EJHaem最新文献

{"title":"A GIMEMA survey on therapeutic use and response rates of FLT3 inhibitors in acute myeloid leukemia: Insights from Italian real-world practice","authors":"Monica Messina,&nbsp;Alfonso Piciocchi,&nbsp;Leonardo M. Siena,&nbsp;Stefano Soddu,&nbsp;Francesco Buccisano,&nbsp;Cristina Mecucci,&nbsp;Giovanni Martinelli,&nbsp;Antonio Curti,&nbsp;Roberto Cairoli,&nbsp;Paola Fazi,&nbsp;Marco Vignetti,&nbsp;Maria Teresa Voso,&nbsp;Adriano Venditti,&nbsp;Anna Candoni","doi":"10.1002/jha2.1045","DOIUrl":"10.1002/jha2.1045","url":null,"abstract":"<p>Given the limited data on the real-life therapeutic use of feline McDonough sarcoma (FMS)-like tyrosine kinase 3 (FLT3) inhibitors in Italy, we surveyed investigators at 59 Italian hematology centers to gain insight into the proportion of acute myeloid leukemia (AML) patients receiving FLT3 inhibitors and we collected data on the efficacy and safety of these agents. The survey results showed that in the real-life setting the response rate of the 3/7 + midostaurin regimen in newly diagnosed FLT3-mutated AML and of gilteritinib in the relapsed/refractory AML were comparable to that reported in the registrative clinical trials. The 3/7 + midostaurin treatment resulted in a 63% of complete remission (CR) rates and gilteritinib in a 44% of CR rates. The discontinuation rate of gilteritinib for intolerance or toxicity was low (accounting for 4% of treated cases).</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1274-1277"},"PeriodicalIF":0.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of secondary-type mutations in acute myeloid leukemia with CEBPA mutation","authors":"Davidson Zhao,&nbsp;Musani Rumina,&nbsp;Mojgan Zarif,&nbsp;Cuihong Wei,&nbsp;Hong Chang","doi":"10.1002/jha2.1055","DOIUrl":"10.1002/jha2.1055","url":null,"abstract":"&lt;p&gt;To the Editor,&lt;/p&gt;&lt;p&gt;Secondary-type mutations (STM: &lt;i&gt;ASXL1&lt;/i&gt;, &lt;i&gt;BCOR&lt;/i&gt;, &lt;i&gt;EZH2&lt;/i&gt;, &lt;i&gt;SF3B1&lt;/i&gt;, &lt;i&gt;SRSF2&lt;/i&gt;, &lt;i&gt;STAG2&lt;/i&gt;, &lt;i&gt;U2AF1&lt;/i&gt;, and &lt;i&gt;ZRSR2&lt;/i&gt;) in acute myeloid leukemia (AML) were reported to be highly specific for secondary disease and associated with inferior event-free survival (EFS) [&lt;span&gt;1, 2&lt;/span&gt;]. In light of these findings, the newly-revised 5th edition of the WHO Classification of Haematolymphoid Tumours (WHO-HAEM5) includes STM in the criteria defining AML, myelodysplasia-related (AML-MR) [&lt;span&gt;3&lt;/span&gt;]. In the newly-published International Consensus of Classification of myeloid neoplasms and acute leukemia (ICC), &lt;i&gt;RUNX1&lt;/i&gt; mutation together with STM as described by WHO-HAEM5 define the entity of AML with myelodysplasia-related gene mutations [&lt;span&gt;4&lt;/span&gt;]. To date, several studies have examined the impact of STM in other molecularly defined entities of AML such as &lt;i&gt;NPM1&lt;/i&gt;+ AML [&lt;span&gt;5-9&lt;/span&gt;]. However, the impact of STM in AML with &lt;i&gt;CEBPA&lt;/i&gt; mutation has not been studied extensively and remains unclear. Thus, we sought to investigate the clinical impact of STM in AML with &lt;i&gt;CEBPA&lt;/i&gt; mutation.&lt;/p&gt;&lt;p&gt;We conducted a retrospective analysis with a single center cohort of 38 cases of AML with &lt;i&gt;CEBPA&lt;/i&gt; mutation diagnosed at our institution from 2015 to 2024. Patients were included if they met WHO-HAEM5 criteria of blasts ≥ 20% and either biallelic &lt;i&gt;CEBPA&lt;/i&gt; mutation or single &lt;i&gt;CEBPA&lt;/i&gt; mutation in the basic leucine zipper (bZIP) domain. Cytogenetic testing, molecular genetic testing, and variant calling in next-generation sequencing were performed according to previously described procedures [&lt;span&gt;10&lt;/span&gt;]. Gene panel for targeted sequencing and exon coverage for hotspot genes are listed in Tables S1 and S2.