Therapeutic Advances in Hematology最新文献

{"title":"Hypoplastic acute myeloid leukemia with aberrant lymphoid antigen expression and <i>EWSR1::FEV</i> fusion: A rare case report and literature review.","authors":"Wenxia Xia, Junyan Zou, Xiaoyong Chen, Jing Luo, Chun Feng, Mao Dai, Yanhong Ding, Jihao Zhou, Peng Ke, Huijun Li, Junjie Hou","doi":"10.1177/20406207261481219","DOIUrl":"https://doi.org/10.1177/20406207261481219","url":null,"abstract":"<p><p>Ewing sarcoma breakpoint region 1 (<i>EWSR1</i>):: Fifth Ewing variant (<i>FEV</i>)-positive acute leukemia is exceptionally rare, and its clinicopathological features, molecular profile, and optimal treatment remain poorly defined. Here, we report a case of acute myeloid leukemia (AML) with bone marrow hypocellularity, aberrant lymphoid antigen expression, and an <i>EWSR1::FEV</i> fusion. A 45-year-old man was admitted with a 1-month history of petechiae and fatigue. Complete blood count (CBC) showed pancytopenia. Bone marrow (BM) examination revealed hypocellular marrow, with blasts accounting for 62% of nucleated cells. Flow cytometry (FCM) revealed a predominantly myeloid immunophenotype accompanied by aberrant expression of lymphoid-associated antigens. Conventional karyotyping did not identify a characteristic balanced translocation. Targeted next-generation sequencing (NGS) detected concurrent <i>PTPN11</i> and <i>NRAS</i> mutations. RNA sequencing (RNA-seq) of the bone marrow sample identified the <i>EWSR1::FEV</i> fusion. Based on these findings, the patient was diagnosed with de novo AML with bone marrow hypocellularity and aberrant lymphoid antigen expression. Given the hypocellular marrow, venetoclax plus azacitidine (VA) was selected as induction therapy. The patient achieved morphological complete remission after one cycle, accompanied by a marked reduction in <i>EWSR1::FEV</i> transcript levels, and remained in morphological remission during approximately 6 months of follow-up after subsequent homoharringtonine combined with venetoclax plus azacitidine (HVA) consolidation. Together with previously reported cases, this case further supports the notion that <i>EWSR1::FEV</i>-positive acute leukemia may represent a distinct molecular subset characterized by lineage ambiguity, fusion-driven biology, and potentially unique therapeutic vulnerabilities. This case also suggests potential activity of venetoclax-based therapy in <i>EWSR1::FEV</i>-positive leukemia and warrants further investigation in additional cases.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"17 ","pages":"20406207261481219"},"PeriodicalIF":2.8,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13490784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of novel <i>UBE2E3::PDE1A</i> and <i>CTC1::MEF2C</i> fusion transcripts in acute myeloid leukemia.","authors":"Jifang Tu, Yungui Wang, Xiangli Gao, Huanping Wang, Huafeng Wang, Jie Jin, Hongyan Tong","doi":"10.1177/20406207261480375","DOIUrl":"https://doi.org/10.1177/20406207261480375","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is a hematologic malignancy caused by the malignant proliferation and differentiation block of immature myeloid cells (blasts) in the bone marrow. The pathogenesis, diagnostic classification, treatment, and prognosis of AML are fundamentally linked to the accumulation of genetic variants, fusion gene formation, and chromosomal karyotype abnormalities. Using mRNA sequencing (next-generation sequencing, NGS), we identified and validated two novel fusion genes, <i>UBE2E3::PDE1A</i> and <i>CTC1::MEF2C</i>, in a case of AML-M2a. This patient also harbored six single nucleotide variants (SNV) (<i>EP300</i>, <i>KRAS</i>, <i>NRAS</i>, <i>RAD21</i>, <i>TET2</i>, and <i>TP53</i>) and complex karyotype (CK). The chromosomes exhibited extreme instability and high variability, with tumor cells containing multiple clones and showing continuous karyotype evolution as the disease progressed. The patient was treated with three chemotherapy regimens (VMA, VHAA, and Decitabine-Venetoclax), but none achieved remission. We propose that the combination of these novel fusion genes, multiple SNVs, and the complex karyotype collectively contributed to the patient's multidrug resistance.