Acta Haematologica最新文献_第9页

Importance of Minimal Residual Disease in the Era of Targeted Therapies in Chronic Lymphocytic Leukemia. MRD在CLL靶向治疗时代的重要性。

IF 1.7 4区医学

Acta Haematologica Pub Date : 2024-01-01 Epub Date: 2023-10-30 DOI: 10.1159/000534846

Othman Al-Sawaf

{"title":"Importance of Minimal Residual Disease in the Era of Targeted Therapies in Chronic Lymphocytic Leukemia.","authors":"Othman Al-Sawaf","doi":"10.1159/000534846","DOIUrl":"10.1159/000534846","url":null,"abstract":"Background: The level of minimal residual disease (MRD), often binarized into detectable or undetectable MRD according to certain thresholds, is strongly associated with long-term outcomes after chemo- and chemoimmunotherapy.Summary: Driven by our improved understanding of the biology of chronic lymphocytic leukemia (CLL), the recent decade has shown a shift from chemotherapy-based regimens to regimens based on targeted agents that exploit distinct biological vulnerabilities of CLL. These targeted agents can be broadly classified into inhibitors of Bruton tyrosine kinase (BTK) and BCL2 as well as CD20-directed antibodies. Depending on which agent and which combination of agents is used, the levels or status of MRD can have varying clinical relevance. This has implications on the prognosis after therapy as well as on possible strategies to guide treatment duration and intensity.Key messages: This review summarizes the main discoveries related to MRD in the context of targeted therapies. Furthermore, it provides an overview on current hurdles and caveats related to the implementation of MRD in regular clinical care and summarize open research questions that need to be addressed with future clinical studies.","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"22-32"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71410150","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}

引用次数: 0

Multiplex Proteomics in the Identification of Potential Biomarkers of Very Severe Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease in Allogeneic Hematopoietic Cell Transplant Patients Treated with Defibrotide. 用多重蛋白质组学鉴定接受非布鲁肽治疗的异体造血细胞移植患者极重度窦道阻塞综合征/静脉闭塞性疾病（SOS/VOD）的潜在生物标记物。

IF 1.7 4区医学

Acta Haematologica Pub Date : 2024-01-01 Epub Date: 2024-02-08 DOI: 10.1159/000535706

Ram Vasudevan Nampoothiri, Lisa Avery, Ivan Pasic, Ioannis Prassas, Eleftherios Diamandis, Fotios V Michelis

{"title":"Multiplex Proteomics in the Identification of Potential Biomarkers of Very Severe Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease in Allogeneic Hematopoietic Cell Transplant Patients Treated with Defibrotide.","authors":"Ram Vasudevan Nampoothiri, Lisa Avery, Ivan Pasic, Ioannis Prassas, Eleftherios Diamandis, Fotios V Michelis","doi":"10.1159/000535706","DOIUrl":"10.1159/000535706","url":null,"abstract":"Introduction: Despite well-established clinical criteria for diagnosis of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) following allogeneic hematopoietic cell transplantation (HCT), there is a lack of established diagnostic protein biomarkers.Methods: Prospective samples were collected from patients with very severe SOS/VOD at diagnosis and days +3, +7, +14, and +30 post-initiation of defibrotide. Samples from age-matched controls with no VOD were collected at days +14, +30, +60, +90, and +180 following allogeneic HCT. Serum samples were analyzed for 2,925 protein levels by antibody-based proximity extension assay (PEA). Mean differences in the log-transformed abundance values were compared using t tests in a volcano plot.Results: Five patients with very severe SOS/VOD and 5 control patients were compared. Ten proteins were identified that showed a statistically significant and log-transformed 3-fold increase in concentration. They were CALCA, CCL20, GPR37, IGFBP4, IL1RL1, SLC39A14, SPINK4, FABP3, MYL3, and CHCHD10. Four different proteins, namely, CD83, leukocyte associated immunoglobulin-like receptor 2 (LAIR2), CD7, and HEM6 showed a significant decrease with defibrotide treatment. SOS/VOD resolved in 80% (n = 4) of patients, while 1 patient deceased due to SOS/VOD.Conclusion: PEA technology identified 10 proteins that were significantly elevated in patients with very severe SOS/VOD. Prospective studies in a larger cohort using this technology may be able to conclusively identify diagnostic protein biomarkers for SOS/VOD.","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"511-524"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139705729","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}

引用次数: 0

Erratum. 勘误。

IF 1.7 4区医学

Acta Haematologica Pub Date : 2024-01-01 Epub Date: 2024-02-27 DOI: 10.1159/000537722

