Acta Haematologica最新文献

{"title":"Exclusion of Acute Myeloid Leukemia Patients with Central Nervous System Involvement from Clinical Trials: An Analysis of the National Institutes of Health Clinical Trials Registry from 2012 to 2022.","authors":"Dahniel Sastow, Grace Van Hyfte, Jonathan Feld, Marina Kremyanskaya, John Mascarenhas, Douglas Tremblay","doi":"10.1159/000533819","DOIUrl":"10.1159/000533819","url":null,"abstract":"<p><strong>Introduction: </strong>Central nervous system (CNS) involvement in acute myeloid leukemia (AML) can be successfully treated with intrathecal chemotherapy and carries debatable prognostic impact. However, patients with CNS involvement are commonly excluded from clinical trials at an unknown rate. We systematically evaluated exclusion criteria of AML clinical trials based on CNS involvement and determined associations with clinical trial characteristics.</p><p><strong>Methods: </strong>The National Institutes of Health Clinical Trials Registry was searched for interventional adult AML trials between 2012 and 2022 that were phase 1, 2, or 3 and relevant trial characteristics were extracted.</p><p><strong>Results: </strong>1,270 trials were included in the analysis with 790 trials (62.1%) explicitly excluding CNS involvement. There was no significant change in rates of CNS exclusion over the past decade. CNS exclusion was higher in trials that included the non-transplant population compared to trials exclusive to the transplant population (66.9% vs. 43.8%, p &lt; 0.01). Non-transplant trials were also more likely to exclude patients with a history of or ambiguous timing of CNS involvement (p &lt; 0.01). Phase 3 trials were associated with more liberal definitions of CNS exclusion (history or ambiguous timing) as compared to phase 1 and 2 trials that had higher rates of excluding patients with only active CNS involvement (p &lt; 0.01).</p><p><strong>Conclusion: </strong>A majority of AML clinical trials, particularly in the non-transplant setting, exclude patients with CNS involvement. Many of these trials, most notably phase 3 trials, exclude patients not only with active but also with any history of CNS involvement. Further research is needed to determine optimal management of these patients in order to increase representation in large clinical trials.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"292-299"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41100654","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":"Non-Immunotherapy Approaches for Relapsed or Refractory AML: An Update for 2024.","authors":"Shira Buchrits, Ofir Wolach","doi":"10.1159/000534897","DOIUrl":"10.1159/000534897","url":null,"abstract":"<p><strong>Background: </strong>Relapsed or refractory (R/R) acute myeloid leukemia (AML) is a challenging, high-risk, clinical scenario with a dismal outcome. Recent insights on the genetic, epigenetic, and metabolic events that drive clonal progression and the advent of novel therapies resulted in the incorporation of several new targeted therapies, alone or in combination, in the R/R setting with the aim of improving response rates and survival. Herein, we review current challenges and future opportunities with non-immunotherapeutic approaches to treat R/R AML.</p><p><strong>Summary: </strong>Inhibitors of FLT3 and IDH 1/2 are now FDA approved for patients with R/R disease and corresponding mutations. These agents are also used in combination with intensive and low-intensity platforms in an attempt to improve response and survival. Several targeted agents are currently being tested alone or in combination in early-phase trials. These include drugs that target apoptotic pathways, drugs that interfere with key survival pathways of the R/R leukemic cell as well as therapies aimed toward the leukemia marrow microenvironment. Menin inhibitors are a promising class of active drugs in NPM1 and KMT2A-rearranged AML.</p><p><strong>Key messages: </strong>Several new targeted therapies are being studied and are moving through pre-clinical and clinical pipelines. Significant remaining challenges include the development of synergistic combination therapies tailored to the specific biology and clinical context of the patient, and re-defining the role and timing of allogeneic transplantation in patients with R/R disease.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"159-174"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71419615","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":"Shikonin Exerts an Antileukemia Effect against FLT3-ITD Mutated Acute Myeloid Leukemia Cells via Targeting FLT3 and Its Downstream Pathways.","authors":"Mu-Nan Zhao, Long Su, Fei Song, Zhi-Feng Wei, Tian-Xue Qin, Yun-Wei Zhang, Wei Li, Su-Jun Gao","doi":"10.1159/000534101","DOIUrl":"10.1159/000534101","url":null,"abstract":"<p><strong>Introduction: </strong>Acute myeloid leukemia (AML) with internal tandem duplication (ITD) mutations in Fms-like tyrosine kinase 3 (FLT3) has an unfavorable prognosis. Recently, using newly emerging inhibitors of FLT3 has led to improved outcomes of patients with FLT3-ITD mutations. However, drug resistance and relapse continue to be significant challenges in the treatment of patients with FLT3-ITD mutations. This study aimed to evaluate the antileukemic effects of shikonin (SHK) and its mechanisms of action against AML cells with FLT3-ITD mutations in vitro and in vivo.