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"17 ","pages":"20406207261480375"},"PeriodicalIF":2.8,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune and cytokine landscape differs between cytopenic and proliferative phenotypes in primary myelofibrosis.","authors":"Sze-Hwei Lee, Yu-Hung Wang, Yu-Sung Chang, Chao-Hung Wei, Chang-Tsu Yuan, Hsin-An Hou, Wen-Chien Chou, Hwei-Fang Tien, Chien-Chin Lin","doi":"10.1177/20406207261474950","DOIUrl":"https://doi.org/10.1177/20406207261474950","url":null,"abstract":"<p><strong>Background: </strong>Cytopenia represents a distinct clinical phenotype in primary myelofibrosis (PMF), often associated with advanced disease and poor prognosis. We propose that while a common driver mutation initiates the disease, the clinical phenotype of PMF is shaped by inter-individual variability in downstream inflammatory responses, contributing to the observed heterogeneity in disease presentation.</p><p><strong>Objectives: </strong>To characterize inflammatory and immune signatures distinguishing cytopenic from proliferative phenotypes of PMF.</p><p><strong>Design: </strong>Retrospective, single-center observational study analyzing clinical, molecular, transcriptomic, and cytokine data from patients with pathologically confirmed PMF.</p><p><strong>Methods: </strong>We analyzed a cohort of 140 patients with PMF, stratified into cytopenic and proliferative phenotypes based on abnormalities in at least one peripheral blood lineage. Bone marrow transcriptomic profiling was performed using the NanoString nCounter PanCancer Immune Panel. Cytokine levels were measured by MILLIPLEX® bead-based multiplex assay, and phosphorylated NFκB p65 expression was evaluated by immunohistochemistry.</p><p><strong>Results: </strong>Compared with the proliferative phenotype, cytopenic PMF showed more advanced disease features, including higher blast counts (P<0.001), elevated LDH (P<0.001), and more frequent overt fibrosis (P<0.001). Cytopenic patients had fewer <i>JAK2</i> mutations (P=0.025) but were enriched for high molecular risk mutations such as <i>ASXL1</i> (P=0.011) and <i>EZH2</i> (P=0.035). Transcriptomic profiling revealed upregulation of inflammatory pathways, notably TNFα-NFκB (P=0.0097) and IL2-STAT5 (P=0.0399), while cytokine analysis showed elevated IL-8 (P=0.021) and G-CSF (P=0.007) independent of fibrosis severity. Immunohistochemistry confirmed enhanced NFκB p65 activation in cytopenic marrow.</p><p><strong>Conclusion: </strong>Our findings highlight cytopenic PMF as a biologically distinct and clinically aggressive phenotype characterized by inflammatory pathway activation, particularly involving NFκB signaling and elevated IL-8. These results support the role of immune dysregulation in the pathogenesis of cytopenia in PMF and provide a basis for further investigation into its clinical implications.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"17 ","pages":"20406207261474950"},"PeriodicalIF":2.8,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel targeted therapies for central nervous system involvement in chronic lymphocytic leukemia: A systematic review.","authors":"Abdulrahman F Al-Mashdali, Mujahid O Abdelraof, Raga M Mukhtar, Shehab F Mohamed","doi":"10.1177/20406207261474934","DOIUrl":"https://doi.org/10.1177/20406207261474934","url":null,"abstract":"<p><strong>Background: </strong>Central nervous system (CNS) involvement in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is rare, diagnostically challenging, and historically associated with poor outcomes. Bruton tyrosine kinase (BTK) and B-cell lymphoma 2 (BCL2) inhibitors may improve outcomes, but evidence remains limited to case reports and small series.</p><p><strong>Objectives: </strong>To summarize the clinical features, diagnostic findings, treatment patterns, efficacy, safety, and outcomes of CNS involvement by CLL/SLL treated with novel targeted therapies.</p><p><strong>Design: </strong>Systematic review of published case reports, case series, and cohorts with extractable individual-level data.</p><p><strong>Methods: </strong>PubMed, Scopus, and Web of Science were searched from database inception to September 15, 2025. Eligible studies reported adults with CNS involvement by CLL/SLL treated with targeted agents, including BTK inhibitors, venetoclax, duvelisib, dasatinib, or other novel therapies. Chemotherapy-only regimens and Richter transformation cases were excluded. Patient-level data were extracted, and study quality was assessed using the Murad tool.