Therapeutic Advances in Hematology最新文献

{"title":"Effect of <i>BCR::ABL1</i> transcript type and droplet digital polymerase chain reaction on successful treatment-free remission in chronic myeloid leukemia patients who discontinued tyrosine kinase inhibitor.","authors":"Hyunkyung Park,&nbsp;Hyeong-Joon Kim,&nbsp;Sang-Kyun Sohn,&nbsp;Yoonsuk Baik,&nbsp;Dongho Kim,&nbsp;Sung-Yeoun Lee,&nbsp;Jee Hyun Kong,&nbsp;Hawk Kim,&nbsp;Dong-Yeop Shin,&nbsp;Jae-Sook Ahn,&nbsp;Jinny Park,&nbsp;Seonyang Park,&nbsp;Inho Kim","doi":"10.1177/20406207231205637","DOIUrl":"https://doi.org/10.1177/20406207231205637","url":null,"abstract":"<p><strong>Background: </strong>Droplet digital polymerase chain reaction (ddPCR) is an exact method of measurement.</p><p><strong>Objectives: </strong>We conducted this study to identify the prognostic factors for successful treatment-free remission in patients with chronic-phase chronic myeloid leukemia who discontinued tyrosine kinase inhibitors (TKIs). We also aimed to validate ddPCR for predicting molecular relapse.</p><p><strong>Design: </strong>This is a prospective, multicenter study.</p><p><strong>Methods: </strong>We enrolled patients treated with TKIs for at least 3 years with a confirmed sustained deep molecular response (DMR) for at least 1 year. TKI was re-administered in patients who experienced the loss of major molecular response (MMR).</p><p><strong>Results: </strong>A total of 66 patients from five institutions in South Korea were enrolled. During a median follow-up period of 16.5 months, 29/66 (43.9%) patients experienced molecular relapse; the probability of molecular relapse-free survival (RFS) at 6 or 12 months after TKI discontinuation was 65.6% or 57.8%, respectively, with most molecular relapses occurring within the first 7 months. All patients who lost MMR were re-treated with TKI, and all re-achieved MMR at a median of 2.8 months. E14a2 transcript type (<i>p</i> = 0.005) and longer DMR duration (⩾48 months) prior to TKI discontinuation (<i>p</i> = 0.002) were associated with prolonged molecular RFS and with sustained DMR. Patients with both e13a2 transcript type and detectable <i>BCR::ABL1</i> (⩾MR^5.0) by ddPCR at the time of TKI discontinuation showed shorter duration of molecular RFS (<i>p</i> = 0.015).</p><p><strong>Conclusion: </strong>Our data suggest that transcript type and <i>BCR::ABL1</i> transcript levels on ddPCR should be taken into consideration when deciding whether to discontinue TKI therapy.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"14 ","pages":"20406207231205637"},"PeriodicalIF":3.4,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71486398","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":"Assessment of risk factors for acute graft-<i>versus</i>-host disease post-hematopoietic stem cell transplantation: a retrospective study based on a proportional odds model using a nonlinear mixed-effects model.","authors":"Ling Xue,&nbsp;Lin Song,&nbsp;Xun Yu,&nbsp;Xiao Yang,&nbsp;Fan Xia,&nbsp;Xiaoliang Ding,&nbsp;Chenrong Huang,&nbsp;Depei Wu,&nbsp;Liyan Miao","doi":"10.1177/20406207231205406","DOIUrl":"10.1177/20406207231205406","url":null,"abstract":"<p><strong>Background: </strong>Acute graft-<i>versus</i>-host disease (aGVHD) is a major complication following hematopoietic stem cell transplantation (HSCT).</p><p><strong>Objective: </strong>This study aimed to explore the risk factors for the incidence of aGVHD in patients post-HSCT.</p><p><strong>Design: </strong>This was a retrospective study.</p><p><strong>Methods: </strong>A total of 407 patients were enrolled. The patients' data were recorded from the medical records. The exposure of cyclosporine was estimated based on a population pharmacokinetics model. The occurrence of aGVHD was clinically graded and staged in severity from grades I to IV. A proportional odds model that estimated the cumulative probabilities of aGVHD was used to analyze the data using a nonlinear mixed-effects model. Then, the model parameters and plausibility were evaluated by bootstrap and visual predictive checks.</p><p><strong>Results: </strong>The typical probabilities were 18.9% and 17.9% for grade II and grades III-IV, respectively. The incidence of grade II and grade III-IV aGVHD for human leukocyte antigen (HLA) haplo sibling donor patients was higher than that for HLA-matched donor patients. The incidence of grade II and grade III-IV aGVHD decreased with increasing early cyclosporine trough concentration; however, cyclosporine exposure was not associated with the incidence of aGVHD.