Pub Date : 2023-06-29DOI: 10.3389/frhem.2023.1205941
Christian Kjellander, E. Hernlund, M. Ivergård, A. Svedbom, T. Dibbern, A. Stenling, F. Sjöö, S. Vertuani, A. Glenthøj, H. Cherif
Introduction Sickle cell disease (SCD) describes a group of inherited disorders of hemoglobin. Globally, SCD occurs in approximately 300,000-400,000 births annually and is most prevalent in malaria-endemic countries. However, migration has impacted the epidemiology of SCD but data on the matter are scarce. The objective of this study was to describe the epidemiology, treatment uptake, and economic burden of SCD in Sweden, a country with substantial immigration over the last decades. Methods This nationwide retrospective observational registry cohort study identified patients with SCD from 2001 to 2018 and followed them from 2006 to 2018. Using data from high-quality population-based Swedish registers, we estimated prevalence, treatment uptake, and SCD-related health care resource use, sick leave and disability pension. Results Between 2006 and 2018 the number of patients with SCD increased from 504 to 670; inpatient hospital stays and outpatient visits increased by 200% and 300%, respectively. Patients with pain crises had approximately twice the number of inpatient episodes and outpatient visit per year, and had higher productivity losses compared to patients without crises. Conclusion In an era of emerging treatments for SCD, we have, to the best of our knowledge, for the first time comprehensively described epidemiological and economic aspects of SCD in a country where the disease is still rare and not well recognized by the healthcare system.
{"title":"Economic burden of sickle cell disease in Sweden: a population-based national register study with 13 years follow up","authors":"Christian Kjellander, E. Hernlund, M. Ivergård, A. Svedbom, T. Dibbern, A. Stenling, F. Sjöö, S. Vertuani, A. Glenthøj, H. Cherif","doi":"10.3389/frhem.2023.1205941","DOIUrl":"https://doi.org/10.3389/frhem.2023.1205941","url":null,"abstract":"Introduction Sickle cell disease (SCD) describes a group of inherited disorders of hemoglobin. Globally, SCD occurs in approximately 300,000-400,000 births annually and is most prevalent in malaria-endemic countries. However, migration has impacted the epidemiology of SCD but data on the matter are scarce. The objective of this study was to describe the epidemiology, treatment uptake, and economic burden of SCD in Sweden, a country with substantial immigration over the last decades. Methods This nationwide retrospective observational registry cohort study identified patients with SCD from 2001 to 2018 and followed them from 2006 to 2018. Using data from high-quality population-based Swedish registers, we estimated prevalence, treatment uptake, and SCD-related health care resource use, sick leave and disability pension. Results Between 2006 and 2018 the number of patients with SCD increased from 504 to 670; inpatient hospital stays and outpatient visits increased by 200% and 300%, respectively. Patients with pain crises had approximately twice the number of inpatient episodes and outpatient visit per year, and had higher productivity losses compared to patients without crises. Conclusion In an era of emerging treatments for SCD, we have, to the best of our knowledge, for the first time comprehensively described epidemiological and economic aspects of SCD in a country where the disease is still rare and not well recognized by the healthcare system.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129575751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-26DOI: 10.3389/frhem.2023.1203369
R. Bergantim, S. Chacim, A. Monteiro, A. M. Macedo, G. Rodrigues, M. G. da Silva
Clinical features of Waldenström Macroglobulinemia (WM) are variable, often leading to heterogeneous decisions regarding patients’ diagnosis, risk stratification, and treatment. This study assessed the agreement rates on WM diagnosis, risk stratification, and active treatment strategies to capture how this heterogeneity may influence national practices among hematologists. A two-round Delphi-like Panel with 22 national hematologists experienced in WM was conducted online, where 33 statements were classified using a 4-point Likert scale. For each statement, the consensus level was set at 70% for “fully agree/disagree”; the majority level was defined as >70% in agreement or disagreement. After two rounds, no statements were categorized as consensus, and 15 out of 33 failed to obtain a qualified majority. Globally, the experts could not reach a qualified majority in approximately half of the sentences from each category (diagnosis, risk assessment, and therapeutic decision), indicating that contradictory opinions are transversal to all the topics involving WM. A lack of consensus in diagnosing and managing WM among Portuguese hematologists became evident. These results illustrate heterogeneity in clinical practices, and future research initiatives should be considered to improve and reinforce accepted guidelines for diagnosing, assessing, and treating WM patients.
