Pub Date : 2023-03-27eCollection Date: 2023-04-01DOI: 10.1097/BS9.0000000000000156
Xiaochen Wang
{"title":"China's top 10 achievements in hematology in 2022.","authors":"Xiaochen Wang","doi":"10.1097/BS9.0000000000000156","DOIUrl":"10.1097/BS9.0000000000000156","url":null,"abstract":"","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2023-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/38/86/bs9-5-075.PMC10205334.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9530766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1097/BS9.0000000000000140
Chen Tian, Zehui Chen
Although complete remission could be achieved in about 60%-70% of acute myeloid leukemia (AML) patients after conventional chemotherapy, relapse and the state of being refractory to treatment remain the main cause of death. In addition, there is a great need for less intensive regimens for all medically frail patients (both due to age/comorbidity and treatment-related). Immune therapy anticipates improved prognosis and reduced toxicities, which may offer novel therapeutic rationales. However, one of the major difficulties in developing immune therapies against AML is that the target antigens are also significantly expressed on healthy hematopoietic stem cells; B-cell malignancies are different because CD20/CD19/healthy B-cells are readily replaceable. Only the anti-CD33 antibody-drug conjugate gemtuzumab-ozogamicin is approved by the FDA for AML. Thus, drug development remains extremely active, although it is still in its infancy. This review summarizes the clinical results of immune therapeutic agents for AML, such as antibody-based drugs, chimeric antigen receptor therapy, checkpoint inhibitors, and vaccines.
{"title":"Immune therapy: a new therapy for acute myeloid leukemia.","authors":"Chen Tian, Zehui Chen","doi":"10.1097/BS9.0000000000000140","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000140","url":null,"abstract":"<p><p>Although complete remission could be achieved in about 60%-70% of acute myeloid leukemia (AML) patients after conventional chemotherapy, relapse and the state of being refractory to treatment remain the main cause of death. In addition, there is a great need for less intensive regimens for all medically frail patients (both due to age/comorbidity and treatment-related). Immune therapy anticipates improved prognosis and reduced toxicities, which may offer novel therapeutic rationales. However, one of the major difficulties in developing immune therapies against AML is that the target antigens are also significantly expressed on healthy hematopoietic stem cells; B-cell malignancies are different because CD20/CD19/healthy B-cells are readily replaceable. Only the anti-CD33 antibody-drug conjugate gemtuzumab-ozogamicin is approved by the FDA for AML. Thus, drug development remains extremely active, although it is still in its infancy. This review summarizes the clinical results of immune therapeutic agents for AML, such as antibody-based drugs, chimeric antigen receptor therapy, checkpoint inhibitors, and vaccines.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6f/18/bs9-5-15.PMC9891447.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10717129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Epstein-Barr virus (EBV) reactivation is one of the most important infections after hematopoietic stem cell transplantation (HSCT) using haplo-identical related donors (HID). We aimed to establish a comprehensive model with machine learning, which could predict EBV reactivation after HID HSCT with anti-thymocyte globulin (ATG) for graft-versus-host disease (GVHD) prophylaxis. We enrolled 470 consecutive acute leukemia patients, 60% of them (n = 282) randomly selected as a training cohort, the remaining 40% (n = 188) as a validation cohort. The equation was as follows: Probability (EBV reactivation) = , where Y = 0.0250 × (age) - 0.3614 × (gender) + 0.0668 × (underlying disease) - 0.6297 × (disease status before HSCT) - 0.0726 × (disease risk index) - 0.0118 × (hematopoietic cell transplantation-specific comorbidity index [HCT-CI] score) + 1.2037 × (human leukocyte antigen disparity) + 0.5347 × (EBV serostatus) + 0.1605 × (conditioning regimen) - 0.2270 × (donor/recipient gender matched) + 0.2304 × (donor/recipient relation) - 0.0170 × (mononuclear cell counts in graft) + 0.0395 × (CD34+ cell count in graft) - 2.4510. The threshold of probability was 0.4623, which separated patients into low- and high-risk groups. The 1-year cumulative incidence of EBV reactivation in the low- and high-risk groups was 11.0% versus 24.5% (P < .001), 10.7% versus 19.3% (P = .046), and 11.4% versus 31.6% (P = .001), respectively, in total, training and validation cohorts. The model could also predict relapse and survival after HID HSCT. We established a comprehensive model that could predict EBV reactivation in HID HSCT recipients using ATG for GVHD prophylaxis.
