Pub Date : 2019-03-20DOI: 10.3760/CMA.J.ISSN.1673-419X.2019.02.013
M. Yi
Core binding factor-acute myeloid leukemia (CBF-AML) is a common cellular genetic subtype in children with acute myeloid leukemia (AML), accounting for 25%-30% of AML, and it has a good clinical prognosis. However, there are still 30%-40% of CBF-AML patients with recurrence, and the cellular molecular genetic abnormal events accompanying such patients may be related to their clinical prognosis. At present, dasatinib has been reported in the therapy of adult CBF-AML. Different molecular genetic backgrounds have become a new idea for precise targeted therapy, but there are still few related studies on pediatric CBF-AML. The author summarizes clinical prognostic impacts of cellular and molecular genetic abnormalities which are commonly seen in pediatric CBF-AML, aiming to provide new ideas for individualized treatment of pediatric CBF-AML. Key words: Core binding factors; Leukemia, myeloid, acute; Chromosome aberrations; Prognosis; Child
{"title":"Prognostic significance of cellular and molecular genetic abnormalities in pediatric core binding factor-acute myeloid leukemia","authors":"M. Yi","doi":"10.3760/CMA.J.ISSN.1673-419X.2019.02.013","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1673-419X.2019.02.013","url":null,"abstract":"Core binding factor-acute myeloid leukemia (CBF-AML) is a common cellular genetic subtype in children with acute myeloid leukemia (AML), accounting for 25%-30% of AML, and it has a good clinical prognosis. However, there are still 30%-40% of CBF-AML patients with recurrence, and the cellular molecular genetic abnormal events accompanying such patients may be related to their clinical prognosis. At present, dasatinib has been reported in the therapy of adult CBF-AML. Different molecular genetic backgrounds have become a new idea for precise targeted therapy, but there are still few related studies on pediatric CBF-AML. The author summarizes clinical prognostic impacts of cellular and molecular genetic abnormalities which are commonly seen in pediatric CBF-AML, aiming to provide new ideas for individualized treatment of pediatric CBF-AML. \u0000 \u0000 \u0000Key words: \u0000Core binding factors; Leukemia, myeloid, acute; Chromosome aberrations; Prognosis; Child","PeriodicalId":13774,"journal":{"name":"International Journal of Blood Transfusion and Hematology","volume":"42 1","pages":"160-164"},"PeriodicalIF":0.0,"publicationDate":"2019-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47952398","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 : 2019-03-20DOI: 10.3760/CMA.J.ISSN.1673-419X.2019.02.001
Zhijian Xiao
The myelodysplastic syndromes (MDS) are a group of clonal myeloid neoplasms characterized by ineffective hematopoiesis, manifested by morphologic dysplasia in hematopoietic cells and by peripheral cytopenia. The first classification was proposed by the French-American-British(FAB) cooperative group in 1982 based on morphologic dysplasia.In 2001, World Health Organization (WHO) proposed an alternative classification for MDS, since then, the WHO classification has been updated twice, once in 2008 and again in 2016. Therefore, the diagnostic mode of MDS has evolved from a simple morphology model to the current morphology, immunology, cytogenetics, and molecular biology (MICM) model. The author intends to systematically introduce the role and status of the MICM model in the diagnosis of MDS, including accurate assessment of cell morphology, flow cytometry immunophenotyping, cytogenetics, and improved genetic mutation analysis.Meanwhile the main problems and future development directions of MDS were also reviewed with the author′s clinical experience and personal views. Key words: Myelodysplastic syndromes; Myeloid cells; Diagnosis; Immunophenotyping; Cytogenetics; Mutation; Morphology
