Annals of Hematology最新文献

{"title":"Clinical characteristics and prognosis of EBV-Positive mature B-Cell lymphoma in children: a retrospective study.","authors":"Yuanyuan Hou, Yiwei Yan, Xiuli Zhu, Jian Chen, Yu Zheng, Yang Li, Wenting Zhang, Xiaofei Lu, Yuqiao Diao, Lian Jiang","doi":"10.1007/s00277-025-06506-8","DOIUrl":"https://doi.org/10.1007/s00277-025-06506-8","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV)-associated pediatric mature B-cell lymphoma is characterized by rapid progression, a poor prognosis, and a high relapse rate. However, research on this condition remains limited. This retrospective study analyzed its clinical features and prognostic factors in children. Kaplan‒Meier analysis was performed to assess the impact of tumor EBV-encoded RNA (EBER)impact status on survival, and LASSO Cox regression was used to identify risk factors. The predictive performance of a model including the identified risk factors was assessed using calibration curves and receiver operating characteristic (ROC) curves. Tumor EBER status was significantly positively correlated with the EBV-DNA level (P < 0.05). EBER-positive pediatric patients presented elevated IgA levels, reduced IgG/IgM levels, decreased CD4 + T-cell counts, and increased CD8 + T-cell counts (P < 0.05). Compared with EBER-negative patients, EBER-positive patients had worse 5-year cumulative progression-free survival (PFS) (73.33%) and cumulative overall survival (OS) (78.30%) (P < 0.05). LASSO Cox regression analysis identified EBER (PFS HR 3.48, 95% CI 1.16-10.47, P = 0.027; OS HR 8.10, 95% CI 1.80-36.38, P = 0.006) and LDH (PFS HR 3.05, 95% CI 1.07-8.68, P = 0.037; OS HR 7.38, 95% CI 1.42-38.47, P = 0.018) as key prognostic markers. The model predicted 3-/5-year survival with high accuracy, with a C-index of 0.699 (95% CI: 0.558-0.841) for PFS and AUC (95% CI) values of 0.730 (0.575-0.886) and 0.691 (0.515-0.868). For OS, the C-index was 0.810 (95% CI: 0.669-0.952), and the AUC (95% CI) values were 0.805 (0.605-1.005) and 0.817 (0.618-1.015). Pediatric patients with EBV-associated mature B-cell lymphoma present distinct clinical and prognostic features that significantly influence the tumor immune microenvironment. The risk prognostic model based on tumor EBER status and LDH level reliably predicts outcomes in these patients.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616030","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":"Enasidenib as treatment for AML with IDH2 mutation: multicenter real-life study of the early-access program in Spain.","authors":"Carlos Jiménez-Vicente, Paola Beneit, Isabel Cano-Ferri, Brayan Merchán, Montserrat Arnan, Antoni García Guiñón, Cristina Martínez-Bilbao, Ana Alfonso, Pilar Martínez-Sánchez, Juan Manuel Alonso-Domínguez, Oriana López-Godino, Sandra Castaño-Díez, Inés Zugasti, Jordi Esteve, Marina Díaz-Beyá, Adolfo de la Fuente","doi":"10.1007/s00277-025-06464-1","DOIUrl":"https://doi.org/10.1007/s00277-025-06464-1","url":null,"abstract":"<p><p>Enasidenib is an oral IDH2 inhibitor that reduces the production of the oncometabolite 2-hydroxyglutarate, differentiating IDH2 mutated leukemic cells with initial promising results for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients. We performed a retrospective study in Spain evaluating enasidenib in patients diagnosed with IDH2-mutated myeloid neoplasms (AML, MDS, myeloid sarcoma and chronic myelomonocytic leukemia (CMML). Twenty-three patients were included, with 20 having a refractory/relapsed (R/R) disease status. The median age was 73 years, and the majority patients were classified as adverse risk by the European LeukemiaNet 2022 criteria. The most frequent mutation was IDH2 R140 (69.6%), while 30.4% had R172 mutation. Enasidenib was administered as a single agent in 18 patients, in combination with azacitidine in four patients, and with low-dose cytarabine in another one. The median number of cycles administered was four, with an overall response rate (ORR) of 39.1% and a morphological complete remission (CR) rate of 26.1%. Median overall survival (OS) was 8.3 months. Patients who achieved a complete response had a better outcome than the rest of the patients in terms of OS (19.8 