Leukemia research最新文献

{"title":"Gene regulatory mechanisms of T cell exhaustion in diffuse large B cell lymphoma based on single-cell transcriptome data","authors":"Zhencang Zhou ,&nbsp;Pinwei Zhu ,&nbsp;Jinli Ge,&nbsp;Qiang Li,&nbsp;Hang Li,&nbsp;Nana Zhe,&nbsp;Zhaoyu Liu,&nbsp;Dengke Chen","doi":"10.1016/j.leukres.2024.107588","DOIUrl":"10.1016/j.leukres.2024.107588","url":null,"abstract":"<div><div>Diffuse large B cell lymphoma (DLBCL) is a heterogeneous and aggressive B cell malignancy that accounts for about 30 % of non-Hodgkin lymphomas. The current standard treatment for DLBCL is rituximab plus chemotherapy, but many patients are refractory or relapse, indicating the need for improved understanding of its molecular pathology. T cell exhaustion is a state of dysfunction or impairment that occurs in chronic infections or cancers, and is associated with poor prognosis in DLBCL. However, the molecular mechanisms of T cell exhaustion in DLBCL are poorly understood. In this study, we performed a comprehensive analysis of T cell exhaustion in DLBCL using public single-cell transcriptome data. We identified different subtypes of T cells and characterized their gene expression features. We found that DLBCL had a significantly higher proportion of exhausted T cells than normal tonsil, and that exhausted T cells had distinct gene expression signatures from non-exhausted T cells. These signatures included genes related to inhibitory receptors, cytokines, transcription factors and metabolic enzymes. We also found that ID3 gene was significantly upregulated in exhausted T cells in DLBCL, which may play a key role in T cell exhaustion. We constructed a protein-protein interaction network, identifying major hub proteins involved in T cell exhaustion or migration. We also performed KEGG and GO enrichment analysis for the differentially expressed genes between exhausted and non-exhausted T cells, and found important signaling pathways related to T cell exhaustion in DLBCL. Our results provide new insights into the molecular mechanisms underlying T cell exhaustion and offer novel therapeutic targets for this complex disease.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"146 ","pages":"Article 107588"},"PeriodicalIF":2.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategies to overcome splicing variants interference in mutational testing for BCR::ABL1 KD","authors":"Juliana Bulchi,&nbsp;Leandro Farias,&nbsp;Daniel Blajberg Schaffel,&nbsp;Bruna Sabioni,&nbsp;Telma França Padilha,&nbsp;Marianne Camile Silva de Sousa,&nbsp;Gustavo Trevizani Stelzer,&nbsp;Ilana Zalcberg,&nbsp;Luciana Mayumi Gutiyama","doi":"10.1016/j.leukres.2024.107594","DOIUrl":"10.1016/j.leukres.2024.107594","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"146 ","pages":"Article 107594"},"PeriodicalIF":2.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142312643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of noncoding RNAs in multiple myeloma","authors":"Ming Lei ,&nbsp;Juan Liang ,&nbsp;Kaiyun Guo ,&nbsp;Langui Tang ,&nbsp;Yuxing He ,&nbsp;Xuefeng Wu","doi":"10.1016/j.leukres.2024.107593","DOIUrl":"10.1016/j.leukres.2024.107593","url":null,"abstract":"<div><div>Noncoding RNAs (ncRNAs) constitute a class of nucleic acid molecules within cells that do not encode proteins but play important roles in regulating gene expression, maintaining cellular homeostasis, and mediating cell signaling. This class encompasses microRNAs (miRNAs), long noncoding RNAs (lncRNAs), transfer RNAs (tRNAs), circular RNAs (circRNAs), small interfering RNAs (siRNAs), and others. miRNAs are pivotal in the regulation of gene expression in hematologic malignancies. Aberrant expression of lncRNAs has been confirmed in cancerous tissues, implicating their involvement in carcinogenesis or tumor suppression processes. tRNAs may induce errors or disturbances in protein synthesis, thereby affecting normal cellular function and proliferation. Moreover, circRNAs influence disease progression in tumors by modulating the expression of relevant genes, and siRNAs can inhibit tumor cell proliferation, invasion, and metastasis while inducing apoptosis. This review will elucidate the biological functions of ncRNAs in multiple myeloma (MM) and explore their potential value as therapeutic targets.