{"title":"State of the art: approaches for the diagnosis of myelodysplastic syndromes","authors":"Zhijian Xiao","doi":"10.3760/CMA.J.ISSN.1673-419X.2019.02.001","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1673-419X.2019.02.001","url":null,"abstract":"The myelodysplastic syndromes (MDS) are a group of clonal myeloid neoplasms characterized by ineffective hematopoiesis, manifested by morphologic dysplasia in hematopoietic cells and by peripheral cytopenia. The first classification was proposed by the French-American-British(FAB) cooperative group in 1982 based on morphologic dysplasia.In 2001, World Health Organization (WHO) proposed an alternative classification for MDS, since then, the WHO classification has been updated twice, once in 2008 and again in 2016. Therefore, the diagnostic mode of MDS has evolved from a simple morphology model to the current morphology, immunology, cytogenetics, and molecular biology (MICM) model. The author intends to systematically introduce the role and status of the MICM model in the diagnosis of MDS, including accurate assessment of cell morphology, flow cytometry immunophenotyping, cytogenetics, and improved genetic mutation analysis.Meanwhile the main problems and future development directions of MDS were also reviewed with the author′s clinical experience and personal views. \u0000 \u0000 \u0000Key words: \u0000Myelodysplastic syndromes; Myeloid cells; Diagnosis; Immunophenotyping; Cytogenetics; Mutation; Morphology","PeriodicalId":13774,"journal":{"name":"International Journal of Blood Transfusion and Hematology","volume":"42 1","pages":"93-97"},"PeriodicalIF":0.0,"publicationDate":"2019-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69910388","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 : 2019-03-20DOI: 10.3760/CMA.J.ISSN.1673-419X.2019.02.007
Dan Zhang
Objective To explore the clinical outcomes and their influencing factors of tyrosine kinase inhibitors (TKI) discontinuation in patients with chronic myeloid leukemia in chronic phase (CML-CP). Methods From January 1999 to April 2018, a total of 16 patients with CML-CP who underwent routine outpatient follow-up in Department of Hematology, West China Hospital of Sichuan University, and discontinued TKI for more than 6 months were selected as subjects. Among them, there were 6 male patients and 10 females; the median age at diagnosis was 39.5 years (24.8-53.8 years). The median age at time of TKI discontinuation was 45.5 years old (30.3-69.0 years old). According to whether molecular recurrence occurred during the follow-up period after TKI discontinuation, the patients were divided into recurrent group (n=5) and non-recurrent group (n=11). The clinical data of patients with TKI before and after discontinuation were collected by retrospective method. The causes of TKI discontinuation, treatment-free remission (TFR) status after TKI discontinuation and its possible influencing factors were analyzed. In this study, composition ratio of gender, stage of CML, and TKI discontinuation causes were compared between the two groups using Fisher′s exact test. The Mann-Whitney U test was used to compare the non-normal distribution measurement data, such as duration of TKI treatment, time from TKI treatment to major molecular response (MMR)/deep molecular response (DMR), time of MMR/DMR maintenance. The TFR rate at 6 and 12 months after TKI discontinuation in patients was calculated by Kaplan-Meier method. The procedure followed in this study was in line with the revised Helsinki Declaration of the World Medical Association in 2013. Results ① Among all the 16 patients with CML-CP, causes of TKI discontinuation included TKI-related adverse reactions (n=5), patients′ expectancy (n=5), pregnancy/planned pregnancy (n=4), financial burden (n=1), and combined solid tumor (n=1). The median time of TKI treatment in 16 patients with CML-CP was 53.0 months (34.0-156.0 months). Among them, 15 patients achieved DMR before TKI discontinuation and 1 patient only obtained MMR. The median time to achieve DMR before TKI discontinuation was 39.0 months (10.0-144.0 months). ② The median follow-up time of 16 patients with CML-CP after TKI discontinuation was 17.0 months (7.0-75.0 months). At the end of follow-up, 11 patients had no molecular recurrence, and the median time of TFR was 12.0 months (2.0-75.0 months). TFR rates at 6 and 12 months after TKI discontinuation were 68.8% and 61.9%, respectively. Molecular recurrence occurred in 5 patients. The median recurrence time was 4.0 months (2.0-5.0 months) after TKI discontinuation, and the BCR-ABLIS level was 0.14%-0.88% at the time of recurrence. Among the 5 patients with molecular recurrence, 4 patients restarted TKI at 3, 4, 6 and 8 months after relapse, obtained MMR after 2, 3, 4, and 5 months of restarting TKI,
