Aurore Perrot, Thierry Facon, Torben Plesner, Saad Z Usmani, Shaji Kumar, Nizar J Bahlis, Cyrille Hulin, Robert Z Orlowski, Hareth Nahi, Peter Mollee, Karthik Ramasamy, Murielle Roussel, Arnaud Jaccard, Michel Delforge, Lionel Karlin, Bertrand Arnulf, Ajai Chari, George Wang, Niodita Gupta-Werner, Shuchita Kaila, Huiling Pei, Kathryn Matt, Katharine S Gries, Robin Carson, Fredrik Borgsten, Katja Weisel
{"title":"Sustained Improvement in Health-Related Quality of Life in Transplant-Ineligible Newly Diagnosed Multiple Myeloma Treated With Daratumumab, Lenalidomide, and Dexamethasone: MAIA Final Analysis of Patient-Reported Outcomes.","authors":"Aurore Perrot, Thierry Facon, Torben Plesner, Saad Z Usmani, Shaji Kumar, Nizar J Bahlis, Cyrille Hulin, Robert Z Orlowski, Hareth Nahi, Peter Mollee, Karthik Ramasamy, Murielle Roussel, Arnaud Jaccard, Michel Delforge, Lionel Karlin, Bertrand Arnulf, Ajai Chari, George Wang, Niodita Gupta-Werner, Shuchita Kaila, Huiling Pei, Kathryn Matt, Katharine S Gries, Robin Carson, Fredrik Borgsten, Katja Weisel","doi":"10.1111/ejh.14392","DOIUrl":"https://doi.org/10.1111/ejh.14392","url":null,"abstract":"<p><strong>Objectives: </strong>This final post hoc analysis evaluated patient-reported outcomes from the Phase 3 MAIA study of daratumumab, lenalidomide, and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) after median 64.5-month follow-up in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM), including patient subgroups.</p><p><strong>Methods: </strong>Key scales from the EORTC QLQ-C30 (global health status [GHS], physical functioning, pain, and fatigue) were assessed. Scores were evaluated every 3 months for 1 year, then every 6 months until disease progression.</p><p><strong>Results: </strong>The intent-to-treat population (n = 737) included 46.3% frail, 35.4% 70 to < 75 years old, and 43.6% ≥ 75 years old. D-Rd-treated patients showed improvements from baseline that were sustained over 5 years in the intent-to-treat population and across subgroups by age, frailty, and bone lesions. Greater proportions of patients treated with D-Rd versus Rd achieved minimally important changes for improvement at cycle 36 (year ~3) in GHS (odds ratio, 1.84 [95% CI, 1.16-2.91]), physical functioning (1.93 [1.18-3.14]), pain (1.41 [0.90-2.22]), and fatigue (2.00 [1.24-3.23]). Greater proportions of patients with bone lesions improved with D-Rd versus Rd on GHS and physical functioning.</p><p><strong>Conclusions: </strong>In transplant-ineligible patients with NDMM, D-Rd improved health-related quality of life over a 5-year period versus Rd.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov: NCT02252172.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tadeusz Robak, Marta Robak, Agata Majchrzak, Anna Krawczyńska, Marcin Braun
{"title":"Atypical Hairy Cell Leukemia-The Current Status and Future Directions.","authors":"Tadeusz Robak, Marta Robak, Agata Majchrzak, Anna Krawczyńska, Marcin Braun","doi":"10.1111/ejh.14388","DOIUrl":"https://doi.org/10.1111/ejh.14388","url":null,"abstract":"<p><p>Hairy cell leukemia (HCL) is a rare, chronic lymphoid leukemia characterized by circulating lymphocytes with pale, hair-like cytoplasmic projections, pancytopenia, marked monocytopenia, and splenomegaly. Classic HCL displays distinct morphological, immunophenotypical, and genetic features. Classic HCL cells exhibit central nuclei, abundant cytoplasm with hair-like projections, and expression of CD20, CD22, CD11c, CD103, CD25, CD123, TBX21, annexin A1 (ANXA1), FMC7, CD200, and weak cyclin D1 (CCND1). While the vast majority of classic HCL cases harbor the BRAF V600E somatic mutation, rare examples have been reported without splenomegaly, with bulky lymphadenopathy, or with an atypical morphology, immunophenotype or genotype. This review analyzes the atypical clinical, morphologic, immunophenotypic, and genetic presentations associated with classic HCL. PubMed, Web of Science, and Google Scholar were searched for articles of hairy cell leukemia, including atypical morphology, atypical immunophenotype, atypical genotype, and rare symptoms. Publications from October 2004 to December 2024 were reviewed, with additional relevant studies obtained by reviewing references from selected articles.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Divaya Bhutani, Rajshekhar Chakraborty, Karan Wats, Michael Sang Hughes, Lotan Dor, Miroslav Sekulic, Suzanne Lentzsch