</p><p><strong>Results: </strong>Twenty-six studies including 32 patients were analyzed. Median age at CNS presentation was 65.5 years, and most cases occurred at relapse. CNS disease was meningeal in 47%, parenchymal in 22%, and combined in 31%. Adverse biological features, including TP53 mutation, del(17p), and unmutated immunoglobulin heavy chain variable region (IGHV), were common. Across 34 treatment regimens, the overall response rate was 94.1%, with 55.9% complete and 38.2% partial responses. Ibrutinib was the most frequently used agent, while venetoclax and ibrutinib-venetoclax showed favorable activity. Other targeted agents showed promising responses in isolated cases. Toxicities were infrequent and consistent with known safety profiles.</p><p><strong>Conclusion: </strong>BTK inhibitor- and venetoclax-based regimens show encouraging activity in CNS involvement by CLL/SLL, including in genomically adverse disease. However, the current evidence remains primarily exploratory and descriptive. Prospective multicenter studies are warranted to establish optimal treatment sequencing, combination strategies, and the role of adjunctive intrathecal therapy or radiotherapy.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"17 ","pages":"20406207261474934"},"PeriodicalIF":2.8,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal prospective analysis of organ stiffness and cardiac function in patients with myelofibrosis treated with ruxolitinib type of study: Prospective single-center cohort study.","authors":"Danijela Lekovic, Isidora Arsenovic, Mirjana Cvetkovic, Dragan Matic, Milica Stojkovic Lalosevic, Tatjana Cvejic Pasic, Jovana Starcevic, Andrija Bogdanovic","doi":"10.1177/20406207261474317","DOIUrl":"https://doi.org/10.1177/20406207261474317","url":null,"abstract":"<p><strong>Background: </strong>In myeloproliferative neoplasms (MPNs), fibrosis occurs not only in the bone marrow but also in extramedullary organs such as the liver and spleen, reflected by increased tissue stiffness. Patients with MPNs frequently present with echocardiographic signs of cardiac dysfunction, which may be modifiable through targeted therapy.</p><p><strong>Objectives: </strong>To evaluate changes in organ stiffness and cardiac function in patients with myelofibrosis (MF) treated with ruxolitinib at baseline, 6, and 12 months.</p><p><strong>Methods: </strong>This prospective, single-center cohort study enrolled 30 MF patients diagnosed according to the current WHO criteria. At each assessment, clinical and laboratory parameters were evaluated, and abdominal ultrasound with shear wave elastography was performed to measure spleen and liver stiffness, alongside echocardiographic evaluation of cardiac function.</p><p><strong>Results: </strong>The median age of patients was 50 years (range, 21-76). After 6 months of treatment, both liver size (p=0.049) and spleen size (p<0.001) significantly decreased, accompanied by reduced liver and spleen stiffness, while echocardiographic parameters remained unchanged. Significant decreases were also observed in hemoglobin (p=0.017), absolute neutrophil count (p=0.025), platelets (p=0.003), neutrophil-to-lymphocyte ratio (p=0.007), and platelet-to-lymphocyte ratio (p=0.04). Patients reported a notable reduction in symptom burden. At 12 months, organ diameters and stiffness remained stable. Echocardiography demonstrated improved systolic pulmonary artery pressure (sPAP) with a significant difference compared with baseline (p<0.001), while NT-proBNP levels decreased by 50%. Laboratory parameters were largely stable, except for a significant decrease of lactate dehydrogenase. Ruxolitinib was initiated earlier in primary MF, but no significant differences between primary and secondary MF were observed regarding organ stiffness or cardiac findings after 12 months.</p><p><strong>Conclusion: </strong>Ruxolitinib demonstrated its greatest benefit at 6 months, significantly reducing organ size, stiffness, and symptom burden, followed by cardiovascular improvement and normalization of sPAP by 12 months. Further larger prospective studies with longer follow up are needed for definitive conclusion.