European Journal of Haematology最新文献

{"title":"Home-Based Daratumumab in Patients With Multiple Myeloma.","authors":"Tine Rosenberg, Jannie Kirkegaard, Michael Tveden Gundesen, Maja Kjær Rasmussen, Karin Brochstedt Dieperink, Thomas Lund","doi":"10.1111/ejh.14409","DOIUrl":"https://doi.org/10.1111/ejh.14409","url":null,"abstract":"<p><strong>Objective: </strong>Multiple myeloma is an incurable cancer with lifelong treatment needs. This, together with a global nursing shortage, calls for new approaches for future treatment. In this study, we therefore investigated the feasibility of home-based subcutaneous daratumumab administered by primary care nurses outside the hospital.</p><p><strong>Methods: </strong>Applying a mixed-methods prospective design, we included 30 patients; 18 had completed ≥ 6 cycles of daratumumab treatment, and 12 were newly started. New patients were followed for six 28-day cycles, with every second treatment administered outside the hospital. Patients already on treatment were followed for seven cycles with 2/3 treatments administered outside the hospital.</p><p><strong>Results: </strong>Of 123 administrations planned at the hospital, 122 (97.6%) were administered and three were cancelled. Of 144 administrations planned outside the hospital, 133 (92.4%) were administered, six were redirected to the hospital, and five were cancelled. No significant difference between numbers of cancellations/redirections was observed. Patients spent significantly longer time on treatment at the hospital, even when deducting travel time. Reducing patients' visits to the hospital did not cause additional unplanned contacts with the healthcare system.</p><p><strong>Conclusion: </strong>This study thus concludes that administration of daratumumab outside the hospital is safe, feasible, and time saving.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov ID: NCT05306587.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751795","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":"Dual Targeting of Pim and PI3 Kinases in Mature T-Cell Lymphoma.","authors":"M Lohrberg, M Heber, L Ries, K Markus, N Ksionsko, N Schmidt, G Nothnick, L Thielking, M O'Neill, S Martínéz-González, C Blanco-Aparicio, J Pastor, D Cunningham, R Koch","doi":"10.1111/ejh.14420","DOIUrl":"https://doi.org/10.1111/ejh.14420","url":null,"abstract":"<p><p>Provirus Integration site for Moloney leukemia virus (Pim) family members are well-known oncogenes, with an expression that is restricted to few cell types including hematopoietic cells in adult organisms, making it a promising target for lymphoma treatment. Indeed, previous studies in mature T-cell lymphoma (mTCL) cells revealed frequent upregulation of Pim expression. Nevertheless, inhibition of Pim kinases showed only minor effects on the viability of mTCL cells so far. Thus, we here addressed cellular responses to therapeutic inhibition of Pim kinases and identified a PI3K/Akt-driven activation of mTOR as a significant escape mechanism mitigating the anti-lymphoma effects of Pim inhibition. Indeed, dual inhibition of Pim and PI3 kinases showed synergistic anti-lymphoma effects in vitro through downregulation of mTOR-induced protein translation and mitigation of BCL-xL-mediated anti-apoptotic mechanisms. Based on this finding, we next explored the therapeutic potential of the dual Pim/PI3K inhibitor IBL-202 in mTCL cell lines. Strikingly, IBL-202 strongly induced cell-cycle-dependent cell death in cell lines of different mTCL subtypes. Together, our study provides mechanistic evidence supporting a therapeutic strategy of dual Pim- and PI3-kinase inhibition in mature T-cell lymphoma.