{"title":"Clinical analysis on outcomes in patients with chronic myeloid leukemia in chronic phase after tyrosine kinase inhibitors discontinuation and their influencing factors","authors":"Dan Zhang","doi":"10.3760/CMA.J.ISSN.1673-419X.2019.02.007","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1673-419X.2019.02.007","url":null,"abstract":"Objective \u0000To explore the clinical outcomes and their influencing factors of tyrosine kinase inhibitors (TKI) discontinuation in patients with chronic myeloid leukemia in chronic phase (CML-CP). \u0000 \u0000 \u0000Methods \u0000From January 1999 to April 2018, a total of 16 patients with CML-CP who underwent routine outpatient follow-up in Department of Hematology, West China Hospital of Sichuan University, and discontinued TKI for more than 6 months were selected as subjects. Among them, there were 6 male patients and 10 females; the median age at diagnosis was 39.5 years (24.8-53.8 years). The median age at time of TKI discontinuation was 45.5 years old (30.3-69.0 years old). According to whether molecular recurrence occurred during the follow-up period after TKI discontinuation, the patients were divided into recurrent group (n=5) and non-recurrent group (n=11). The clinical data of patients with TKI before and after discontinuation were collected by retrospective method. The causes of TKI discontinuation, treatment-free remission (TFR) status after TKI discontinuation and its possible influencing factors were analyzed. In this study, composition ratio of gender, stage of CML, and TKI discontinuation causes were compared between the two groups using Fisher′s exact test. The Mann-Whitney U test was used to compare the non-normal distribution measurement data, such as duration of TKI treatment, time from TKI treatment to major molecular response (MMR)/deep molecular response (DMR), time of MMR/DMR maintenance. The TFR rate at 6 and 12 months after TKI discontinuation in patients was calculated by Kaplan-Meier method. The procedure followed in this study was in line with the revised Helsinki Declaration of the World Medical Association in 2013. \u0000 \u0000 \u0000Results \u0000① Among all the 16 patients with CML-CP, causes of TKI discontinuation included TKI-related adverse reactions (n=5), patients′ expectancy (n=5), pregnancy/planned pregnancy (n=4), financial burden (n=1), and combined solid tumor (n=1). The median time of TKI treatment in 16 patients with CML-CP was 53.0 months (34.0-156.0 months). Among them, 15 patients achieved DMR before TKI discontinuation and 1 patient only obtained MMR. The median time to achieve DMR before TKI discontinuation was 39.0 months (10.0-144.0 months). ② The median follow-up time of 16 patients with CML-CP after TKI discontinuation was 17.0 months (7.0-75.0 months). At the end of follow-up, 11 patients had no molecular recurrence, and the median time of TFR was 12.0 months (2.0-75.0 months). TFR rates at 6 and 12 months after TKI discontinuation were 68.8% and 61.9%, respectively. Molecular recurrence occurred in 5 patients. The median recurrence time was 4.0 months (2.0-5.0 months) after TKI discontinuation, and the BCR-ABLIS level was 0.14%-0.88% at the time of recurrence. Among the 5 patients with molecular recurrence, 4 patients restarted TKI at 3, 4, 6 and 8 months after relapse, obtained MMR after 2, 3, 4, and 5 months of restarting TKI, ","PeriodicalId":13774,"journal":{"name":"International Journal of Blood Transfusion and Hematology","volume":"42 1","pages":"127-133"},"PeriodicalIF":0.0,"publicationDate":"2019-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47534472","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 : 2019-03-20DOI: 10.3760/CMA.J.ISSN.1673-419X.2019.02.014
Z. Gu, J. Xia, Tian-yu Li
MLL-rearranged leukemia is caused by rearrangement of the MLL gene located on chromosome 11q23, which is one of the common types in childhood leukemia. It can be clinically manifested as acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myelodysplastic syndrome, and treatment-related leukemia. At present, the treatments of MLL-rearranged leukemia are combined chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT). The survival rate has been improved, but the outcomes and prognosis of most MLL-rearrangement leukemia are not excellent. Targeted therapy and immunotherapy are expected to become new treatments for the disease, which improve prognosis and survival rate. This article reviews the progress in the treatment of MLL-rearranged leukemia, and highlights the progress and potential of targeted therapy in recent years. Key words: Leukemia; Gene rearrangement; Antineoplastic combined chemotherapy protocols; Hematopoietic stem cell transplantation; Molecular targeted therapy; Immunotherapy; MLL gene
