Pub Date : 2022-12-09DOI: 10.1182/hematology.2022000383
Kochawan Boonyawat, Pantep Angchaisuksiri
There are clinical issues of special importance and practice variation in the management of venous thromboembolism (VTE) and in the use of anticoagulants among hematologists who practice in Asia. In Asian-inherited thrombophilia, coagulation is disturbed due to loss-of-function mutations of protein S and protein C causing protein S and protein C deficiencies, whereas the gain-of-function factor V Leiden and prothrombin G20210A mutations are almost absent. Thrombophilia screening is not recommended in patients with VTE patients who have major provoking factors. However, it can be considered in unprovoked young patients with VTE who have a strong family history of VTE. Cancer is the most important acquired risk factor for VTE in Asians. Limited cancer screening at the initial presentation of unprovoked VTE is appropriate, especially in the elderly. Direct oral anticoagulants have been shown to have similar efficacy and reduce risk of major bleeding, including intracranial hemorrhage and bleeding requiring hospitalization, compared with warfarin. Most clinical trials evaluating therapies for treatment and prevention of VTE have included small numbers of Asian patients. Despite this lack of evidence, direct oral anticoagulants have been increasingly used in Asia for cancer-associated thrombosis. Individualized assessment of thrombotic and bleeding risks should be used for all hospitalized Asian patients when deciding on pharmacologic thromboprophylaxis. More research is needed to understand the factors that contribute to risks of VTE and anticoagulant-associated bleeding in Asian patients as these may differ from Western populations.
{"title":"Thrombosis and anticoagulation: clinical issues of special importance to hematologists who practice in Asia.","authors":"Kochawan Boonyawat, Pantep Angchaisuksiri","doi":"10.1182/hematology.2022000383","DOIUrl":"https://doi.org/10.1182/hematology.2022000383","url":null,"abstract":"<p><p>There are clinical issues of special importance and practice variation in the management of venous thromboembolism (VTE) and in the use of anticoagulants among hematologists who practice in Asia. In Asian-inherited thrombophilia, coagulation is disturbed due to loss-of-function mutations of protein S and protein C causing protein S and protein C deficiencies, whereas the gain-of-function factor V Leiden and prothrombin G20210A mutations are almost absent. Thrombophilia screening is not recommended in patients with VTE patients who have major provoking factors. However, it can be considered in unprovoked young patients with VTE who have a strong family history of VTE. Cancer is the most important acquired risk factor for VTE in Asians. Limited cancer screening at the initial presentation of unprovoked VTE is appropriate, especially in the elderly. Direct oral anticoagulants have been shown to have similar efficacy and reduce risk of major bleeding, including intracranial hemorrhage and bleeding requiring hospitalization, compared with warfarin. Most clinical trials evaluating therapies for treatment and prevention of VTE have included small numbers of Asian patients. Despite this lack of evidence, direct oral anticoagulants have been increasingly used in Asia for cancer-associated thrombosis. Individualized assessment of thrombotic and bleeding risks should be used for all hospitalized Asian patients when deciding on pharmacologic thromboprophylaxis. More research is needed to understand the factors that contribute to risks of VTE and anticoagulant-associated bleeding in Asian patients as these may differ from Western populations.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2022-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820496/pdf/hem.2022000383.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10557808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"教育学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-09DOI: 10.1182/hematology.2022000344
Lydia Scarfò
Patients with chronic lymphocytic leukemia (CLL) refractory to covalent BTK and BCL2 inhibitors have a new unmet clinical need. Standard treatment options are able to obtain only limited and short-lasting disease control associated with reduced overall survival, and thus these patients have become ideal candidates for enrollment in clinical trials. Favorable results have been obtained with the use of noncovalent BTK inhibitors (roughly 70% overall response rate regardless of the actual resistance or intolerance to previous covalent BTK inhibitors) and anti-CD19 chimeric antigen receptor (CAR) T-cell therapy (with complete responses in up to 45% of cases and an undetectable measurable residual disease rate of 65% in the bone marrow). These 2 approaches should be considered valid options in this setting, although not yet approved. For young fit patients achieving remissions with salvage treatments, the option of allogeneic stem cell transplantation should be discussed as the outcome appears to be unaffected by number and type of previous targeted agents. Novel treatment strategies interfering with different mechanisms of CLL cell survival and proliferation are warranted, including small molecules with novel targets (eg, CDK9, MCL1, ERK inhibitors), CAR T cells targeting different antigens, CAR natural killer cells, or bispecific antibodies.