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751791","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":"Comparison of Hetrombopag and Eltrombopag Added to First-Line Immunosuppressive Therapy in Severe Aplastic Anemia.","authors":"Baohang Zhang, Wenrui Yang, Rui Kang, Yimeng Shi, Xiangrong Hu, Li Zhang, Liping Jing, Weiping Yuan, Jun Shi, Fengkui Zhang, Xin Zhao","doi":"10.1111/ejh.14418","DOIUrl":"https://doi.org/10.1111/ejh.14418","url":null,"abstract":"<p><p>The addition of thrombopoietin receptor agonists (TPO-RAs) to immunosuppressive therapy (IST) improves the hematologic response rate and quality in patients with severe aplastic anemia (SAA). However, no studies have yet reported on whether there are differences in the efficacy of TPO-RAs. Here, we retrospectively analyzed the clinical data of SAA patients who received hetrombopag (HPAG) or eltrombopag (EPAG) as part of first-line standard IST to compare the efficacy. Sixty-seven patients were enrolled in the HPAG group and 42 patients in the EPAG group. The overall hematologic response (OR) rates of the HPAG group at 3 and 6 months after IST were 50.7% and 65.6%, respectively, close to that of the EPAG group (50%, p = 0.973; 73.8%, p = 0.494). The rates of complete response (CR) at 3 and 6 months were 13.4% and 31.3% in the HPAG group, respectively, which were like those in the EPAG group (11.9% and 28.6%), with no statistical difference (p = 1.00 and 0.59). The median time to first response (3.0 vs. 3.2 months, p = 0.79) was similar in HPAG and EPAG. The overall survival (OS) rates were 91.0% and 92.8% in the HPAG group and EPAG group (p = 0.53), respectively. Monosomy 7 was detected in one patient in the EPAG group and her disease transformed into acute myelocytic leukemia (AML) at 25 months after ATG treatment. One patient in HPAG had trisomy 8 at 9 months of ATG treatment, and bone marrow examination showed no disease progression. CONCLUSION: The addition of HPAG to standard IST in SAA patients showed similar response rates and response quality to that of EPAG. HPAG could be an alternative to EPAG for the first-line treatment of SAA patients.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751788","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":"Clinicopathologic Characteristics and Prognostic Profile of Chronic Myeloid Neoplasms With Somatic NF1 Mutations in Adult Patients.","authors":"Hamza Tariq, Margarita Loxas, Mir B Alikhan, Juehua Gao, Xinyan Lu, Qing Ching Chen, Yi-Hua Chen, Jessica K Altman, Lawrence J Jennings, Madina Sukhanova","doi":"10.1111/ejh.14419","DOIUrl":"https://doi.org/10.1111/ejh.14419","url":null,"abstract":"<p><strong>Objectives: </strong>The clinicopathologic and prognostic features of somatic NF1 mutations have been well studied in pediatric myeloid neoplasms and adult acute myeloid leukemia (AML) but not in adult chronic myeloid neoplasms (CMNs), including myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), and myelodysplastic/myeloproliferative neoplasms (MDS/MPNs).</p><p><strong>Methods: </strong>A retrospective review was performed to identify adult patients diagnosed with NF1-mutated CMNs between 1/2010 and 8/2023. Patients with NF1 wildtype (NF1-WT) CMNs concurrently diagnosed during the same time were used as a comparative group. Clinicopathologic and genetic characteristics and overall survival (OS) were compared between the two groups.</p><p><strong>Results: </strong>A total of 36 NF1-mutated CMNs were identified (4.7% of all CMNs), including 19 MDS, 4 MPNs, and 13 MDS/MPNs (all CMML). NF1-mutated CMMLs showed significantly higher absolute monocyte counts (AMC), more frequent complex karyotypes, and higher frequencies of SRSF2 and KRAS mutations compared to NF1-WT CMMLs. NF1-mutated MDS also showed significantly higher AMC, lower frequency of SF3B1, and higher frequencies of SRSF2 and KRAS mutations compared to NF1-WT MDS. The OS of NF1-mutated CMNs was significantly inferior to NF1-WT CMNs (median survival: 2.05 vs. 4.8 years; log-rank p = 0.03).</p><p><strong>Conclusions: </strong>Adult CMNs with mutated NF1 show higher AMC, high-risk molecular cytogenetic features, and inferior survival. Therefore, testing for NF1 mutations could be considered part of risk assessment for patients with CMNs.