{"title":"Waldenström Macroglobulinemia diagnosis, risk assessment and treatment in Portugal – results from a Delphi-like Panel","authors":"R. Bergantim, S. Chacim, A. Monteiro, A. M. Macedo, G. Rodrigues, M. G. da Silva","doi":"10.3389/frhem.2023.1203369","DOIUrl":"https://doi.org/10.3389/frhem.2023.1203369","url":null,"abstract":"Clinical features of Waldenström Macroglobulinemia (WM) are variable, often leading to heterogeneous decisions regarding patients’ diagnosis, risk stratification, and treatment. This study assessed the agreement rates on WM diagnosis, risk stratification, and active treatment strategies to capture how this heterogeneity may influence national practices among hematologists. A two-round Delphi-like Panel with 22 national hematologists experienced in WM was conducted online, where 33 statements were classified using a 4-point Likert scale. For each statement, the consensus level was set at 70% for “fully agree/disagree”; the majority level was defined as >70% in agreement or disagreement. After two rounds, no statements were categorized as consensus, and 15 out of 33 failed to obtain a qualified majority. Globally, the experts could not reach a qualified majority in approximately half of the sentences from each category (diagnosis, risk assessment, and therapeutic decision), indicating that contradictory opinions are transversal to all the topics involving WM. A lack of consensus in diagnosing and managing WM among Portuguese hematologists became evident. These results illustrate heterogeneity in clinical practices, and future research initiatives should be considered to improve and reinforce accepted guidelines for diagnosing, assessing, and treating WM patients.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"187 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133670427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-20DOI: 10.3389/frhem.2023.1187681
G. Forni, G. Grazzini, J. Boudreaux, V. Agostini, L. Omert
Beta thalassemia (β-thalassemia) is part of a group of inherited hemoglobinopathies caused by a mutation in the beta globin gene, leading to minimal functional hemoglobin and resulting in damaged red blood cells and anemia. β-Thalassemia is most common in the Mediterranean region, South-East Asia, the Indian subcontinent, and the Middle East. Many of these regions include low- and middle-income countries where there are significant unmet needs in the adequate care and management of thalassemia. Patients with transfusion-dependent β-thalassemia, the most severe form of the disease, require regular blood transfusions. Chronic transfusions are often accompanied by iron chelation therapy to manage ferritin levels. Complications caused by transfusions and iron overload are only partially addressed by current treatment strategies, which negatively affect the quality of life of patients with transfusion-dependent β-thalassemia. Until curative modalities become available for all patients worldwide, methods of optimizing supportive treatments are needed to reduce the symptoms of ineffective erythropoiesis; minimize transfusion-related reactions and side effects; reduce rates of alloimmunization and transfusion-transmitted infections; and to reduce the psychosocial burden on both patients and their caregivers. This review aims to provide an overview and comparison of the ways transfusion-dependent β-thalassemia is identified and treated in different geographic regions, to assess unmet needs specific to these regions, and to discuss how therapies currently in development may improve care.
{"title":"Global burden and unmet needs in the treatment of transfusion-dependent β-thalassemia","authors":"G. Forni, G. Grazzini, J. Boudreaux, V. Agostini, L. Omert","doi":"10.3389/frhem.2023.1187681","DOIUrl":"https://doi.org/10.3389/frhem.2023.1187681","url":null,"abstract":"Beta thalassemia (β-thalassemia) is part of a group of inherited hemoglobinopathies caused by a mutation in the beta globin gene, leading to minimal functional hemoglobin and resulting in damaged red blood cells and anemia. β-Thalassemia is most common in the Mediterranean region, South-East Asia, the Indian subcontinent, and the Middle East. Many of these regions include low- and middle-income countries where there are significant unmet needs in the adequate care and management of thalassemia. Patients with transfusion-dependent β-thalassemia, the most severe form of the disease, require regular blood transfusions. Chronic transfusions are often accompanied by iron chelation therapy to manage ferritin levels. Complications caused by transfusions and iron overload are only partially addressed by current treatment strategies, which negatively affect the quality of life of patients with transfusion-dependent β-thalassemia. Until curative modalities become available for all patients worldwide, methods of optimizing supportive treatments are needed to reduce the symptoms of ineffective erythropoiesis; minimize transfusion-related reactions and side effects; reduce rates of alloimmunization and transfusion-transmitted infections; and to reduce the psychosocial burden on both patients and their caregivers. This review aims to provide an overview and comparison of the ways transfusion-dependent β-thalassemia is identified and treated in different geographic regions, to assess unmet needs specific to these regions, and to discuss how therapies currently in development may improve care.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"94 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129808093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-20DOI: 10.3389/frhem.2023.1171991
D. Derudas, S. Massidda, M. P. Simula, D. Dessì, S. Usai, G. Longhitano, Daniela Ibba, Loredana Aracu, M. Atzori, G. La Nasa
Background Non-Hodgkin’s lymphoma (NHL) and Hodgkin’s lymphoma (HL) are two of the most common hematologic diseases that require an infusion of immunochemotherapies in conjunction with radiotherapy, often in an outpatient setting. For relapsed/refractory disease, autologous peripheral hematopoietic stem cell transplantation and sometimes allogeneic transplantation (HSCT) are considered standard treatment options. Recently, chimeric antigen receptor (CAR) T cells and bispecific antibodies have emerged as an important and effective option for the treatment of relapsed/refractory patients. These medical approaches deserve effective, safe, and durable vascular access, especially for the ambulatory population undergoing discontinuous treatment associated with high rates of complications and life-threatening toxicities. Peripherally inserted central catheters (PICCs) are vascular devices with an intermediate-to-long-term lifespan that are inserted ultrasonically into a peripheral brachial vein. Their ease of insertion by trained nurses and low rate of catheter-related infectious and thrombotic complications make them ideal devices for treating oncology and hematology patients. Purpose In this study, we aim to demonstrate that PICCs are an essential tool for the treatment of HL and NHL patients in terms of efficiency and safety Methods and results From March 2007 to June 2020, 316 PICC implantations were performed by our PICC team in 276 HL patients and 363 PICC in 322 NHL patients. The total lifespan of the PICCs was 50,660 days in HL and 43,919 days in NHL patients. Most PICCs were removed at the end of therapy, and the rate of mechanical complications was low. Only one and four episodes of confirmed PICC-related catheter-related bloodstream infections (CRBSIs) (0.3%; 0.02/1,000 days/PICC and 1.2%; 0.07/1,000 days/PICC) were recorded in HL and NHL patients, respectively. There were only 11 (3.6%; 0.25/1,000 days/PICC) and nine (2.6%; 0.17/1,000 days/PICC) episodes of symptomatic PICC-related thrombotic complications in HL and NHL patients, respectively, without removal. Conclusion Our data indicate that the PICC can be considered the device of choice for treating HL and NHL patients because it is easy to insert, safe to use, long-lasting, and has a low complication rate, especially in the outpatient setting.