{"title":"Novel therapies and combinations in CLL refractory to BTK inhibitors and venetoclax.","authors":"Lydia Scarfò","doi":"10.1182/hematology.2022000344","DOIUrl":"10.1182/hematology.2022000344","url":null,"abstract":"<p><p>Patients with chronic lymphocytic leukemia (CLL) refractory to covalent BTK and BCL2 inhibitors have a new unmet clinical need. Standard treatment options are able to obtain only limited and short-lasting disease control associated with reduced overall survival, and thus these patients have become ideal candidates for enrollment in clinical trials. Favorable results have been obtained with the use of noncovalent BTK inhibitors (roughly 70% overall response rate regardless of the actual resistance or intolerance to previous covalent BTK inhibitors) and anti-CD19 chimeric antigen receptor (CAR) T-cell therapy (with complete responses in up to 45% of cases and an undetectable measurable residual disease rate of 65% in the bone marrow). These 2 approaches should be considered valid options in this setting, although not yet approved. For young fit patients achieving remissions with salvage treatments, the option of allogeneic stem cell transplantation should be discussed as the outcome appears to be unaffected by number and type of previous targeted agents. Novel treatment strategies interfering with different mechanisms of CLL cell survival and proliferation are warranted, including small molecules with novel targets (eg, CDK9, MCL1, ERK inhibitors), CAR T cells targeting different antigens, CAR natural killer cells, or bispecific antibodies.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2022-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820511/pdf/hem.2022000344.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10268582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"教育学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-09DOI: 10.1182/hematology.2022000362
Michele Merli, Luca Arcaini
Marginal zone lymphomas (MZLs) represent about 7% of B-cell non-Hodgkin lymphomas and include 3 different subtypes-namely, extranodal (EMZL), nodal, and splenic (SMZL). The initial assessment requires specific diagnostic and staging procedures depending on organ-related peculiarities. In particular, although positron emission tomography/computed tomography was not initially recommended, recent data have reassessed its role in the routine staging of MZL, especially when only localized treatment is planned or there is a suspicion of histologic transformation. Recent findings have improved the risk stratification of MZL patients, highlighting the association of early progression after frontline therapy with worse overall survival. A significant fraction of MZL cases may be related to specific bacterial (ie, Helicobacter pylori in gastric EMZL) or viral infections (hepatis C virus), and in the earlier phases of disease, a variable percentage of patients may respond to anti-infective therapy. Involved-site radiotherapy has a central role in the management of localized EMZL not amenable to or not responding to anti-infective therapy. Although rituximab-based treatments (bendamustine- rituximab in advanced EMZL or rituximab monotherapy in SMZL) have demonstrated favorable results, the current therapeutic scenario is predicted to rapidly change as emerging novel agents, especially Bruton's tyrosine kinase inhibitors, have demonstrated promising efficacy and safety profiles, leading to their approval in the relapsed setting. Moreover, a large variety of novel agents (phosphatidylinositol 3-kinase inhibitors, chimeric antigen receptor T-cells, bispecific antibodies) are being tested in MZL patients with encouraging preliminary results.