{"title":"Progress in treatment of MLL-rearranged leukemia in children","authors":"Z. Gu, J. Xia, Tian-yu Li","doi":"10.3760/CMA.J.ISSN.1673-419X.2019.02.014","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1673-419X.2019.02.014","url":null,"abstract":"MLL-rearranged leukemia is caused by rearrangement of the MLL gene located on chromosome 11q23, which is one of the common types in childhood leukemia. It can be clinically manifested as acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myelodysplastic syndrome, and treatment-related leukemia. At present, the treatments of MLL-rearranged leukemia are combined chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT). The survival rate has been improved, but the outcomes and prognosis of most MLL-rearrangement leukemia are not excellent. Targeted therapy and immunotherapy are expected to become new treatments for the disease, which improve prognosis and survival rate. This article reviews the progress in the treatment of MLL-rearranged leukemia, and highlights the progress and potential of targeted therapy in recent years. \u0000 \u0000 \u0000Key words: \u0000Leukemia; Gene rearrangement; Antineoplastic combined chemotherapy protocols; Hematopoietic stem cell transplantation; Molecular targeted therapy; Immunotherapy; MLL gene","PeriodicalId":13774,"journal":{"name":"International Journal of Blood Transfusion and Hematology","volume":"42 1","pages":"165-169"},"PeriodicalIF":0.0,"publicationDate":"2019-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47116207","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 : 2019-03-20DOI: 10.3760/CMA.J.ISSN.1673-419X.2019.02.017
Yongwei Su
There has been an accumulating body of studies provided to reveal that blood transfusion is more frequently and liberally administered to older than younger patients. Older patients have a higher transfusion rate than the younger; even they are just suspected but not diagnosed of co-morbidities. It is still under controversial whether older patients should adopt liberal or restrictive transfusion strategy. This review seeks to find a proper blood transfusion strategy for older patients by summarizing the current situation and progress of relevant studies in recent years, and analyzing the risks and complication of blood transfusion for older patients in different clinical settings. Key words: Blood transfusion; Aged; Younger adult; Restrictive transfusion strategy; Liberal transfusion strategy
{"title":"Clinical current status and research progress on transfusion strategy of older patients","authors":"Yongwei Su","doi":"10.3760/CMA.J.ISSN.1673-419X.2019.02.017","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1673-419X.2019.02.017","url":null,"abstract":"There has been an accumulating body of studies provided to reveal that blood transfusion is more frequently and liberally administered to older than younger patients. Older patients have a higher transfusion rate than the younger; even they are just suspected but not diagnosed of co-morbidities. It is still under controversial whether older patients should adopt liberal or restrictive transfusion strategy. This review seeks to find a proper blood transfusion strategy for older patients by summarizing the current situation and progress of relevant studies in recent years, and analyzing the risks and complication of blood transfusion for older patients in different clinical settings. \u0000 \u0000 \u0000Key words: \u0000Blood transfusion; Aged; Younger adult; Restrictive transfusion strategy; Liberal transfusion strategy","PeriodicalId":13774,"journal":{"name":"International Journal of Blood Transfusion and Hematology","volume":"42 1","pages":"181-185"},"PeriodicalIF":0.0,"publicationDate":"2019-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48256076","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 : 2019-03-20DOI: 10.3760/CMA.J.ISSN.1673-419X.2019.02.011
Yuqian Zhu
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal diseases that originate from hematopoietic stem cells. The recurrence and development of MDS is a multi-step pathological process. Genetic mutations and epigenetic abnormalities are closely related to the initiation of MDS. Mutations in U2AF1 are identified as a higher frequency in MDS, which will lead to abnormal recognition of the pre-mRNA 3′splice site (3′SS) by the spliceosome and result in aberrant mRNA. Recently, intensive studies have shown that U2AF1 mutations are likely to be the early events of MDS and acute myeloid leukemia (AML), and patients with U2AF1 mutations have an inherent transformation to leukemia and low survival rate. Considering U2AF1 mutations and related molecular changes contributes to predict the clinical outcomes of patients with MDS. This review mainly discusses the molecular mechanisms of U2AF1 mutations and its functional significance, in order to provide theoretical basis to accelerate the discovery of new targeted treatments for MDS. Key words: Myelodysplastic syndromes; Splicing factor U2AF; Spliceosomes; Mutation; Prognosis