{"title":"Machine learning algorithm as a prognostic tool for Epstein-Barr virus reactivation after haploidentical hematopoietic stem cell transplantation.","authors":"Shuang Fan, Hao-Yang Hong, Xin-Yu Dong, Lan-Ping Xu, Xiao-Hui Zhang, Yu Wang, Chen-Hua Yan, Huan Chen, Yu-Hong Chen, Wei Han, Feng-Rong Wang, Jing-Zhi Wang, Kai-Yan Liu, Meng-Zhu Shen, Xiao-Jun Huang, Shen-Da Hong, Xiao-Dong Mo","doi":"10.1097/BS9.0000000000000143","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000143","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV) reactivation is one of the most important infections after hematopoietic stem cell transplantation (HSCT) using haplo-identical related donors (HID). We aimed to establish a comprehensive model with machine learning, which could predict EBV reactivation after HID HSCT with anti-thymocyte globulin (ATG) for graft-versus-host disease (GVHD) prophylaxis. We enrolled 470 consecutive acute leukemia patients, 60% of them (n = 282) randomly selected as a training cohort, the remaining 40% (n = 188) as a validation cohort. The equation was as follows: Probability (EBV reactivation) = <math><mstyle><mtext> </mtext> <mfrac><mn>1</mn> <mrow><mn>1</mn> <mrow><mtext> </mtext></mrow> <mtext> </mtext> <mrow><mtext> </mtext></mrow> <mo>+</mo> <mrow><mtext> </mtext></mrow> <mtext> </mtext> <mrow><mtext> </mtext> <mi>e</mi> <mi>x</mi> <mi>p</mi></mrow> <mrow><mo>(</mo> <mo>-</mo> <mrow><mi>Y</mi></mrow> <mo>)</mo></mrow> </mrow> </mfrac> </mstyle> </math> , where Y = 0.0250 × (age) - 0.3614 × (gender) + 0.0668 × (underlying disease) - 0.6297 × (disease status before HSCT) - 0.0726 × (disease risk index) - 0.0118 × (hematopoietic cell transplantation-specific comorbidity index [HCT-CI] score) + 1.2037 × (human leukocyte antigen disparity) + 0.5347 × (EBV serostatus) + 0.1605 × (conditioning regimen) - 0.2270 × (donor/recipient gender matched) + 0.2304 × (donor/recipient relation) - 0.0170 × (mononuclear cell counts in graft) + 0.0395 × (CD34+ cell count in graft) - 2.4510. The threshold of probability was 0.4623, which separated patients into low- and high-risk groups. The 1-year cumulative incidence of EBV reactivation in the low- and high-risk groups was 11.0% versus 24.5% (<i>P</i> < .001), 10.7% versus 19.3% (<i>P</i> = .046), and 11.4% versus 31.6% (<i>P</i> = .001), respectively, in total, training and validation cohorts. The model could also predict relapse and survival after HID HSCT. We established a comprehensive model that could predict EBV reactivation in HID HSCT recipients using ATG for GVHD prophylaxis.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9891443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10658894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1097/BS9.0000000000000136
Yong-Xin Ru, Shu-Xu Dong, Jing Liu, Brian Eyden
Peripheral cisternae and double membranes (PCDMs) in erythroid cells are a landmark of type II congenital dyserythropoietic anemia (CDA). To gain further insights into the mechanism of dyserythropoiesis, erythroblasts and erythrocytes in bone marrow were studied in 22 Chinese patients with CDA Ⅱ by transmission electron microscopy. The study demonstrated an increase in all patients in erythroblasts with PCDMs with development from pro-erythroblast to red blood cells. PCDMs often connected with cisternae of endoplasmic reticulum (ER) and the perinuclear space, and were accompanied by karyopyknosis, karyolysis and disruption in polychromatic and orthochromatic erythroblasts. The results suggest that PCDMs are transformed from ER during erythropoiesis and participate in the dissolution and deletion of late erythroid cells in patients with CDA II.
{"title":"Ultrastructural characteristics of erythroid cells in congenital dyserythropoietic anemia type II, with a focus on peripheral cisternae and double membranes.","authors":"Yong-Xin Ru, Shu-Xu Dong, Jing Liu, Brian Eyden","doi":"10.1097/BS9.0000000000000136","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000136","url":null,"abstract":"<p><p>Peripheral cisternae and double membranes (PCDMs) in erythroid cells are a landmark of type II congenital dyserythropoietic anemia (CDA). To gain further insights into the mechanism of dyserythropoiesis, erythroblasts and erythrocytes in bone marrow were studied in 22 Chinese patients with CDA Ⅱ by transmission electron microscopy. The study demonstrated an increase in all patients in erythroblasts with PCDMs with development from pro-erythroblast to red blood cells. PCDMs often connected with cisternae of endoplasmic reticulum (ER) and the perinuclear space, and were accompanied by karyopyknosis, karyolysis and disruption in polychromatic and orthochromatic erythroblasts. The results suggest that PCDMs are transformed from ER during erythropoiesis and participate in the dissolution and deletion of late erythroid cells in patients with CDA II.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9891439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10717133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