边缘区淋巴瘤(MZL)约占B细胞非霍奇金淋巴瘤的7%,包括3种不同的亚型,即结外型(EMZL)、结节型和脾型(SMZL)。初步评估需要根据器官相关的特殊性进行特定的诊断和分期。特别是,虽然最初并不推荐使用正电子发射断层扫描/计算机断层扫描,但最近的数据重新评估了它在MZL常规分期中的作用,尤其是在只计划进行局部治疗或怀疑有组织学转化的情况下。最近的研究结果改善了对MZL患者的风险分层,强调了一线治疗后早期进展与总生存率降低的关系。相当一部分MZL病例可能与特定的细菌(即胃EMZL中的幽门螺杆菌)或病毒(丙型肝炎病毒)感染有关,在疾病的早期阶段,不同比例的患者可能对抗感染治疗产生反应。对于无法接受抗感染治疗或对抗感染治疗无效的局部EMZL,局部放射治疗在治疗中起着核心作用。尽管基于利妥昔单抗的治疗(苯达莫司汀-利妥昔单抗治疗晚期EMZL或利妥昔单抗单药治疗SMZL)已取得了良好的疗效,但由于新出现的新型药物,特别是布鲁顿酪氨酸激酶抑制剂,已显示出良好的疗效和安全性,并已获准用于复发病例,因此预计目前的治疗方案将迅速发生变化。此外,大量新型药物(磷脂酰肌醇 3- 激酶抑制剂、嵌合抗原受体 T 细胞、双特异性抗体)正在 MZL 患者中进行试验,并取得了令人鼓舞的初步结果。
{"title":"Management of marginal zone lymphomas.","authors":"Michele Merli, Luca Arcaini","doi":"10.1182/hematology.2022000362","DOIUrl":"10.1182/hematology.2022000362","url":null,"abstract":"<p><p>Marginal zone lymphomas (MZLs) represent about 7% of B-cell non-Hodgkin lymphomas and include 3 different subtypes-namely, extranodal (EMZL), nodal, and splenic (SMZL). The initial assessment requires specific diagnostic and staging procedures depending on organ-related peculiarities. In particular, although positron emission tomography/computed tomography was not initially recommended, recent data have reassessed its role in the routine staging of MZL, especially when only localized treatment is planned or there is a suspicion of histologic transformation. Recent findings have improved the risk stratification of MZL patients, highlighting the association of early progression after frontline therapy with worse overall survival. A significant fraction of MZL cases may be related to specific bacterial (ie, Helicobacter pylori in gastric EMZL) or viral infections (hepatis C virus), and in the earlier phases of disease, a variable percentage of patients may respond to anti-infective therapy. Involved-site radiotherapy has a central role in the management of localized EMZL not amenable to or not responding to anti-infective therapy. Although rituximab-based treatments (bendamustine- rituximab in advanced EMZL or rituximab monotherapy in SMZL) have demonstrated favorable results, the current therapeutic scenario is predicted to rapidly change as emerging novel agents, especially Bruton's tyrosine kinase inhibitors, have demonstrated promising efficacy and safety profiles, leading to their approval in the relapsed setting. Moreover, a large variety of novel agents (phosphatidylinositol 3-kinase inhibitors, chimeric antigen receptor T-cells, bispecific antibodies) are being tested in MZL patients with encouraging preliminary results.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9901419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10723022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"教育学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-09DOI: 10.1182/hematology.2022000351
Kristin L Koenig, Uma Borate
Myelodysplastic syndromes (MDS) are typically a hematologic malignancy of older adults characterized by dysplastic hematopoiesis, cytopenia(s), and risk of acute myeloid leukemia transformation. The treatment approach to MDS depends largely on risk stratification of an individual's disease, most commonly using the Revised International Prognostic Scoring System, which takes into account peripheral blood cytopenias and bone marrow blast percentage and cytogenetics. The current standard of care for patients with higher-risk MDS (HR-MDS) includes hypomethylating agents (HMAs), decitabine and azacitidine, and allogenic stem cell transplant for patients able to undergo this therapy. However, leukemic transformation remains a significant challenge, and outcomes with these current therapies are still dismal. There are several novel therapies in development aiming to improve upon the outcomes of single-agent HMA therapy using combination strategies with HMAs. Here we discuss the current standard of care for HR-MDS treatment and explore some of the most promising combination therapies coming out of the pipeline for HR-MDS.