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729498","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":"TP53-Mutated Acute Myeloid Leukemia and Blast Phase Myeloproliferative Neoplasm: Distinct Mutation Leads to Poorer Prognosis.","authors":"Dong Chen, Miguel Cantu, Alexa Siddon, Olga K Weinberg","doi":"10.1111/ejh.14421","DOIUrl":"https://doi.org/10.1111/ejh.14421","url":null,"abstract":"<p><p>Patients with TP53 mutations in acute myeloid leukemia (AML) and blast phase myeloproliferative neoplasms (MPN-BP) experience similar poor clinical outcomes. A retrospective analysis of 39 patients with TP53 mutations (23 with AML and 16 with MPN-BP) revealed comparable mutation patterns associated with prognostic significance. A total of 47 distinct TP53 mutations were identified, including seven patients with multiple mutations. Based on clinical outcomes, we propose a two-tiered risk stratification for TP53-mutated AML and MPN-BP. The high-risk group mutations, such as splice site variants in Intron 4 (especially c.376), missense mutations in Exon 5 (notably p.R175H), and mutations in the oligomerization domain (OD), were associated with, particularly, worse overall survival (OS < 3 months). Conversely, single missense mutations in Exons 6 and 7 (notably p.Y220C, p.R248N, p.R248Q, and p.R248W), and mutations in the transactivation domain (TAD), constituted a low-risk group and were associated with relatively better prognosis (median OS: 10.15 months for the low-risk group vs. 1.3 months for the high-risk group, p < 0.0001). These findings support the hypothesis that distinct TP53 mutations can lead to varying cellular effects, therapeutic responses, and clinical outcomes. Consequently, acute myeloid neoplasms (AML and MPN-BP) harboring certain TP53 mutations may exhibit increased aggressiveness compared to other TP53 mutants, underscoring the need for prioritized clinical research and therapeutic targeting.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729499","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":"Allogeneic Haematopoietic Stem Cell Transplantation Using Reduced-Intensity Fludarabine, Busulfan and Anti-T-Lymphocyte Globulin With Strategic Donor Lymphocyte Infusion in Older Patients With Myeloid Malignancy.","authors":"Chris Armstrong, Eibhlin Conneally, Catherine Flynn, Paul Browne, Mairead Ni Chonghaile, Carmel Ann Galligan, Hayley Foy-Stones, Nicola Gardiner, Greg Lee, Nina Orfali","doi":"10.1111/ejh.14417","DOIUrl":"https://doi.org/10.1111/ejh.14417","url":null,"abstract":"<p><p>Fludarabine, busulfan, and anti-T-lymphocyte globulin (FLUBU3+ATLG) reduced-intensity conditioning is an established preparative regimen for allogeneic haematopoietic stem cell transplantation in older patients with myeloid malignancy. We examined its modern-day performance in 175 sequentially treated patients on our national programme. Overall survival was 72.4% at 2 years (95% CI 64.6%-78.6%) with a cumulative incidence of non-relapse mortality of 11%. The cumulative 2-year relapse incidence was 27% (95% CI 22.8%-37.6%) and was partially ameliorated by chronic graft-versus-host disease (HR 0.35, 95% CI 0.12-0.98, p = 0.02). Mixed donor chimerism was observed in 51.5% beyond day 90, but relapse was significantly reduced in these patients by adopting a pre-emptive donor lymphocyte infusion (DLI) strategy (HR 0.22, 95% CI 0.07-0.69, p = 0.005). The use of DLI as part of post-relapse salvage was also effective, with an improved median survival duration of 6 months in recipients (HR 0.43, 95% CI 0.18-0.98, p = 0.01). Outcomes in patients > 65 years and a limited cohort > 70 years are encouraging and compare favourably to published survival results using alternate reduced-intensity regimens. FLUBU3+ATLG, supported by modern supportive care and a pre-emptive DLI strategy, is well tolerated by older patients across a spectrum of myeloid disease with modest toxicity and favourable long-term outcomes.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729496","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":"Prognostic Significance of +1q Alterations in Relapsed/Refractory Multiple Myeloma Treated With Daratumumab-, Elotuzumab-, and Carfilzomib-Based Triplet Regimens: A Multicenter Real-World Analysis of 635 Patients.","authors":"Fortunato Morabito, Enrica Antonia Martino, Monica Galli, Massimo Offidani, Renato Zambello, Sara Bringhen, Nicola Giuliani, Catello Califano, Marino Brunori, Alfredo Gagliardi, Nicola Sgherza, Angela Maria Quinto, Gregorio Barilà, Angelo Belotti, Claudio Cerchione, Gloria Margiotta Casaluci, Raffaele Fontana, Velia Bongarzoni, Giuseppe