</p><p><strong>Conclusion: </strong>HLA matching and early cyclosporine trough concentration were important factors for the occurrence of aGVHD.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"14 ","pages":"20406207231205406"},"PeriodicalIF":3.4,"publicationDate":"2023-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a4/18/10.1177_20406207231205406.PMC10590544.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49692440","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":"Rilzabrutinib <i>versus</i> placebo in adults and adolescents with persistent or chronic immune thrombocytopenia: LUNA 3 phase III study.","authors":"David J Kuter,&nbsp;James B Bussel,&nbsp;Waleed Ghanima,&nbsp;Nichola Cooper,&nbsp;Terry Gernsheimer,&nbsp;Michele P Lambert,&nbsp;Howard A Liebman,&nbsp;Michael D Tarantino,&nbsp;Michelle Lee,&nbsp;Hailing Guo,&nbsp;Ahmed Daak","doi":"10.1177/20406207231205431","DOIUrl":"10.1177/20406207231205431","url":null,"abstract":"<p><strong>Background: </strong>Immune thrombocytopenia (ITP) is characterized by primarily autoantibody-mediated platelet destruction and impaired platelet production resulting in thrombocytopenia and an increased risk of bleeding. Other manifestations include increased risk of thrombosis and diminished quality of life. Current treatment approaches are directed toward lowering the rate of platelet destruction or stimulating platelet production to prevent bleeding. Rilzabrutinib is an oral, reversible, potent Bruton tyrosine kinase inhibitor that was specifically designed to treat immune-mediated diseases and mediates its therapeutic effect through a dual mechanism of action: (1) inhibiting B-cell activation and (2) interrupting antibody-coated cell phagocytosis by Fc gamma receptor in spleen and liver. A 24-week dose-finding phase I/II study of rilzabrutinib in patients with ITP showed a 40% platelet response (⩾2 consecutive platelet counts of ⩾50 × 10⁹/L and increase from baseline ⩾20 × 10⁹/L without rescue medication use) and a well-tolerated safety profile with only grade 1/2 transient adverse events across dose levels.</p><p><strong>Objectives: </strong>Assess the efficacy and safety of oral rilzabrutinib in adult and adolescent patients with persistent or chronic ITP.</p><p><strong>Design: </strong>Rilzabrutinib 400 mg BID is being evaluated in the ongoing LUNA 3 multicenter, double-blind, placebo-controlled phase III study.</p><p><strong>Methods and analysis: </strong>The primary endpoint is durable platelet response, defined as achieving platelet counts of ⩾50 × 10⁹/L for at least two-thirds of ⩾8 available weekly scheduled platelet measurements during the last 12 weeks (including ⩾2 available measurements within the last 6 weeks) of the 24-week blinded treatment period in the absence of rescue therapy.</p><p><strong>Ethics: </strong>Ethical guidelines and informed consent are followed.</p><p><strong>Discussion: </strong>The LUNA 3 trial will further investigate rilzabrutinib's safety and efficacy in adult and adolescent patients, with the primary goal of addressing a major objective in treating patients with ITP: durability of platelet response.</p><p><strong>Trail registration: </strong>ClinicalTrials.gov NCT04562766: https://clinicaltrials.gov/ct2/show/NCT04562766; EU Clinical Trials Register EudraCT 2020-002063-60: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2020-002063-60.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"14 ","pages":"20406207231205431"},"PeriodicalIF":3.4,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d8/57/10.1177_20406207231205431.PMC10585997.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49692441","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":"Infrastructural considerations of implementing gene therapy for hemophilia in the Nordic context.","authors":"Jan Astermark,&nbsp;Fariba Baghaei,&nbsp;Karin Strandberg,&nbsp;Petra Gabric Toplican,&nbsp;Maj Friberg Birkedal,&nbsp;Emma Engman Grahn,&nbsp;Charlotta Hansson,&nbsp;Peter Kampmann,&nbsp;Anna-Elina Lehtinen,&nbsp;Kinga Täckström,&nbsp;Pål Andre Holme,&nbsp;Maria Magnusson","doi":"10.1177/20406207231202306","DOIUrl":"https://doi.org/10.1177/20406207231202306","url":null,"abstract":"<p><strong>Background: </strong>Despite improvements in hemophilia care, challenges remain, including treatment burden and impaired quality of life. Gene therapy may overcome these. However, its introduction presents a challenge.