骨髓增生异常综合征(MDS)是一种典型的老年人血液系统恶性肿瘤,其特点是造血功能障碍、全血细胞减少以及急性髓性白血病转化的风险。MDS 的治疗方法在很大程度上取决于个人疾病的风险分层,最常见的是使用修订版国际预后评分系统(Revised International Prognostic Scoring System),该系统考虑了外周血细胞减少症、骨髓造血干细胞百分比和细胞遗传学。目前治疗高危MDS(HR-MDS)患者的标准疗法包括低甲基化药物(HMAs)、地西他滨和阿扎胞苷,以及对能够接受这种疗法的患者进行异基因干细胞移植。然而,白血病转化仍是一项重大挑战,目前这些疗法的疗效仍然令人沮丧。目前有几种新型疗法正在研发中,旨在通过与HMAs的联合策略,改善单药HMA疗法的疗效。在此,我们将讨论目前治疗 HR-MDS 的标准,并探索一些最有希望的 HR-MDS 联合疗法。
{"title":"New investigational combinations for higher-risk MDS.","authors":"Kristin L Koenig, Uma Borate","doi":"10.1182/hematology.2022000351","DOIUrl":"10.1182/hematology.2022000351","url":null,"abstract":"<p><p>Myelodysplastic syndromes (MDS) are typically a hematologic malignancy of older adults characterized by dysplastic hematopoiesis, cytopenia(s), and risk of acute myeloid leukemia transformation. The treatment approach to MDS depends largely on risk stratification of an individual's disease, most commonly using the Revised International Prognostic Scoring System, which takes into account peripheral blood cytopenias and bone marrow blast percentage and cytogenetics. The current standard of care for patients with higher-risk MDS (HR-MDS) includes hypomethylating agents (HMAs), decitabine and azacitidine, and allogenic stem cell transplant for patients able to undergo this therapy. However, leukemic transformation remains a significant challenge, and outcomes with these current therapies are still dismal. There are several novel therapies in development aiming to improve upon the outcomes of single-agent HMA therapy using combination strategies with HMAs. Here we discuss the current standard of care for HR-MDS treatment and explore some of the most promising combination therapies coming out of the pipeline for HR-MDS.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2022-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820246/pdf/hem.2022000351.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10557811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"教育学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-09DOI: 10.1182/hematology.2022000373
Rohini Chakravarthy, Debra L Friedman
Treatment options for patients with sickle cell disease (SCD) continue to rapidly expand and evolve. The goal of therapies such as an allogeneic hematopoietic stem cell transplant (HSCT), gene therapy, and gene editing is to cure rather than control SCD. The benefits of these therapies must be accompanied by minimizing long-term adverse health outcomes from SCD and its treatment. SCD can have adverse effects on a variety of organ systems, including the heart, lung, kidney, and reproductive system, leading to high disease burden, morbidity, and premature mortality in both pediatric and adult patients. While curative therapies are being increasingly used, there remains a paucity of data on the long-term health outcomes associated with these treatments in children and adults with SCD. There are data available regarding the effects of HSCT performed largely for malignant diseases, from which data on SCD outcomes may be extrapolated. However, given the significant differences between these 2 populations of patients who undergo HSCT, such extrapolation is imprecise at best. Furthermore, there are currently no published data on long-term health outcomes following gene therapy for SCD due to current short follow-up times. We summarize the limited data reported on health outcomes following HSCT for SCD and emphasize the need for more research within this area.
{"title":"Long-term health outcomes following curative therapies for sickle cell disease.","authors":"Rohini Chakravarthy, Debra L Friedman","doi":"10.1182/hematology.2022000373","DOIUrl":"https://doi.org/10.1182/hematology.2022000373","url":null,"abstract":"<p><p>Treatment options for patients with sickle cell disease (SCD) continue to rapidly expand and evolve. The goal of therapies such as an allogeneic hematopoietic stem cell transplant (HSCT), gene therapy, and gene editing is to cure rather than control SCD. The benefits of these therapies must be accompanied by minimizing long-term adverse health outcomes from SCD and its treatment. SCD can have adverse effects on a variety of organ systems, including the heart, lung, kidney, and reproductive system, leading to high disease burden, morbidity, and premature mortality in both pediatric and adult patients. While curative therapies are being increasingly used, there remains a paucity of data on the long-term health outcomes associated with these treatments in children and adults with SCD. There are data available regarding the effects of HSCT performed largely for malignant diseases, from which data on SCD outcomes may be extrapolated. However, given the significant differences between these 2 populations of patients who undergo HSCT, such extrapolation is imprecise at best. Furthermore, there are currently no published data on long-term health outcomes following gene therapy for SCD due to current short follow-up times. We summarize the limited data reported on health outcomes following HSCT for SCD and emphasize the need for more research within this area.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2022-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820909/pdf/hem.2022000373.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10868886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"教育学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-09DOI: 10.1182/hematology.2022000411
Rushad Patell, Jeffrey I Zwicker
Co-incident venous thromboembolism and thrombocytopenia are frequent in patients with active malignancies. The optimal approach for anticoagulation in patients with cancer and thrombocytopenia is not established. Different strategies are often utilized including dose-reduced anticoagulation dictated by degree of thrombocytopenia or transfusing platelets in order to facilitate therapeutic anticoagulation. This minireview provides an overview of the data and we outline our approach toward anticoagulation in patients with venous thromboembolism and thrombocytopenia in the setting of cancer.