Tarantini, Daniele Derudas, Francesca Patriarca, Alessandro Gozzetti, Adelina Sementa, Elisabetta Antonioli, Angela Rago, Flavia Lotti, Claudio De Magistris, Maria Teresa Petrucci, Loredana Pettine, Niccolò Bolli, Concetta Conticello, Elena Zamagni, Salvatore Palmieri, Maurizio Musso, Anna Mele, Roberta Della Pepa, Ernesto Vigna, Antonella Bruzzese, Francesca Fazio, Roberto Mina, Laura Paris, Iolanda Donatella Vincelli, Giuliana Farina, Clotilde Cangialosi, Katia Mancuso, Antonietta Pia Falcone, Giuseppe Mele, Antonello Sica, Sonia Morè, Giovanni Reddiconto, Giovanni Tripepi, Graziella D'Arrigo, Emiliano Barbieri, Micol Quaresima, Claudio Salvatore Cartia, Sara Pezzatti, Magda Marcatti, Francesca Farina, Anna Cafro, Michele Palumbo, Valeria Masoni, Virginia Valeria Ferretti, Francesco Di Raimondo, Pellegrino Musto, Antonino Neri, Silvia Mangiacavalli, Massimo Gentile","doi":"10.1111/ejh.14413","DOIUrl":"https://doi.org/10.1111/ejh.14413","url":null,"abstract":"<p><p>Relapsed/refractory multiple myeloma (RRMM) research on the impact of +1q abnormalities in real-world settings is limited. This study evaluated the prognostic and predictive significance of 1q gain [gain(1q)] and amplification [ampl(1q)] in 635 RRMM patients treated with daratumumab-, elotuzumab-, and carfilzomib-based triplet regimens. Patients with +1q abnormalities had lower deep response rates [≥ CR: 9.4% for gain(1q), 11.6% for ampl(1q)] versus 20.2% in +1q-negative patients. Multivariable ordinal logistic analysis showed significantly lower odds of achieving ≥ CR in patients with gain(1q) (OR = 0.49, p < 0.001) or ampl(1q) (OR = 0.58, p = 0.0037). Progression-free survival (PFS) was longer in +1q-negative patients (28 months) compared to those with gain(1q) (8 months) or ampl(1q) (7.4 months). Multivariable models identified gain(1q) (HR = 1.9, p < 0.001) and ampl(1q) (HR = 2.2, p < 0.001) as independent negative prognostic factors alongside del17p, t(4;14), creatinine clearance < 60 mL/min, and ISS Stages II and III. Similarly, overall survival (OS) was reduced for patients with gain(1q) (25 months) and ampl(1q) (19.5 months) versus 42.2 months in +1q-negative patients. Multivariable analysis showed gain(1q) (HR = 1.6, p = 0.007) and ampl(1q) (HR = 2.0, p = 0.002) as independent predictors of increased mortality. Ancillary +1q abnormalities associated with high-risk cytogenetic changes were linked to both shorter PFS and OS. Stratification into no-hit, single-hit, double-hit, and triple-hit groups showed significant survival differences, emphasizing the impact of cumulative cytogenetic abnormalities on outcomes. In conclusion, +1q abnormalities significantly impact prognosis in RRMM and should be considered in risk stratification. The study emphasizes the importance of comprehensive cytogenetic profiling in real-world settings and highlights the need for personalized treatment strategies to improve patient outcomes.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656520","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":"Effect of NPM1 Mutation Subtype and Co-Mutation Patterns on the Outcomes of Acute Myeloid Leukemia.","authors":"Kittika Poonsombudlert, Ratdanai Yodsuwan, Sarah Mott, Kathryn Crawford, Sarah Hornberg, Anthony N Snow, Grerk Sutamtewagul, Margarida Magalhaes-Silverman, Prajwal Dhakal","doi":"10.1111/ejh.14415","DOIUrl":"https://doi.org/10.1111/ejh.14415","url":null,"abstract":"<p><strong>Introduction: </strong>NPM1 mutated AML without FLT3-ITD is considered \"favorable\" per the recent ELN 2022 criteria. However, our center has been challenged with treatment-refractory patients, prompting a search for additional prognostic factors.</p><p><strong>Methods: </strong>We reviewed records of NPM1 AML patients from 2015 to 2024. Factors associated with event-free survival (EFS) and overall survival (OS) were evaluated using Cox regression.