</p><p><strong>Methods: </strong>The CCK-8 assay was used to analyze cell viability, and flow cytometry was used to detect cell apoptosis and differentiation. Western blotting and real-time polymerase chain reaction were used to examine the expression of certain proteins and genes. Leukemia mouse model was created to evaluate the antileukemia effect of SHK against FLT3-ITD mutated leukemia in vivo.</p><p><strong>Results: </strong>After screening a series of leukemia cell lines, those with FLT3-ITD mutations were found to be more sensitive to SHK in terms of proliferation inhibition and apoptosis induction than those without FLT3-ITD mutation. SHK suppresses the expression and phosphorylation of FLT3 receptors and their downstream molecules. Inhibition of the NF-κB/miR-155 pathway is an important mechanism through which SHK kills FLT3-AML cells. Moreover, a low concentration of SHK promotes the differentiation of AML cells with FLT3-ITD mutations. Finally, SHK could significantly inhibit the growth of MV4-11 cells in leukemia bearing mice.</p><p><strong>Conclusion: </strong>The findings of this study indicate that SHK may be a promising drug for the treatment of FLT3-ITD mutated AML.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"310-324"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11251672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71476843","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":"[Momelotinib bei Myelofibrose und Anämie].","authors":"","doi":"10.1159/000538289","DOIUrl":"10.1159/000538289","url":null,"abstract":"","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":"147 2","pages":"251-253"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140100712","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":"Prognostic Factors of Adult Hemophagocytic Lymphohistiocytosis and Clinical Utility of HLH-2004 Diagnostic Criteria and HScore: A Real-World Multicenter Study from Thailand.","authors":"Pitchayaporn Jongdee, Jakrawadee Julamanee, Ekarat Rattarittamrong, Sarita Mukura, Chinadol Wanitpongpun, Rawisut Deoisares, Anoree Surawong, Thunyamon Chajuwan, Chantiya Chanswangphuwana","doi":"10.1159/000536287","DOIUrl":"10.1159/000536287","url":null,"abstract":"<p><strong>Introduction: </strong>Adult hemophagocytic lymphohistiocytosis (HLH) is a rare disease with a dismal prognosis. Early diagnosis and prompt management are necessary for improved outcomes.</p><p><strong>Methods: </strong>This multicenter retrospective study investigated the etiologies, survival, and prognostic factors of HLH, including the utility of HLH-2004 criteria and HScore in real-life clinical practice.</p><p><strong>Results: </strong>A total of 147 HLH patients were identified by using a combination of hemophagocytosis identification in bone marrow and the HLH-related international classification disease-10. A total of 116 (78.9%) patients fulfilled the HLH diagnosis by HScore, while 91 (61.9%) patients fulfilled 5 of 8 HLH-2004 criteria. In Thailand, the clinical application of HLH-2004 criteria needed to be reduced from 8 to 6 due to a lack of sCD25 and natural killer cell activity tests. Using the adapted HLH-2004 with a cutoff value of 4 resulted in 132 (89.9%) cases meeting the diagnostic criteria. Among these 132 confirmed HLH patients by using adapted HLH-2004, HLH was triggered by infection (29.5%), autoimmune disease (12.9%), malignancy (40.9%), and unknown cause (16.7%). Median overall survival of HLH patients was extremely short (67 days). Ferritin &gt;6,000 μg/L, HLH from infection, malignancy, and unknown etiology were demonstrated as independent prognostic factors for inferior survival (hazard ratio [HR] 2.47; 95% confidence interval [CI] 1.39-4.37, HR 4.69; 95% CI 1.38-15.92, HR 6.09; 95% CI 1.84-20.14, and HR 6.02; 95% CI 1.64-22.05, respectively).</p><p><strong>Conclusion: </strong>Ferritin is a helpful biomarker for HLH diagnosis and prognostic prediction. Autoimmune disease-triggered HLH has favorable outcomes. Future prospective study is required to verify the use of the adapted HLH-2004 criteria.