David Yashar, Bernard Regidor, Marissa-Skye Goldwater, Sean Bujarski, Ashley Del Dosso, James R. Berenson
{"title":"Targeting B-cell maturation antigen for treatment and monitoring of relapsed/refractory multiple myeloma patients: a comprehensive review","authors":"David Yashar, Bernard Regidor, Marissa-Skye Goldwater, Sean Bujarski, Ashley Del Dosso, James R. Berenson","doi":"10.1177/20406207241275797","DOIUrl":"https://doi.org/10.1177/20406207241275797","url":null,"abstract":"Despite major therapeutic advancements in recent years, multiple myeloma (MM) remains an incurable disease with nearly all patients experiencing relapsed and refractory disease over the course of treatment. Extending the duration and durability of clinical responses will necessitate the development of therapeutics with novel targets that are capable of robustly and specifically eliminating myeloma cells. B-cell maturation antigen (BCMA) is a membrane-bound protein expressed predominantly on malignant plasma cells and has recently been the target of several novel therapeutics to treat MM patients. This review will focus on recently approved and currently in development agents that target this protein, including bispecific antibodies, antibody-drug conjugates, and chimeric antigen receptor T-cell therapies. In addition, this protein also serves as a novel serum biomarker to predict outcomes and monitor disease status for MM patients; the studies demonstrating this use of BCMA will be discussed in detail.","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"65 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142251405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Vedolizumab for second-line treatment of steroid-refractory gastrointestinal late acute graft-versus-host disease.","authors":"Yingling Zu, Ruirui Gui, Zhen Li, Juan Wang, Pei Li, Ying Liu, Xiaofeng Dong, Jian Zhou","doi":"10.1177/20406207241276982","DOIUrl":"10.1177/20406207241276982","url":null,"abstract":"<p><strong>Background: </strong>Late acute graft-versus-host disease (aGVHD) is a complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with little data regarding treatment and outcomes. There is no standard treatment for gastrointestinal (GI) late aGVHD, especially for steroid-refractory (SR) GI late aGVHD. Vedolizumab, a monoclonal antibody inhibiting the migration of both naive and activated lymphocytes into the GI endothelium, has been verified to be effective for SR GI aGVHD.</p><p><strong>Methods: </strong>We retrospectively analyzed the clinical efficacy and safety of vedolizumab as the second line for SR GI late aGVHD in seven patients after allo-HSCT.</p><p><strong>Results: </strong>Four patients received two doses of vedolizumab infusion, while three patients received only one dose of vedolizumab infusion. The complete response and partial response rates were 57.1% (4/7) and 42.9% (3/7), respectively. No patient progressed to chronic GVHD during the period of follow-up. There was no severe adverse event related to vedolizumab.</p><p><strong>Conclusion: </strong>Our data suggest that vedolizumab is expected to ameliorate SR GI late aGVHD. Further data on the treatment timing, efficacy, and safety of vedolizumab are warranted in prospective clinical trials.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"15 ","pages":"20406207241276982"},"PeriodicalIF":3.4,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154997","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}
Wolfgang Miesbach, Nicola Curry, Paul Knöbl, Charles Percy, Rita Santoro, Alvin H Schmaier, Karolin Trautmann-Grill, Kayode Badejo, Jie Chen, Masoud Nouri, Pooja Oberai, Robert Klamroth