{"title":"Evidence-Based Minireview: Full dose, modified dose, or no anticoagulation for patients with cancer and acute VTE and thrombocytopenia.","authors":"Rushad Patell, Jeffrey I Zwicker","doi":"10.1182/hematology.2022000411","DOIUrl":"https://doi.org/10.1182/hematology.2022000411","url":null,"abstract":"<p><p>Co-incident venous thromboembolism and thrombocytopenia are frequent in patients with active malignancies. The optimal approach for anticoagulation in patients with cancer and thrombocytopenia is not established. Different strategies are often utilized including dose-reduced anticoagulation dictated by degree of thrombocytopenia or transfusing platelets in order to facilitate therapeutic anticoagulation. This minireview provides an overview of the data and we outline our approach toward anticoagulation in patients with venous thromboembolism and thrombocytopenia in the setting of cancer.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2022-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9821225/pdf/hem.2022000411.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10666483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"教育学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-09DOI: 10.1182/hematology.2022000325
Kieran D Sahasrabudhe, Alice S Mims
The treatment landscape in acute myeloid leukemia (AML) is rapidly evolving, with multiple new therapies approved in recent years. However, the prognosis for patients with high-risk genetic subsets of AML remains poor, and the development of more effective treatment options for these patients is ongoing. Three of these high-risk AML patient subsets include TP53-mutated AML, FLT3-internal tandem duplication (ITD)-mutated AML, and AML harboring rearrangements affecting the KMT2A locus (KMT2A-r AML). The prognosis for TP53-mutated AML remains poor with both intensive and targeted regimens, including those incorporating the BCL-2 inhibitor, venetoclax. Allogeneic hematopoietic stem cell transplantation is the only potentially curative therapy for these patients, but posttransplant relapse rates remain high. Patients with FLT3-ITD-mutated AML continue to have suboptimal outcomes with standard therapies and experience high rates of relapse following transplant. KMT2A-r AML is also associated with poor outcomes with current treatment approaches, and effective standards of care are lacking for patients with relapsed/refractory disease. This article discusses current treatment approaches, along with the investigational agents being explored for the treatment of these 3 AML subsets, focusing primarily on agents that are further along in development.
{"title":"Novel investigational approaches for high-risk genetic subsets of AML: TP53, KMT2A, FLT3.","authors":"Kieran D Sahasrabudhe, Alice S Mims","doi":"10.1182/hematology.2022000325","DOIUrl":"https://doi.org/10.1182/hematology.2022000325","url":null,"abstract":"<p><p>The treatment landscape in acute myeloid leukemia (AML) is rapidly evolving, with multiple new therapies approved in recent years. However, the prognosis for patients with high-risk genetic subsets of AML remains poor, and the development of more effective treatment options for these patients is ongoing. Three of these high-risk AML patient subsets include TP53-mutated AML, FLT3-internal tandem duplication (ITD)-mutated AML, and AML harboring rearrangements affecting the KMT2A locus (KMT2A-r AML). The prognosis for TP53-mutated AML remains poor with both intensive and targeted regimens, including those incorporating the BCL-2 inhibitor, venetoclax. Allogeneic hematopoietic stem cell transplantation is the only potentially curative therapy for these patients, but posttransplant relapse rates remain high. Patients with FLT3-ITD-mutated AML continue to have suboptimal outcomes with standard therapies and experience high rates of relapse following transplant. KMT2A-r AML is also associated with poor outcomes with current treatment approaches, and effective standards of care are lacking for patients with relapsed/refractory disease. This article discusses current treatment approaches, along with the investigational agents being explored for the treatment of these 3 AML subsets, focusing primarily on agents that are further along in development.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2022-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820850/pdf/hem.2022000325.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10557807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"教育学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-09DOI: 10.1182/hematology.2022000337C
Kristen M O'Dwyer
T-lineage acute lymphoblastic leukemia (T-ALL) is curable for most children and adolescent and young adult patients with contemporary frontline chemotherapy regimens. During the past decade, improved survival rates have resulted from the optimization of frontline chemotherapy regimens, the use of minimal residual disease (MRD) assessment for evaluating a patient's risk for relapse, and the intensification of treatment based on the persistence of MRD. Optimization of initial therapy is critical because relapsed T-ALL after initial intensive chemotherapy is incurable for most adult patients. Current T-ALL salvage chemotherapy regimens are minimally effective, and unlike in B-cell ALL, there are no approved antibody therapies or chimeric antigen receptor T-cell therapies for relapsed disease. Immunotherapy and small-molecule inhibitors are beginning to be tested in relapsed T-ALL and have the potential to advance the treatment. Until effective salvage strategies are discovered, however, intensive frontline therapy is required for cure. In this article I review the current frontline chemotherapy regimens for adult patients with T-ALL, summarize the novel targeted and immune therapeutics currently in early-phase clinical trials, and outline how these therapies are helping to define an optimal approach for T-ALL.
