Pub Date : 2022-12-01DOI: 10.1016/j.beha.2022.101403
Lia Gore
Despite cure rates approaching 100% for some subsets of patients, survivors of childhood acute lymphoblastic leukemia (ALL) report a multitude of short- and long-term side effects. Indeed, the long-term complications of pediatric ALL treatment regimens can be associated with significant morbidity and mortality. Identifying mitigation strategies and developing more effective, less toxic therapies is a central goal of current research.
{"title":"What are the long-term complications of pediatric ALL treatments and how can they be mitigated? Perspectives on long-term consequences of curative treatment in childhood ALL","authors":"Lia Gore","doi":"10.1016/j.beha.2022.101403","DOIUrl":"10.1016/j.beha.2022.101403","url":null,"abstract":"<div><p>Despite cure rates approaching 100% for some subsets of patients, survivors of childhood acute lymphoblastic leukemia<span> (ALL) report a multitude of short- and long-term side effects. Indeed, the long-term complications of pediatric<span> ALL treatment regimens can be associated with significant morbidity and mortality. Identifying mitigation strategies and developing more effective, less toxic therapies is a central goal of current research.</span></span></p></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"35 4","pages":"Article 101403"},"PeriodicalIF":2.1,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10473774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01DOI: 10.1016/j.beha.2022.101409
Areej El-Jawahri
{"title":"How can we design a better care model to address the acute distress of an acute leukemia diagnosis? Care models to address the acute distress of an acute leukemia diagnosis","authors":"Areej El-Jawahri","doi":"10.1016/j.beha.2022.101409","DOIUrl":"10.1016/j.beha.2022.101409","url":null,"abstract":"","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"35 4","pages":"Article 101409"},"PeriodicalIF":2.1,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10762652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01DOI: 10.1016/j.beha.2022.101411
Jonathan A. Gutman
Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative approach for patients with acute myeloid leukemia (AML), relapse is a common occurrence. Several strategies, such as choice of conditioning regimen, donor lymphocyte infusions, pharmacologic agents, and cellular therapy approaches, are currently being developed to improve transplantation outcomes. This review outlines some important interventions and considerations to lower the burden of post-transplantation relapse in AML.
{"title":"How can we intervene to mitigate post-transplantation relapse in AML? Strategies to mitigate post-transplantation relapse in AML","authors":"Jonathan A. Gutman","doi":"10.1016/j.beha.2022.101411","DOIUrl":"10.1016/j.beha.2022.101411","url":null,"abstract":"<div><p>Although allogeneic hematopoietic stem cell transplantation<span> (allo-HSCT) is a curative approach for patients with acute myeloid leukemia<span> (AML), relapse is a common occurrence. Several strategies, such as choice of conditioning regimen, donor lymphocyte infusions, pharmacologic agents, and cellular therapy approaches, are currently being developed to improve transplantation outcomes. This review outlines some important interventions and considerations to lower the burden of post-transplantation relapse in AML.</span></span></p></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"35 4","pages":"Article 101411"},"PeriodicalIF":2.1,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10473777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01DOI: 10.1016/j.beha.2022.101410
Rafael Bejar
{"title":"How can we incorporate molecular data into the IPSS?","authors":"Rafael Bejar","doi":"10.1016/j.beha.2022.101410","DOIUrl":"10.1016/j.beha.2022.101410","url":null,"abstract":"","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"35 4","pages":"Article 101410"},"PeriodicalIF":2.1,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521692622000652/pdfft?md5=0cace80c68e2060bb5aaed2bd9effdf7&pid=1-s2.0-S1521692622000652-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10473778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01DOI: 10.1016/j.beha.2022.101408
Richard M. Stone
The safe diminution of leukemic cell numbers to a level such that the patient will not succumb to their disease has been an achievable, yet often elusive goal in AML. Disease heterogeneity based both on biological features as well as on patient characteristics such as age, exposure to prior to anti-cancer chemotherapy and co-morbidities play a role in an allowing the physician to predict which patient has a greater or lesser chance to be cured after a diagnosis of acute myeloid leukemia. Cure rates range from 95% in younger patients with non-high-risk acute promyelocytic leukemia to essentially zero in older adults with intrinsically resistant biologies such as complex karyotype and/or TP53 mutations. One unifying feature of all AMLs, however, is the notion that whatever initial therapy is used, while possible to eradicate all morphological evidence of disease in a sizeable fraction of patients, an initial cycle (or two) is not sufficient to yield a low enough disease burden to prevent eventual relapse. Thus, the application of additional chemotherapy after the initial complete remission is received (post-remission therapy generally or consolidation therapy if a myelointense approach is used) is absolutely required for the patient to have a reasonable chance at cure. The widely accepted principle of the need to provide post-remission therapy leads to multiple controversies pertaining to the appropriate intensity, drug choice, and duration of exposure to consolidation chemotherapy, which can range from repetitive cycles of non-intensive therapy, up to and including a myeloblative allogeneic stem cell transplant. In this review, both the principles and the individual strategies that can be used once remission is achieved, will be examined.