</p><p><strong>Objectives: </strong>To outline a function-based gene therapy working model describing critical milestones associated with gene therapy handling, administration, and follow-up to facilitate and implement an effective infrastructure for gene therapy introduction.</p><p><strong>Design: </strong>Literature review and consensus discussion among Hemophilia Comprehensive Care centers (HCCCs) in the Nordic region.</p><p><strong>Methods: </strong>Representatives from six HCCCs sought to pinpoint milestones and key stakeholders for site readiness at the pre-, peri-, and post-infusion stages, including authority and genetically modified organism (GMO) product requirements, awareness, medical eligibility, logistics and product handling for infusion, laboratory monitoring, and follow-up.</p><p><strong>Results: </strong>A gene therapy transit map was developed with key stakeholders identified. The approach to prepare the vector will differ between the Nordic centers, but the contracted pharmacy unit will be a key stakeholder. Therefore, a pharmacy checklist for the implementation of gene therapy was developed. For the future, Advanced Therapy Medicinal Product centers will also be implemented. Patients' expectations, commitments, and concerns need to be addressed repeatedly and education of patients and the expanded health-care professionals team will be the key to successful and optimal clinical management. Eligibility testing according to the product's summary of product characteristics and frequent follow-up and monitoring post-infusion according to the World Federation of Hemophilia chart will be crucial.</p><p><strong>Conclusion: </strong>The approach to deliver gene therapy in the Nordic region will differ partly between the hemophilia centers, but the defined road map with checklists for the implementation of this advanced therapy will be applicable to all. The map may also serve as a platform for the use of future GMO product options both within and outside the area of hemophilia.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"14 ","pages":"20406207231202306"},"PeriodicalIF":3.4,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e5/3b/10.1177_20406207231202306.PMC10583513.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49682593","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":"The history of oral decitabine/cedazuridine and its potential role in acute myeloid leukemia.","authors":"Robert Briski,&nbsp;Guillermo Garcia-Manero,&nbsp;Hagop Kantarjian,&nbsp;Farhad Ravandi","doi":"10.1177/20406207231205429","DOIUrl":"https://doi.org/10.1177/20406207231205429","url":null,"abstract":"<p><p>Decitabine, a member of the 5-azanucleosides, has a dose-dependent mechanism of action <i>in vitro</i>: termination of DNA replication at high doses, and inhibition of DNA methyltransferase at low doses. The alteration of DNA methylation patterns by low-dose decitabine is hypothesized to upregulate genes, which promote myeloblast differentiation. In a phase III clinical trial, low-dose decitabine achieved a superior overall response rate (ORR) when compared with 'treatment choice' [consisting of low-dose cytarabine (80%) and supportive care (20%)] as a frontline treatment for elderly patients with acute myeloid leukemia (AML). Despite an improved ORR, the median overall survival (OS) for elderly patients with AML was poor, <1 year. In turn, venetoclax was added to low-dose decitabine, the combination of which significantly improved the ORR and median OS in elderly patients with AML. Currently, hypomethylating agents are being combined with other novel therapies as investigational strategies for elderly and unfit patients with AML. They are also being evaluated as components of maintenance therapy in patients achieving remission. An oral formulation of decitabine has been developed which relies on the concomitant use of oral cedazuridine to protect against first pass metabolism. This oral formulation, which has been approved in myelodysplastic syndrome, is intended to increase convenience of use and therefore compliance in patients. This review characterizes the evolution of decitabine, its oral formulation, and its future in the treatment of AML.