&lt;/p&gt;&lt;p&gt;The baseline clinicopathological characteristics and co-mutation landscape of the study cohort are summarized in Table 1 and Figure 1A. Of the 38 patients with AML with &lt;i&gt;CEBPA&lt;/i&gt; mutation, 11 (29%) had STM. &lt;i&gt;SRSF2&lt;/i&gt; and &lt;i&gt;STAG2&lt;/i&gt; were the most common STMs (both 8/38, 21%), followed by &lt;i&gt;ASXL1&lt;/i&gt; (6/38, 16%), &lt;i&gt;BCOR&lt;/i&gt; (2/38, 5%), and &lt;i&gt;U2AF1&lt;/i&gt; (1/38, 3%). &lt;i&gt;RUNX1&lt;/i&gt; mutations were found in two (5%) patients, both of whom had concurrent WHO-HAEM5-defined STMs. &lt;i&gt;EZH2&lt;/i&gt;, &lt;i&gt;ZRSR2&lt;/i&gt;, and &lt;i&gt;SF3B1&lt;/i&gt; mutations were not detected. The most common recurrent (&gt;10%) co-mutated genes in the cohort were &lt;i&gt;TET2&lt;/i&gt; (10/38; 26%), &lt;i&gt;GATA2&lt;/i&gt; (9/38, 24%), &lt;i&gt;WT1&lt;/i&gt; (8/38, 21%), &lt;i&gt;NRAS&lt;/i&gt; (6/38, 16%) and &lt;i&gt;FLT3&lt;/i&gt;-ITD (4/38, 11%). Compared to patients without STM, patients with STM were older, had less proliferative disease, had lower hemoglobin levels, and had significantly lower variant allele frequency of mutant &lt;i&gt;CEBPA&lt;/i&gt; and infrequent in-frame bZIP &lt;i&gt;CEBPA&lt;/i&gt; mutation.&lt;/p&gt;&lt;p&gt;Consistent with the older age of the STM+ group, only five (46%) patients received intensive chemotherapy compared to all 27 (100%) patients in the STM-ve group. Of note,","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1370-1372"},"PeriodicalIF":0.0,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immediate improvement in patient care: Auditing adherence to the British Society for Haematology guidelines on screening and management of the long-term consequences of multiple myeloma and treatment","authors":"Kerrie Sweeney,&nbsp;Aaron Niblock,&nbsp;Diana Greenfield,&nbsp;John Snowden","doi":"10.1002/jha2.999","DOIUrl":"10.1002/jha2.999","url":null,"abstract":"<p>Advances in myeloma have resulted in improved prognosis for patients. However complications of the disease and treatment, pose a risk of specific long-term consequences. An audit tool was adapted to assess adherence to the British Society for Haematology guidelines for screening and management of long-term myeloma consequences. Thereafter a screening checklist was developed to prompt the implementation of guideline recommendations, followed by a re-audit evaluating the effectiveness of the checklist.</p><p>Good baseline practice was identified relating to vaccinations, herpes prophylaxis, dental assessment, bisphosphonates, calcium/ vitamin D supplementation and holistic needs assessments. However gaps in practice included monitoring of lipids, HBA1C, NT-pro-BNP/ BNP, BMI, calcium/ vitamin D and parathyroid hormone in kidney disease, endocrine screening and geriatric assessments. Re-audit demonstrated that geriatric assessment remains a gap in practice, however other standards now scored between 80 to 100% compliance, highlighting the benefits of a screening checklist, to increase adherence to recommendations.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1359-1362"},"PeriodicalIF":0.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between microenvironment-related genes and prognosis of primary central nervous system lymphoma","authors":"Keiichiro Hattori,&nbsp;Kenichi Makishima,&nbsp;Sakurako Suma,&nbsp;Yoshiaki Abe,&nbsp;Yasuhito Suehara,&nbsp;Tatsuhiro Sakamoto,&nbsp;Naoki Kurita,&nbsp;Ryota Ishii,&nbsp;Ryota Matsuoka,&nbsp;Masahide Matsuda,&nbsp;Takao Tsurubuchi,&nbsp;Ryo Nishikawa,&nbsp;Shota Tanaka,&nbsp;Akitake Mukasa,&nbsp;Yoshitaka Narita,&nbsp;Koichi Ichimura,&nbsp;Motoo Nagane,&nbsp;Shingo Takano,&nbsp;Bryan J. Mathis,&nbsp;Eiichi Ishikawa,&nbsp;Daisuke Matsubara,&nbsp;Shigeru Chiba,&nbsp;Mamiko