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}
Pub Date : 2023-03-17DOI: 10.3389/frhem.2023.1127322
A. Tridente, Nina C Dempsey, M. Khalifa, Jacklyn Goddard, K. Shuker, J. Hall, Y. Sorour, J. Wright, S. Webber, G. Mills, J. Snowden
Background Critical care (CC) admission has traditionally been viewed as likely to result in a poor outcome for hematological malignancy (HM) patients. Such a view can have implications for decisions surrounding CC admission. Recent studies have challenged this poor prognostication, however, there still remains limited data to support CC admission and escalation decisions and to elucidate risk factors which independently predict short- and longer-term survival outcomes. Methods We retrospectively analyzed a large cohort of adult HM patients (n=437) admitted to CC over a sixteen-year period, with the specific aim of identifying risk factors present at CC unit admission that could help to predict outcome. We assessed all-cause mortality at CC discharge (CC mortality, primary outcome) and at further time points (hospital discharge and 12-months post-discharge from CC). Single variable and multivariate analyses were performed to identify independent predictors of outcome. Results CC unit and hospital mortality rates were 33.4% (146 patients) and 46.2% (202 patients) respectively. At six-month and one-year follow-up, mortality increased to 59.5% and 67.9% respectively. At single variable adjusted regression analysis, eight factors were associated with CC mortality: APACHE II score, the number of organs supported, requirement for continuous renal replacement therapy (CRRT), cardiovascular support, or respiratory support (invasive and non-invasive), the ratio between arterial partial pressure of oxygen (PaO2) and the inspired oxygen concentration (FiO2) (P/F ratio) on CC admission, and the lowest P/F ratio during CC admission. However, only three factors showed independent predictive capacity for CC outcome at multivariate logistic regression analysis; APACHE II score on admission, requirement for ventilation and lowest P/F ratio. Conclusion One third of HM patients admitted to CC died on the unit and, following admission to CC, approximately one-third of HM patients survived over 1 year. Our data show that, while a diagnosis of HM should not preclude admission of patients who might otherwise benefit from CC support, the prognosis of those with a high APACHE II score upon admission, or those requiring IMV remains poor, despite considerable advances in IMV techniques.
{"title":"Predicting outcomes of hematological malignancy patients admitted to critical care","authors":"A. Tridente, Nina C Dempsey, M. Khalifa, Jacklyn Goddard, K. Shuker, J. Hall, Y. Sorour, J. Wright, S. Webber, G. Mills, J. Snowden","doi":"10.3389/frhem.2023.1127322","DOIUrl":"https://doi.org/10.3389/frhem.2023.1127322","url":null,"abstract":"Background Critical care (CC) admission has traditionally been viewed as likely to result in a poor outcome for hematological malignancy (HM) patients. Such a view can have implications for decisions surrounding CC admission. Recent studies have challenged this poor prognostication, however, there still remains limited data to support CC admission and escalation decisions and to elucidate risk factors which independently predict short- and longer-term survival outcomes. Methods We retrospectively analyzed a large cohort of adult HM patients (n=437) admitted to CC over a sixteen-year period, with the specific aim of identifying risk factors present at CC unit admission that could help to predict outcome. We assessed all-cause mortality at CC discharge (CC mortality, primary outcome) and at further time points (hospital discharge and 12-months post-discharge from CC). Single variable and multivariate analyses were performed to identify independent predictors of outcome. Results CC unit and hospital mortality rates were 33.4% (146 patients) and 46.2% (202 patients) respectively. At six-month and one-year follow-up, mortality increased to 59.5% and 67.9% respectively. At single variable adjusted regression analysis, eight factors were associated with CC mortality: APACHE II score, the number of organs supported, requirement for continuous renal replacement therapy (CRRT), cardiovascular support, or respiratory support (invasive and non-invasive), the ratio between arterial partial pressure of oxygen (PaO2) and the inspired oxygen concentration (FiO2) (P/F ratio) on CC admission, and the lowest P/F ratio during CC admission. However, only three factors showed independent predictive capacity for CC outcome at multivariate logistic regression analysis; APACHE II score on admission, requirement for ventilation and lowest P/F ratio. Conclusion One third of HM patients admitted to CC died on the unit and, following admission to CC, approximately one-third of HM patients survived over 1 year. Our data show that, while a diagnosis of HM should not preclude admission of patients who might otherwise benefit from CC support, the prognosis of those with a high APACHE II score upon admission, or those requiring IMV remains poor, despite considerable advances in IMV techniques.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"175 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134104954","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 : 2023-03-10DOI: 10.3389/frhem.2023.1134837
Kieran D Sahasrabudhe, Weiqiang Zhao, Miriam Berg, B. Bhatnagar