{"title":"Real-world use of recombinant porcine sequence factor VIII in the treatment of acquired hemophilia A: EU PASS.","authors":"Wolfgang Miesbach, Nicola Curry, Paul Knöbl, Charles Percy, Rita Santoro, Alvin H Schmaier, Karolin Trautmann-Grill, Kayode Badejo, Jie Chen, Masoud Nouri, Pooja Oberai, Robert Klamroth","doi":"10.1177/20406207241260332","DOIUrl":"10.1177/20406207241260332","url":null,"abstract":"<p><strong>Background: </strong>Recombinant porcine factor VIII (rpFVIII; susoctocog alfa) is indicated for the treatment of bleeding events (BEs) in adults with acquired hemophilia A (AHA).</p><p><strong>Objectives: </strong>To assess the safety, utilization, and effectiveness of rpFVIII in clinical practice.</p><p><strong>Design: </strong>EU post-authorization safety study (PASS) (NCT03199794) was a multicenter, noninterventional, post-authorization safety study conducted in adults with AHA.</p><p><strong>Methods: </strong>Data were collected retrospectively or prospectively for up to 180 days after the last rpFVIII dose. The primary objective was safety, as assessed by adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs) (e.g. immunogenicity, hypersensitivity reactions, thromboembolic events). Secondary endpoints included immunogenicity, rpFVIII hemostatic effectiveness, and rpFVIII utilization.</p><p><strong>Results: </strong>Fifty patients were enrolled; 31 completed the study. The median (range) follow-up for patients who completed or discontinued the study was 178 (26-371) days. The median (range) first dose of rpFVIII was 54.0 (11-200) U/kg. Thirty patients reported 46 SAEs; 5 SAEs were considered probably related to rpFVIII, of which 1 was lack of rpFVIII efficacy, and 4 were AESIs: drug resistance due to FVIII inhibition (one patient), antibody test positive for anti-pFVIII inhibitors (one patient), and <i>de novo</i> anti-pFVIII inhibitors (two patients). No hypersensitivity reactions or thromboembolic events were reported. Of the 50 initial BEs, 37 resolved [in a median (interquartile range) of 8.0 (4.0-16.0) days].</p><p><strong>Conclusion: </strong>Results from this real-world study support the use of rpFVIII for AHA, aligning with findings from the clinical trial of rpFVIII (NCT01178294) in the treatment of BEs in adults with AHA.</p><p><strong>Trial registration: </strong>EUPAS16055; NCT03199794.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"15 ","pages":"20406207241260332"},"PeriodicalIF":3.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126734","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":"Comparable efficacy and safety of generic and branded imatinib for patients with chronic myeloid leukemia in China.","authors":"Fang Cheng, Di Wu, Zheng Cui, Qiang Li, Weiming Li, Yu Zhang","doi":"10.1177/20406207241270806","DOIUrl":"10.1177/20406207241270806","url":null,"abstract":"<p><strong>Background: </strong>Generics imatinib became an alternative treatment option for chronic myeloid leukemia (CML) patients in China. However, clinicians and patients alike harbor concerns regarding the long-term safety of generic imatinib.</p><p><strong>Objectives: </strong>Patients with chronic phase CML receiving frontline imatinib treatment.</p><p><strong>Design: </strong>A retrospective study was used to evaluate the blood concentration, effectiveness, and safety of generic in 170 CML patients.</p><p><strong>Methods: </strong>Imatinib plasma concentrations were detected by high-performance liquid chromatography-tandem mass spectrometry.</p><p><strong>Results: </strong>Among the 170 patients, 73 (42.9%) patients treated with branded imatinib as first-line therapy, while 22 (12.9%) switched to generic imatinib during treatment due to economic considerations. No significant differences in trough concentrations between branded and generic imatinib (1549.9 ± 648.8 ng/mL vs 1479.0 ± 507.0 ng/mL; <i>p</i> = 0.95). During the 2-year follow-up, there were no significant differences in molecular response rates (major molecular response (MMR): 33.3% vs 37.0%; deep molecular response: 56.9% vs 42.9%, <i>p</i> = 0.17) between the branded and generic imatinib. Both groups showed similar rates of switching to second-generation tyrosine kinase inhibitor (11.8% vs 15.1%, <i>p</i> = 0.56). Furthermore, there were no significant differences in event-free survival or failure-free survival between branded and generic imatinib. Twenty-two (12.9%) switched to generic imatinib during treatment, 68.2% maintained their level of response, 27.3% improved, and only one patient (4.5%) lost MMR. There were no significant differences in the incidence of various adverse events.</p><p><strong>Conclusion: </strong>Generic imatinib are equally effective and safe compared to branded molecules, both for newly diagnosed patients and those who switch from branded.