引用次数: 0

Fluoroquinolone Prophylaxis during Conventional Chemotherapy or Hematopoietic Stem Cell Transplantation for Acute Leukemia - Pros and Cons. 急性白血病常规化疗或造血干细胞移植期间氟喹诺酮类药物的预防——利弊。

IF 1.7 4区医学

Acta Haematologica Pub Date : 2024-01-01 Epub Date: 2023-11-21 DOI: 10.1159/000535119

Tomer Hoffman, Alaa Atamna, Vladislav Litchevsky, Irina Amitai, Dafna Yahav

{"title":"Fluoroquinolone Prophylaxis during Conventional Chemotherapy or Hematopoietic Stem Cell Transplantation for Acute Leukemia - Pros and Cons.","authors":"Tomer Hoffman, Alaa Atamna, Vladislav Litchevsky, Irina Amitai, Dafna Yahav","doi":"10.1159/000535119","DOIUrl":"10.1159/000535119","url":null,"abstract":"Background: Prophylaxis with fluoroquinolones (FQ) is commonly used in patients with acute leukemia (AL) during neutropenia. This practice is supported by an older meta-analysis reporting reduced mortality using FQ prophylaxis. Later meta-analyses have failed to reproduce this finding, presumably due to higher background FQ resistance rates limiting their effectiveness.Summary: This article reviews the pros and cons of FQ prophylaxis mainly in patients with AL. Most current guidelines do not support universal prophylaxis but rather recommend a selective approach, weighing the benefits against the risks. This recommendation is based on the lack of mortality benefit reported in more recent meta-analyses. FQ prophylaxis was demonstrated to reduce bacteremia and febrile neutropenia episodes, although mostly in trials performed in low-resistance settings (<20%), whereas current FQ resistance rates may reach 30-60%. Other disadvantages of FQ include potential adverse events, antibiotic resistance development, cost, increase in Gram-positive infections and resistant Gram-negative infections following prophylaxis, Clostridioides difficile infection, and an effect on gut microbiota.Key messages: Taking the above into consideration, alternative approaches other than universal FQ prophylaxis should be considered. Centers with high FQ resistance rates may consider either withholding prophylaxis or providing selective prophylaxis for high-risk patients screened negative for FQ-resistant bacteria.","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"186-197"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290029","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}

引用次数: 0

Donor Lymphocyte Infusion Is a Feasible Way to Improve Survival in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndromes Who Relapse after Allogeneic Stem Cell Transplantation. 供体淋巴细胞输注是提高异基因干细胞移植后复发的急性髓细胞白血病和骨髓增生异常综合征患者生存率的可行方法。

IF 1.7 4区医学

Acta Haematologica Pub Date : 2024-01-01 Epub Date: 2023-10-12 DOI: 10.1159/000534315

Lia Minculescu, Joanne Reekie, Soeren Lykke Petersen, Brian Thomas Kornblit, Ida Schjoedt, Niels Smedegaard Andersen, Lisbeth Pernille Andersen, Anne Fischer-Nielsen, Eva Kannik Haastrup, Lone Smidstrup Friis, Henrik Sengelov

{"title":"Donor Lymphocyte Infusion Is a Feasible Way to Improve Survival in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndromes Who Relapse after Allogeneic Stem Cell Transplantation.","authors":"Lia Minculescu, Joanne Reekie, Soeren Lykke Petersen, Brian Thomas Kornblit, Ida Schjoedt, Niels Smedegaard Andersen, Lisbeth Pernille Andersen, Anne Fischer-Nielsen, Eva Kannik Haastrup, Lone Smidstrup Friis, Henrik Sengelov","doi":"10.1159/000534315","DOIUrl":"10.1159/000534315","url":null,"abstract":"Introduction: Donor lymphocyte infusion (DLI) is used to induce remission in patients who relapse after allogeneic stem cell transplantation (allo-HSCT). During the last decade, the hypomethylating agent Azacitidine has been used together with DLI for a synergistic graft-versus-leukemia (GVL) effect. Here, we report results of DLI/Azacitidine treatment from a retrospective single-center study.Methods: Fifty AML/MDS patients treated for relapse after allo-HSCT between 2001 and 2020 with DLI at the Department of Hematology, at Rigshospitalet, Copenhagen University Hospital were included for analyses. A subgroup of patients who obtained complete remission (CR) after reinduction chemotherapy, received DLI in combination with low-dose (32 mg/m2) Azacitidine.Results: Overall survival in all patients after DLI treatment was 59% at 2 years and 20% at 5 years. Relapse-free survival in patients in CR prior to DLI was 32% after 2 years and 7% after 5 years. In the DLI + low-dose-Azacitidine group, 5-year relapse-free survival was 40%.Conclusion: DLI remains an effective treatment in post-transplant relapse leaving one-fifth of patients' long-term survivors. Our results support the concomitant use of low-dose Azacitidine in the future use of DLI in order to enhance the GVL effect of donor lymphocytes.","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"325-332"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41187817","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}