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"146 ","pages":"Article 107593"},"PeriodicalIF":2.1,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factors and mortality associated with venous thromboembolism in the elderly US population with chronic lymphocytic leukemia","authors":"Ambarina S. Faiz ,&nbsp;Shuang Guo ,&nbsp;Ashwin Sridharan ,&nbsp;Yong Lin ,&nbsp;Claire S. Philipp","doi":"10.1016/j.leukres.2024.107585","DOIUrl":"10.1016/j.leukres.2024.107585","url":null,"abstract":"<div><h3>Background</h3><p>Venous thromboembolism (VTE) causes morbidity and mortality in cancer patients. The association of VTE with known risk factors in chronic lymphocytic leukemia (CLL) is not known.</p></div><div><h3>Objective</h3><p>To examine risk factors and mortality associated with VTE in White, Black, and Asian CLL patients.</p></div><div><h3>Methods</h3><p>The United States SEER-Medicare database (2000–2015) was used for CLL patients ≥ 65 years. Logistic regression was used to examine VTE risk factors and Cox proportional regression was used to evaluate the effect of VTE on mortality in White, Black, and Asian CLL patients.</p></div><div><h3>Results</h3><p>Among 34,075 CLL patients, VTE was diagnosed in 11.6 % of 31,395 White, 14.6 % of 2062 Black and 6.3 % of 618 Asian patients. Risk of having VTE was, OR_a = 1.2 (95 % CI, 1.0–1.4) for Black patients and OR_a = 0.5 (95 % CI, 0.4–0.7) for Asian patients compared to White patients. Anemia and heart failure were associated with VTE in all three racial cohorts and were the only risk factors in Asian patients. Other risk factors in White patients were the same as in the overall population, including hypertension, obesity, COPD, kidney disease, diabetes, hyperlipidemia, myocardial infarction, and chemotherapy. In Black patients, other risk factors were hypertension, and chemotherapy. Mortality was slightly higher with VTE in the overall population and in White patients.</p></div><div><h3>Conclusion</h3><p>There was difference in VTE risk factors in White, Black, and Asian patients. VTE was marginally associated with mortality in CLL patients. Our findings may help to identify patients at higher risk of VTE in racially diverse CLL populations.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"146 ","pages":"Article 107585"},"PeriodicalIF":2.1,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0145212624001516/pdfft?md5=51d092e7cce9aeb3921a627202776d5e&pid=1-s2.0-S0145212624001516-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142162963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes of patients with acute myeloid leukemia treated with intensive therapy after failure of venetoclax-inclusive, less-intensive therapy","authors":"Rohan K. Achar,&nbsp;Benjamin J. McCormick,&nbsp;Emily Dworkin,&nbsp;Emily M. Geramita,&nbsp;Annie Im,&nbsp;Anand A. Patel,&nbsp;Talha Badar,&nbsp;Rory M. Shallis","doi":"10.1016/j.leukres.2024.107577","DOIUrl":"10.1016/j.leukres.2024.107577","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"146 ","pages":"Article 107577"},"PeriodicalIF":2.1,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142232415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between myeloid disorders and adult onset-inflammatory syndromes, successful treatment with JAK-inhibitors: Case series and literature review","authors":"Rahul Mishra ,&nbsp;Cassandra Calabrese ,&nbsp;Akriti G. Jain ,&nbsp;Abhay Singh","doi":"10.1016/j.leukres.2024.107584","DOIUrl":"10.1016/j.leukres.2024.107584","url":null,"abstract":"<div><p>Approximately one-third of patients with myeloid disorders like myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) exhibit inflammatory and autoimmune disorders (IADs). These IADs often include atypical and incomplete forms of common autoimmune conditions, and exhibit resistance to conventional immunosuppressive therapies. There is growing interest in molecular relationships between IADs and MDS/CMML to find potential targeted therapies. Recently, patients with somatic mutations in the <em>UBA1</em> gene were identified as having VEXAS syndrome. Herein, we present a concise case-series illustrating concurrent elderly-onset inflammatory manifestations and myeloid disorders (MDS, CMML, and idiopathic cytopenia of undetermined significance). These patients manifested inflammatory or autoimmune symptoms, including erythema nodosum, Raynaud's phenomenon, Sjogren syndrome, and refractory pruritus, having onset after 60-years of age. The inflammatory manifestations were largely refractory to traditional immunosuppressive regimens. Remarkably, treatment with a JAK-1 inhibitor, upadacitinib, in two cases yielded marked resolution of inflammatory symptoms, facilitating the gradual tapering of corticosteroids, improvement of hemoglobin levels, and reduction in serum C-reactive protein levels. Upon loss of response to upadacitinib, JAK-2 inhibitor ruxolitinib provided clinical benefit in one of the cases, facilitating further tapering of glucocorticoids. This arena warrants further exploration through prospective studies of larger cohorts to delineate optimal management strategies.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"146 ","pages":"Article 107584"},"PeriodicalIF":2.1,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0145212624001504/pdfft?md5=274bd766483a1347ea587531359afb0f&pid=1-s2.0-S0145212624001504-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germline genetic variants that predispose to myeloproliferative neoplasms and hereditary myeloproliferative phenotypes","authors":"Jonathan Lim ,&nbsp;David M. Ross ,&nbsp;Anna L. Brown ,&nbsp;Hamish S. Scott ,&nbsp;Christopher N. Hahn","doi":"10.1016/j.leukres.2024.107566","DOIUrl":"10.1016/j.leukres.2024.107566","url":null,"abstract":"<div><div>Epidemiological evidence of familial predispositions to myeloid malignancies and myeloproliferative neoplasms (MPN) has long been recognised, but recent studies have added to knowledge of specific germline variants in multiple genes that contribute to the familial risk. These variants may be common risk alleles in the general population but have low penetrance and cause sporadic MPN, such as the <em>JAK2</em> 46/1 haplotype, the variant most strongly associated with MPN. Association studies are increasingly identifying other MPN susceptibility genes such as <em>TERT</em>, <em>MECOM</em>, and <em>SH2B3</em>, while some common variants in <em>DDX41</em> and <em>RUNX1</em> appear to lead to a spectrum of myeloid malignancies. <em>RBBP6</em> and <em>ATM</em> variants have been identified in familial MPN clusters and very rare germline variants such as chromosome 14q duplication cause hereditary MPN with high penetrance. Rarely, there are hereditary non-malignant diseases with an MPN-like phenotype. Knowledge of those genes and germline genetic changes which lead to MPN or diseases that mimic MPN helps to improve accuracy of diagnosis, aids with counselling regarding familial risk, and may contribute to clinical decision-making. Large scale population exome and genome sequencing studies will improve our knowledge of both common and rare germline genetic contributions to MPN.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"146 ","pages":"Article 107566"},"PeriodicalIF":2.1,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142312641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of spliceosome mutation on outcomes of myelodysplastic syndrome and chronic myelomonocytic leukemia patients undergoing allogeneic hematopoietic cell transplantation","authors":"Amrita Desai ,&nbsp;Yazeed Samara ,&nbsp;Dongyun Yang ,&nbsp;Brian Ball ,&nbsp;Adam Braun ,&nbsp;Paul Koller ,&nbsp;Amanda Blackmon ,&nbsp;Vaibhav Agrawal ,&nbsp;Hoda Pourhassan ,&nbsp;Idoroenyi Amanam ,&nbsp;Shukaib Arslan ,&nbsp;Salman Otoukesh ,&nbsp;Karamjeet Sandhu ,&nbsp;Ibrahim Aldoss ,&nbsp;Haris Ali ,&nbsp;Amandeep Salhotra ,&nbsp;Monzr M. Al Malki ,&nbsp;Andrew Artz ,&nbsp;Pamela Becker ,&nbsp;Eileen Smith ,&nbsp;Vinod Pullarkat","doi":"10.1016/j.leukres.2024.107565","DOIUrl":"10.1016/j.leukres.2024.107565","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;p&gt;Allogeneic Hematopoietic cell transplantation (allo-HCT) remains the only curative therapy for myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). The impact of spliceosome mutations on allo-HCT outcome is unclear and further understanding is needed to assess the implications of this class of mutations on risk of relapse, overall survival (OS) and non-relapse mortality (NRM) in order to make decision regarding timing of allo-HCT. We examined the allo-HCT outcomes of MDS/CMML patients based on their spliceosome mutation profile to understand the impact of these mutations on transplant outcomes.