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"14 ","pages":"20406207231205429"},"PeriodicalIF":3.4,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10580721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49682594","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":"Survival outcomes in patients with relapsed/refractory or MRD-positive B-cell acute lymphoblastic leukemia treated with blinatumomab.","authors":"Hagop M Kantarjian,&nbsp;Aaron C Logan,&nbsp;Faraz Zaman,&nbsp;Nicola Gökbuget,&nbsp;Ralf C Bargou,&nbsp;Yi Zeng,&nbsp;Gerhard Zugmaier,&nbsp;Franco Locatelli","doi":"10.1177/20406207231201454","DOIUrl":"10.1177/20406207231201454","url":null,"abstract":"<p><p>Blinatumomab has demonstrated significant efficacy in adult and pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-cell ALL) and patients with measurable residual disease (MRD). This review aimed to compare median relapse-free survival (RFS) and median overall survival (OS) in adult and pediatric patients with R/R or MRD-positive B-cell ALL from pivotal studies [MT-103-211 and TOWER for adults with Philadelphia chromosome (Ph)-negative R/R B-cell ALL, ALCANTARA for adults with Ph-positive R/R B-cell ALL, MT-103-203 for adults with MRD-positive B-cell ALL, and MT-103-205 for pediatric patients with R/R B-cell ALL], with the median RFS and OS from retrospective analyses, country or ethnicity-specific studies, and studies based on real-world evidence (RWE) identified from a literature search. Adults with Ph-negative R/R B-cell ALL who received blinatumomab as first salvage demonstrated a numerically longer median OS compared with that in patients from pivotal studies (MT-103-211 and TOWER) without additional safety concerns. In pediatric patients with R/R B-cell ALL treated with blinatumomab, the median RFS and OS from retrospective analyses and country/ethnicity-specific studies were comparable with the median RFS and OS from the pivotal study MT-103-205. The median RFS and OS from RWE studies in adults with R/R B-cell ALL were numerically longer than the median RFS and OS from pivotal studies (MT-103-211, TOWER, and ALCANTARA); however, this trend was not observed in pediatric patients with R/R B-cell ALL. In conclusion, this analysis identified first salvage adults with Ph-negative R/R B-cell ALL as particularly well-suited for treatment with blinatumomab since survival outcomes from retrospective analyses reported in this patient subgroup were numerically better compared with those from pivotal studies without additional safety signals.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"14 ","pages":"20406207231201454"},"PeriodicalIF":3.4,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10563488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41213714","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":"Long-term outcome of progressive multifocal leukoencephalopathy with recombinant interleukin-2 treatment and an associated increase in the number of HPyV-2-specific T-cells: a case report.","authors":"Fieke W Hoff,&nbsp;John Rolwes,&nbsp;Paula A Hardeman,&nbsp;Molly Perkins,&nbsp;Eugene O Major,&nbsp;Daniel Douek,&nbsp;Robert H Collins,&nbsp;Benjamin M Greenberg","doi":"10.1177/20406207231201721","DOIUrl":"https://doi.org/10.1177/20406207231201721","url":null,"abstract":"<p><p>Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by reactivation of the human polyomavirus 2 (HPyV-2). PML is associated with a high morbidity and mortality rate and there is currently no standard curative therapy. We report short-term immunologic response and long-term clinical outcomes in a patient diagnosed with follicular lymphoma (FL) who developed PML. Diagnosis of PML was established conclusively based on findings from a brain biopsy. The patient was treated with recombinant interleukin 2 (IL-2) and showed rapid clinical improvement. HPyV-2-specific T-cells were tracked longitudinally and correlation with clinical status, viral load, and radiographic imaging was documented. After the progression of the patient's FL, which required an allogeneic bone marrow transplant, the patient prophylactically received human leukocyte antigen-matched donor-derived HPyV-2 T-cells to prevent the recurrence of the PML as part of a clinical trial. Twelve years after the initial diagnosis of PML, he did not develop a relapse of his PML, supporting data that therapies that increase HPyV-2-specific T-cells, including IL-2, may be effective in the management of PML.