Sakata-Yanagimoto","doi":"10.1002/jha2.1046","DOIUrl":"10.1002/jha2.1046","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Primary central nervous system lymphoma (PCNSL) is a rare lymphoid malignancy. Systemic profiling of the PCNSL tumor microenvironment (TME) was previously conducted through gene expression analysis. We investigated the prognostic impact of TME on survival to establish novel prognostic biomarkers in PCNSL patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed expression levels of 770 neuroinflammation-related (NFR) genes via NanoString nCounter technology in tumor samples from 30 PCNSL patients. Genes related to the “recurrence group (RG)” or “non-recurrence group (NRG)” were identified and validated using whole transcriptomic analysis of an independent PCNSL cohort (<i>n</i> = 30).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Forty-five of 770 NFR genes were highly expressed in the RG (3-year overall survival (OS, 22.2%), compared with the NRG group (3-year OS 66.7%). Signatures related to glial cells were enriched in the RG-associated gene set. Multivariate analysis revealed that high expressions of <i>TUBB4A</i> (<i>p</i> = 0.028, HR: 3.88), <i>S100B</i> (<i>p</i> = 0.046, HR: 3.093), and <i>SLC6A1</i> (<i>p</i> = 0.034, HR: 3.765) were significantly related to death. Expression levels of these three genes were also significantly associated with poor OS in the validation cohort. Immunohistochemical staining against TUBB4A, S100B, and proteins specific to glial cells (GFAP, OLIG2, and CD68) revealed significantly higher positivity in RG glial cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These data suggest that TME-related genes play a crucial role in the pathogenesis of PCNSL, complementing the well-known involvement of the NF-kB signaling pathway. TME targeting, especially glial cell-specific proteins, may thus open new and complementary avenues of therapy for all stages of PCNSL.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1201-1214"},"PeriodicalIF":0.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Congestive heart failure after anthracycline-containing treatment for Hodgkin lymphoma: A Swedish matched cohort study","authors":"Joachim Baech,&nbsp;Tarec Christoffer El-Galaly,&nbsp;Joshua P. Entrop,&nbsp;Ingrid Glimelius,&nbsp;Daniel Molin,&nbsp;Sissel Johanne Godtfredsen,&nbsp;Michael J. Crowther,&nbsp;Karin E. Smedby,&nbsp;Sandra Eloranta,&nbsp;Caroline E. Dietrich","doi":"10.1002/jha2.1048","DOIUrl":"10.1002/jha2.1048","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Congestive heart failure (CHF) is a known complication after anthracyclines and radiotherapy for classical Hodgkin lymphoma (cHL). Contemporary cHL treatment may be associated with less risk because radiotherapy use and techniques have changed substantially over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, Swedish cHL patients diagnosed in 2000–2018, and treated with adriamycin [doxorubicin], bleomycin, vinblastine, and dacarbazine (ABVD) or bleomycin, etoposide, Adriamycin [doxorubicin], cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), were matched 1:10 to the general population on birth year and sex to investigate relative rates and cumulative risks of CHF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 1994 cHL patients were included, with a median age of 34 years. The median follow-up was 8.1 years. The CHF rate was higher for patients versus comparators (adjusted hazard ratio [HR] = 3.02, 95% confidence interval [CI]: 2.26–4.02). Patients treated with ≤200 mg/m² of anthracyclines had HR of 2.89 (95% CI: 1.51–3.47) versus 3.91 (95% CI: 2.72–5.60) for &gt;200 mg/m². Treatment with ABVD was associated with a significantly higher CHF rate (adjusted HR = 3.25, 95% CI: 2.31–4.23), while BEACOPP was not (adjusted HR = 1.95, 95% CI: 0.91–4.16). The increase in relative rates translated to the absolute scale, with an increased risk persisting up to 18 years for low cumulative doses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings highlight that cHL survivors still face a substantial excess risk of CHF in the modern treatment era and that focus on cardiovascular health remains relevant.