{"title":"Peripherally inserted central catheter insertion and management in Hodgkin and non-Hodgkin lymphomas: a 13-year monocentric experience","authors":"D. Derudas, S. Massidda, M. P. Simula, D. Dessì, S. Usai, G. Longhitano, Daniela Ibba, Loredana Aracu, M. Atzori, G. La Nasa","doi":"10.3389/frhem.2023.1171991","DOIUrl":"https://doi.org/10.3389/frhem.2023.1171991","url":null,"abstract":"Background Non-Hodgkin’s lymphoma (NHL) and Hodgkin’s lymphoma (HL) are two of the most common hematologic diseases that require an infusion of immunochemotherapies in conjunction with radiotherapy, often in an outpatient setting. For relapsed/refractory disease, autologous peripheral hematopoietic stem cell transplantation and sometimes allogeneic transplantation (HSCT) are considered standard treatment options. Recently, chimeric antigen receptor (CAR) T cells and bispecific antibodies have emerged as an important and effective option for the treatment of relapsed/refractory patients. These medical approaches deserve effective, safe, and durable vascular access, especially for the ambulatory population undergoing discontinuous treatment associated with high rates of complications and life-threatening toxicities. Peripherally inserted central catheters (PICCs) are vascular devices with an intermediate-to-long-term lifespan that are inserted ultrasonically into a peripheral brachial vein. Their ease of insertion by trained nurses and low rate of catheter-related infectious and thrombotic complications make them ideal devices for treating oncology and hematology patients. Purpose In this study, we aim to demonstrate that PICCs are an essential tool for the treatment of HL and NHL patients in terms of efficiency and safety Methods and results From March 2007 to June 2020, 316 PICC implantations were performed by our PICC team in 276 HL patients and 363 PICC in 322 NHL patients. The total lifespan of the PICCs was 50,660 days in HL and 43,919 days in NHL patients. Most PICCs were removed at the end of therapy, and the rate of mechanical complications was low. Only one and four episodes of confirmed PICC-related catheter-related bloodstream infections (CRBSIs) (0.3%; 0.02/1,000 days/PICC and 1.2%; 0.07/1,000 days/PICC) were recorded in HL and NHL patients, respectively. There were only 11 (3.6%; 0.25/1,000 days/PICC) and nine (2.6%; 0.17/1,000 days/PICC) episodes of symptomatic PICC-related thrombotic complications in HL and NHL patients, respectively, without removal. Conclusion Our data indicate that the PICC can be considered the device of choice for treating HL and NHL patients because it is easy to insert, safe to use, long-lasting, and has a low complication rate, especially in the outpatient setting.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116782310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-30DOI: 10.3389/frhem.2023.1160049
Y. Jin, F. Ren, Shuyan Wang, Jin Xu, Ying-Hua Wu, Jin-fen Tang, Jianfeng Xu
Large granular lymphocytic leukemia (LGLL) is a clonal lymphoproliferative disease with a slow course and considerable difficulties in correct diagnosis and therapy. T-LGLL is the most prevalent subtype of LGLL, accounting for approximately 85%. T-LGLL co-existence with solid malignancies is relatively rare. CD20-positive T-cell neoplasm is a rare disease in clinics. In this study, we report a case of CD20-positive T-LGLL with renal cell carcinoma (RCC) that was eventually diagnosed by splenectomy and nephrectomy. The accumulation of cases will contribute to diagnosing and treating CD20-positive T-LGLL complicated with solid tumors.