{"title":"Optimal approach to T-cell ALL.","authors":"Kristen M O'Dwyer","doi":"10.1182/hematology.2022000337C","DOIUrl":"https://doi.org/10.1182/hematology.2022000337C","url":null,"abstract":"<p><p>T-lineage acute lymphoblastic leukemia (T-ALL) is curable for most children and adolescent and young adult patients with contemporary frontline chemotherapy regimens. During the past decade, improved survival rates have resulted from the optimization of frontline chemotherapy regimens, the use of minimal residual disease (MRD) assessment for evaluating a patient's risk for relapse, and the intensification of treatment based on the persistence of MRD. Optimization of initial therapy is critical because relapsed T-ALL after initial intensive chemotherapy is incurable for most adult patients. Current T-ALL salvage chemotherapy regimens are minimally effective, and unlike in B-cell ALL, there are no approved antibody therapies or chimeric antigen receptor T-cell therapies for relapsed disease. Immunotherapy and small-molecule inhibitors are beginning to be tested in relapsed T-ALL and have the potential to advance the treatment. Until effective salvage strategies are discovered, however, intensive frontline therapy is required for cure. In this article I review the current frontline chemotherapy regimens for adult patients with T-ALL, summarize the novel targeted and immune therapeutics currently in early-phase clinical trials, and outline how these therapies are helping to define an optimal approach for T-ALL.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2022-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9821176/pdf/hem.2022000337.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10499514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"教育学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-09DOI: 10.1182/hematology.2022000376
Eugenia Vicky Asare, Michael R DeBaun, Edeghonghon Olayemi, Theodore Boafor, Samuel A Oppong
Pregnancy in women with sickle cell disease (SCD) is a life-threatening condition. In both high- and low-income countries, there is an 11-fold increased risk of maternal death and a 4-fold increased risk of perinatal death. We highlight the epidemiology of SCD-specific and obstetric complications commonly seen during pregnancy in SCD and propose definitions for acute pain and acute chest syndrome (ACS) episodes during pregnancy. We conducted a systematic review of the recent obstetric and hematology literature using full research articles published within the last 5 years that reported outcomes in pregnant women with SCD. The prevalence of acute pain episodes during pregnancy ranged between 4% and 75%. The prevalence of ACS episodes during pregnancy ranged between 4% and 13%. The estimated prevalence of pulmonary thromboembolism in women with SCD during pregnancy is approximately 0.5 to 1%. ACS is the most common cause of death and is often preceded by acute pain episodes. The most crucial time to develop these complications in pregnancy is during the third trimester and postpartum period. In a pooled analysis from studies in low- and middle-income settings, maternal death in women with SCD is approximately 2393 and 4300 deaths per 100 000 live births with and without multidisciplinary care, respectively. In comparison, in the US and northern Europe, the general maternal mortality rate is approximately 23.8 and 8 deaths per 100 000 live births, respectively. A multidisciplinary SCD obstetrics care approach reduces maternal and perinatal morbidity and mortality in low- and middle-income countries.