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"15 ","pages":"20406207241270806"},"PeriodicalIF":3.4,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11325334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988974","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":"Successful treatment of hemophagocytic intravascular large B-cell lymphoma with CNS involvement with BTK inhibitor combined with rituximab and high-dose methotrexate.","authors":"Fangfei Shao, Wei Su, Xiujie Zhao, Jianping He, Xiaofen Wang, Feng Guo, Haowen Xiao","doi":"10.1177/20406207241270788","DOIUrl":"10.1177/20406207241270788","url":null,"abstract":"<p><p>This is a case of hemophagocytic intravascular large B-cell lymphoma (IVLBCL) with central nervous system (CNS) involvement. Although R-CHOP chemotherapy regimen has been shown significant improvement in survival rate. The prognosis and outcomes remain unsatisfactory, which is identified as outstanding challenges and need solutions. Gene and molecular profiling studies may provide new therapeutic strategies, especially the BCR/TLR/IL-1R/NF-κB signaling pathway in IVLBCL. Here, we treated the hemophagocytic IVLBCL CNS-involved patient with the Bruton tyrosine kinase inhibitor (BTKi) to block NF-κB pathway, and indicated that the second-generation BTKi zanubrutinib-based treatment was feasible and efficient.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"15 ","pages":"20406207241270788"},"PeriodicalIF":3.4,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11325336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988975","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}
Priyanka Raheja, Nana Kragh, Linda Bystrická, Daniel Eriksson, Khaoula Aroui, Marwa Mezghani, Sylvaine Barbier, Silvia Linari
{"title":"Long-term efmoroctocog alfa prophylaxis improves perceived pain, mental, and physical health in patients with hemophilia A: post hoc analysis of phase III trials using patient-reported outcomes","authors":"Priyanka Raheja, Nana Kragh, Linda Bystrická, Daniel Eriksson, Khaoula Aroui, Marwa Mezghani, Sylvaine Barbier, Silvia Linari","doi":"10.1177/20406207241257917","DOIUrl":"https://doi.org/10.1177/20406207241257917","url":null,"abstract":"Background:Hemophilia-associated bleeding and resultant joint pain and mobility restrictions can predispose patients to poor health-related quality of life (HRQoL). Therefore, efficacy of a treatment needs to address more than just annualized bleed rates.Objectives:Describe the evolution of HRQoL, pain, and activity in patients with hemophilia A, treated with efmoroctocog alfa prophylaxis.Design:A post hoc analysis from Kids A-LONG (NCT01458106), A-LONG (NCT01181128), and long-term extension study ASPIRE (NCT01454739) assessed change in pain and activity-related patient-reported outcomes (PROs).Methods:Physical health, pain, and HRQoL were assessed by PROs for a cumulative treatment duration of up to ~6 years. The primary endpoint was change from baseline in EuroQoL (EQ)-5D and Haemophilia Quality of Life Questionnaire (Haem-A-QoL).Results:118 adult/adolescents and 71 pediatric patients were included. The proportion of adults and adolescents reporting no problem in the EQ-5D analysis of ‘ pain/discomfort’ significantly increased from A-LONG baseline (35.04%; 41/117) to ASPIRE month 30 (44.68%; 21/47; p = 0.024). Mean (standard deviation) Haem-A-QoL subdomain scores for ‘ feeling’ and ‘ physical health’ at A-LONG baseline improved by −3.24 (15.13; p = 0.018) and −3.85 (23.07; p = 0.047), respectively, at study end. Proportion of pediatric patients reporting no problem on the EQ-5D analysis of ‘ pain/discomfort’, significantly increased from A-LONG baseline (75.0%; 42/56) to ASPIRE baseline (95.56%; 43/45; p = 0.046). Satisfaction levels for pediatric patients were high at A-LONG baseline and maintained until study end.Conclusion:Long-term efmoroctocog alfa prophylaxis reduces pain and improves HRQoL in adult and adolescent patients with hemophilia A. In pediatric patients, it reduces perceived pain and maintains satisfaction levels.Trial registration:NCT01458106, NCT01181128, NCT01454739.","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"46 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141866676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A