Older patients with acute lymphoblastic leukemia (ALL) have a poor prognosis, with a 5-year overall survival rate of only 10%–20%. This is attributable to patient comorbidities, poor performance status, and high-risk disease biology. The prognosis for patients with relapsed/refractory (R/R) disease remains poor, particularly for patients who are not candidates for therapies targeting CD19 or CD22. Additional treatment options are needed for these patient populations. The patient presented here is a 76-year-old man diagnosed with precursor B-cell ALL with aberrant expression of myeloid markers and lacking significant CD19 or CD22 expression. A 3-year remission was achieved with one cycle of CVP (cyclophosphamide, vincristine, and prednisone) followed by 22 months of maintenance DOMP (dexamethasone, vincristine, methotrexate, and 6-mercaptopurine) prior to relapse. He was then treated with one cycle of salvage CVP, which was complicated by a stroke resulting in hemiparesis. Next-generation sequencing (NGS) was performed on the relapsed bone marrow, which revealed the presence of an R132H mutation in the isocitrate dehydrogenase 1 (IDH1) gene. He was subsequently treated with the IDH1 inhibitor ivosidenib and remained in a second remission for nearly 1 year. IDH1 mutations are present in up to 14% of acute myeloid leukemia (AML) cases but are also seen more rarely in ALL, particularly in cases involving aberrant expression of myeloid markers. Ivosidenib has demonstrated efficacy in patients with IDH1-mutated AML but has not been extensively studied in other hematologic malignancies. This case demonstrates the role of NGS in revealing treatment options in patients with otherwise limited available therapies.
{"title":"Case report: Sustained complete remission with ivosidenib in a patient with relapsed, IDH1-mutated acute leukemia","authors":"Kieran D Sahasrabudhe, Weiqiang Zhao, Miriam Berg, B. Bhatnagar","doi":"10.3389/frhem.2023.1134837","DOIUrl":"https://doi.org/10.3389/frhem.2023.1134837","url":null,"abstract":"Older patients with acute lymphoblastic leukemia (ALL) have a poor prognosis, with a 5-year overall survival rate of only 10%–20%. This is attributable to patient comorbidities, poor performance status, and high-risk disease biology. The prognosis for patients with relapsed/refractory (R/R) disease remains poor, particularly for patients who are not candidates for therapies targeting CD19 or CD22. Additional treatment options are needed for these patient populations. The patient presented here is a 76-year-old man diagnosed with precursor B-cell ALL with aberrant expression of myeloid markers and lacking significant CD19 or CD22 expression. A 3-year remission was achieved with one cycle of CVP (cyclophosphamide, vincristine, and prednisone) followed by 22 months of maintenance DOMP (dexamethasone, vincristine, methotrexate, and 6-mercaptopurine) prior to relapse. He was then treated with one cycle of salvage CVP, which was complicated by a stroke resulting in hemiparesis. Next-generation sequencing (NGS) was performed on the relapsed bone marrow, which revealed the presence of an R132H mutation in the isocitrate dehydrogenase 1 (IDH1) gene. He was subsequently treated with the IDH1 inhibitor ivosidenib and remained in a second remission for nearly 1 year. IDH1 mutations are present in up to 14% of acute myeloid leukemia (AML) cases but are also seen more rarely in ALL, particularly in cases involving aberrant expression of myeloid markers. Ivosidenib has demonstrated efficacy in patients with IDH1-mutated AML but has not been extensively studied in other hematologic malignancies. This case demonstrates the role of NGS in revealing treatment options in patients with otherwise limited available therapies.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131335576","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 : 2023-03-07DOI: 10.3389/frhem.2023.1135261
Kunapa Iam-arunthai, Supat Chamnanchanunt, Pravinwan Thungthong, Chajchawan Nakhahes, T. Suwanban, P. Rojnuckarin
Purpose Recent studies suggested that adding other agents to corticosteroids as a first-line treatment for immune thrombocytopenia (ITP) could improve outcomes. However, combination regimens may increase side effects and costs. To determine clinical factors associated with responses to the first-line steroid at 1 month. Materials and methods We retrospectively reviewed the medical records of patients with ITP aged ≥ 18 years, who were treated at Rajavithi Hospital between 2012 and 2020. Clinical data, laboratory results, treatment regimens, and responses to therapy were analyzed. Results Of the 226 patients, 76.6% were female. The mean age was 46.5 ± 18.1 years, and the median follow-up duration was 40 months. The proportion of chronic ITP was 97.3%. The complete response and response rates to first-line therapy were 65.5% and 88.9%, respectively. The age over 26 years, presentation clinically non-significant bleeding and a difference in platelet count of >50 x 109/L between days 1 and 7 after initial treatment were associated with the response to first-line treatment (adjusted odds ratio [OR] 5.09, 95% confidence interval [CI] 1.50-17.28, p = 0.009); OR 5.87, 95%CI 1.19-28.91, p = 0.029, and OR 3.60, 95%CI 1.10-11.73, p = 0.034, respectively. Younger patients and a difference in platelet count between day 1 and 7 ≤ 50 x 109/L were more likely to require second-line treatments. There were significant increases in the median platelet counts after prescribing azathioprine (baseline vs. 3 months, p = 0.001), cyclophosphamide (baseline vs. 6 months, p = 0.021), or danazol (baseline vs. 12 months, p = 0.039). Conclusion Adult, severity of bleeding at presentation, and rapid platelet increases within 1 week were related to excellent corticosteroid responses in ITP patients. These patients may not need combination regimens.