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"14 ","pages":"20406207231201721"},"PeriodicalIF":3.4,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10563476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41213713","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":"Alterations of erythropoiesis in Covid-19 patients: prevalence of positive Coombs tests and iron metabolism.","authors":"Léa Schmitz,&nbsp;Michelle Pirotte,&nbsp;Alizée Lebeau,&nbsp;Marie Ernst,&nbsp;Marianne Fillet,&nbsp;Anais Devey,&nbsp;Justine Schmitt,&nbsp;Gaël Cobraiville,&nbsp;Marilène Binsfeld,&nbsp;Stéphanie Gofflot,&nbsp;Yves Beguin,&nbsp;Gaëlle Vertenoeil","doi":"10.1177/20406207231199837","DOIUrl":"https://doi.org/10.1177/20406207231199837","url":null,"abstract":"<p><strong>Background: </strong>For more than 2 years medical practice has been dealing with the Covid-19 pandemic. Atypical symptoms, such as frostbites and acrosyndromes, have appeared, and autoimmune anemias (some of which with cold agglutinins) have been described.</p><p><strong>Objectives: </strong>We planned to study the prevalence of positive direct Coombs tests (DCTs) and hemolytic autoimmune anemia in patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its correlation with complications, and then investigate the impact of the infection on iron metabolism.</p><p><strong>Design: </strong>This is an observational, cross-sectional, single-center, exploratory study.</p><p><strong>Methods: </strong>We obtained Coombs tests in a population of 179 infected patients at the CHU of Liège. We then studied iron metabolism in some of these patients, by measuring serum ferritin, erythropoietin (EPO), erythroferrone and hepcidin.</p><p><strong>Results: </strong>We did not identify any case of autoimmune hemolysis. However, there was a 20.3% prevalence of positive DCT, mainly with IgG (91.7%). These patients, compared to DCT-negative patients, were not only more anemic and transfused, but also required more transfers to intensive care units and had longer hospital stays and mechanical ventilation. The pattern of anemia was consistent with the anemia of inflammation, showing elevated hepcidin and ferritin levels, while EPO and erythroferrone values were lower than expected at this degree of anemia. Erythroferrone was higher and Hb was lower in DCT-positive patients. Finally, we identified a correlation between iron parameters and complicated forms of infection.</p><p><strong>Conclusion: </strong>Covid-19 patients suffered from inflammatory anemia with more severe forms of infection correlated to positive DCT status. This could potentially be of interest for future clinical practice.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"14 ","pages":"20406207231199837"},"PeriodicalIF":3.4,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b7/e5/10.1177_20406207231199837.PMC10540584.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41148394","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":"Comparison of eltrombopag and avatrombopag in the treatment of refractory/relapsed aplastic anemia: a single-center retrospective study in China.","authors":"Zhuxin Zhang, Qinglin Hu, Chen Yang, Miao Chen, Bing Han","doi":"10.1177/20406207231191310","DOIUrl":"10.1177/20406207231191310","url":null,"abstract":"<p><strong>Background: </strong>Eltrombopag (ELT), a thrombopoietin receptor agonist (TPO-RA), has been approved for relapsed/refractory aplastic anemia (AA). However, data on avatrombopag (AVA), another TPO-RA, are limited, and the comparisons between the two TPO-RAs are lacking.</p><p><strong>Objectives: </strong>We aimed to compare the efficacy and safety between ELT and AVA in relapsed/refractory AA patients.</p><p><strong>Design: </strong>In this retrospective study, patients with relapsed/refractory AA who had been treated with ELT (<i>N</i> = 45) or AVA (<i>N</i> = 30) alone and had compatible baseline hematological parameters were compared.</p><p><strong>Methods: </strong>Data from patients diagnosed with acquired AA were retrospectively collected. All patients were refractory/relapsed to standard immunosuppressive therapy (IST) for at least 6 months before ELT or AVA. Patients had to be treated with ELT or AVA alone for at least 6 months before evaluation if they did not respond. Baseline characteristics, overall response (OR), complete response (CR), relapse, adverse events, and factors that may affect efficacy were analyzed.</p><p><strong>Results: </strong>Of the 75 patients enrolled, 45 received ELT and 30 received AVA. Patients with AVA had a higher percentage of abnormal liver or renal function than those with ELT (<i>p =</i> 0.036). No significant difference was found in the OR/CR rate in the first/second/third/sixth month between the two cohorts (<i>p ></i> 0.05). Patients treated with AVA had a shorter median time to response than those treated with ELT (<i>p =</i> 0.012) and had a higher platelet level in the second month (<i>p =</i> 0.041). AVA had fewer adverse events than ELT (<i>p =</i> 0.046). Under compatible follow-up time (<i>p =</i> 0.463), no difference was found between the ELT and AVA cohorts in relapse (<i>p =</i> 1.000) or clone evolution (<i>p =</i> 0.637). No predictive factors for OR and CR in the sixth month were found for either ELT or AVA.