months (95%CI: 15.7-NR) vs. 4.2 (95%CI: 1.5-NR), p = 0.01). Drug-related events included leukocytosis in five patients (21.7%), hyperbilirubinemia in six patients (26.1%) and differentiation syndrome (DS) in four patients (17.4%), including one grade 3 DS and one death related to this latter adverse event (AE), similar to previous findings. Although enasidenib failed to demonstrate a clear overall survival advantage in phase 3 trials, the extended responses and long-term survivors observed herein underscore its therapeutic potential. Ultimately, our data support enasidenib's role as a targeted therapy for IDH2-mutated AML, indicating that expanded access to this agent is warranted to optimize outcomes in these challenging patient populations, especially for R/R AML patients.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616031","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":"Identification of a novel complex variant in a patient involving the α-globin gene cluster by third-generation sequencing.","authors":"Hui Liu, Yepei Du, Yanting Yang, Di Cui, Libao Chen, Cong Zhou, Jing Wang","doi":"10.1007/s00277-025-06488-7","DOIUrl":"https://doi.org/10.1007/s00277-025-06488-7","url":null,"abstract":"<p><p>Various methods are available to detect common deletions and mutations of genes related to thalassemia, including gap-polymerase chain reaction (Gap-PCR), next-generation sequencing (NGS), multiplex ligation-dependent probe amplification (MLPA), and quantitative real-time polymerase chain reaction (qRT-PCR). Unequal crossover during the recombination of α1 and α2 hemoglobin can be detected but hardly accurately defined by above-mentioned technologies. A couple with abnormal hematological test results arrived at our department for genetic consultation. Preliminary analysis using NGS revealed a 3.7 kb (chr16:223462-227311) heterozygote deletion in the wife and nearly six copies in the chr16:223462-227311 (GRCh37/hg19) region of the husband. Further Gap-PCR results for the wife were consistent with the NGS results. MLPA and qRT-PCR were performed to detect the potential extra copies of the α-globin gene of the husband. The analyses simultaneously showed that the copy numbers of HBA1/HBA2 genes were nearly six. A specialized primer of the α-globin gene was designed to elucidate the structure of the 4.2 or 3.7 kb repeats of the husband. Third-generation sequencing (TGS) revealed the existence of the four extra tandem duplications of 3.7 kb in DNA strand 1 (chr16:173302-177106, hg38) of the α-globin gene and the existence of a heterozygous c.301-31_301-24delinsG insertion and deletion (InDel) in DNA strand 2 in the HBA1 gene (chr16:177252-177259, hg38). These results were confirmed by Sanger sequencing. Integrative Genomics Viewer analysis of the BAM files of NGS detected a low-level (reference/alternative, 0.19%) heterozygous InDel (c.301-31_301-24delinsG) in HBA1. Compared to traditional methods, TGS was better able to detect variants accurately and find rare genotypes and rearrangements of the α-globin gene cluster.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616032","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":"Cladribine and medium-dose cytarabine intensified busulfan plus cyclophosphamide conditioning regimen for adults high-risk B-cell acute lymphoblastic leukemia.","authors":"Tingting Cheng, Jie Peng, Yi Liu, Shuanghui Yang, Yan Chen, Yajing Xu","doi":"10.1007/s00277-025-06471-2","DOIUrl":"https://doi.org/10.1007/s00277-025-06471-2","url":null,"abstract":"<p><p>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective salvage strategy for B-cell acute lymphoblastic leukemia (B-ALL). In this study, we explored the efficacy and safety of cladribine and medium-dose cytarabine intensified busulfan plus cyclophosphamide conditioning regimen (CBAC) for high-risk B-ALL patients at complete remission (CR) after chemotherapy undergoing allo-HSCT. And compared it with patients historical received traditional total body irradiation plus cyclophosphamide (TBI-Cy) regimen. The 3-year non-relapse mortality (NRM), cumulative incidence of relapse (CIR), disease-free survival (DFS) and overall survival (OS) of CBAC and TBI-Cy group were 15.0% vs. 11.1% (p = 0.576), 17.3% vs. 35.7% (p = 0.077), 67.7% vs. 53.2% (p = 0.235) and 74.3% vs. 66.8% (p = 0.482). Overall cohort multivariate analysis indicated TBI-Cy increased the risk of relapse after transplantation compared with CBAC (HR: 2.544, p = 0.049). Subgroup analysis revealed that among cytogenetic high-risk patients, the CBAC group showed a trend of higher 3-year DFS (75.1% vs 52.6%, p = 0.073). Among patients with minimal residual disease positive (MRD⁺) at transplantation, the CBAC group showed higher 3-year DFS (60.0% vs 11.1%, p = 0.018). In conclusion, CBAC conditioning regimen may reduce relapse without increasing NRM, improving the prognosis of high-risk B-ALL patients, especially those with cytogenetic high-risk factors or MRD⁺ at transplantation.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607231","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":"A pharmacovigilance study of adverse events associated with polycythemia vera treatments using the FDA Adverse Event Reporting System (FAERS) database.","authors":"Brandi N Reeves, Lucia Masarova, Ghaith Abu-Zeinah, Anthony M Hunter, Joseph J Shatzel, Albert Qin, Chang Ho Yoon, Ling-Yu Cai, Yu-Feng Wei, Ruben A Mesa","doi":"10.1007/s00277-025-06480-1","DOIUrl":"https://doi.org/10.1007/s00277-025-06480-1","url":null,"abstract":"","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599212","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":"The incidence of paroxysmal nocturnal hemoglobinuria cell clones in the Nordic countries.","authors":"Torkild Høieggen Pedersen, Eirik Tjønnfjord, Eva-Stina Korkama, Mariann Vikman, Ahmad Ahmadi, Ulrik Malthe Overgaard, Christian Kjellander","doi":"10.1007/s00277-025-06450-7","DOIUrl":"https://doi.org/10.1007/s00277-025-06450-7","url":null,"abstract":"<p><p>Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired stem cell disorder associated with hemolysis, thrombosis, organ dysfunction and immune mediated bone marrow failure. Studies estimate the incidence of PNH between 1.3-3.1/million/year. However, there are no studies on the incidence of PNH in the Nordic countries. Here we report 126 patients diagnosed with a PNH clone between 2011 and 2016 with an annual incidence of 1.71 cases/million in Denmark, Finland, Norway and Sweden. The number of new cases varied from 15 to 28 yearly with a mean clone size of 23.8% at diagnosis. For the smaller clone sizes < 10% the test indications were predominantly aplastic anemia and unexplained cytopenias, while test indication for larger clone sizes > 50% typically was direct antiglobuline (DAT) negative hemolytic anemia. 23 patients (18.2%) had a history of venous or arterial thrombosis and 30 patients (22.2%) experienced kidney failure. This is the first study to report on the incidence of PNH in the Nordic countries. As expected, the PNH test indications varied according to clone size, while the high number of thromboses and kidney failures underlines the need for knowledge about this rare disease. Cross-country collaboration gives us the opportunity to gather larger patient populations and encourage further studies on PNH in the Nordic countries.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590321","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":"VINCENT: A randomized-controlled trial evaluating venetoclax plus azacitidine versus intensive chemotherapy in patients with newly diagnosed, NPM1-mutated AML.","authors":"Lydia Kretschmer, Leo Ruhnke, Christoph Schliemann, Lars Fransecky, Björn Steffen, Martin Kaufmann, Andreas Burchert, Christoph Schmid, Maher Hanoun, Tim Sauer, Klaus H Metzeler, Kerstin Schäfer-Eckart, Mathias Hänel, Martina Crysandt, Paul Jäger, Stefan W Krause, Christine Dierks, Stefan Klein, Nadia Maguire, Lukas P Frenzel, Veit L Bücklein, Wolfgang Blau, Ulrich Kaiser, Kai Wegehenkel, Alexander Höllein, Ruth Seggewiss-Bernhardt, Wenke Markgraf, Frank Fiebig, Anna Harig, Katharina Schmidt-Brücken, Christian Thiede, Jan Moritz Middeke, Richard Dillon, Claudia D Baldus, Hubert Serve, Karsten Spiekermann, Wolfgang Hiddemann, Richard F Schlenk, Carsten Müller-Tidow, Martin Bornhäuser, Christoph Röllig","doi":"10.1007/s00277-025-06496-7","DOIUrl":"https://doi.org/10.1007/s00277-025-06496-7","url":null,"abstract":"<p><p>For