{"title":"Consolidation chemotherapy in AML: Are we playing with a full deck of cards?","authors":"Richard M. Stone","doi":"10.1016/j.beha.2022.101408","DOIUrl":"10.1016/j.beha.2022.101408","url":null,"abstract":"<div><p><span><span><span>The safe diminution of leukemic cell numbers to a level such that the patient will not succumb to their disease has been an achievable, yet often elusive goal in AML. Disease heterogeneity based both on biological features as well as on </span>patient characteristics such as age, exposure to prior to anti-cancer chemotherapy and co-morbidities play a role in an allowing the physician to predict which patient has a greater or lesser chance to be cured after a diagnosis of </span>acute myeloid leukemia<span><span>. Cure rates range from 95% in younger patients with non-high-risk acute promyelocytic leukemia to essentially zero in older adults with intrinsically resistant biologies such as complex </span>karyotype and/or </span></span><em>TP53</em><span><span> mutations. One unifying feature of all AMLs, however, is the notion that whatever initial therapy is used, while possible to eradicate all morphological evidence of disease in a sizeable fraction of patients, an initial cycle (or two) is not sufficient to yield a low enough disease burden<span> to prevent eventual relapse. Thus, the application of additional chemotherapy after the initial complete remission is received (post-remission therapy generally or consolidation therapy if a myelointense approach is used) is absolutely required for the patient to have a reasonable chance at cure. The widely accepted principle of the need to provide post-remission therapy leads to multiple controversies pertaining to the appropriate intensity, drug choice, and duration of exposure to consolidation chemotherapy, which can range from repetitive cycles of non-intensive therapy, up to and including a myeloblative allogeneic </span></span>stem cell transplant. In this review, both the principles and the individual strategies that can be used once remission is achieved, will be examined.</span></p></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"35 4","pages":"Article 101408"},"PeriodicalIF":2.1,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10473779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01DOI: 10.1016/j.beha.2022.101415
Hetty E. Carraway , Daniel A. Pollyea , Eytan M. Stein
The advances and progress in the understanding and management of acute leukemia and myelodysplasia continue to occur at an exponential rate. While this has led to more therapy options, clinicians and researchers are now facing more challenges in terms of clinical decision-making and more unanswered questions. This paper has outlined some conundrums in acute leukemia and myelodysplasia, and the efforts that are underway to address these.
{"title":"Recent progress in acute leukemia and myelodysplasia","authors":"Hetty E. Carraway , Daniel A. Pollyea , Eytan M. Stein","doi":"10.1016/j.beha.2022.101415","DOIUrl":"10.1016/j.beha.2022.101415","url":null,"abstract":"<div><p>The advances and progress in the understanding and management of acute leukemia and myelodysplasia continue to occur at an exponential rate. While this has led to more therapy options, clinicians and researchers are now facing more challenges in terms of clinical decision-making and more unanswered questions. This paper has outlined some conundrums in acute leukemia and myelodysplasia, and the efforts that are underway to address these.</p></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"35 4","pages":"Article 101415"},"PeriodicalIF":2.1,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10473775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01DOI: 10.1016/j.beha.2022.101405
Rafael Bejar
Evaluating response to treatment in MDS represents a major challenge due to its associated complexity and heterogeneity. Although response criteria have been proposed by the IWG and revised on several occasions, these criteria have limitations. This review has outlined some refinements that can be used to improve response assessment and to ensure the identification of clinically meaningful endpoints.