</p><p><strong>Results: </strong>Among 141 patients with NPM1 AML, subtype A was the most common (N = 99), followed by subtype D (N = 10), subtype B (N = 6), subtype G/I/J/K/R (N = 3/5/3/2/1) and other subtypes (N = 12). Ninety patients received chemotherapy (chemo), 41 received hypomethylating agent +/- venetoclax (HMA/ven) and 10 did not receive specific anti-AML therapy. At 12 months, EFS for subtypes A, D, B, G/I/J/K/R, and other subtypes were 49%, 58%, 50%, 49%, and 31%, and OS were 71%, 79%, 50%, 44%, and 56%, respectively. Fifty patients had allogeneic stem cell transplants: 33 in CR1 and 17 in CR2+. EFS at 12 months post-HSCT was 72%. On multivariable analysis, co-mutation with KRAS (HR: 2.69, 95% CI: 1.20-6.00) or TET2 (HR: 1.99, 95% CI: 1.22-3.26) was associated with worse EFS. For each 50 k/mm³ increase in WBC at diagnosis, the risk of relapse or death increased by 21%. For OS, co-mutation with IDH1/IDH2 (HR: 0.40, 95% CI: 0.21-0.74) was associated with better OS, whereas co-mutation with SRSF2 (HR: 2.70, 95% CI: 1.35-5.40) was associated with worse OS.</p><p><strong>Conclusion: </strong>We did not find a statistically significant difference in EFS and OS among the NPM1 subtypes. However, our results showed that the prognoses of NPM1 AML can be influenced by other co-occurring mutations. A larger study is needed to confirm our findings.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656517","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":"Genomic Landscape of Mixed Phenotype Acute Leukemia Associated With Immunophenotypic Lineage Predominance: Impact on Diagnosis and Treatment.","authors":"Ruifang Zheng, Jeffrey R Gagan, Giovanni A Botten, Prasad Koduru, Olga K Weinberg, Mingyi Chen, Miguel D Cantu, Jesse Jaso, Sharon Germans, Hung S Luu, Lina Han, Tamra L Slone, Kathryn E Dickerson, Samuel John, Yazan F Madanat, Stephen Chung, Robert Collins, Alejandro Marinos, Franklin Fuda, Weina Chen","doi":"10.1111/ejh.14414","DOIUrl":"https://doi.org/10.1111/ejh.14414","url":null,"abstract":"<p><strong>Objectives: </strong>Mixed phenotype acute leukemia (MPAL) often poses challenges in diagnosis and clinical management. This is the first study to assess the lineage/immunophenotype-genotype association and the significance of AML-myelodysplasia-related changes (MR, cytogenetic abnormalities and gene mutations, AML-MR-CG-Gene) in MPAL classification.</p><p><strong>Methods: </strong>We conducted a clinicopathologic and genomic evaluation of 25 MPAL cases by the WHO-HEM5/ICC classification criteria, except for retaining those MPAL cases with AML-MR-CG-Gene (Conditional-MPAL).</p><p><strong>Results: </strong>The majority of MPAL cases (22/25, 88%) showed distinct genotypes that overlapped with those of lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). The genomic profile of ALL-like and AML-like was associated with immunophenotypically lymphoid and myeloid lineage predominance, respectively. The lineage/immunophenotype-genotype association may provide a rationale to develop a lineage-immunophenotypically/biologically guided therapy selection. Additionally, 64% of MPAL cases carried AML-MR-CG-Gene, half of which were MPAL with lymphoid-lineage predominance and had ALL-like molecular signatures, and most of these patients responded well to the ALL-based induction regimens. These results support that Conditional-MPAL with AML-MR-CG-Gene may be better diagnosed as MPAL rather than AML-MR.</p><p><strong>Conclusion: </strong>Genomic landscape of AML-like or ALL-like MPAL is associated with the immunophenotypic lineage predominance, and such association could impact treatment decisions and provide supporting evidence to refine MPAL diagnostic criteria in future studies.</p>","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647687","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":"Central Nervous System Manifestations of Graft-Versus-Host Disease.","authors":"Nihar Desai, Niranjan Khaire, Sunu Cyriac, Aseem Saleh Alrumeh, Phedias Diamandis, Daniel M Mandell, Tommy Alfaro Moya, Eshrak Al-Shaibani, Igor Novitzky-Basso, Ivan Pasic, Arjun Datt Law, Fotios V Michelis, Rajat Kumar, Dennis Dong Hwan Kim, Jonas Mattsson, Auro Viswabandya","doi":"10.1111/ejh.14416","DOIUrl":"https://doi.org/10.1111/ejh.14416","url":null,"abstract":"","PeriodicalId":11955,"journal":{"name":"European Journal of Haematology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647665","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}