{"title":"Research progress of U2AF1 mutations in patients with myelodysplastic syndromes","authors":"Yuqian Zhu","doi":"10.3760/CMA.J.ISSN.1673-419X.2019.02.011","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1673-419X.2019.02.011","url":null,"abstract":"Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal diseases that originate from hematopoietic stem cells. The recurrence and development of MDS is a multi-step pathological process. Genetic mutations and epigenetic abnormalities are closely related to the initiation of MDS. Mutations in U2AF1 are identified as a higher frequency in MDS, which will lead to abnormal recognition of the pre-mRNA 3′splice site (3′SS) by the spliceosome and result in aberrant mRNA. Recently, intensive studies have shown that U2AF1 mutations are likely to be the early events of MDS and acute myeloid leukemia (AML), and patients with U2AF1 mutations have an inherent transformation to leukemia and low survival rate. Considering U2AF1 mutations and related molecular changes contributes to predict the clinical outcomes of patients with MDS. This review mainly discusses the molecular mechanisms of U2AF1 mutations and its functional significance, in order to provide theoretical basis to accelerate the discovery of new targeted treatments for MDS. \u0000 \u0000 \u0000Key words: \u0000Myelodysplastic syndromes; Splicing factor U2AF; Spliceosomes; Mutation; Prognosis","PeriodicalId":13774,"journal":{"name":"International Journal of Blood Transfusion and Hematology","volume":"42 1","pages":"149-153"},"PeriodicalIF":0.0,"publicationDate":"2019-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46792734","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 : 2019-03-20DOI: 10.3760/CMA.J.ISSN.1673-419X.2019.02.006
Minglu Xu, K. Qi, Jiang Cao, Zhenyu Li
Objective To explore the correlation between levels of inflammatory factor in peripheral blood and cytokine release syndrome (CRS) in patients with B cell acute lymphoblastic leukemia (B-ALL) after receiving chimeric antigen receptor T cells (CAR-T) immunotherapy. Methods From April 1, 2016 to September 30, 2018, a total of 38 patients with B-ALL who underwent CAR-T immunotherapy in the Department of Hematology, Affiliated Hospital of Xuzhou Medical University, and had complete clinical data, were selected as subjects. And 21 patients were male and 17 ones were female with median age of 16 years (8-35 years). All patients received the fludarabine combined with cyclophosphamide (FC) conditioning regimen before CAR-T immunotherapy. In this study, all of the 38 patients were treated with humanized CD19 CAR-T (hCART19s), and the total infused number of CAR-T in each patient was calculated as 1×106/kg. A retrospective research method was used to collect results of relevant clinical data, laboratory and auxiliary examination. The peak levels of ferritin, C-reactive protein (CRP) and interleukin (IL)-6 in peripheral blood were recorded on d0-30 after CAR-T immunotherapy. According to the clinical data of patients on d0-30 after CAR-T immunotherapy, the CRS of the patients was diagnosed and graded. Correlation analysis between CRS grades and peak levels of ferritin, CRP and IL-6 in peripheral blood was performed using Spearman rank correlation analysis. The Mann-Whitney U test was used to compare the peak levels of ferritin, CRP and IL-6 in peripheral blood between patients with grade 1-2 CRS and grade 3-5 CRS. The procedure followed in this study was in accordance with the ethical standards established by the Human Experimental Committee of the Affiliated Hospital of Xuzhou Medical University, and was approved by the committee (Approval No. XYFY2016-KL002-01). All subjects or their guardians signed an informed consent for this clinical research. Results ① Among the 38 patients with B-ALL in this study, there were 34 patients who developed CRS after CAR-T immunotherapy, and the incidence rate of