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1190-1200"},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New insights into the mechanisms of red blood cell enucleation: From basics to clinical applications","authors":"Qianli Zhuo,&nbsp;Zhaojun Zhang,&nbsp;Xiangdong Fang","doi":"10.1002/jha2.1051","DOIUrl":"10.1002/jha2.1051","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Red blood cell (RBC) enucleation is a crucial step in the process of erythropoiesis. By removing the nucleus, RBCs gain greater flexibility, enabling them to traverse narrow capillaries with ease, thereby enhancing the efficiency of oxygen and carbon dioxide transport. This transformation underscores the intricate balance between cellular structure and function essential for maintaining homeostasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Topic</h3>\u0000 \u0000 <p>This review delves into the multifaceted enucleation process, outlining its complex steps that encompass protein sorting, vesicle trafficking, cytoskeletal remodeling, and apoptosis regulation, while also exploring the potential of enhancing the enucleation rate of RBCs in vitro. We emphasize the intricate regulation of this process, which is orchestrated by multiple factors. This includes transcription factors that meticulously guide protein synthesis and sorting through the modulation of gene expression, as well as non-coding RNAs that play a pivotal role in post-transcriptional regulation during various stages of RBC enucleation. Additionally, macrophages participate in the enucleation process by engulfing and clearing the extruded nuclei, further ensuring the proper development of RBCs. Although many studies have deeply explored the molecular mechanisms of enucleation, the roles of apoptosis and anti-apoptotic processes in RBC enucleation remain incompletely understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Implication</h3>\u0000 \u0000 <p>In this review, we aim to comprehensively summarize the RBC enucleation process and explore the progress made in ex vivo RBC generation. In the future, a deeper understanding of the enucleation process could provide significant benefits to patients suffering from anemia and other related conditions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1301-1311"},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolated thrombocytopenia in pregnancy: A monocentric retrospective study of 63 pregnancies in 59 women","authors":"Giulia Freddi,&nbsp;Enea Parimbelli,&nbsp;Federico Vai,&nbsp;Silvana Quaglini,&nbsp;Valeria Bozzi,&nbsp;Serena Barozzi,&nbsp;Fausta Beneventi,&nbsp;Irene De Maggio,&nbsp;Chiara Cavagnoli,&nbsp;Antonio Di Sabatino,&nbsp;Patrizia Noris,&nbsp;Federica Melazzini","doi":"10.1002/jha2.957","DOIUrl":"10.1002/jha2.957","url":null,"abstract":"<p>Thrombocytopenia during pregnancy is often thought to be associated with severe bleeding manifestations. Three are the main disorders associated with this condition: gestational thrombocytopenia (GT), immune thrombocytopenia (ITP), and inherited thrombocytopenias (ITs). Reaching the correct diagnosis of this condition has relevant therapeutic and outcome implications. We performed a retrospective, observational, monocentric study enrolling 59 consecutive women with isolated thrombocytopenia, attended to our referral center in the last 3 years. Together with personal and family history, platelet (PLT) count trend and mean platelet volume (MPV) in