{"title":"Case Report: A rare case of CD20-positive T-cell large granular lymphocyte leukemia with renal cell carcinoma: a challenging diagnosis","authors":"Y. Jin, F. Ren, Shuyan Wang, Jin Xu, Ying-Hua Wu, Jin-fen Tang, Jianfeng Xu","doi":"10.3389/frhem.2023.1160049","DOIUrl":"https://doi.org/10.3389/frhem.2023.1160049","url":null,"abstract":"Large granular lymphocytic leukemia (LGLL) is a clonal lymphoproliferative disease with a slow course and considerable difficulties in correct diagnosis and therapy. T-LGLL is the most prevalent subtype of LGLL, accounting for approximately 85%. T-LGLL co-existence with solid malignancies is relatively rare. CD20-positive T-cell neoplasm is a rare disease in clinics. In this study, we report a case of CD20-positive T-LGLL with renal cell carcinoma (RCC) that was eventually diagnosed by splenectomy and nephrectomy. The accumulation of cases will contribute to diagnosing and treating CD20-positive T-LGLL complicated with solid tumors.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"23 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124030260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-15DOI: 10.3389/frhem.2023.1180156
G. Sayed, S. Elkourashy, M. Alnajjar, Naela Al Mallahi, Shehab Fareed
Immune thrombocytopenia (ITP) affects 0.1 to 1 per 1000 pregnancies and severe ITP, with platelet counts less than 10,000/µL, is difficult to manage. Two pregnant patients with ITP who were successfully treated with thrombopoietin receptor agonists (TPO-RA) at a tertiary institution are discussed. The first patient had chronic ITP, achieved complete remission with eltrombopag, but was resistant to intravenous immunoglobulin (IVIG) and steroids in her second pregnancy. Romiplostim was effective, and she had an uneventful cesarean section. The second patient responded well to eltrombopag at 35 weeks of gestation and had a vaginal delivery. ITP in pregnancy is managed based on clinical expertise, and TPO-RA use during pregnancy is largely from case reports. For severe ITP, eltrombopag or romiplostim from around 34 weeks can be used if other treatments fail, with a goal of achieving a platelet count of over 80,000/µL. The mother’s response to medication may vary in different pregnancies. Induction of labor may be appropriate in some cases.
{"title":"Case Report: Thrombopoietin receptor agonists in resistant thrombocytopenia in pregnancy: a case series and review of literature","authors":"G. Sayed, S. Elkourashy, M. Alnajjar, Naela Al Mallahi, Shehab Fareed","doi":"10.3389/frhem.2023.1180156","DOIUrl":"https://doi.org/10.3389/frhem.2023.1180156","url":null,"abstract":"Immune thrombocytopenia (ITP) affects 0.1 to 1 per 1000 pregnancies and severe ITP, with platelet counts less than 10,000/µL, is difficult to manage. Two pregnant patients with ITP who were successfully treated with thrombopoietin receptor agonists (TPO-RA) at a tertiary institution are discussed. The first patient had chronic ITP, achieved complete remission with eltrombopag, but was resistant to intravenous immunoglobulin (IVIG) and steroids in her second pregnancy. Romiplostim was effective, and she had an uneventful cesarean section. The second patient responded well to eltrombopag at 35 weeks of gestation and had a vaginal delivery. ITP in pregnancy is managed based on clinical expertise, and TPO-RA use during pregnancy is largely from case reports. For severe ITP, eltrombopag or romiplostim from around 34 weeks can be used if other treatments fail, with a goal of achieving a platelet count of over 80,000/µL. The mother’s response to medication may vary in different pregnancies. Induction of labor may be appropriate in some cases.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"6 11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122108620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-10DOI: 10.3389/frhem.2023.1151744
C. Phillips, Christa Krupski, Ruby Khoury, C. Dandoy, A. Nelson, Thomas J. Galletta, Angela Faulhaber, S. Davies, Jeremy D. Rubinstein
Background Tisagenlecleucel (tisa-cel) is increasingly being used in hematopoietic stem cell transplantation (HSCT)-naive patients. Outcomes for HSCT patients following chimeric antigen receptor (CAR) T-cell therapy demonstrate low relapse rates; however, a significant number of patients who receive tisa-cel can maintain remission without an HSCT. Multiple factors are considered when choosing whether or not to proceed with HSCT. Methods We retrospectively reviewed 31 patients who had received tisa-cel at our institution and who were transplant naive at the time of infusion. The aim was to determine the rate and timing of consolidative HSCT, factors that led to HSCT, and overall survival. Results Three of the 31 patients were non-responders to tisa-cel and ultimately died of disease. Twelve of the 28 responders remain alive with no evidence of disease (NED) without subsequent therapy. Of these patients, 5 of the 12 had isolated extramedullary acute lymphoblastic leukemia (ALL) (CNS, n = 4; testes, n = 1) and 2 of the 12 had Down syndrome, so no transplantation was planned. In the remaining 5 of 12 patients, close monitoring for signs of relapsed ALL, using serial next-generation sequencing (NGS) minimal residual disease (MRD) and lymphocyte subpopulation measurements, was performed. Owing to continued negative findings, no HSCT was chosen. Ultimately, 43% (12 of 28) of responders proceeded to HSCT, with three receiving tisa-cel as a planned bridge to HSCT as a result of CD22 negativity and/or provider preference (two patients survived with NED); three proceeded to HSCT as a result of early loss of B-cell aplasia (BCA) (all survived with NED); and six had salvage HSCT following relapse (three patients survived with NED and one patient was alive in relapse). Three of the 28 patients died following relapse post CAR T-cell therapy without HSCT. The final patient had an isolated extramedullary soft tissue CD19+ relapse 1 year post tisa-cel treatment, and is now NED without HSCT and persistent BCA. Conclusion Close monitoring of NGS results and BCA, as well as consideration of the site of the disease, can spare a subset of patients HSCT with the maintenance of leukemia-free remission, while still allowing for later HSCT in others. In our cohort, only a small subset of patients was unable to proceed to HSCT following relapse post-CAR T-cell therapy.