{"title":"Acute pain episodes, acute chest syndrome, and pulmonary thromboembolism in pregnancy.","authors":"Eugenia Vicky Asare, Michael R DeBaun, Edeghonghon Olayemi, Theodore Boafor, Samuel A Oppong","doi":"10.1182/hematology.2022000376","DOIUrl":"https://doi.org/10.1182/hematology.2022000376","url":null,"abstract":"<p><p>Pregnancy in women with sickle cell disease (SCD) is a life-threatening condition. In both high- and low-income countries, there is an 11-fold increased risk of maternal death and a 4-fold increased risk of perinatal death. We highlight the epidemiology of SCD-specific and obstetric complications commonly seen during pregnancy in SCD and propose definitions for acute pain and acute chest syndrome (ACS) episodes during pregnancy. We conducted a systematic review of the recent obstetric and hematology literature using full research articles published within the last 5 years that reported outcomes in pregnant women with SCD. The prevalence of acute pain episodes during pregnancy ranged between 4% and 75%. The prevalence of ACS episodes during pregnancy ranged between 4% and 13%. The estimated prevalence of pulmonary thromboembolism in women with SCD during pregnancy is approximately 0.5 to 1%. ACS is the most common cause of death and is often preceded by acute pain episodes. The most crucial time to develop these complications in pregnancy is during the third trimester and postpartum period. In a pooled analysis from studies in low- and middle-income settings, maternal death in women with SCD is approximately 2393 and 4300 deaths per 100 000 live births with and without multidisciplinary care, respectively. In comparison, in the US and northern Europe, the general maternal mortality rate is approximately 23.8 and 8 deaths per 100 000 live births, respectively. A multidisciplinary SCD obstetrics care approach reduces maternal and perinatal morbidity and mortality in low- and middle-income countries.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2022-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9821602/pdf/hem.2022000376.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10499975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"教育学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-09DOI: 10.1182/hematology.2022000327
Arnon Nagler, Mohamad Mohty
Allogeneic hematopoietic stem cell transplantation is the treatment of choice for high-risk hematological malignancies such as acute myeloid and lymphocytic leukemia, myelodysplastic syndrome, and myeloproliferative disorders. Alternative donor transplantation from either haploidentical (haplo-SCT) or cord blood donor (CBT) is an established therapeutic alternative for patients who need transplants but lack a human leukocyte antigen-matched donor. Although haplo-SCT (mainly non-T-cell-depleted haplo-SCT with posttransplant cyclophosphamide) is increasing while CBT is decreasing worldwide (Figure 1), recent developments in CBT, especially cord blood expansion and other strategies to improve engraftment and immune reconstitution post-CBT, make CBT still a valuable option. This article discusses the 2 options based on the currently available data, focusing on adults, and tries to give some clues to help the transplant physician choose a haploidentical vs a cord blood donor. Given the limited numbers of published or ongoing well-designed randomized controlled trials comparing haplo-SCT to CBT and the overall similar clinical results in the available, mostly registry-based, and single-center studies, with substantial heterogeneity and variability, the decision to perform haplo-SCT or CBT in a given patient depends not only on the patient, disease, and donor characteristics and donor availability (although most if not all patients should have in principle an alternative donor) but also on the transplant physician's discretion and, most importantly, the center's experience and preference and ongoing protocols and strategies.
{"title":"In 2022, which is preferred: haploidentical or cord transplant?","authors":"Arnon Nagler, Mohamad Mohty","doi":"10.1182/hematology.2022000327","DOIUrl":"https://doi.org/10.1182/hematology.2022000327","url":null,"abstract":"<p><p>Allogeneic hematopoietic stem cell transplantation is the treatment of choice for high-risk hematological malignancies such as acute myeloid and lymphocytic leukemia, myelodysplastic syndrome, and myeloproliferative disorders. Alternative donor transplantation from either haploidentical (haplo-SCT) or cord blood donor (CBT) is an established therapeutic alternative for patients who need transplants but lack a human leukocyte antigen-matched donor. Although haplo-SCT (mainly non-T-cell-depleted haplo-SCT with posttransplant cyclophosphamide) is increasing while CBT is decreasing worldwide (Figure 1), recent developments in CBT, especially cord blood expansion and other strategies to improve engraftment and immune reconstitution post-CBT, make CBT still a valuable option. This article discusses the 2 options based on the currently available data, focusing on adults, and tries to give some clues to help the transplant physician choose a haploidentical vs a cord blood donor. Given the limited numbers of published or ongoing well-designed randomized controlled trials comparing haplo-SCT to CBT and the overall similar clinical results in the available, mostly registry-based, and single-center studies, with substantial heterogeneity and variability, the decision to perform haplo-SCT or CBT in a given patient depends not only on the patient, disease, and donor characteristics and donor availability (although most if not all patients should have in principle an alternative donor) but also on the transplant physician's discretion and, most importantly, the center's experience and preference and ongoing protocols and strategies.</p>","PeriodicalId":12973,"journal":{"name":"Hematology. American Society of Hematology. Education Program","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2022-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9820258/pdf/hem.2022000327.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10501737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"教育学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}