{"title":"Treatment of Refractory Monoclonal Immunoglobulin Deposition Disease With BCMA Bispecific Antibody","authors":"Divaya Bhutani, Rajshekhar Chakraborty, Karan Wats, Michael Sang Hughes, Lotan Dor, Miroslav Sekulic, Suzanne Lentzsch","doi":"10.1111/ejh.14393","DOIUrl":"10.1111/ejh.14393","url":null,"abstract":"<div>\u0000 \u0000 <p>Monoclonal immunoglobulin deposition disease (MIDD) is characterized by deposits of intact monoclonal immunoglobulin protein, most commonly in the kidney, but other organs such as the heart can be involved. Patients are treated with plasma cell-directed therapies. Here we describe the first reported case of a patient with refractory MIDD with renal and cardiac involvement who was successfully treated with a BCMA-drected therapy. After achieving a deep hematologic response, the patient achieved a cardiac organ response as well. BCMA-directed therapy can be valuable for patients with refractory monoclonal immunoglobulin deposition disease.</p>\u0000 </div>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":"114 4","pages":"700-703"},"PeriodicalIF":2.3,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Avatrombopag for the Treatment of Immune Thrombocytopenia.","authors":"Caterina Labanca, Ernesto Vigna, Enrica Antonia Martino, Antonella Bruzzese, Francesco Mendicino, Giulio Caridà, Eugenio Lucia, Virginia Olivito, Noemi Puccio, Antonino Neri, Fortunato Morabito, Massimo Gentile","doi":"10.1111/ejh.14395","DOIUrl":"https://doi.org/10.1111/ejh.14395","url":null,"abstract":"<p><p>Avatrombopag, a second-generation thrombopoietin receptor agonist (TPO-RA), represents a significant advancement in the treatment of chronic immune thrombocytopenic purpura (cITP) and a potential therapeutic option for other thrombocytopenic disorders. Approved in both the USA and Europe, avatrombopag offers a convenient oral dosing regimen, initiated at 20 mg daily with food, to achieve and maintain platelet counts ≥ 50 × 10<sup>9</sup>/L. Its favorable safety profile, characterized by minimal hepatic toxicity and the absence of dietary restrictions, distinguishes it from older TPO-RAs such as eltrombopag and romiplostim. Clinical trials and real-world data support its efficacy, with over 90% of patients that fail to standard first- and second-line treatments or become unresponsive, achieving target platelet counts, and its hepatotoxicity-free profile makes it particularly advantageous for patients with liver disease or complex comorbidities. Economic evaluations, including a budget impact analysis for the Italian National Health Service, have projected significant healthcare cost savings associated with avatrombopag use, reinforcing its value as a cost-effective therapeutic option. However, challenges remain, including limited data on long-term safety. In this review, we aim to provide a comprehensive synthesis of clinical evidence and real-world data on avatrombopag's efficacy, safety, and pharmacological advantages, while exploring its current and potential therapeutic applications, such as chemotherapy-induced thrombocytopenia and aplastic anemia.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Myrte Zijlstra, Rolf A H Snijders, Fransien de Boer, Martine E D Chamuleau, Heidi P Fransen, Simone Oerlemans, Annemieke van der Padt-Pruijsten, Eduardus F M Posthuma, Otto Visser, Sonja Zweegman, Natasja J H Raijmakers, Avinash G Dinmohamed