{"title":"How can we improve response assessments in MDS? Strategies to improve response assessment in MDS treatment paradigms","authors":"Rafael Bejar","doi":"10.1016/j.beha.2022.101405","DOIUrl":"10.1016/j.beha.2022.101405","url":null,"abstract":"<div><p>Evaluating response to treatment in MDS represents a major challenge due to its associated complexity and heterogeneity. Although response criteria have been proposed by the IWG and revised on several occasions, these criteria have limitations. This review has outlined some refinements that can be used to improve response assessment and to ensure the identification of clinically meaningful endpoints.</p></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"35 4","pages":"Article 101405"},"PeriodicalIF":2.1,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521692622000603/pdfft?md5=9bc84f65f51306c6fdf8d51271a2e202&pid=1-s2.0-S1521692622000603-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10762651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-01DOI: 10.1016/j.beha.2022.101402
Ayesha Butt , Doruk Erkan , Alfred Ian Lee
Antiphospholipid syndrome and the coagulopathy of COVID-19 share many pathophysiologic features, including endotheliopathy, hypercoagulability, and activation of platelets, complement pathways, and neutrophil extracellular traps, all acting in concert via a model of immunothrombosis. Antiphospholipid antibody production in COVID-19 is common, with 50% of COVID-19 patients being positive for lupus anticoagulant in some studies, and with non-Sapporo criteria antiphospholipid antibodies being prevalent as well. The biological significance of antiphospholipid antibodies in COVID-19 is uncertain, as such antibodies are usually transient, and studies examining clinical outcomes in COVID-19 patients with and without antiphospholipid antibodies have yielded conflicting results. In this review, we explore the biology of antiphospholipid antibodies in COVID-19 and other infections and discuss mechanisms of thrombogenesis in antiphospholipid syndrome and parallels with COVID-19 coagulopathy. In addition, we review the existing literature on safety of COVID-19 vaccination in patients with antiphospholipid antibodies and antiphospholipid syndrome.
{"title":"COVID-19 and antiphospholipid antibodies","authors":"Ayesha Butt , Doruk Erkan , Alfred Ian Lee","doi":"10.1016/j.beha.2022.101402","DOIUrl":"10.1016/j.beha.2022.101402","url":null,"abstract":"<div><p>Antiphospholipid syndrome and the coagulopathy of COVID-19 share many pathophysiologic features, including endotheliopathy, hypercoagulability, and activation of platelets, complement pathways, and neutrophil extracellular traps, all acting in concert via a model of immunothrombosis. Antiphospholipid antibody production in COVID-19 is common, with 50% of COVID-19 patients being positive for lupus anticoagulant in some studies, and with non-Sapporo criteria antiphospholipid antibodies being prevalent as well. The biological significance of antiphospholipid antibodies in COVID-19 is uncertain, as such antibodies are usually transient, and studies examining clinical outcomes in COVID-19 patients with and without antiphospholipid antibodies have yielded conflicting results. In this review, we explore the biology of antiphospholipid antibodies in COVID-19 and other infections and discuss mechanisms of thrombogenesis in antiphospholipid syndrome and parallels with COVID-19 coagulopathy. In addition, we review the existing literature on safety of COVID-19 vaccination in patients with antiphospholipid antibodies and antiphospholipid syndrome.</p></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"35 3","pages":"Article 101402"},"PeriodicalIF":2.1,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9568270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9549699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-01DOI: 10.1016/j.beha.2022.101377
Heng Zhang , Qifang Lao , Jue Zhang , Jieqing Zhu
Severe acute respiratory disease coronavirus 2 (SARS-COV-2) first emerged in Wuhan, China, in December 2019 and has caused a global pandemic of a scale unprecedented in the modern era. People infected with SARS-CoV-2 can be asymptomatic, moderate symptomatic or develop severe COVID-19. Other than the typical acute respiratory distress syndrome (ARDS), patients with moderate or severe COVID-19 also develop a distinctive systemic coagulopathy, known as COVID-19-associated coagulopathy (CAC), which is different from sepsis-related forms of disseminated intravascular coagulation (DIC). Endotheliopathy or endotheliitis are other unique features of CAC. The endothelial cell perturbation can further increase the risk of thrombotic events in COVID-19 patients. In this review, we will summarize the current knowledge on COVID-19 coagulopathy and the possible mechanisms for the condition. We also discuss the results of clinical trials testing methods for mitigating thrombosis events in COVID-19 patients.