Tisagenlecleucel(组织细胞)越来越多地用于造血干细胞移植(HSCT)初治患者。嵌合抗原受体(CAR) t细胞治疗后的HSCT患者复发率低;然而，相当一部分接受组织细胞移植的患者在不接受造血干细胞移植的情况下也能维持缓解。在选择是否进行HSCT时，要考虑多种因素。方法回顾性分析31例在本院接受组织细胞移植并在输注时进行移植的患者。目的是确定巩固性HSCT的发生率和时间，导致HSCT的因素和总生存率。结果31例患者中有3例对组织细胞治疗无反应，最终死于疾病。在没有后续治疗的情况下，28例应答者中有12例存活且无疾病迹象(NED)。在这些患者中，12例中有5例患有分离性髓外急性淋巴细胞白血病(ALL) (CNS, n = 4;12例患者中有2例患有唐氏综合症，因此没有移植计划。在12例患者中的其余5例中，使用串行下一代测序(NGS)最小残留病(MRD)和淋巴细胞亚群测量密切监测复发性ALL的迹象。由于持续的阴性结果，没有选择HSCT。最终，43%(28人中有12人)的应答者进行了HSCT治疗，其中3人接受了组织细胞治疗，因为CD22阴性和/或提供者偏好(2例患者存活于NED);3例由于早期b细胞发育不全(BCA)的丧失而进行了HSCT(所有患者都存活于NED);6例患者复发后进行了补救性HSCT(3例患者因NED存活，1例患者复发后存活)。28例患者中有3例在CAR - t细胞治疗后复发死亡。最后一位患者在组织细胞治疗1年后出现了孤立的髓外软组织CD19+复发，现在是NED，没有HSCT和持续性BCA。结论:密切监测NGS结果和BCA，并考虑疾病的部位，可以避免一部分患者进行HSCT，维持无白血病缓解，同时仍然允许其他患者进行后续HSCT。在我们的队列中，只有一小部分患者在car - t细胞治疗后复发后无法进行HSCT。
{"title":"Post CAR T-cell therapy outcomes and management in HSCT-naive patients: a single-center experience","authors":"C. Phillips, Christa Krupski, Ruby Khoury, C. Dandoy, A. Nelson, Thomas J. Galletta, Angela Faulhaber, S. Davies, Jeremy D. Rubinstein","doi":"10.3389/frhem.2023.1151744","DOIUrl":"https://doi.org/10.3389/frhem.2023.1151744","url":null,"abstract":"Background Tisagenlecleucel (tisa-cel) is increasingly being used in hematopoietic stem cell transplantation (HSCT)-naive patients. Outcomes for HSCT patients following chimeric antigen receptor (CAR) T-cell therapy demonstrate low relapse rates; however, a significant number of patients who receive tisa-cel can maintain remission without an HSCT. Multiple factors are considered when choosing whether or not to proceed with HSCT. Methods We retrospectively reviewed 31 patients who had received tisa-cel at our institution and who were transplant naive at the time of infusion. The aim was to determine the rate and timing of consolidative HSCT, factors that led to HSCT, and overall survival. Results Three of the 31 patients were non-responders to tisa-cel and ultimately died of disease. Twelve of the 28 responders remain alive with no evidence of disease (NED) without subsequent therapy. Of these patients, 5 of the 12 had isolated extramedullary acute lymphoblastic leukemia (ALL) (CNS, n = 4; testes, n = 1) and 2 of the 12 had Down syndrome, so no transplantation was planned. In the remaining 5 of 12 patients, close monitoring for signs of relapsed ALL, using serial next-generation sequencing (NGS) minimal residual disease (MRD) and lymphocyte subpopulation measurements, was performed. Owing to continued negative findings, no HSCT was chosen. Ultimately, 43% (12 of 28) of responders proceeded to HSCT, with three receiving tisa-cel as a planned bridge to HSCT as a result of CD22 negativity and/or provider preference (two patients survived with NED); three proceeded to HSCT as a result of early loss of B-cell aplasia (BCA) (all survived with NED); and six had salvage HSCT following relapse (three patients survived with NED and one patient was alive in relapse). Three of the 28 patients died following relapse post CAR T-cell therapy without HSCT. The final patient had an isolated extramedullary soft tissue CD19+ relapse 1 year post tisa-cel treatment, and is now NED without HSCT and persistent BCA. Conclusion Close monitoring of NGS results and BCA, as well as consideration of the site of the disease, can spare a subset of patients HSCT with the maintenance of leukemia-free remission, while still allowing for later HSCT in others. In our cohort, only a small subset of patients was unable to proceed to HSCT following relapse post-CAR T-cell therapy.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125107446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-03DOI: 10.3389/frhem.2023.1181216
R. Shimizu, Masayuki Yamamoto
GATA1 is an essential master regulator of erythropoiesis and megakaryopoiesis. Accumulating lines of evidence have shown that dynamic changes in GATA1 gene expression levels during erythropoiesis are crucial for proper erythroid differentiation. Since GATA1 is an X-chromosome gene, GATA1 knockout leads to embryonic lethal dyserythropoiesis in male mice, while heterozygous female mice can survive. In the past decade, it has become clear that germline GATA1 gene mutations leading to structural changes in the GATA1 protein are involved in congenital dyserythropoiesis in males. In contrast, decreased GATA1 expression levels, which cause embryonic lethal dyserythropoiesis in male mice, increase the risk of erythroleukemia development in female mice, while female GATA1-knockout mice do not show substantial phenotypic alterations in erythroid or megakaryocyte lineages. In this review, we summarize the recent progress in elucidating the roles of GATA1 in normal and pathogenetic erythropoiesis and discuss the possible mechanisms of pathogenesis of dyserythropoiesis and erythroleukemia.