{"title":"Factors and Considerations in No-Treatment Decisions in Patients With Key Hematological Malignancies: A Nationwide, Population-Based Study in the Netherlands.","authors":"Myrte Zijlstra, Rolf A H Snijders, Fransien de Boer, Martine E D Chamuleau, Heidi P Fransen, Simone Oerlemans, Annemieke van der Padt-Pruijsten, Eduardus F M Posthuma, Otto Visser, Sonja Zweegman, Natasja J H Raijmakers, Avinash G Dinmohamed","doi":"10.1111/ejh.14390","DOIUrl":"https://doi.org/10.1111/ejh.14390","url":null,"abstract":"<p><p>Comprehensive insights are lacking into why patients with hematological malignancies (HMs) receive no cancer-directed treatment. We evaluated socio-demographic and cancer-related characteristics, decision-making rationales, and overall survival in patients with three common HMs-diffuse large B-cell lymphoma (DLBCL), symptomatic multiple myeloma (MM), and acute myeloid leukemia (AML)-who do not receive cancer-directed treatment, using the nationwide Netherlands Cancer Registry. A total of 26 945 patients diagnosed with DLBCL (47%), symptomatic MM (29%), or AML (25%) between 2014 and 2021 were included. About 16% of the patients did not receive cancer-directed treatment, ranging from 26% in AML to 15% in DLBCL and 10% in MM. The primary reason for not receiving cancer-directed treatment in all three HMs was related to physical condition. The second main reason was patient/family choice in DLBCL and MM, whereas in AML it was rapid disease progression. In female patients, patient/family choice was a more prevalent reason for not receiving cancer-directed treatment than in male patients. Patients with a lower socio-economic position more often did not receive cancer-directed treatment. Median OS varied by reason for not receiving cancer-directed treatment, with the shortest OS in patients experiencing rapid disease progression or death before treatment initiation (0·4 to 0·6 months).</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Iron Overload, Oxidative Stress, and Somatic Mutations in MDS: What Is the Association?","authors":"Heather A Leitch","doi":"10.1111/ejh.14385","DOIUrl":"https://doi.org/10.1111/ejh.14385","url":null,"abstract":"<p><strong>Introduction: </strong>Iron overload (IOL) accumulates in myelodysplastic syndromes (MDS) from expanded erythropoiesis and transfusions. Somatic mutations (SM) are frequent in MDS and stratify patient risk. MDS treatments reversing or limiting transfusion dependence are limited.</p><p><strong>Methods: </strong>The literature was reviewed on how IOL and oxidative stress interact with specific SM in MDS to influence cellular physiology. PubMed searches included keywords of each specific mutation combined with iron, oxidative stress, and reactive oxygens species (ROS). Papers relevant to hematopoietic stem/progenitor cells, the bone marrow microenvironment, MDS, AML or other myeloid disorders were preferred. Included were the most frequent SM in MDS, SM of the International Prognostic Scoring System-Molecular (IPSS-M), of familial predisposing conditions and the CMML PSS-molecular.</p><p><strong>Results: </strong>About 31 SM plus four familial conditions were searched. Discussed are the frequency of each SM, whether function is gained or lost, early or late SM status, a function of the unmutated gene, and function considering iron and oxidative stress.</p><p><strong>Discussion: </strong>Given limited effective MDS therapies, considering how IOL and ROS interact with SM to influence cellular physiology in the hematopoietic system, increasing bone marrow failure progression or malignant transformation may be of benefit and support optimization of measures to reduce IOL or neutralize ROS.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mira Muxi Yang, Revika Singh, Maureen Haugen, Ashley Duff, Jenny Shoop, Elaine R Morgan, Jenna E Rossoff, Joanna L Weinstein, Mallorie B Heneghan, Sherif M Badawy