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"17 ","pages":"20406207261474317"},"PeriodicalIF":2.8,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolated del(5q) with myeloproliferative driver mutations: A systematic review of published cases and clinical implications.","authors":"Mohammed Abdulgayoom, Abdulrahman F Al-Mashdali, Awni Alshurafa, Mohammad S Afana, Anas M Babiker, Mohammad Bakheet, Shehab F Mohamed, Mohamed A Yassin","doi":"10.1177/20406207261474937","DOIUrl":"https://doi.org/10.1177/20406207261474937","url":null,"abstract":"<p><strong>Background: </strong>Myeloid neoplasms harboring both an isolated deletion of chromosome 5q (del(5q)) and myeloproliferative neoplasm (MPN) driver mutations (<i>JAK2, CALR, MPL</i>) constitute a rare and diagnostically challenging subset, often described with features overlapping those of myelodysplastic syndromes (MDS) and MPN.</p><p><strong>Methods: </strong>We systematically reviewed published case reports and case series of adult patients with myeloid neoplasms and concomitant isolated del(5q) and MPN driver mutations. A comprehensive search of PubMed and Google Scholar from inception through 31 December 2024 was performed using terms related to \"del(5q)\", \"<i>JAK2\", \"CALR\", \"MPL\"</i>, and \"myeloid neoplasm\". Eligible reports required documentation of isolated del(5q) and at least one MPN driver mutation with extractable clinical, cytogenetic, and/or molecular data. Data were synthesised descriptively; no quantitative meta-analysis was feasible. The review followed PRISMA 2020 guidelines and was registered post-study at INPLASY2025120046.</p><p><strong>Results: </strong>Twenty publications reporting 24 patients (diagnosed between 2006 and 2021) met the inclusion criteria. The median age was 70.5 years with a female predominance. Most patients presented with macrocytic anemia, thrombocytosis, and megakaryocytic dysplasia, frequently accompanied by marrow fibrosis. <i>JAK2 V617F</i> was the predominant mutation, whereas <i>CALR</i> and <i>MPL</i> were rarely described. Lenalidomide achieved hematologic responses in 14 of 17 evaluable patients and cytogenetic responses in 8 of 16; <i>JAK2 V617F</i> clearance occurred in 4 of 13. During a median follow-up of approximately two years, 5 of 24 patients progressed to acute myeloid leukemia.</p><p><strong>Conclusion: </strong>Reported cases with isolated del(5q) and an MPN driver mutation suggest a rare overlap presentation with mixed dysplastic and proliferative features. Lenalidomide appears to provide hematologic and cytogenetic benefit in some patients, although molecular persistence and progression to AML have been observed. Given the limited number and heterogeneity of published cases, these observations should be interpreted with caution. Larger, systematically collected datasets are needed to better understand the clinical significance and optimal management of this combination.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"17 ","pages":"20406207261474937"},"PeriodicalIF":2.8,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Romiplostim during pregnancy in refractory primary immune thrombocytopenia: Literature review and case series.","authors":"Dina Weinstein Mezan, Efrat Shekel, Batia Roth, Yosef Kalish, Doron Kabiri","doi":"10.1177/20406207261474927","DOIUrl":"https://doi.org/10.1177/20406207261474927","url":null,"abstract":"<p><p>Primary immune thrombocytopenia (ITP) in pregnancy presents significant therapeutic challenges, particularly when refractory to standard treatments such as corticosteroids, intravenous immunoglobulin, and immunosuppressants. Data on thrombopoietin receptor agonists (TPO-RAs) during pregnancy remain scarce. This study reports four pregnancies in three women with refractory ITP who received Romiplostim during gestation. All cases were retrospectively analyzed, with detailed documentation of treatment courses, platelet trajectories, and maternal and neonatal outcomes. Romiplostim was introduced in the second or third trimester at doses ranging from 3.1 to 6.25 µg/kg/week, following inadequate response to conventional therapy. All patients demonstrated hematologic improvement, often within one to two weeks of initiation, enabling corticosteroid tapering and preparation for delivery. Delivery outcomes were favorable, including four term vaginal deliveries without major hemorrhagic or thromboembolic complications. Neonatal outcomes were reassuring, with all infants born healthy, exhibiting platelet counts between 73,000 and 233,000/µL and no