引用次数: 0

Frontline Therapy in Chronic Lymphocytic Leukemia. 慢性淋巴细胞白血病的一线治疗。

IF 1.7 4区医学

Acta Haematologica Pub Date : 2024-01-01 Epub Date: 2023-10-27 DOI: 10.1159/000534730

Miguel Arguello-Tomas, Nil Albiol, Carol Moreno

引用次数: 0

Prognostic Markers in the Era of Targeted Therapies. 靶向治疗时代的预后标志物

IF 1.7 4区医学

Acta Haematologica Pub Date : 2024-01-01 Epub Date: 2023-09-13 DOI: 10.1159/000533704

Sorang Kang, Inhye E Ahn

{"title":"Prognostic Markers in the Era of Targeted Therapies.","authors":"Sorang Kang, Inhye E Ahn","doi":"10.1159/000533704","DOIUrl":"10.1159/000533704","url":null,"abstract":"Background: Small molecules targeting Bruton's tyrosine kinase (BTK) and B-cell lymphoma-2 have become the standard of care for the treatment of chronic lymphocytic leukemia (CLL), replacing chemoimmunotherapy (CIT) in most clinical settings. Ongoing trials explore targeted combinations and minimal residual disease-driven treatment cessation. These dramatic shifts in the current and upcoming treatment landscape of CLL raise the need to reevaluate existing prognostic markers and develop novel ones.Summary: This review examines prognostic markers in CLL patients treated with standard and investigational targeted therapies. Specifically, initial treatment of TP53 aberrant patients with a BTK inhibitor can achieve 70% progression-free survival (PFS) at 5 years, outperforming the 15% 5-year PFS with a CIT regimen containing fludarabine, cyclophosphamide, and rituximab (FCR). The prognostic implications of the immunoglobulin heavy chain variable gene (IGHV) mutation status have also changed. Unmutated IGHV is associated with inferior PFS and overall survival after FCR and inferior PFS with fixed-duration therapy with venetoclax and anti-CD20 monoclonal antibody but not with continuous BTK inhibitor treatment.Key messages: (1) Genetic variables (e.g., TP53 aberration, IGHV mutation, complex karyotype) have a prognostic significance in CLL patients treated with targeted therapy. (2) Understanding the prognostic and predictive values of these markers is critical for the development of a risk-adapted treatment strategy in CLL.","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"33-46"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10230923","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}

引用次数: 0

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. 将中枢神经系统受累的急性髓细胞白血病患者排除在临床试验之外：2012年至2022年美国国立卫生研究院临床试验注册中心的分析。

IF 1.7 4区医学

Acta Haematologica Pub Date : 2024-01-01 Epub Date: 2023-09-26 DOI: 10.1159/000533819

Dahniel Sastow, Grace Van Hyfte, Jonathan Feld, Marina Kremyanskaya, John Mascarenhas, Douglas Tremblay

{"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":"Introduction: 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.Methods: 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.Results: 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 < 0.01). Non-transplant trials were also more likely to exclude patients with a history of or ambiguous timing of CNS involvement (p < 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 < 0.01).Conclusion: 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.","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}

引用次数: 0

Non-Immunotherapy Approaches for Relapsed or Refractory AML: An Update for 2024. 复发性或难治性AML的非免疫治疗方法：2024年更新。

IF 1.7 4区医学

Acta Haematologica Pub Date : 2024-01-01 Epub Date: 2023-10-31 DOI: 10.1159/000534897

Shira Buchrits, Ofir Wolach

{"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":"Background: 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.Summary: 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.Key messages: 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.","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}

引用次数: 0

Shikonin Exerts an Antileukemia Effect against FLT3-ITD Mutated Acute Myeloid Leukemia Cells via Targeting FLT3 and Its Downstream Pathways. 紫草素通过靶向FLT3酪氨酸激酶及其下游途径对FLT3-ITD突变的急性髓系白血病细胞发挥抗白血病作用。

IF 1.7 4区医学

Acta Haematologica Pub Date : 2024-01-01 Epub Date: 2023-11-03 DOI: 10.1159/000534101

Mu-Nan Zhao, Long Su, Fei Song, Zhi-Feng Wei, Tian-Xue Qin, Yun-Wei Zhang, Wei Li, Su-Jun Gao

{"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":"Introduction: 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.Methods: 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.Results: 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.Conclusion: The findings of this study indicate that SHK may be a promising drug for the treatment of FLT3-ITD mutated AML.","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}

引用次数: 0