case report of refractory advanced-stage mycosis fungoides: successful treatment and improved patient quality of life with mogamulizumab","authors":"Nina Frischhut, Van Anh Nguyen","doi":"10.1177/20406207241260340","DOIUrl":"https://doi.org/10.1177/20406207241260340","url":null,"abstract":"Mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma, is characterized by patches, plaques, and, in advanced stages, tumors and erythroderma. Early-stage MF may progress to advanced-stage disease in up to one-third of patients, conferring a worse prognosis and typically requiring systemic treatment for extracutaneous involvement. The most frequently reported signs and symptoms are pain, pruritus, scaling, and skin redness, with pruritus, the most bothersome symptom, exerting a profound impact on patients’ health-related quality of life (HRQoL). These dermatologic signs and symptoms can overlap with those of other benign inflammatory dermatoses, such as eczema and psoriasis, and therefore, diagnostic delay is common in patients with MF. Moreover, identifying patients with features adversely affecting prognosis (e.g. large-cell transformation or folliculotropic variant) is a significant challenge. We report the case of a 75-year-old female patient who was misdiagnosed with eczema and then pityriasis rubra pilaris and consequently did not receive treatment for MF for 4 years. The patient was eventually correctly diagnosed with MF [stage IIIB (T4 N1 M0 B1)] in September 2018. The patient received several systemic treatments; however, she did not respond to or tolerate the treatments. Due to lack of treatment response, in July 2021, she was initiated on mogamulizumab, an anti-CC chemokine receptor 4 antibody with demonstrated effectiveness and licensed approval for adults with MF/Sézary syndrome who have received one or more prior systemic therapies. Treatment rapidly led to a complete response in blood after 1 week and in skin after 4 months. Mogamulizumab was well tolerated by the patient, who also reported a significant improvement in her HRQoL. After 1 year in complete response, mogamulizumab was discontinued. This case highlights the need for accurate and early diagnosis of MF to initiate disease-specific treatment and the importance of considering patient HRQoL when treating this condition.","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"48 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141866524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amer M. Zeidan, Kate Perepezko, Tehseen Salimi, Terri Washington, Robert S. Epstein
{"title":"Patients’ perspectives on oral decitabine/cedazuridine for the treatment of myelodysplastic syndromes/neoplasms","authors":"Amer M. Zeidan, Kate Perepezko, Tehseen Salimi, Terri Washington, Robert S. Epstein","doi":"10.1177/20406207241257313","DOIUrl":"https://doi.org/10.1177/20406207241257313","url":null,"abstract":"Background:Hypomethylating agents (HMAs) are guideline-recommended treatment for higher-risk myelodysplastic syndromes/neoplasms (MDS). However, a prior survey of patients with MDS reported challenges with intravenous (IV) and subcutaneous (SC) HMA therapies, including pain related to treatment administration and interference with daily activities; most patients also indicated a preference to switch to an oral therapy if one were available.Objectives:This study evaluated the perspectives of US patients with MDS receiving oral decitabine/cedazuridine (DEC-C), an alternative to IV/SC HMAs.Methods:An online survey was conducted among adult patients with MDS in the United States (10 November 2022 to 5 December 2022) who had filled a prescription for oral DEC-C between 2021 and 2022.Results:A total of 150 patients completed the survey; 61% were aged ⩾60 years and 63% were male. Of these, 123 (82%) were still receiving oral DEC-C, and 27 (18%) had stopped oral DEC-C treatment. Half (50%) of patients had received oral DEC-C for ⩾6 months. The majority reported that treatment was convenient (83%) and that they were satisfied with treatment (86%). Most patients also reported very little/no interference with regular daily activities (82%), social activities (78%), and productivity (78%). When