CRS was 89.5% (34/38). There were 24 patients (63.2%) developed grade 1-2 CRS, and 10 cases (26.3%) developed grade 3-5 CRS. The main clinical manifestations of patients with CRS were fever, hypotension, liver or kidney dysfunction, coagulation abnormalities, central nervous system adverse reactions, etc.. ② The CRS grades of patients with B-ALL after CAR-T immunotherapy were positively correlated with peak levels of ferritin, CRP and IL-6 levels in peripheral blood (rs=0.779, P<0.001; rs=0.673, P<0.001; rs=0.612, P<0.001). ③ The median peak levels of peripheral blood ferritin, CRP and IL-6 in patients with grade 3-5 CRS were 33 080 ng/mL (2 352-69 614 ng/mL), 200.0 mg/L (151.4-203.5 mg/L) and 799.5 pg/mL (220.9-1 677.5 pg/mL) respectively, which were higher than those of 1 979 ng/mL (1 133-2 147 ng/mL), 86.1 mg/L (33.8-136.6 mg/L) and 70.7 pg/mL (18
{"title":"Correlation analysis between levels of inflammatory cytokine in peripheral blood and cytokine release syndrome in patients with B-ALL after CAR-T immunotherapy","authors":"Minglu Xu, K. Qi, Jiang Cao, Zhenyu Li","doi":"10.3760/CMA.J.ISSN.1673-419X.2019.02.006","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1673-419X.2019.02.006","url":null,"abstract":"Objective \u0000To explore the correlation between levels of inflammatory factor in peripheral blood and cytokine release syndrome (CRS) in patients with B cell acute lymphoblastic leukemia (B-ALL) after receiving chimeric antigen receptor T cells (CAR-T) immunotherapy. \u0000 \u0000 \u0000Methods \u0000From April 1, 2016 to September 30, 2018, a total of 38 patients with B-ALL who underwent CAR-T immunotherapy in the Department of Hematology, Affiliated Hospital of Xuzhou Medical University, and had complete clinical data, were selected as subjects. And 21 patients were male and 17 ones were female with median age of 16 years (8-35 years). All patients received the fludarabine combined with cyclophosphamide (FC) conditioning regimen before CAR-T immunotherapy. In this study, all of the 38 patients were treated with humanized CD19 CAR-T (hCART19s), and the total infused number of CAR-T in each patient was calculated as 1×106/kg. A retrospective research method was used to collect results of relevant clinical data, laboratory and auxiliary examination. The peak levels of ferritin, C-reactive protein (CRP) and interleukin (IL)-6 in peripheral blood were recorded on d0-30 after CAR-T immunotherapy. According to the clinical data of patients on d0-30 after CAR-T immunotherapy, the CRS of the patients was diagnosed and graded. Correlation analysis between CRS grades and peak levels of ferritin, CRP and IL-6 in peripheral blood was performed using Spearman rank correlation analysis. The Mann-Whitney U test was used to compare the peak levels of ferritin, CRP and IL-6 in peripheral blood between patients with grade 1-2 CRS and grade 3-5 CRS. The procedure followed in this study was in accordance with the ethical standards established by the Human Experimental Committee of the Affiliated Hospital of Xuzhou Medical University, and was approved by the committee (Approval No. XYFY2016-KL002-01). All subjects or their guardians signed an informed consent for this clinical research. \u0000 \u0000 \u0000Results \u0000① Among the 38 patients with B-ALL in this study, there were 34 patients who developed CRS after CAR-T immunotherapy, and the incidence rate of CRS was 89.5% (34/38). There were 24 patients (63.2%) developed grade 1-2 CRS, and 10 cases (26.3%) developed grade 3-5 CRS. The main clinical manifestations of patients with CRS were fever, hypotension, liver or kidney dysfunction, coagulation abnormalities, central nervous system adverse reactions, etc.. ② The CRS grades of patients with B-ALL after CAR-T immunotherapy were positively correlated with peak levels of ferritin, CRP and IL-6 levels in peripheral blood (rs=0.779, P<0.001; rs=0.673, P<0.001; rs=0.612, P<0.001). ③ The median peak levels of peripheral blood ferritin, CRP and IL-6 in patients with grade 3-5 CRS were 33 080 ng/mL (2 352-69 614 ng/mL), 200.0 mg/L (151.4-203.5 mg/L) and 799.5 pg/mL (220.9-1 677.5 pg/mL) respectively, which were higher than those of 1 979 ng/mL (1 133-2 147 ng/mL), 86.1 mg/L (33.8-136.6 mg/L) and 70.7 pg/mL (18","PeriodicalId":13774,"journal":{"name":"International Journal of Blood Transfusion and Hematology","volume":"42 1","pages":"121-126"},"PeriodicalIF":0.0,"publicationDate":"2019-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49435880","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 : 2019-03-20DOI: 10.3760/CMA.J.ISSN.1673-419X.2019.02.016
