,&nbsp;Adriana Roque,&nbsp;Konstantinos Kostikas,&nbsp;Meletios A. Dimopoulos,&nbsp;Cristina João,&nbsp;Evangelos Terpos","doi":"10.1002/ajh.70479","DOIUrl":"10.1002/ajh.70479","url":null,"abstract":"<div>\u0000 \u0000 <p>Established disease-centered prognostic systems may be less tailored to elderly/non-transplant-eligible (NTE) patients with multiple myeloma (MM), in whom host-related factors such as age, performance status, and renal function strongly influence all-cause outcomes. We developed and evaluated the Myeloma Elderly Prognostic Score (MEPS), a pragmatic four-factor score integrating age ≥ 75 years, renal function &lt; 40 by eGFR or available creatinine clearance (CrCl), ECOG performance status ≥ 2, and ultra-high-risk cytogenetics, using baseline registry data from 881 newly diagnosed NTE MM patients from Greece, with OS analyses performed in the 878 patients with evaluable survival follow-up, and externally evaluated it in an independent Portuguese cohort. In the Greek OS-evaluable cohort, 485 deaths were observed. Median OS by MEPS group was 96, 65, 39, and 15.3 months for scores 0, 1, 2, and ≥ 3, respectively. In a baseline score-level Cox model, each ordinal MEPS category increase was associated with inferior OS (HR 1.74, 95% CI 1.58–1.92; <i>p</i> &lt; 0.001). MEPS showed higher OS discrimination than R2-ISS in the Greek cohort (C-index 0.655 vs. 0.602; bootstrap delta 0.053, 95% CI 0.021–0.085). The Portuguese validation dataset included 300 patients, of whom 290 were evaluable for the primary OS analysis, with 151 deaths. Median OS was 59.6 months (95% CI 52.4–75.7), and MEPS again showed higher discrimination than R2-ISS (C-index 0.729 vs. 0.647; bootstrap delta 0.082, 95% CI 0.041–0.127). MEPS provides a simple all-cause prognostic tool for elderly/NTE MM, complementing biologically oriented staging with routinely available host-related variables.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 11","pages":"2758-2765"},"PeriodicalIF":9.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148807899","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":"Plasma Exchange and Daratumumab for Myeloma Cast Nephropathy.","authors":"Christina I Shincovich, Api Chewcharat, Motohiko Adomi, Emma E McGee, Raphael Kim, Marta Pirovano, Jason Prosek, Srinivas S Devarakonda, Joshua Leisring, Eshetu Obole, Jasmin Tharakan, Arti Vaishnav, Nattawat Klomjit, Pornlada Likasitwatanakul, Chester Andrzejewski, Sajjad Hassan, Annie Elizabeth Abraham, Lynne O'Hearn, Oscar Garcia Valencia, Jennifer S McDonald, M Salman Sheikh, Boyoung Michelle Kim, Priscilla Koirala, A Bilal Malik, Anip Bansal, Blaithin A McMahon, Benjamin Teruel, Jaya Kala, Abdallah Geara, Kristen Tillquist, Swetha Kanduri, Raphael Szalat, Ali Aijaz, Omar Mamlouk, Susan L Ziolkowski, Jillian Caldwell, Marco Bonilla, Nader Ismail, Pooja D Amarapurkar, Joseph K Franz, Rasheed A Balogun, Eibhlin Goggins, Claude Bassil, Shrinjaya Thapa, Rachid Baz, Daniel Sanghoon Shin, Jonathan E Zuckerman, Kanwarpal Kahlon, Yesha Shah, Kenar D Jhaveri, Richa Thakur, Jingjing Zhang, Priya Deshpande, Matthew H Abramson, Dureya Syed, Arun Rajasekaran, Ashwini Pujari, Jay S Raval, Linette Bosques, Florence H Porterfield, Eashwar V Somasundaram, Sophia L Wells, Mia B Rubman, Robert Seitter Pérez, Alexa C Peterkin, Carolina Saldanha Neves Horta Lima, Naoka Murakami, Maho Terashita, E Bridget Kim, Kareem Mosaheb, Paul E Hanna, Omar Nadeem, David E Leaf, Raad B Chowdhury, Sean R Stowell, Andrew J Yee, Nelson Leung, Shruti Gupta","doi":"10.1002/ajh.70516","DOIUrl":"https://doi.org/10.1002/ajh.70516","url":null,"abstract":"<p><p>Multiple myeloma light chain cast nephropathy (LCCN) is often treated with plasma exchange (PLEX) or the anti-CD38 monoclonal antibody, daratumumab. However, rigorous studies supporting these therapies for LCCN are limited. Using data from 25 U.S.-based academic cancer centers, we conducted two target trials examining the association between early receipt of PLEX or early receipt of daratumumab and kidney recovery in patients with newly diagnosed LCCN. Kidney recovery was defined as being alive, not on kidney replacement therapy, and with an improvement of at least one stage of AKI severity, all assessed at 90 days. Secondary outcomes included kidney recovery at 60 and 180 days. Logistic regression with propensity score overlap weights was used to adjust for confounders. Of 549 eligible patients for the PLEX target trial, 158 (28.8%) received PLEX. There was no association between PLEX and kidney recovery at 90 days (OR 1.48, 95% CI: 0.96-2.30). However, in subgroup analyses, PLEX was associated with higher odds of kidney recovery at 90 days among patients with newly diagnosed multiple myeloma compared to those with relapsed disease, as well as higher odds of kidney recovery among those with Stage 3 versus Stage 1 or 2 AKI at the time of LCCN diagnosis. Of 474 patients eligible for the daratumumab target trial, 136 (28.7%) received daratumumab. Daratumumab was not associated with kidney recovery at 90 days (OR 1.46, 95% CI: 0.84-2.55). Thus, in this multicenter cohort study, neither PLEX nor daratumumab was associated with kidney recovery at 90 days.