queried about negative impacts on quality of life (QOL), treatment side effects were the most commonly reported (30% of respondents). Among patients who had previously received IV/SC HMAs ( n = 91), most agreed that oral DEC-C interfered less with daily life (91%) and had experienced improvement in QOL (85%) compared with previous treatment; 91% reported that oral DEC-C reduced the number of times they needed to travel to a healthcare facility.Conclusion:Survey results suggest very little/no impact on regular daily activities and improved QOL with oral DEC-C relative to IV/SC HMAs, highlighting the potential for oral DEC-C to reduce the treatment burden associated with parenteral HMA therapy.","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"51 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141866525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chenyu Zha, Jialu Song, Ming Wan, Xiao Lin, Xiaolin He, Ming Wu, Rui Huang
{"title":"Recent advances in CAR-T therapy for the treatment of acute myeloid leukemia.","authors":"Chenyu Zha, Jialu Song, Ming Wan, Xiao Lin, Xiaolin He, Ming Wu, Rui Huang","doi":"10.1177/20406207241263489","DOIUrl":"https://doi.org/10.1177/20406207241263489","url":null,"abstract":"<p><p>Chimeric antigen receptor T-cell (CAR-T) therapy, which has demonstrated notable efficacy against B-cell malignancies and is approved by the US Food and Drug Administration for clinical use in this context, represents a significant milestone in cancer immunotherapy. However, the efficacy of CAR-T therapy for the treatment of acute myeloid leukemia (AML) is poor. The challenges associated with the application of CAR-T therapy for the clinical treatment of AML include, but are not limited to, nonspecific distribution of AML therapeutic targets, difficulties in the production of CAR-T cells, AML blast cell heterogeneity, the immunosuppressive microenvironment in AML, and treatment-related adverse events. In this review, we summarize the recent findings regarding various therapeutic targets for AML (CD33, CD123, CLL1, CD7, etc.) and the results of the latest clinical studies on these targets. Thereafter, we also discuss the challenges related to CAR-T therapy for AML and some promising strategies for overcoming these challenges, including novel approaches such as gene editing and advances in CAR design.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"15 ","pages":"20406207241263489"},"PeriodicalIF":3.4,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11268017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761003","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}
Nicola R Mason, Hilary Cahill, Yonatan Diamond, Karen McCleary, Rishi S Kotecha, Glenn M Marshall, Marion K Mateos
{"title":"Down syndrome-associated leukaemias: current evidence and challenges.","authors":"Nicola R Mason, Hilary Cahill, Yonatan Diamond, Karen McCleary, Rishi S Kotecha, Glenn M Marshall, Marion K Mateos","doi":"10.1177/20406207241257901","DOIUrl":"https://doi.org/10.1177/20406207241257901","url":null,"abstract":"<p><p>Children with Down syndrome (DS) are at increased risk of developing haematological malignancies, in particular acute megakaryoblastic leukaemia and acute lymphoblastic leukaemia. The microenvironment established by abnormal haematopoiesis driven by trisomy 21 is compounded by additional genetic and epigenetic changes that can drive leukaemogenesis in patients with DS. GATA-binding protein 1 (<i>GATA1</i>) somatic mutations are implicated in the development of transient abnormal myelopoiesis and the progression to myeloid leukaemia of DS (ML-DS) and provide a model of the multi-step process of leukaemogenesis in DS. This review summarises key genetic drivers for the development of leukaemia in patients with DS, the biology and treatment of ML-DS and DS-associated acute lymphoblastic leukaemia, late effects of treatments for DS-leukaemias and the focus for future targeted therapy.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":"15 ","pages":"20406207241257901"},"PeriodicalIF":3.4,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11268035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761002","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}