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;p&gt;To compare outcomes of MDS/CMML patients with and without spliceosome mutations undergoing allo-HCT.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;This is a single institution, retrospective study of MDS/CMML patients who underwent allo-HCT with myeloablative or reduced intensity conditioning (RIC) regimen at City of Hope from January 2016 to December 2021. Among them, patients who underwent molecular mutation profiling by NGS (Next Generation Sequencing) for a set of genes known to be mutated in myeloid neoplasms are included in this analysis. We compared OS, relapse free survival, NRM and acute/chronic graft versus host disease (GVHD) incidence between the spliceosome-mutated and unmutated groups.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;We identified 258 consecutive MDS/CMML patients who underwent allo-HCT. Of these, 126 (48.8 %) patients had molecular profiling done among whom 57 (45.2 %) patients carried a spliceosome mutation. 84.9 % of patients had MDS and 55.6 % underwent a matched unrelated donor transplant. The median age for the whole cohort was 66 years (range 12–77).78.6 % and 73.7 % received RIC in the spliceosome and non-spliceosome groups, respectively. The 2-year OS for the whole cohort was 66.5 % (95 %CI 0.55–0.75) with a day 100 NRM of 7.1 % and 2-year cumulative incidence of relapse of 20 %. Grade II-IV acute GVHD at day 100 was 36.3 % (95 % CI 0.27–0.44) and any chronic GVHD at 2-years was 48.4 % (95 % CI 0.37–0.58). Patients who carried a spliceosome mutation had a significantly better 2-year survival of 83.8 % vs 55.9 % in the non-spliceosome group (P=0.002) and a better PFS of 73.7 % vs 50.0 % (P=0.007). There was no difference in the cumulative incidence of relapse at 2-years 15.9 % vs 18.5 % (P=0.59) between two groups but the spliceosome group had a significantly lower NRM at 2-years 10.4 % vs 31.5 % (P=0.009). There was no difference in incidence of acute or chronic GVHD between the two groups.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;Among patients with MDS or CMML who underwent allo-HCT, our study shows better OS for patients who have spliceosome mutations due to lower NRM compared to those carrying non- spliceosome mutations. This favorable outcome of the spliceosome-mutated patients could have implications for timing of allo-HCT, particularly for patients in the in","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"145 ","pages":"Article 107565"},"PeriodicalIF":2.1,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142088143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution of transcriptomic profiles in relapsed inv(16) acute myeloid leukemia","authors":"Serena Travaglini ,&nbsp;Giorgia Silvestrini ,&nbsp;Enrico Attardi ,&nbsp;Maurizio Fanciulli ,&nbsp;Stefano Scalera ,&nbsp;Silvia Antonelli ,&nbsp;Luca Maurillo ,&nbsp;Raffaele Palmieri ,&nbsp;Mariadomenica Divona ,&nbsp;Ludovica Ciuffreda ,&nbsp;Arianna Savi ,&nbsp;Giovangiacinto Paterno ,&nbsp;Tiziana Ottone ,&nbsp;Caterina Barbieri ,&nbsp;Jaroslaw P. Maciejewski ,&nbsp;Carmelo Gurnari ,&nbsp;Gennaro Ciliberto ,&nbsp;Maria Teresa Voso","doi":"10.1016/j.leukres.2024.107568","DOIUrl":"10.1016/j.leukres.2024.107568","url":null,"abstract":"<div><p>Acute myeloid leukemia (AML) with inv(16) is typically associated with a favourable prognosis. However, up to 40 % of patients will eventually experience disease relapse. Herein, we dissected the genomic and transcriptomic profile of inv(16) AML to identify potential prognostic markers and therapeutic vulnerabilities. Sequencing data from 222 diagnostic samples, including 44 relapse/refractory patients, revealed a median of 1 concomitant additional mutation, cooperating with inv(16) in leukemogenesis. Notably, the mutational landscape at diagnosis did not differ significantly between patients experiencing primary induction failure or relapse when compared to the rest of the cohort, except for an increase