{"title":"Recent progress in analyses of GATA1 in hematopoietic disorders: a mini-review","authors":"R. Shimizu, Masayuki Yamamoto","doi":"10.3389/frhem.2023.1181216","DOIUrl":"https://doi.org/10.3389/frhem.2023.1181216","url":null,"abstract":"GATA1 is an essential master regulator of erythropoiesis and megakaryopoiesis. Accumulating lines of evidence have shown that dynamic changes in GATA1 gene expression levels during erythropoiesis are crucial for proper erythroid differentiation. Since GATA1 is an X-chromosome gene, GATA1 knockout leads to embryonic lethal dyserythropoiesis in male mice, while heterozygous female mice can survive. In the past decade, it has become clear that germline GATA1 gene mutations leading to structural changes in the GATA1 protein are involved in congenital dyserythropoiesis in males. In contrast, decreased GATA1 expression levels, which cause embryonic lethal dyserythropoiesis in male mice, increase the risk of erythroleukemia development in female mice, while female GATA1-knockout mice do not show substantial phenotypic alterations in erythroid or megakaryocyte lineages. In this review, we summarize the recent progress in elucidating the roles of GATA1 in normal and pathogenetic erythropoiesis and discuss the possible mechanisms of pathogenesis of dyserythropoiesis and erythroleukemia.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114839520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-25DOI: 10.3389/frhem.2023.1150134
Helena Lamptey, Zakaria Seidu, Mary Lopez-Perez, Eric Kyei-Baafour, L. Hviid, G. Adjei, M. Ofori
Background The protective effect of certain haemoglobinopathies, such as HbS, HbC, and α-thalassaemia, against severe malaria has long been established; however, there is only limited and equivocal evidence regarding their impact on asymptomatic parasitaemia. Here, we investigated the effect of HbS, HbC, and α-thalassaemia on asymptomatic P. falciparum parasitaemia and acquired immunity among children in Northern Ghana. Materials and methods A cross-sectional study was conducted among 1,017 healthy children (1-17 years) in 13 malaria-endemic communities in Northern Ghana. The children were screened for structural Hb phenotypes using SickleSCAN, for P. falciparum infection using anti-HRP2 malaria RDT and subsequently confirmed by capillary electrophoresis and PCR, respectively. α-thalassaemia genotyping was done using PCR. Levels of IgG specific for six recombinant malaria antigens (PfCSP, GLURP, MSP3, Pfs230, HB3VAR06, and IT4VAR60) and crude asexual blood-stage antigens were evaluated by ELISA. Results 266 out of the 1,017 participants had either HbAC (18%) or HbAS (8.4%), whereas 35% had α‐thalassaemia. Twenty-five percent and 6% HbAC individuals co-inherited heterozygous and homozygous α-thalassaemia respectively. Similarly, 25% and 10.5% of HbAS co-inherited heterozygous and homozygous α-thalassaemia. Asymptomatic parasitaemia rates were 23%, 24%, and 19% in those with HbAA, HbAC and HbAS, respectively. The overall parasite carriage rates in heterozygous (21%) and homozygous α-thalassaemia (25%) individuals were similar to that of individuals without α-thalassaemia (23%). P. falciparum parasite carriage risk was about three times higher among homozygous α-thalassaemia individuals with HbAC (OR = 2.97; 95% CI 0.83-10.62) and heterozygous carriers with HbAS variants (OR = 2.86; 95% CI 0.85-9.60) compared to the wildtype. In HbAS individuals, IgG levels to IT4VAR60 and HB3VAR06 were significantly lower, whereas anti-CSP levels were higher than in HbAA and HbAC. Conclusions Co-inheritance of HbAS and HbAC with α-thalassaemia increased the risk of asymptomatic parasitaemia, an indication of a negative epistatic effect between these Hb variants. Antibody levels against non-PfEMP1 antigens were slightly higher among HbAS children, but quite similar in all study groups, indicating differences in parasite exposure.