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"447-456"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139541174","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":"Primary Nodal Epstein-Barr Virus-Positive T-Cell/NK-Cell Lymphoma: Real-World Experience.","authors":"Dae-Ho Choi, Sang Eun Yoon, Junhun Cho, Seok Jin Kim, Won Seog Kim","doi":"10.1159/000537962","DOIUrl":"10.1159/000537962","url":null,"abstract":"<p><strong>Introduction: </strong>Primary nodal Epstein-Barr virus-positive T-cell/NK-cell lymphoma (PTCL-EBV) is a disease entity newly recognized in the World Health Organization's classification of hematolymphoid tumors, 5th edition (WHO-HAEMS5) and the International Consensus Classification of Mature Lymphoid Neoplasms (ICC). Previously, it was classified as a subtype within peripheral T-cell lymphoma, not otherwise specified, and was known to have a poor prognosis. However, the clinical features and treatment outcomes are not well known.</p><p><strong>Methods: </strong>This retrospective observational study was conducted on patients diagnosed with PTCL-EBV at Samsung Medical Center through a pathology review from 2000 to 2020. We analyzed the clinical data from 14 patients, immunohistochemistry, and survival outcomes including overall survival (OS) and progression-free survival (PFS) for each treatment regimen. PFS was defined as the time from the start of chemotherapy to the confirmation of disease progression on imaging, and hematopoietic stem-cell transplantation (HSCT) was considered a consolidation treatment. OS was defined as the time from diagnosis to the time of death.</p><p><strong>Results: </strong>25% (1 out of 4) were beta-F1 positive, and 67% (4 out of 6) were T-cell receptor gamma (TCRγ) positive. T-cell intracellular antigen (TIA-1) and granzyme B exhibited positive results in all cases (3 out of 3), whereas the NK-cell marker CD56 was positive in only 11% of patients (1 out of 9). CD3 was observed in all of the patients (11 out of 11). The CD4 was 43% positive (3 out of 7). The CD8 was investigated in 8 patients, with 37.5% positive (3 out of 8). Hepatosplenomegaly was observed in 55% of patients (6 out of 11), and 70% (7 out of 10) of patients displayed B symptoms at the time of diagnosis. Patients who received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) or CVP (cyclophosphamide, vincristine, prednisolone) treatment had a median PFS of 2.2 months (95% CI: 1.9-2.5 months), and patients who received other treatments had a median PFS of 5.1 months (NA). The objective response rate (ORR) for ICE/dexa (ifosfamide, carboplatin, etoposide, dexamethasone) as the first- or second-line treatment was 100% (3 out of 3). But ORR of CHOP or CVP as the first-line treatment was 33.3% (3 out of 9). The median OS for the group that received HSCT (3 out of 11) after achieving a response was 34.6 months (95% CI: 0-74.6 months), and the median OS for the group that did not receive HSCT (8 out of 11) was 5.0 months (95% CI: 2.1-7.9 months) (p = 0.04).</p><p><strong>Conclusions: </strong>In conclusion, in the context of PTCL-EBV, despite a limited sample size, the ICE/Dexa regimen shows potential benefits in terms of ORR and PFS. Furthermore, the application of HSCT following the attainment of a complete response may prove advantageous.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"625-633"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140020713","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":"Immunotherapy for Acute Myeloid Leukemia: Current Trends, Challenges, and Strategies.","authors":"Evan C Chen, Jacqueline S Garcia","doi":"10.1159/000533990","DOIUrl":"10.1159/000533990","url":null,"abstract":"<p><strong>Background: </strong>In the past decade, there have been significant breakthroughs in immunotherapies for B-cell lymphoid malignancies and multiple myeloma, but progress has been much less for acute myeloid leukemia (AML). Nevertheless, challenge begets innovation and several therapeutic strategies are under investigation.</p><p><strong>Summary: </strong>In this review, we review the state of the art in AML immunotherapy including CD33- and CD123-targeted agents, immune checkpoint inhibition, and adoptive cell therapy strategies. We also share conceptual frameworks for approaching the growing catalog of investigational AML immunotherapies and propose future directions for the field.</p><p><strong>Key messages: </strong>Immunotherapies for AML face significant challenges but novel strategies are in development.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"198-218"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10226340","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":"Cellular Therapy in Chronic Lymphocytic Leukemia: Have We Advanced in the Last Decade?","authors":"Ofrat Beyar Katz, Dana Yehudai-Ofir, Tsila Zuckerman","doi":"10.1159/000534341","DOIUrl":"10.1159/000534341","url":null,"abstract":"<p><strong>Background: </strong>Chronic lymphocytic leukemia (CLL) is a heterogeneous B-cell malignancy, affecting mainly older adults. Despite the recent introduction of multiple targeted agents, CLL remains an incurable disease. Cellular therapy is a promptly evolving area that has developed over the last decades from such standard of care as hematopoietic cell transplantation (HCT) to the novel treatment modalities employing genetically engineered immune cells.