{"title":"Coagulopathy in COVID-19 and anticoagulation clinical trials","authors":"Heng Zhang , Qifang Lao , Jue Zhang , Jieqing Zhu","doi":"10.1016/j.beha.2022.101377","DOIUrl":"10.1016/j.beha.2022.101377","url":null,"abstract":"<div><p>Severe acute respiratory disease coronavirus 2 (SARS-COV-2) first emerged in Wuhan, China, in December 2019 and has caused a global pandemic of a scale unprecedented in the modern era. People infected with SARS-CoV-2 can be asymptomatic, moderate symptomatic or develop severe COVID-19. Other than the typical acute respiratory distress syndrome (ARDS), patients with moderate or severe COVID-19 also develop a distinctive systemic coagulopathy, known as COVID-19-associated coagulopathy (CAC), which is different from sepsis-related forms of disseminated intravascular coagulation (DIC). Endotheliopathy or endotheliitis are other unique features of CAC. The endothelial cell perturbation can further increase the risk of thrombotic events in COVID-19 patients. In this review, we will summarize the current knowledge on COVID-19 coagulopathy and the possible mechanisms for the condition. We also discuss the results of clinical trials testing methods for mitigating thrombosis events in COVID-19 patients.</p></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"35 3","pages":"Article 101377"},"PeriodicalIF":2.1,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9395291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9800898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-01DOI: 10.1016/j.beha.2022.101376
Martha M.S. Sim , Jeremy P. Wood
Coronavirus Disease 2019 (COVID-19) has been widely associated with increased thrombotic risk, with many different proposed mechanisms. One such mechanism is acquired deficiency of protein S (PS), a plasma protein that regulates coagulation and inflammatory processes, including complement activation and efferocytosis. Acquired PS deficiency is common in patients with severe viral infections and has been reported in multiple studies of COVID-19. This deficiency may be caused by consumption, degradation, or clearance of the protein, by decreased synthesis, or by binding of PS to other plasma proteins, which block its anticoagulant activity. Here, we review the functions of PS, the evidence of acquired PS deficiency in COVID-19 patients, the potential mechanisms of PS deficiency, and the evidence that those mechanisms may be occurring in COVID-19.
{"title":"Dysregulation of Protein S in COVID-19","authors":"Martha M.S. Sim , Jeremy P. Wood","doi":"10.1016/j.beha.2022.101376","DOIUrl":"10.1016/j.beha.2022.101376","url":null,"abstract":"<div><p>Coronavirus Disease 2019 (COVID-19) has been widely associated with increased thrombotic risk, with many different proposed mechanisms. One such mechanism is acquired deficiency of protein S (PS), a plasma protein that regulates coagulation and inflammatory processes, including complement activation and efferocytosis. Acquired PS deficiency is common in patients with severe viral infections and has been reported in multiple studies of COVID-19. This deficiency may be caused by consumption, degradation, or clearance of the protein, by decreased synthesis, or by binding of PS to other plasma proteins, which block its anticoagulant activity. Here, we review the functions of PS, the evidence of acquired PS deficiency in COVID-19 patients, the potential mechanisms of PS deficiency, and the evidence that those mechanisms may be occurring in COVID-19.</p></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":"35 3","pages":"Article 101376"},"PeriodicalIF":2.1,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9395234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9578815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}