Xuan Zhou
Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease. The classic pathogenesis of ITP is that the production of autoantibodies against platelet membrane glycoproteins, which mediates platelet destruction. In recent years, it has been found that there are still many other mechanisms in ITP inducing thrombocytopenia and platelet damage, among which abnormal cellular immunity plays an important role. In cellular immunity, CD4+ CD25high CD127- regulatory T cells (Treg) are a group of T cell subsets that exist in human peripheral blood and spleen and can inhibit auto-reactive T cell responses; T helper cells (Th)17 is a newly discovered T cell subset that secretes interleukin (IL)-17, involved in mediating inflammatory response, which is of great significance in autoimmune diseases. Several studies showed that Treg/Th17 imbalance and abnormal expression of specific transcription factors folkhead box protein (Foxp)3 and retinoic acid-related orphan nuclear receptor (ROR)-γt were observed in peripheral blood of ITP patients. DNA methylation induces Foxp3 gene silencing and abnormal activation of IL-6/STAT3 signaling pathway, which may be the mechanism leading to Treg/Th17 imbalance and causes of ITP. The proposed demethylation treatment may provide new ideas for the molecular targeted treatment of ITP, but its scientificity, effectiveness and safety still need to be confirmed by further studies. The author reviews literature on the role of Treg/Th17 imbalance and relevant gene methylation mechanism in the occurrence, development and treatment of ITP. Key words: T-lymphocytes, regulatory; T-lymphocyte subsets; DNA methylation; Thrombocytopenia; Helper T lymphocyte 17; Decitabine
{"title":"Research progress of peripheral blood regulatory T cell/helper T cell 17 imbalance and relevant gene methylation in immune thrombocytopenia","authors":"Xuan Zhou","doi":"10.3760/CMA.J.ISSN.1673-419X.2019.02.016","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1673-419X.2019.02.016","url":null,"abstract":"Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease. The classic pathogenesis of ITP is that the production of autoantibodies against platelet membrane glycoproteins, which mediates platelet destruction. In recent years, it has been found that there are still many other mechanisms in ITP inducing thrombocytopenia and platelet damage, among which abnormal cellular immunity plays an important role. In cellular immunity, CD4+ CD25high CD127- regulatory T cells (Treg) are a group of T cell subsets that exist in human peripheral blood and spleen and can inhibit auto-reactive T cell responses; T helper cells (Th)17 is a newly discovered T cell subset that secretes interleukin (IL)-17, involved in mediating inflammatory response, which is of great significance in autoimmune diseases. Several studies showed that Treg/Th17 imbalance and abnormal expression of specific transcription factors folkhead box protein (Foxp)3 and retinoic acid-related orphan nuclear receptor (ROR)-γt were observed in peripheral blood of ITP patients. DNA methylation induces Foxp3 gene silencing and abnormal activation of IL-6/STAT3 signaling pathway, which may be the mechanism leading to Treg/Th17 imbalance and causes of ITP. The proposed demethylation treatment may provide new ideas for the molecular targeted treatment of ITP, but its scientificity, effectiveness and safety still need to be confirmed by further studies. The author reviews literature on the role of Treg/Th17 imbalance and relevant gene methylation mechanism in the occurrence, development and treatment of ITP. \u0000 \u0000 \u0000Key words: \u0000T-lymphocytes, regulatory; T-lymphocyte subsets; DNA methylation; Thrombocytopenia; Helper T lymphocyte 17; Decitabine","PeriodicalId":13774,"journal":{"name":"International Journal of Blood Transfusion and Hematology","volume":"42 1","pages":"175-180"},"PeriodicalIF":0.0,"publicationDate":"2019-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47440597","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 : 2019-03-20DOI: 10.3760/CMA.J.ISSN.1673-419X.2019.02.015
Meng Zhang, N. Zhang, Xiao-li Ma