pregnancy are helpful for the diagnosis, with the highest PLT count in GT and lowest in ITs, with different timing of count decrease. MPV is significantly increased in both ITs and ITP. Misdiagnosis with ITP was responsible for unnecessary and unsuccessful therapy in some GT or ITs pregnant women, determining relevant side effects. Excluding inherited platelet function disorders (IPFDs), the bleeding risk for mother with thrombocytopenia and their newborns is similar to the general population. Vaginal delivery is associated with a lower risk of bleeding than cesarean section and therefore is preferable whenever obstetrical–gynecological conditions permit.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1125-1132"},"PeriodicalIF":0.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Circulating tumor DNA for monitoring classic Hodgkin lymphoma patients: Correlation with FDG-PET/CT","authors":"","doi":"10.1002/jha2.1044","DOIUrl":"10.1002/jha2.1044","url":null,"abstract":"<p>EJHaem. 2024 Feb; 5(1): 70–75.</p><p>The authors regret that the Acknowledgments section contains a mistake in the reference to the funding by the “Instituto de Salud Carlos III (ISCIII)” in the published article.</p><p>The correct reference is “This work was supported by Instituto de Salud Carlos III (ISCIII), projects PI19/00083 and PI22/00556 (co-funded by the European Union)”.</p><p>The authors would like to apologize for any inconvenience caused.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1373"},"PeriodicalIF":0.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluctuation of physical function during chimeric antigen receptor T-cell therapy during rehabilitation intervention: Real-world data and risk factor analyses","authors":"Ryota Hamada,&nbsp;Yasuyuki Arai,&nbsp;Toshio Kitawaki,&nbsp;Naokazu Nakamura,&nbsp;Masanobu Murao,&nbsp;Michiko Matsushita,&nbsp;Junsuke Miyasaka,&nbsp;Tsugumi Asano,&nbsp;Tomoyasu Jo,&nbsp;Momoko Nishikori,&nbsp;Junya Kanda,&nbsp;Chisaki Mizumoto,&nbsp;Kouhei Yamashita,&nbsp;Ryosuke Ikeguchi,&nbsp;Akifumi Takaori-Kondo","doi":"10.1002/jha2.1043","DOIUrl":"10.1002/jha2.1043","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Patients undergoing chimeric antigen receptor (CAR) T-cell therapy face prolonged treatment timelines and are prone to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) after infusion. Disabilities in physical function and the importance of rehabilitation during CAR-T-cell therapy to maintain physical function have been poorly documented.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>We performed a retrospective cohort study to assess changes in exercise tolerance via differences in a 6-min-walking distance (Δ6MWD) and factors influencing it.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 77 patients who underwent rehabilitation during CAR-T-cell therapy were enrolled, and their 6MWD was 450 m (median, range 180–705 m) before and 450.5 m (107.0–735.0 m) 30 days after CAR-T treatment. No significant alteration in Δ6MWD was observed overall (11.0 m, 95% confidence interval, −56.1 to 88.2 m). Multiple regression analyses indicated that age (over vs. under 65 years) revealed no notable differences in Δ6MWD (20 vs. 10 m), while ΔHb (<i>β</i> = 0.24, <i>p</i> = 0.03), moderate/severe CRS (grade 1 with continuous fever or grade ≥2; <i>β</i> = −0.25, <i>p</i> = 0.03), and ICANS (any grade; <i>β</i> = −0.22, <i>p</i> = 0.04) were significantly associated with lower Δ6MWD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This real-world study indicated that CAR-T-cell therapy is less likely to reduce physical function even in older patients if rehabilitation is properly performed, whereas CRS and ICANS can be risk factors to deprive exercise tolerance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1252-1259"},"PeriodicalIF":0.