younger, medically fit patients with NPM1-mutated, FLT3-wildtype acute myeloid leukemia (AML) intensive chemotherapy represents standard of care (SOC), with complete remission (CR) rates observed in up to 85% of patients and 5-year overall survival (OS) rates of 40-50%. However, significant toxicity and need for hospitalization pose challenges on patients' outcome and quality of life (QoL). Venetoclax (VEN) combined with azacitidine (AZA) has demonstrated encouraging efficacy in older, unfit AML patients, achieving high CR/CRi rates and promising OS with lower toxicity. Prospective, randomized data comparing VEN/AZA to SOC in younger, fit patients are currently missing. VINCENT is a randomized-controlled, multicenter, non-inferiority, phase 2 trial (NCT05904106) evaluating VEN/AZA versus SOC in adults aged 18-70 years with newly diagnosed, NPM1-mutated, FLT3-wildtype AML. Patients medically fit for intensive chemotherapy (ECOG ≤ 2) with adequate organ function are eligible, while patients with relapsed/refractory AML or prior cytotoxic treatment are excluded. A total of 146 patients will be randomized 1:1 to receive either VEN/AZA or SOC. Hematologic remission is evaluated according to ELN 2022 guidelines. The primary endpoint is the modified event-free survival, defined as either primary induction failure, hematologic relapse, molecular failure or death. Secondary endpoints include safety, tolerability, CR/CRi/CRh/CR_MRD- rates, MRD kinetics (using NPM1 RT-qPCR and MFC), relapse-free survival, OS, early mortality, health-related QoL and cumulative health-care-resource use. Patients will be followed up for at least two years post enrollment. The VINCENT trial will be the first study to provide comprehensive prospective data comparing VEN/AZA to SOC, addressing both efficacy and patient-centered outcomes.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590322","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":"Romiplostim versus Recombinant human thrombopoietin in umbilical cord blood transplantation: a single-center retrospective study.","authors":"Yuntian Ding, Hengyu Liu, Yaqun Wang, Haimei Deng, Yanfeng Sun, Tiantian Sun, Yin Wang, Yunxin Zeng","doi":"10.1007/s00277-025-06490-z","DOIUrl":"https://doi.org/10.1007/s00277-025-06490-z","url":null,"abstract":"<p><p>Delayed platelet engraftment (DPE) is a prevalent complication following umbilical cord blood transplantation (UCBT), accompanied by increased transplant-related mortality. This study aims to evaluate the efficacy, safety, and tolerability of romiplostim and recombinant human thrombopoietin (rhTPO) in enhancing platelet engraftment after UCBT. A total of 19 patients scheduled to receive UCBT were randomly assigned to the romiplostim group (250 µg once weekly from day 5 to platelet engraftment after UCBT, n = 7) or rhTPO group (300 U/kg once daily from days 5 to 18 after UCBT, n = 12). The median time of PLT engraftment was no statistical difference between rhTPO and romiplostim group: 29.5 days (range: 13-43 days) compared to 31 days (range: 23-40 days; P =.269). The median dose of romiplostim was 4 (range: 2-5 doses). Furthermore, the consumption of PLT was equivalent between the Ro group and the rhTPO group: 10 units (range: 7-26 units) and 10 units (range: 3-24 units; P =.694). All patients survived for one year and remained relapse-free. Romiplostim group had a lower incidence of acute graft versus host disease (aGvHD). No severe adverse effects were observed in any of the patients. This study demonstrated that romiplostim and rhTPO are both effective in promoting platelet engraftment after UCBT. Romiplostim was more practical and tolerable due to its cost and labor-saving benefits.