Mature B-cell non-Hodgkin lymphoma (B-NHL) is a common malignant tumor in children. In recent years, with the development of tumor immunology, immunotherapy has become a hot spot, and the changes of humoral immunity levels before and after treatment have attracted more attention. This article reviews the issues of humoral immunity before chemotherapy in children with B-NHL, the effect of chemotherapy on humoral immunity in children, and the latest research progress. Key words: B-lymphocytes; Lymphoma, non-Hodgkin; Immunity, humoral; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M
{"title":"Progress in humoral immunity of mature B-cell non-Hodgkin lymphoma in children","authors":"Meng Zhang, N. Zhang, Xiao-li Ma","doi":"10.3760/CMA.J.ISSN.1673-419X.2019.02.015","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1673-419X.2019.02.015","url":null,"abstract":"Mature B-cell non-Hodgkin lymphoma (B-NHL) is a common malignant tumor in children. In recent years, with the development of tumor immunology, immunotherapy has become a hot spot, and the changes of humoral immunity levels before and after treatment have attracted more attention. This article reviews the issues of humoral immunity before chemotherapy in children with B-NHL, the effect of chemotherapy on humoral immunity in children, and the latest research progress. \u0000 \u0000 \u0000Key words: \u0000B-lymphocytes; Lymphoma, non-Hodgkin; Immunity, humoral; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M","PeriodicalId":13774,"journal":{"name":"International Journal of Blood Transfusion and Hematology","volume":"42 1","pages":"170-174"},"PeriodicalIF":0.0,"publicationDate":"2019-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48119774","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 : 2019-03-20DOI: 10.3760/CMA.J.ISSN.1673-419X.2019.02.012
S. Qi
Mesenchymal stem cells (MSC) are non-hematopoietic stem cells with self-renewal and multi-directional differentiation potential, and have low immunogenicity and immune regulation. After years of experiments and preclinical and clinical research experience, MSC are gradually becoming a treatment for preventing and alleviating graft-versus-host disease (GVHD). The characteristics, differentiation potential and surface markers of MSC have been studied in the past, and relevant clinical reports have also been proved that simultaneous infusion of MSC and hematopoietic stem cells (HSC) could promote HSC implantation and support hematopoiesis, as well as prevent and alleviate the occurrence of GVHD. However, the mechanisms are still unclear, so this article reviews the research progress of mechanisms of MSC in GVHD. In order to provide new ideas for the prevention, diagnosis and treatment of GVHD. Key words: Hematopoietic stem cell transplantation; Mesenchymal stem cells; Mesenchymal stem cell transplantation; Graft vs host disease; Immunotherapy; Immunomodulation; Allogeneic hematopoietic stem cell transplantation; Prevention
{"title":"Research progress in mechanisms of mesenchymal stem cells on graft versus host disease","authors":"S. Qi","doi":"10.3760/CMA.J.ISSN.1673-419X.2019.02.012","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1673-419X.2019.02.012","url":null,"abstract":"Mesenchymal stem cells (MSC) are non-hematopoietic stem cells with self-renewal and multi-directional differentiation potential, and have low immunogenicity and immune regulation. After years of experiments and preclinical and clinical research experience, MSC are gradually becoming a treatment for preventing and alleviating graft-versus-host disease (GVHD). The characteristics, differentiation potential and surface markers of MSC have been studied in the past, and relevant clinical reports have also been proved that simultaneous infusion of MSC and hematopoietic stem cells (HSC) could promote HSC implantation and support hematopoiesis, as well as prevent and alleviate the occurrence of GVHD. However, the mechanisms are still unclear, so this article reviews the research progress of mechanisms of MSC in GVHD. In order to provide new ideas for the prevention, diagnosis and treatment of GVHD. \u0000 \u0000 \u0000Key words: \u0000Hematopoietic stem cell transplantation; Mesenchymal stem cells; Mesenchymal stem cell transplantation; Graft vs host disease; Immunotherapy; Immunomodulation; Allogeneic hematopoietic stem cell transplantation; Prevention","PeriodicalId":13774,"journal":{"name":"International Journal of Blood Transfusion and Hematology","volume":"42 1","pages":"154-159"},"PeriodicalIF":0.0,"publicationDate":"2019-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42383751","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：