evidence of bleeding or congenital anomalies. One patient experienced transient postpartum thrombocytosis managed with low-molecular-weight heparin prophylaxis. No maternal or neonatal adverse events were attributed to Romiplostim exposure. These findings are consistent with previous limited reports suggesting that Romiplostim may be a viable rescue therapy for severe, refractory ITP in pregnancy. The favorable hematologic responses and reassuring neonatal outcomes observed in this series highlight the potential role of Romiplostim as an alternative treatment in carefully selected cases, provided that therapy is conducted under close multidisciplinary supervision.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"17 ","pages":"20406207261474927"},"PeriodicalIF":2.8,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the value of fibro scan in the detection of liver fibrosis among patients with sickle cell disease- a single center study.","authors":"Rehab Y Al-Ansari, Mays Hassan Mahasneh, Alexander Woodman, Mohammed Yousef Alghamdi, Saleh A Alqahtani, Rawan Rashed Aljohani, Mariam Seria, Tawasoul Fadoul, Muhammad Amjad, Hind Hamid, Amal Shilash, Nawaf Zakary","doi":"10.1177/20406207261475906","DOIUrl":"https://doi.org/10.1177/20406207261475906","url":null,"abstract":"<p><strong>Background: </strong>Sickle cell hepatopathy (SCH) is a general term used to describe the acute and chronic manifestations of liver damage in sickle cell disease (SCD). One of the most effective methods used to examine the liver is transient elastography (Fibro Scan), a noninvasive, rapid, and reproducible method that can assess liver fibrosis by measuring liver stiffness. Objectives: This single-center study aims to investigate the role of transient elastography (Fibro Scan) in the detection of liver disease among patients with SCD in the Eastern Province of Saudi Arabia, where the rates of SCD are found to be among the highest. Design: This is a prospective, observational study.</p><p><strong>Methods: </strong>The study was conducted among n=101 SCD patients of any phenotype between January and December 2024. Data on demographics, hospitalization rates, hydroxyurea use, transfusion, and complications were obtained from the health informatics system. All included patients were examined using non-invasive transient elastography (Fibro Scan) for the presence of fibrotic changes.</p><p><strong>Results: </strong>Among n = 101 SCD patients, 13.9% had G6PD deficiency, 40.6% required one hospitalization per year, and 65.3% required blood transfusion. The transient elastography through Fibro Scan assessments revealed that 94.1% of patients had normal liver tissue (fibrosis score 2-7 kPa), 4.0% showed moderate scarring (7-11 kPa), and 2.0% had moderate to severe scarring (11-15 kPa). Radiographic evidence of fatty liver was present in 24.8% of cases, with a significant association with moderate or severe fibrosis (p = 0.049).</p><p><strong>Conclusions: </strong>Patients with SCD without iron overload had a low prevalence of liver fibrosis. However, fatty liver in SCD likely leads to a risk of fibrosis progression, which is an area for further study.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"17 ","pages":"20406207261475906"},"PeriodicalIF":2.8,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual targeting of BCR::ABL1 and DNA methylation in advanced CML: A 3-year survival analysis of TKI-Azacitidine combination therapy.","authors":"Zhuming Yang, Danlei Han, Renying Ge, Zhenhao Wang, Hanlin Du, Yigang Guo, Zhe Zhao, Li Liu, Jun Qin, Bangwei Yu, Jie Hu, Xiya Gui, Meifang Su, Shiming Chen, Daozi Jiang, Jing Zheng, Hongxiang Wang, Li Meng, Weiming Li, Zhenya Hong","doi":"10.1177/20406207261474931","DOIUrl":"https://doi.org/10.1177/20406207261474931","url":null,"abstract":"<p><strong>Background: </strong>Advanced-phase chronic myeloid leukemia (CML) remains associated with poor outcomes despite advances in tyrosine kinase inhibitor (TKI) therapy, underscoring the need for more effective treatment approaches.</p><p><strong>Objectives: </strong>This multicenter study evaluated the efficacy and safety of tyrosine kinase inhibitor (TKI) plus azacitidine (with optional low-dose chemotherapy) in advanced-phase CML.</p><p><strong>Design: </strong>Prospective multicenter single-arm study.