某些血红蛋白疾病，如HbS、HbC和α-地中海贫血，对严重疟疾的保护作用早已确立;然而，关于它们对无症状寄生虫病的影响，只有有限和模棱两可的证据。在这里，我们研究了HbS、HbC和α-地中海贫血对加纳北部儿童无症状恶性疟原虫寄生虫病和获得性免疫的影响。材料和方法在加纳北部13个疟疾流行社区的1,017名健康儿童(1-17岁)中进行了一项横断面研究。使用SickleSCAN筛查儿童Hb结构表型，使用抗hrp2疟疾RDT筛查恶性疟原虫感染，随后分别通过毛细管电泳和PCR确认。采用PCR方法进行α-地中海贫血基因分型。ELISA法检测6种重组疟疾抗原(PfCSP、GLURP、MSP3、Pfs230、HB3VAR06、IT4VAR60)和原始无性血期抗原的IgG特异性水平。结果1017名参与者中有266人患有HbAC(18%)或HbAS(8.4%)，而35%患有α -地中海贫血。25%和6%的HbAC个体分别共遗传杂合型和纯合型α-地中海贫血。同样，25%和10.5%的HbAS共同遗传杂合型和纯合型α-地中海贫血。无症状寄生虫血症发生率在HbAA、HbAC和HbAS患者中分别为23%、24%和19%。杂合子α-地中海贫血个体(21%)和纯合子α-地中海贫血个体(25%)的总体寄生虫携带率与非α-地中海贫血个体(23%)相似。纯合子α-地中海贫血患者携带恶性疟原虫的风险约为HbAC患者的3倍(OR = 2.97;95% CI 0.83-10.62)和HbAS变异的杂合携带者(OR = 2.86;95% CI 0.85-9.60)。HbAS个体IT4VAR60和HB3VAR06的IgG水平明显低于HbAA和HbAC，而抗csp水平高于HbAA和HbAC。结论HbAS和HbAC与α-地中海贫血的共同遗传增加了无症状寄生虫血症的风险，表明这些Hb变体之间存在负的遗传效应。针对非pfemp1抗原的抗体水平在HbAS儿童中略高，但在所有研究组中非常相似，表明寄生虫暴露的差异。
{"title":"Impact of haemoglobinopathies on asymptomatic Plasmodium falciparum infection and naturally acquired immunity among children in Northern Ghana","authors":"Helena Lamptey, Zakaria Seidu, Mary Lopez-Perez, Eric Kyei-Baafour, L. Hviid, G. Adjei, M. Ofori","doi":"10.3389/frhem.2023.1150134","DOIUrl":"https://doi.org/10.3389/frhem.2023.1150134","url":null,"abstract":"Background The protective effect of certain haemoglobinopathies, such as HbS, HbC, and α-thalassaemia, against severe malaria has long been established; however, there is only limited and equivocal evidence regarding their impact on asymptomatic parasitaemia. Here, we investigated the effect of HbS, HbC, and α-thalassaemia on asymptomatic P. falciparum parasitaemia and acquired immunity among children in Northern Ghana. Materials and methods A cross-sectional study was conducted among 1,017 healthy children (1-17 years) in 13 malaria-endemic communities in Northern Ghana. The children were screened for structural Hb phenotypes using SickleSCAN, for P. falciparum infection using anti-HRP2 malaria RDT and subsequently confirmed by capillary electrophoresis and PCR, respectively. α-thalassaemia genotyping was done using PCR. Levels of IgG specific for six recombinant malaria antigens (PfCSP, GLURP, MSP3, Pfs230, HB3VAR06, and IT4VAR60) and crude asexual blood-stage antigens were evaluated by ELISA. Results 266 out of the 1,017 participants had either HbAC (18%) or HbAS (8.4%), whereas 35% had α‐thalassaemia. Twenty-five percent and 6% HbAC individuals co-inherited heterozygous and homozygous α-thalassaemia respectively. Similarly, 25% and 10.5% of HbAS co-inherited heterozygous and homozygous α-thalassaemia. Asymptomatic parasitaemia rates were 23%, 24%, and 19% in those with HbAA, HbAC and HbAS, respectively. The overall parasite carriage rates in heterozygous (21%) and homozygous α-thalassaemia (25%) individuals were similar to that of individuals without α-thalassaemia (23%). P. falciparum parasite carriage risk was about three times higher among homozygous α-thalassaemia individuals with HbAC (OR = 2.97; 95% CI 0.83-10.62) and heterozygous carriers with HbAS variants (OR = 2.86; 95% CI 0.85-9.60) compared to the wildtype. In HbAS individuals, IgG levels to IT4VAR60 and HB3VAR06 were significantly lower, whereas anti-CSP levels were higher than in HbAA and HbAC. Conclusions Co-inheritance of HbAS and HbAC with α-thalassaemia increased the risk of asymptomatic parasitaemia, an indication of a negative epistatic effect between these Hb variants. Antibody levels against non-PfEMP1 antigens were slightly higher among HbAS children, but quite similar in all study groups, indicating differences in parasite exposure.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"40 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125218338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-11DOI: 10.3389/frhem.2023.1040720
D. Kandonga, Raphael Zozimus Sangeda, U. Masamu, Eliah Kazumali, A. Jonathan, M. Msangawale, Winfrida T. Kaihula, Julieth Rwegalulila, Jesca Ondego, H. Tutuba, J. Ndunguru, Emmanuela E Ambrose, B. Kidenya, Mbonea Yonazi, I. Kyomugisha, Wilson Mupfururirwa, Mario Jonas, V. Nembaware, G. Mazandu, A. Kengne, A. Wonkam, J. Makani, E. Balandya