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Luspatercept in β-thalassemia: Who and when. Strengths and weaknesses points of a real-world evidence","authors":"Lorenza Torti,&nbsp;Nicolina Ardu,&nbsp;Laura Maffei,&nbsp;Paolo De Fabritiis,&nbsp;Francesco Sorrentino","doi":"10.1002/jha2.1032","DOIUrl":"10.1002/jha2.1032","url":null,"abstract":"&lt;p&gt;The treatment landscape for transfusion-dependent β-thalassemia (TDT) has evolved, with safer transfusion practices and advances in iron overload management.&lt;/p&gt;&lt;p&gt;Nevertheless, limitations of blood supply, and adverse events related to transfusions and iron chelation, can lead to increased morbidity and reduced quality of life [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Luspatercept (ACE-536) was recently approved for managing anemia in TDT based on data from the BELIEVE trial [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;However, management in routine clinical practice is only initial, and clear criteria for treatment prioritization are still lacking.&lt;/p&gt;&lt;p&gt;Here, we report our real-life experience regarding its use in 10 TDT patients followed from March 2023 to June 2024 (Table 1), presenting predicting factors of quality response and the best timing of starting treatment (Tables 2 and 3).&lt;/p&gt;&lt;p&gt;ACE-536 was administered subcutaneously every 21 days at a starting dose of 1 mg/Kg, adjusted up to 1.25 mg/Kg in two patients, without changes in iron chelation therapy.&lt;/p&gt;&lt;p&gt;All our patients were studied by magnetic resonance imaging of the spine and by thrombophilia tests.&lt;/p&gt;&lt;p&gt;Prior evaluation of BetaHcg in female patients was performed to exclude a concomitant pregnancy. We have strongly recommended, regardless of the kind of sex, the use of effective contraceptive methods, due to the unknown effects on embryogenesis.&lt;/p&gt;&lt;p&gt;We have ruled out all patients with a previous medical history of thrombotic events.&lt;/p&gt;&lt;p&gt;Psychological support was provided to all patients.&lt;/p&gt;&lt;p&gt;We performed B vitamins intravenously administration, with folates and cyanocobalamin to support the increased erythropoiesis process.&lt;/p&gt;&lt;p&gt;We have reported  ACE-536 efficacy in terms of transfusional burden reduction, transfusional interval extended, increase of hemoglobin values preblood transfusion and ferritin values decrease, comparing 12 weeks before and after the first drug administration (Table 2 and Figures 1 and 2).&lt;/p&gt;&lt;p&gt;Statistical analysis was performed with an independent two-sample &lt;i&gt;t&lt;/i&gt;-test, with values of &lt;i&gt;p&lt;/i&gt; &lt; 0.05 considered statistically significant.&lt;/p&gt;&lt;p&gt;Two patients were excluded from the statistical analysis due to short follow-up.&lt;/p&gt;&lt;p&gt;Two patients in our cohort (B0/alpha −3,7 and with B+/HbE) have won until now their transfusional independence of respectively 20 and 18 weeks, without relevant adverse events (respectively, number 1 and 7 of Table 1).&lt;/p&gt;&lt;p&gt;The impact of ACE-536 in patients affected by beta-thalassemia intermedia appeared of particular interest, with a better response when compared to thalassemia major in our experience.&lt;/p&gt;&lt;p&gt;Notably, the magnitude of the effect was influenced by genotype aspects. In our experience, it was higher in patients with non-beta0–beta0 patients as shown by a subanalysis of BELIEVE trial.&lt;/p&gt;&lt;p&gt;Our data herein reported showed significant advantages in the HbE-beta patients are the same as results presented in the last American Society of ","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"5 6","pages":"1354-1358"},"PeriodicalIF":0.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11647712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}