</p><p><strong>Methods: </strong>41 patients with accelerated- (AP) or blast-phase (BP) CML received azacitidine 75 mg/m²/day for 7 days per 28-day cycle (6 cycles) plus TKIs selected by ABL1 mutation status; chemotherapy was added based on early response. Major hematologic response (MaHR) was the primary endpoint. The secondary endpoints included cytogenetic/molecular responses-major cytogenetic response (MCyR), major molecular response (MMR), and undetectable minimal disease (UMD) - along with progression-free survival (PFS) and overall survival (OS). Adverse events (AEs) were documented.</p><p><strong>Results: </strong>Among 36 evaluable patients (median age 51 years; range: 24-77; AP: 13, BP: 23) after excluding 5 noncompliant patients, 63.9% achieved MaHR, with a median response time of 1.33 months. The cumulative 3-year response rates were as follows: MCyR, 48.5%; MR2.0 (BCR::ABL1 IS ≤1%), 16.3%; MMR, 21.8%; and UMD, 14.2%. Patients maintained sustainable responses during follow-up. Four hematopoietic stem cell transplantation (HSCT) recipients maintained durable remission with TKI consolidation. At 28.1-month median follow-up, median OS was not reached and median PFS was 8.17 months; estimated 3-year OS and PFS rates were 50.3% and 41.1%, respectively. Elevated baseline WBC count and BCR::ABL1 transcript levels predicted poor survival. Hematologic toxicities of grade 3 or higher occurred in 55.6% of patients, including neutropenia (36.1%), thrombocytopenia (33.3%).</p><p><strong>Conclusion: </strong>TKI-azacitidine therapy demonstrated promising efficacy and acceptable tolerability in patients with advanced-phase CML and may represent a feasible treatment option for this high-risk population.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"17 ","pages":"20406207261474931"},"PeriodicalIF":2.8,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hetrombopag for enhancement of platelet engraftment after allogeneic hematopoietic stem cell transplantation: A single-center experience.","authors":"Li Wang, Ailin Zhao, Tian Dong, Jinjin Wang, Zhigang Liu, Pu Kuang, Qiuhui Wu, Jie Ji, Ting Niu","doi":"10.1177/20406207261475878","DOIUrl":"https://doi.org/10.1177/20406207261475878","url":null,"abstract":"<p><strong>Background: </strong>Delayed platelet engraftment is a significant complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><strong>Objectives: </strong>This retrospective study evaluates the efficacy and safety of hetrombopag, an oral thrombopoietin receptor agonist, in promoting platelet engraftment post-allo-HSCT.</p><p><strong>Design: </strong>Retrospective observational cohort study.</p><p><strong>Methods: </strong>A cohort of 133 patients was analyzed, including 68 treated with hetrombopag post-transplant and 65 controls. Cumulative incidence function evaluated platelet engraftment, with propensity score matching and competing risk analysis to strengthen robustness. Factors associated with platelet engraftment were examined using multivariate Cox models with time-dependent coding of hetrombopag exposure.</p><p><strong>Results: </strong>Hetrombopag significantly reduced the time to overall response (OR: 15.0 days vs. 20.0 days; <i>p</i> = 0.009) and complete response (CR: 17.5 days vs. 34.0 days; <i>p</i> < 0.001). The cumulative incidence of CR was higher in the hetrombopag group (92.78% vs. 86.58%; <i>p</i> = 0.001), with a significantly shorter median time to CR (19 days vs. 38 days) defined by the cumulative incidence function. Multivariate Cox regression identified hetrombopag as a protective factor for platelet recovery (HR: 2.04; <i>p</i> = 0.004). Competing risk and PSM analyses confirmed hetrombopag's role in faster platelet engraftment. The treatment was well-tolerated, with manageable mild liver enzyme elevations and hypomagnesemia but no grade 3/4 adverse events.</p><p><strong>Conclusion: </strong>Hetrombopag significantly accelerates platelet engraftment and has a favorable safety profile, suggesting its potential as a therapeutic adjunct in managing thrombocytopenia post-allo-HSCT. This study complements and validates findings from prior prospective studies, providing external confirmation in a real-world cohort.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"17 ","pages":"20406207261475878"},"PeriodicalIF":2.8,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148798231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}