最近的研究表明，在皮质类固醇的基础上添加其他药物作为治疗免疫性血小板减少症(ITP)的一线治疗可以改善预后。然而，联合用药可能会增加副作用和费用。确定与一线类固醇治疗1个月反应相关的临床因素。材料和方法回顾性分析2012年至2020年在Rajavithi医院治疗的年龄≥18岁的ITP患者的医疗记录。分析了临床资料、实验室结果、治疗方案和对治疗的反应。结果226例患者中，女性占76.6%。平均年龄46.5±18.1岁，中位随访时间40个月。慢性ITP占97.3%。一线治疗的完全缓解率和有效率分别为65.5%和88.9%。年龄大于26岁、出现临床无显著性出血以及初始治疗后第1天至第7天血小板计数>50 × 109/L的差异与一线治疗的疗效相关(校正优势比[OR] 5.09, 95%可信区间[CI] 1.50-17.28, p = 0.009);OR分别为5.87,95%CI 1.19-28.91, p = 0.029; OR为3.60,95%CI 1.10-11.73, p = 0.034。年轻患者和第1天和第7天血小板计数差异≤50 × 109/L的患者更有可能需要二线治疗。在处方硫唑嘌呤(基线vs. 3个月，p = 0.001)、环磷酰胺(基线vs. 6个月，p = 0.021)或那那唑(基线vs. 12个月，p = 0.039)后，血小板计数中位数显著增加。结论成人、就诊时出血严重程度和1周内血小板快速升高与ITP患者良好的皮质类固醇反应有关。这些患者可能不需要联合治疗。
{"title":"Identification factors to adjust early combination regimens in adult primary immune thrombocytopenia: An 8-year data analysis","authors":"Kunapa Iam-arunthai, Supat Chamnanchanunt, Pravinwan Thungthong, Chajchawan Nakhahes, T. Suwanban, P. Rojnuckarin","doi":"10.3389/frhem.2023.1135261","DOIUrl":"https://doi.org/10.3389/frhem.2023.1135261","url":null,"abstract":"Purpose Recent studies suggested that adding other agents to corticosteroids as a first-line treatment for immune thrombocytopenia (ITP) could improve outcomes. However, combination regimens may increase side effects and costs. To determine clinical factors associated with responses to the first-line steroid at 1 month. Materials and methods We retrospectively reviewed the medical records of patients with ITP aged ≥ 18 years, who were treated at Rajavithi Hospital between 2012 and 2020. Clinical data, laboratory results, treatment regimens, and responses to therapy were analyzed. Results Of the 226 patients, 76.6% were female. The mean age was 46.5 ± 18.1 years, and the median follow-up duration was 40 months. The proportion of chronic ITP was 97.3%. The complete response and response rates to first-line therapy were 65.5% and 88.9%, respectively. The age over 26 years, presentation clinically non-significant bleeding and a difference in platelet count of >50 x 109/L between days 1 and 7 after initial treatment were associated with the response to first-line treatment (adjusted odds ratio [OR] 5.09, 95% confidence interval [CI] 1.50-17.28, p = 0.009); OR 5.87, 95%CI 1.19-28.91, p = 0.029, and OR 3.60, 95%CI 1.10-11.73, p = 0.034, respectively. Younger patients and a difference in platelet count between day 1 and 7 ≤ 50 x 109/L were more likely to require second-line treatments. There were significant increases in the median platelet counts after prescribing azathioprine (baseline vs. 3 months, p = 0.001), cyclophosphamide (baseline vs. 6 months, p = 0.021), or danazol (baseline vs. 12 months, p = 0.039). Conclusion Adult, severity of bleeding at presentation, and rapid platelet increases within 1 week were related to excellent corticosteroid responses in ITP patients. These patients may not need combination regimens.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114776987","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 : 2023-03-07DOI: 10.3389/frhem.2023.1055086
Anne-Sophie Cloos, M. Rab, P. van der Smissen, B. V. van Oirschot, E. Mignolet, J. B. van der Net, A. Koster, Kelly Kleinen, Y. Larondelle, Romano Terrasi, G. Muccioli, R. van Wijk, D. Tyteca
Sitosterolemia is a metabolic disorder leading to excessive accumulation of phytosterols. Hemolytic stomatocytosis and macrothrombocytopenia are part of the clinical picture. However, the impact of phytosterols on red blood cell (RBC) deformability, membrane lipid composition and distribution and the efficiency of the reference treatment, Ezetimibe, are largely unknown. This study addresses these issues using RBCs from three patients with sitosterolemia and healthy RBCs exposed to β-sitosterol. Patients presented an increased proportion of stomatocytes, decreased RBC deformability and increased RBC hydration and osmotic fragility compared to healthy donors. At the membrane level, patient RBCs