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164915","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":"Clinically Relevant Outcomes With Romiplostim in Patients With Solid Tumors and Persistent Chemotherapy Induced Thrombocytopenia","authors":"Cy R. Wilkins,&nbsp;Divyash Shah,&nbsp;Andriy Derkach,&nbsp;David Nemirovsky,&nbsp;Laurent Frenzel,&nbsp;Jodi V. Mones,&nbsp;Rekha Parameswaran,&nbsp;Emily Shteynberg,&nbsp;Galia Spectre,&nbsp;Simon Mantha,&nbsp;Jeffrey I. Zwicker,&nbsp;Avi Leader","doi":"10.1002/ajh.70476","DOIUrl":"10.1002/ajh.70476","url":null,"abstract":"<div>\u0000 \u0000 <p>Thrombopoietin receptor agonists (TPO-RAs), such as romiplostim, are commonly utilized to facilitate timely platelet recovery and administration of chemotherapy in patients with cancer and chemotherapy-induced thrombocytopenia (CIT). However, there are limited data on the effect of TPO-RAs on clinically important outcomes. A target trial emulation study was implemented to assess the effects of romiplostim in patients with solid tumors and persistent CIT, compared to controls. Patients were exact-matched on chemotherapy, cancer type, degree of thrombocytopenia, and 1:1 propensity-score-matched on clinical/laboratory variables on Day 1 of romiplostim treatment or quasi-index date for controls. Study outcomes included overall survival over 24 months and venous thromboembolism (VTE) at 6 months. This study included 165 romiplostim-treated patients and 165 controls. Baseline characteristics were well-balanced. The median age was 61 years and 52% were female. The median romiplostim duration was 1.38 months. Median overall survival was 13 months (95% CI: 9.9–23) in the romiplostim group and 9.5 months (95% CI: 7.1–14.0) in controls (hazard ratio [HR] 0.86 [95% CI: 0.65–1.13]). There was a numerical improvement in survival with romiplostim (0.80 [95% CI: 0.60–1.06]) which was statistically significant in the subgroup of patients with metastatic disease (HR 0.70 [95% CI: 0.52–0.95]). The 6-month cumulative incidence of VTE was 10.0% (95% CI: 6.3%–16.0%) in the romiplostim group and 8.0% (95% CI: 4.5%–13.0%) in controls (HR 1.31 [95% CI: 0.64–2.70]), with death as a competing risk. In conclusion, these results support the safety of romiplostim in CIT with observed numerical improvement in overall survival at 2 years.</p>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 11","pages":"2726-2735"},"PeriodicalIF":9.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768631","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":"Multiple Myeloma: 2026 Update on Diagnosis, Risk-Stratification and Management","authors":"S. Vincent Rajkumar","doi":"10.1002/ajh.70475","DOIUrl":"10.1002/ajh.70475","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Diagnosis</h3>\u0000 \u0000 <p>The diagnosis of multiple myeloma requires ≥ 10% clonal bone marrow plasma cells or a biopsy proven plasmacytoma <i>plus</i> evidence of one or more multiple myeloma defining events (MDE): CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) attributable to the plasma cell disorder, bone marrow clonal plasmacytosis ≥ 60%, serum involved/uninvolved free light chain (FLC) ratio ≥ 100 (provided involved FLC is ≥ 100 mg/L and urine monoclonal protein is ≥ 200 mg/24 h), or &gt; 1 focal lesion on magnetic resonance imaging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Risk Stratification</h3>\u0000 \u0000 <p>High-risk multiple myeloma is defined by the presence of del(17p), p53 mutation, or bi-allelic del(1p); t(4;14), t(14;16), t(14;20) in combination with gain(1q) or del(1p); or gain(1q) plus del(1p).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Initial Therapy</h3>\u0000 \u0000 <p>Initial therapy consists of a quadruplet regimen consisting of anti-CD38 monoclonal antibody (daratumumab or isatuximab) plus bortezomib, lenalidomide, dexamethasone (VRd) followed by autologous stem cell transplantation in eligible patients. Selected standard risk patients can delay transplant until first relapse. Frail patients who are not candidates for transplant are treated with a triplet regimen, either anti-CD 38 antibody plus lenalidomide and dexamethasone, or VRd.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Maintenance Therapy</h3>\u0000 \u0000 <p>Standard maintenance is lenalidomide in combination with daratumumab or isatuximab. Lenalidomide is discontinued after 2 years in standard-risk patients. Bortezomib plus lenalidomide is an alternative option for high-risk myeloma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Management of Relapsed Disease</h3>\u0000 \u0000 <p>Major options are chimeric antigen receptor T (CAR-T) cell therapy, bispecific antibodies, various triplet regimens, and belantamab mafadotin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Management of Smoldering Multiple Myeloma</h3>\u0000 \u0000 <p>Daratumumab for 3 years should be considered in high-risk smoldering multiple myeloma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"101 11","pages":"2866-2889"},"PeriodicalIF":9.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ajh.70475","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768634","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}