{"title":"Adherence to 6-Mercaptopurine (6-MP) and Habit Strength in Pediatric Acute Lymphoblastic Leukemia (ALL).","authors":"Mira Muxi Yang, Revika Singh, Maureen Haugen, Ashley Duff, Jenny Shoop, Elaine R Morgan, Jenna E Rossoff, Joanna L Weinstein, Mallorie B Heneghan, Sherif M Badawy","doi":"10.1111/ejh.14386","DOIUrl":"https://doi.org/10.1111/ejh.14386","url":null,"abstract":"<p><strong>Background: </strong>Low 6-mercaptopurine (6-MP) adherence (< 95%) is associated with increased relapse in pediatric acute lymphoblastic leukemia (ALL). Stronger habit has been associated with higher adherence. We examined the relationship of 6-MP adherence to habit strength and health-related quality of life in pediatric ALL.</p><p><strong>Methods: </strong>A single-center, cross-sectional study of 52 participants: 11 patients (mean age 16 ± 4) and 41 parents/caregivers (age 37 ± 5). Participants completed Visual Analogue Scale (VAS<sub>dose</sub>), Patient Reported Outcomes Measurement Information System Medication Adherence Scale, and the Self-Regulated Habit Index (SRHI). Twelve semi-structured participant interviews were analyzed using thematic analysis.</p><p><strong>Results: </strong>81% (42/52) of participants reported high 6-MP adherence (VAS<sub>dose</sub> ≥ 95%): patients 91% (10/11), parents 78% (32/41). No significant correlation was found between adherence and habit strength. Reported adherence facilitators included reminders, care team communications, personalized tools, administration experience, self-efficacy, and social support. Conversely, financial burden, scheduling conflicts, and medication access were cited as barriers.</p><p><strong>Conclusions: </strong>One-fifth of participants reported low 6-MP adherence, with habit strength not associated with adherence. Variability of 6-MP routines may prohibit automaticity. While 6-MP adherence may not correlate with habit strength, interventions promoting and strengthening habit formation may overcome barriers to 6-MP adherence and improve outcomes.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Increased Non-Relapse Mortality in Older People With Allogeneic Hematopoietic Stem Cell Transplantation Using Fludarabine and Myeloablative Dose of Busulfan-Based Regimen.","authors":"Akihito Shinohara, Michiho Shindo, Nobuaki Nakano, Emiko Sakaida, Naoyuki Uchida, Kentaro Fukushima, Hideyuki Nakazawa, Kentaro Serizawa, Yoshinobu Kanda, Toshiro Kawakita, Takashi Ikeda, Hiroyuki Ohigashi, Ayumu Ito, Toshio Wakayama, Ken-Ichi Matsuoka, Takahiro Fukuda, Junji Tanaka, Yoshiko Atsuta, Hideki Nakasone","doi":"10.1111/ejh.14374","DOIUrl":"https://doi.org/10.1111/ejh.14374","url":null,"abstract":"<p><p>Fludarabine and myeloablative busulfan (FluBu4) in allogeneic hematopoietic stem cell transplantation (HSCT) for older people have not been adequately examined. This retrospective study analyzed data from a large-scale, nationwide database in Japan. Adult patients (> 15 years old, y/o) who received their first HSCT with FluBu4 for hematological malignancies were included. They were categorized into the younger (< 60 y/o, N = 1295) and the older group (≥ 60 y/o, N = 993). The 3-year overall survival (OS) rate after HSCT was significantly worse in the older group than in the other (p < 0.01, 39.9% vs. 48.5%). The 3-year non-relapse mortality (NRM) was significantly higher in the older group than in the other (p < 0.01, 30.9% vs. 23.0%), and the 3-year cumulative incidence of relapse was comparable between them. According to the multivariate analysis, age ≥ 60 years was significantly associated with poor OS and high NRM. In a subgroup analysis of the older group, the use of additional chemotherapeutic drugs to FluBu4 was significantly associated with poor OS and high NRM. Total body irradiation was significantly associated with high NRM and 1-year incidence of sinusoidal obstruction syndrome but not with OS. Thus, FluBu4 should be used with caution in older people.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}