showed (i) very high content in β-sitosterols, (ii) increased proportions of saturated fatty acids and polyunsaturated fatty acid species with long and unsaturated carbon chains, and (iii) decreased content in phosphatidylethanolamine species. These lipid changes were accompanied by an almost complete abrogation of cholesterol-enriched domains, which could result from: (i) the reduced phosphatidylethanolamine content which positively correlated with domain abundance; and (ii) the fatty acid modifications and increased phytosterol content, both compatible with higher membrane stiffness. The role of β-sitosterol was supported by comparable changes in RBC morphology and cholesterol-enriched domains upon β-sitosterol integration at the healthy RBC membrane. Finally, Ezetimibe treatment combined with a sterol restricted diet lowered phytosterols and improved anemia and RBC deformability and hydration. However, this treatment had no or limited effect on RBC morphology and cholesterol-enriched domain abundance. This study reveals for the first time that phytosterols affect RBC membrane lipid composition and distribution but also RBC morphology, hydration, deformability and fragility.
{"title":"Red blood cells from patients with sitosterolemia exhibit impaired membrane lipid composition and distribution and decreased deformability","authors":"Anne-Sophie Cloos, M. Rab, P. van der Smissen, B. V. van Oirschot, E. Mignolet, J. B. van der Net, A. Koster, Kelly Kleinen, Y. Larondelle, Romano Terrasi, G. Muccioli, R. van Wijk, D. Tyteca","doi":"10.3389/frhem.2023.1055086","DOIUrl":"https://doi.org/10.3389/frhem.2023.1055086","url":null,"abstract":"Sitosterolemia is a metabolic disorder leading to excessive accumulation of phytosterols. Hemolytic stomatocytosis and macrothrombocytopenia are part of the clinical picture. However, the impact of phytosterols on red blood cell (RBC) deformability, membrane lipid composition and distribution and the efficiency of the reference treatment, Ezetimibe, are largely unknown. This study addresses these issues using RBCs from three patients with sitosterolemia and healthy RBCs exposed to β-sitosterol. Patients presented an increased proportion of stomatocytes, decreased RBC deformability and increased RBC hydration and osmotic fragility compared to healthy donors. At the membrane level, patient RBCs showed (i) very high content in β-sitosterols, (ii) increased proportions of saturated fatty acids and polyunsaturated fatty acid species with long and unsaturated carbon chains, and (iii) decreased content in phosphatidylethanolamine species. These lipid changes were accompanied by an almost complete abrogation of cholesterol-enriched domains, which could result from: (i) the reduced phosphatidylethanolamine content which positively correlated with domain abundance; and (ii) the fatty acid modifications and increased phytosterol content, both compatible with higher membrane stiffness. The role of β-sitosterol was supported by comparable changes in RBC morphology and cholesterol-enriched domains upon β-sitosterol integration at the healthy RBC membrane. Finally, Ezetimibe treatment combined with a sterol restricted diet lowered phytosterols and improved anemia and RBC deformability and hydration. However, this treatment had no or limited effect on RBC morphology and cholesterol-enriched domain abundance. This study reveals for the first time that phytosterols affect RBC membrane lipid composition and distribution but also RBC morphology, hydration, deformability and fragility.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"57 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126963034","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 : 2023-02-06DOI: 10.3389/frhem.2023.1055484
A. K. Haugaard, H. Madsen, T. Masmas, K. Vettenranta, J. Buechner, K. Mellgren, D. Turkiewicz, S. Rosthøj, H. Marquart, C. Heilmann, Klaus Gottlob Müller, M. Ifversen