</p><p><strong>Conclusion: </strong>With worse liver or renal function, AVA had a similar OR/CR rate but a shorter median time to response and fewer adverse events for patients with relapsed/refractory AA.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"14 ","pages":"20406207231191310"},"PeriodicalIF":3.4,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/65/49/10.1177_20406207231191310.PMC10503291.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10672041","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":"Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in hematologic malignancies: a living systematic review on comparative studies.","authors":"Luis Carlos Saiz, Leire Leache, Marta Gutiérrez-Valencia, Juan Erviti, María Ximena Rojas Reyes","doi":"10.1177/20406207231168211","DOIUrl":"10.1177/20406207231168211","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Chimeric antigen receptor T-cell (CAR-T) cell therapies have been claimed to be curative in responsive patients. Nonetheless, response rates can vary according to different characteristics, and these therapies are associated with important adverse events such as cytokine release syndrome, neurologic adverse events, and B-cell aplasia.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;This living systematic review aims to provide a timely, rigorous, and continuously updated synthesis of the evidence available on the role of CAR-T therapy for the treatment of patients with hematologic malignancies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;A systematic review with meta-analysis of randomized controlled trials (RCTs) and comparative non-randomized studies of interventions (NRSI), evaluating the effect of CAR-T therapy versus other active treatments, hematopoietic stem cell transplantation, standard of care (SoC) or any other intervention, was performed in patients with hematologic malignancies. The primary outcome is overall survival (OS). Certainty of the evidence was determined using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Data sources and methods: &lt;/strong&gt;Searches were performed in the Epistemonikos database, which collates information from multiple sources to identify systematic reviews and their included primary studies, including Cochrane Database of Systematic Reviews, MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, DARE, HTA Database, Campbell database, JBI Database of Systematic Reviews and Implementation Reports, EPPI-Centre Evidence Library. A manual search was also carried out. We included the evidence published up to 1 July 2022.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;We included the evidence published up to 1 July 2022. We considered 139 RCTs and 1725 NRSI as potentially eligible. Two RCTs (&lt;i&gt;N&lt;/i&gt; = 681) comparing CAR-T therapy with SoC in patients with recurrent/relapsed (R/R) B-cell lymphoma were included. RCTs did not show statistical differences in OS, serious adverse events, or total adverse events with grade ⩾ 3. Higher complete response with substantial heterogeneity [risk ratio = 1.59; 95% confidence interval (CI) = (1.30-1.93); &lt;i&gt;I&lt;/i&gt; &lt;sup&gt;2&lt;/sup&gt; = 89%; 2 studies; 681 participants; very low certainty evidence] and higher progression-free survival [hazard ratio for progression or death = 0.49; 95% CI = (0.37-0.65); 1 study; 359 participants; moderate certainty evidence] were reported with CAR-T therapies. Nine NRSI (&lt;i&gt;N&lt;/i&gt; = 540) in patients with T or B-cell acute lymphoblastic leukemia or R/R B-cell lymphoma were also included, providing secondary data. In general, the GRADE certainty of the evidence for main outcomes was mostly low or very low.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;So far, assuming important limitations in the level of certainty due to scarce and heterogenous comparative studies, CAR-T therapies have shown some benefit in terms of progression-free ","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"14 ","pages":"20406207231168211"},"PeriodicalIF":3.4,"publicationDate":"2023-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5a/37/10.1177_20406207231168211.PMC10150428.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9779262","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}