</p><p><strong>Summary: </strong>Tailoring the proper treatment for each patient is warranted and should take into account the disease biology, patient characteristics, and the available treatment modalities. Nowadays, the most broadly applied cellular therapies for CLL management are HCT and chimeric antigen receptor-T (CAR-T) cells. However, CAR-T cell therapy is currently not yet approved in CLL, and the appropriate sequencing for the administration of these agents remains to be clarified.</p><p><strong>Key messages: </strong>The current review will discuss various available cellular treatment options, their advances and limitations, as well as the optimal timing for the employment of such therapies in CLL patients.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"99-112"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41181753","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":"Addendum to the German Consensus Recommendations on Ponatinib in the Treatment of Chronic Myeloid Leukemia.","authors":"Susanne Saussele, Paul La Rosée, Alexander Kiani, Wilhelm Haverkamp, Kathleen Jentsch-Ullrich, Frank Stegelmann, Christina Rieger, Cornelius F Waller, Georg-Nikolaus Franke, Christian Junghanss, Rudolf Kirchmair, Markus Theurl, Philipp le Coutre","doi":"10.1159/000533666","DOIUrl":"10.1159/000533666","url":null,"abstract":"<p><strong>Background: </strong>Based on the new data from the primary analysis of the OPTIC (Optimizing Ponatinib Treatment in CP-CML) trial on dose optimization of ponatinib in patients with chronic phase (CP)-CML, the German consensus paper on ponatinib published in 2020 (Saussele S et al., Acta Haematol. 2020) has been updated in this addendum.</p><p><strong>Summary: </strong>Focus is on the update of efficacy and safety of ponatinib, reflecting the new data set, as well as the update of the benefit-risk assessment and recommendations for ponatinib starting dose in CP-CML - provided that the decision to use ponatinib has already been made. Furthermore, based on OPTIC and additional empirical data, the expert panel collaborated to develop a decision tree for ponatinib dosing, specifically for intolerant and resistant patients. The recommendations on cardiovascular management have also been updated based on the most recent 2021 guidelines of the European Society of Cardiology (ESC) on cardiovascular disease prevention in clinical practice.</p><p><strong>Key messages: </strong>The OPTIC data confirm the high efficacy of ponatinib in patients with CP-CML and provide the basis for individualized dose adjustment during the course of treatment.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"344-351"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11152025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41231535","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":"Long Non-Coding RNA RP11-252C15.1 Is a Potential Biomarker of Prognosis and Hallmark for Leukemogenesis in Children with B-Cell Precursor Acute Lymphoblastic Leukemia.","authors":"Lili Pan, Yongzhi Zheng, Hao Zheng","doi":"10.1159/000535461","DOIUrl":"10.1159/000535461","url":null,"abstract":"<p><strong>Introduction: </strong>Improved understanding of the prognostic biomarkers associated with childhood acute lymphoblastic leukemia (ALL) is needed for accurate risk group stratification. This study aimed to identify potential long non-coding RNA (lncRNA) markers and evaluate their prognostic value in children with ALL.</p><p><strong>Methods: </strong>We selected 50 children with newly diagnosed ALL and 20 age-matched patients with idiopathic immune thrombocytopenia (controls). RNA sequencing was performed to identify differentially expressed lncRNAs between the ALL and control groups. Correlation analysis was performed to determine the relationships between candidate lncRNAs, clinical features, and the risk of leukemogenesis.</p><p><strong>Results: </strong>A total of 1,019 differentially expressed lncRNAs were identified between the ALL and control groups. Reverse transcriptase (RT-qPCR) revealed that lncRNA RP11-252C15.1 and lncRNA RP11-701P16.2 were significantly upregulated in patients with ALL. Furthermore, correlation analysis showed that lncRNA RP11-252C15.1 and lncRNA RP11-701P16.2 represent potential predictors of leukemogenesis; however, only lncRNA RP11-252C15.1 was associated with clinical features and outcome in children with B-cell precursor ALL (BCP-ALL). In vitro experiments confirmed that lncRNA RP11-252C15.1 was significantly overexpressed in BCP-ALL cell lines and promoted proliferation and repressed apoptosis in MHH-CALL-3 cells.</p><p><strong>Conclusion: </strong>lncRNA RP11-252C15.1 is a potential oncogene in BCP-ALL pathogenesis and a prognostic biomarker in children with BCP-ALL.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"646-660"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140287962","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}