in the mutational burden in the relapse/refractory group. RNA-Seq of unpaired diagnostic(n=7) and relapse(n=6) samples allowed the identification of oxidative phosphorylation (OXPHOS) as one of the most significantly downregulated pathways at relapse. Considering that OXPHOS could be targeted by Venetoclax/Azacitidine combination, we explored its biological effects on an inv(16) cell-line ME-1, but there was no additional advantage in terms of cell death over Azacitidine alone. To enhance Venetoclax efficacy, we tested <em>in vitro</em> effects of Metformin as a potential drug able to enhance chemosensitivity of AML cells by inhibiting the mitochondrial transfer. By challenging ME-1 with this combination, we observed a significant synergistic interaction at least similar to that of Venetoclax/Azacitidine. In conclusions, we identified a downregulated expression of oxidative phosphorylation (OXPHOS) at relapse in AML with inv(16), and explored the in vitro effects of metformin as a potential drug to enhance chemosensitivity in this setting.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"145 ","pages":"Article 107568"},"PeriodicalIF":2.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-effectiveness of blinatumomab for the treatment of B‑precursor acute lymphoblastic leukemia pediatric patients with high‑risk first‑relapse in Mexico","authors":"Juan Pablo Diaz Martinez ,&nbsp;Therese Aubry de Maraumont ,&nbsp;Luis Miguel Camacho ,&nbsp;Laura Garcia","doi":"10.1016/j.leukres.2024.107560","DOIUrl":"10.1016/j.leukres.2024.107560","url":null,"abstract":"<div><h3>Background</h3><p>Blinatumomab is a CD3/CD19-directed bispecific T-cell engager molecule that engages T cells to lyse CD19-expressing B cells. Based on a multicenter, open-label, phase 3, randomized clinical trial (Clinical Trials ID: NCT02393859), we aimed to evaluate the cost-effectiveness (CE) of blinatumomab compared to standard consolidation chemotherapy (SC) for the treatment of pediatric patients with high-risk first-relapsed Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (B-ALL) from a Mexico healthcare payer perspective.</p></div><div><h3>Methods</h3><p>A decision-analytic model, a partitioned survival model, was used to estimate the life-years (LYs) and costs over a lifetime horizon. We assumed that patients who remained alive beyond a 5-year period were cured. To account for the lingering impacts of cancer treatment, an excess mortality rate was incorporated into the model. Event-free survival (EFS) and overall survival (OS) were estimated by fitting mixture-cure and standard parametric survival distributions to the time-to-event data from the phase 3 trial. The model accounted for treatment costs, adverse event costs, follow-up costs, subsequent allogeneic hematopoietic stem cell transplantation (alloHSCT) costs, and subsequent treatment costs.</p></div><div><h3>Results</h3><p>Blinatumomab was associated with a lifetime gained of 5.11 years at an incremental cost of $621,111 MXN, relative to SC. The ICER for blinatumomab vs Standard of care was estimated to be $121,526 MXN/LY gained in the base case. Cost-effectiveness was sensitive to varying the time horizon. Blinatumomab had a probability of 99 % of being cost-effective, relative to SC, at the willingness to pay threshold defined in Mexico.</p></div><div><h3>Limitations</h3><p>Health-related quality of life values were not included in the analysis and therefore we did not estimate the quality-adjusted life-years gained.</p></div><div><h3>Conclusions</h3><p>Blinatumomab was associated with greater benefit in terms of OS and EFS relative to SC. Probabilistic, deterministic, and scenario analyses indicate that blinatumomab represents the best value for money. Therefore, blinatumomab administered as part of consolidation therapy in B-ALL pediatric patients with high-risk first relapse is a cost-effective option.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"145 ","pages":"Article 107560"},"PeriodicalIF":2.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0145212624001267/pdfft?md5=04f550091c780aeebd987c84b18fa905&pid=1-s2.0-S0145212624001267-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142089415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}