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590320","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":"Efficacy and safety analysis of different treatment regimens in newly diagnosed acute promyelocytic leukemia.","authors":"Di Zhang, Yongjian Li, Tingting Liu, Xiaomin Liu, Jingru Zhang","doi":"10.1007/s00277-025-06495-8","DOIUrl":"https://doi.org/10.1007/s00277-025-06495-8","url":null,"abstract":"<p><p>This retrospective study analyzed the clinical data of 151 newly diagnosed adult acute promyelocytic leukemia (APL) patients during induction therapy at Qilu Hospital of Shandong University to compare the efficacy and complications of different treatment regimens in low-to-intermediate-risk (WBC < 10 × 10⁹/L) and high-risk (WBC ≥ 10 × 10⁹/L) patients. Low-to-intermediate-risk patients were divided into three groups: ATRA + ATO dual induction (n = 18), ATRA + ATO + single-agent chemotherapy (n = 63), and ATRA + ATO + dual-agent chemotherapy (n = 18). High-risk patients were divided into two groups: ATRA + chemotherapy (n = 11) and ATRA + ATO + chemotherapy (n = 41). Results showed no significant differences in early mortality (0% vs. 3.17% vs. 5.56%), complete remission rates (94.44% vs. 96.83%), or molecular remission rates (94.44% vs. 100%) among low-to-intermediate-risk groups (P > 0.05). However, the dual induction group demonstrated superior relapse-free survival (100% vs. 93.65% vs. 88.89%) and lower rates of infection (66.67%) and hepatic dysfunction (22.22%), whereas the dual-agent chemotherapy group exhibited the highest infection (100%) and liver injury rates (61.11%) (P < 0.05). In high-risk patients, the ATRA + ATO + chemotherapy group showed significantly lower relapse rates (4.88% vs. 27.27%, P = 0.025) and higher overall survival (87.80% vs. 81.81%) compared to the ATRA + chemotherapy group. Complications analysis revealed myelosuppression (78.81%) and infections (83.44%) as the most common adverse events in low-to-intermediate-risk patients, with infections reaching 95.12% in high-risk patients. The dual induction group had a higher incidence of differentiation syndrome (5.56%) but lower risks of severe bleeding and DIC. For low-to-intermediate-risk APL patients during induction therapy, ATRA + ATO dual induction reduces relapse and hepatic toxicity but requires vigilance for differentiation syndrome. High-risk patients benefit from ATRA + ATO combined with chemotherapy to improve survival. Treatment should be individualized to balance efficacy and complications, with supportive care critical for mitigating infections and bleeding. This study provides clinical evidence for optimizing APL regimens in the chemotherapy-free era.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582911","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":"Venetoclax plus azacitidine as genetic-driven bridge-to-transplant therapy for IDH2-mutated acute myeloid leukaemia (AML) refractory to intensive chemotherapy: proof-of-concept case reports.","authors":"Gaetano Cimino, Matteo Caridi, Valeria Cardinali, Sofia Sciabolacci, Sara De Santis, Camilla Rellini, Caterina Matteucci, Cristina Mecucci, Paolo Sportoletti, Francesco Zorutti, Alessandra Carotti, Roberta La Starza, Antonio Pierini, Maria Paola Martelli","doi":"10.1007/s00277-025-06500-0","DOIUrl":"https://doi.org/10.1007/s00277-025-06500-0","url":null,"abstract":"<p><p>Despite the greater biological understanding and the new drugs available, acute myeloid leukaemia (AML) patients who are refractory to intensive induction chemotherapy represents an unmet clinical need, especially in young/fit adults who are eligible for bone marrow transplantation. Since venetoclax/azacitidine (ven/aza) was introduced in AML management in 2020, survival of elderly/unfit patients has dramatically improved, especially in those carrying NPM1 or IDH2 mutations. However, the use of ven/aza in young and fit adults remains limited, raising ongoing debate about its potential role beyond patients ineligible to intensive chemotherapy. Here, we discuss three under 60 years chemorefractory AML patients, who, given the concomitant IDH2 mutations, were started to ven/aza as bridge-to-transplant and successfully treated. These cases confirm the extraordinary sensitivity of IDH2-mutated AML to aza/ven even in the refractoriness setting and show that such less-intensive regimen can be driven by genetics offering a promising alternative to intensive salvage chemotherapy, while preserving patient fitness for allo-transplant.</p>","PeriodicalId":8068,"journal":{"name":"Annals of Hematology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582913","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}