Analysis of chimerism in blood post‐HCT using STR‐PCR is routinely applied in parallel with quantification of MRD to predict relapse of leukemia. Real time quantitative PCR (RQ-PCR) chimerism is 10‐ to 100‐fold more sensitive, but clinical studies in children are sparse. In a prospective multicenter study, we analyzed increasing mixed chimerism (IMC) in blood samples following transplantation for leukemia in 64 children. IMC was defined as a minimum increase of either 0.1% or 0.05% recipient DNA between two samples or a ≥10-fold increase. Samples closer than 30 days to diagnosis of relapse were omitted. The risk of relapse was higher in children with IMC of both 0.1% and 0.05% compared to children without IMC (27.8 (95% CI 4.4-175.8; P<.001), and 18.4 (95% CI 2.8-120.5; P=0.002), respectively). From the date of IMC, the 3-year CI of relapse or MRD-positivity was 26.7% (CI 9.4-47.0) and 18.5% (6.4-35.3) for IMC ≥ 0.1% (n=27) and ≥ 0.05% (n= 40), respectively. In the subset of children without an IMC ≥ 0.1% or ≥ 0.05%, CI of relapse or molecular relapse were 16.7% (5.0 -34.1) and 10.8% (3.4 -23.3), respectively. In all cases with a relapse undetectable by IMC, MRD remained undetectable prior to relapse and standard chimerism negative. In a landmark analysis, neither an IMC ≥ 0.1% nor ≥ 0.05% prior to 90 days post‐HCT was significantly associated with an increased relapse incidence. These results indicate that the serial monitoring of RQ‐PCR chimerism in peripheral blood post-HCT may be a valuable supplement to the minimal residual disease analysis for an early detection of relapse in acute childhood leukemia.
{"title":"Highly-sensitive chimerism analysis in blood after allogeneic hematopoietic cell transplantation in childhood leukemia: Results from the Nordic Microchimerism Study","authors":"A. K. Haugaard, H. Madsen, T. Masmas, K. Vettenranta, J. Buechner, K. Mellgren, D. Turkiewicz, S. Rosthøj, H. Marquart, C. Heilmann, Klaus Gottlob Müller, M. Ifversen","doi":"10.3389/frhem.2023.1055484","DOIUrl":"https://doi.org/10.3389/frhem.2023.1055484","url":null,"abstract":"Analysis of chimerism in blood post‐HCT using STR‐PCR is routinely applied in parallel with quantification of MRD to predict relapse of leukemia. Real time quantitative PCR (RQ-PCR) chimerism is 10‐ to 100‐fold more sensitive, but clinical studies in children are sparse. In a prospective multicenter study, we analyzed increasing mixed chimerism (IMC) in blood samples following transplantation for leukemia in 64 children. IMC was defined as a minimum increase of either 0.1% or 0.05% recipient DNA between two samples or a ≥10-fold increase. Samples closer than 30 days to diagnosis of relapse were omitted. The risk of relapse was higher in children with IMC of both 0.1% and 0.05% compared to children without IMC (27.8 (95% CI 4.4-175.8; P<.001), and 18.4 (95% CI 2.8-120.5; P=0.002), respectively). From the date of IMC, the 3-year CI of relapse or MRD-positivity was 26.7% (CI 9.4-47.0) and 18.5% (6.4-35.3) for IMC ≥ 0.1% (n=27) and ≥ 0.05% (n= 40), respectively. In the subset of children without an IMC ≥ 0.1% or ≥ 0.05%, CI of relapse or molecular relapse were 16.7% (5.0 -34.1) and 10.8% (3.4 -23.3), respectively. In all cases with a relapse undetectable by IMC, MRD remained undetectable prior to relapse and standard chimerism negative. In a landmark analysis, neither an IMC ≥ 0.1% nor ≥ 0.05% prior to 90 days post‐HCT was significantly associated with an increased relapse incidence. These results indicate that the serial monitoring of RQ‐PCR chimerism in peripheral blood post-HCT may be a valuable supplement to the minimal residual disease analysis for an early detection of relapse in acute childhood leukemia.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124786031","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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