Background Sickle cell disease (SCD) is a severe hereditary form of anemia that contributes between 50% and 80% of under-five mortality in Africa. Eleven thousand babies are born with SCD annually in Tanzania, ranking 4th after Nigeria, the Democratic Republic of Congo and India. The absence of well-described SCD cohorts is a major barrier to health research in SCD in Africa. Objective This paper describes the Sickle Pan African Consortium (SPARCO) database in Tanzania, from the development, design of the study instruments, data collection, analysis of data and management of data quality issues. Methods The SPARCO registry used existing Muhimbili Sickle Cell Cohort (MSC) study case report forms (CRF) and later harmonized data elements from the SickleInAfrica consortium to develop Research Electronic Data Capture (REDCap) instruments. Patients were enrolled through various strategies, including mass screening following media sensitization and health education events during World Sickle Cell Day each June and the SCD awareness month in September. Additional patients were identified through active surveillance of previously participating patients in the MSC. Results Three thousand eight hundred patients were enrolled between October 2017 and May 2021. Of these, 1,946 (51.21%) were males and 1,864 (48.79%) were females. The hemoglobin phenotype distribution was 3,762 (99%) HbSS, 3 (0.08%) HbSC and 35 (0.92%) HbSβ +thalassemia. Hemoglobin levels, admission history, blood transfusion and painful events were recorded from December 2017 to May 2021. Conclusion The Tanzania SPARCO registry will improve healthcare for SCD in Africa through the facilitation of collaborative data-driven research for SCD.
{"title":"Development of the sickle Pan-African research consortium registry in Tanzania: opportunity to harness data science for sickle cell disease","authors":"D. Kandonga, Raphael Zozimus Sangeda, U. Masamu, Eliah Kazumali, A. Jonathan, M. Msangawale, Winfrida T. Kaihula, Julieth Rwegalulila, Jesca Ondego, H. Tutuba, J. Ndunguru, Emmanuela E Ambrose, B. Kidenya, Mbonea Yonazi, I. Kyomugisha, Wilson Mupfururirwa, Mario Jonas, V. Nembaware, G. Mazandu, A. Kengne, A. Wonkam, J. Makani, E. Balandya","doi":"10.3389/frhem.2023.1040720","DOIUrl":"https://doi.org/10.3389/frhem.2023.1040720","url":null,"abstract":"Background Sickle cell disease (SCD) is a severe hereditary form of anemia that contributes between 50% and 80% of under-five mortality in Africa. Eleven thousand babies are born with SCD annually in Tanzania, ranking 4th after Nigeria, the Democratic Republic of Congo and India. The absence of well-described SCD cohorts is a major barrier to health research in SCD in Africa. Objective This paper describes the Sickle Pan African Consortium (SPARCO) database in Tanzania, from the development, design of the study instruments, data collection, analysis of data and management of data quality issues. Methods The SPARCO registry used existing Muhimbili Sickle Cell Cohort (MSC) study case report forms (CRF) and later harmonized data elements from the SickleInAfrica consortium to develop Research Electronic Data Capture (REDCap) instruments. Patients were enrolled through various strategies, including mass screening following media sensitization and health education events during World Sickle Cell Day each June and the SCD awareness month in September. Additional patients were identified through active surveillance of previously participating patients in the MSC. Results Three thousand eight hundred patients were enrolled between October 2017 and May 2021. Of these, 1,946 (51.21%) were males and 1,864 (48.79%) were females. The hemoglobin phenotype distribution was 3,762 (99%) HbSS, 3 (0.08%) HbSC and 35 (0.92%) HbSβ +thalassemia. Hemoglobin levels, admission history, blood transfusion and painful events were recorded from December 2017 to May 2021. Conclusion The Tanzania SPARCO registry will improve healthcare for SCD in Africa through the facilitation of collaborative data-driven research for SCD.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"181 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132702405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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