With rapid developments in genetic engineering, tumor immunology, and cellular engineering, chimeric antigen receptor T cell (CAR-T) cell therapy has become a novel immunotherapy for oncology and other medical fields.1 The promising results of CD19 CAR-T treating B-cell malignancies were reported.2,3 Simultaneously, there existed many adverse events, the most reported of which including B-cell aplasia, hematological toxicity, cytokine release syndrome (CRS), and immune effector-cell–associated neurotoxicity syndrome (ICANS),3,4 but there is still lack of reports demonstrating the impact of CD19 CAR-T on the ABO blood group potency of patient’s serum. Blood transfusion plays an important role in treating diseases, especially in treating hematological diseases, and the accurate identification of ABO blood groups is a prerequisite for the safe blood transfusion. Meanwhile, the valid measurement of patient’s serum ABO blood group antibody potency is essential for the identification of the patient’s ABO blood group type. In this case report, we summarized the data of 10 patients receiving CD19 CAR-T cell immunotherapy in our hospital in recent years and had their potency measured after treatment, with a view to conducting a preliminary analysis of the impact of CD19 CAR-T cell therapy on the ABO blood group antibody potency in patients’ serum. 2. CASE REPORTS
{"title":"Reduced ABO blood group antibody titers in patients after CD19 CAR-T cell therapy.","authors":"Qiang Li, Zhihuan Yang, Kuo Fang, Shuning Wei, Jiali Sun, Wei Liu, Xiaojuan Chen, Wenyang Huang, Guangji Zhang, Yin Shi, Yuntao Liu, Xiaoyuan Gong, Fang Liu, Xueli Zhou, Jianxiang Wang, Ying Wang","doi":"10.1097/BS9.0000000000000137","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000137","url":null,"abstract":"With rapid developments in genetic engineering, tumor immunology, and cellular engineering, chimeric antigen receptor T cell (CAR-T) cell therapy has become a novel immunotherapy for oncology and other medical fields.1 The promising results of CD19 CAR-T treating B-cell malignancies were reported.2,3 Simultaneously, there existed many adverse events, the most reported of which including B-cell aplasia, hematological toxicity, cytokine release syndrome (CRS), and immune effector-cell–associated neurotoxicity syndrome (ICANS),3,4 but there is still lack of reports demonstrating the impact of CD19 CAR-T on the ABO blood group potency of patient’s serum. Blood transfusion plays an important role in treating diseases, especially in treating hematological diseases, and the accurate identification of ABO blood groups is a prerequisite for the safe blood transfusion. Meanwhile, the valid measurement of patient’s serum ABO blood group antibody potency is essential for the identification of the patient’s ABO blood group type. In this case report, we summarized the data of 10 patients receiving CD19 CAR-T cell immunotherapy in our hospital in recent years and had their potency measured after treatment, with a view to conducting a preliminary analysis of the impact of CD19 CAR-T cell therapy on the ABO blood group antibody potency in patients’ serum. 2. CASE REPORTS","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6a/d3/bs9-5-62.PMC9891450.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10661695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1097/BS9.0000000000000139
Lili Song, Peifeng Li, Huiying Sun, Lixia Ding, Jing Wang, Benshang Li, Bin-Bing S Zhou, Haizhong Feng, Yanxin Li
Tumor relapse is the major cause of treatment failure in childhood acute lymphoblastic leukemia (ALL), yet the underlying mechanisms are still elusive. Here, we demonstrate that phosphoribosyl pyrophosphate synthetase 2 (PRPS2) mutations drive ALL relapse through influencing PRPS1/2 hexamer stability. Ultra-deep sequencing was performed to identify PRPS2 mutations in ALL samples. The effects of PRPS2 mutations on cell survival, cell apoptosis, and drug resistance were evaluated. In vitro PRPS2 enzyme activity and ADP/GDP feedback inhibition of PRPS enzyme activity were assessed. Purine metabolites were analyzed by ultra-performance liquid-chromatography tandem mass spectrometry (UPLC-MS/MS). Integrating sequencing data with clinical information, we identified PRPS2 mutations only in relapsed childhood ALL with thiopurine therapy. Functional PRPS2 mutations mediated purine metabolism specifically on thiopurine treatment by influencing PRPS1/2 hexamer stability, leading to reduced nucleotide feedback inhibition of PRPS activity and enhanced thiopurine resistance. The 3-amino acid V103-G104-E105, the key difference between PRPS1 and PRPS2, insertion in PRPS2 caused severe steric clash to the interface of PRPS hexamer, leading to its low enzyme activity. In addition, we demonstrated that PRPS2 P173R increased thiopurine resistance in xenograft models. Our work describes a novel mechanism by which PRPS2 mutants drive childhood ALL relapse and highlights PRPS2 mutations as biomarkers for relapsed childhood ALL.
{"title":"PRPS2 mutations drive acute lymphoblastic leukemia relapse through influencing PRPS1/2 hexamer stability.","authors":"Lili Song, Peifeng Li, Huiying Sun, Lixia Ding, Jing Wang, Benshang Li, Bin-Bing S Zhou, Haizhong Feng, Yanxin Li","doi":"10.1097/BS9.0000000000000139","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000139","url":null,"abstract":"<p><p>Tumor relapse is the major cause of treatment failure in childhood acute lymphoblastic leukemia (ALL), yet the underlying mechanisms are still elusive. Here, we demonstrate that <i>phosphoribosyl pyrophosphate synthetase 2 (PRPS2</i>) mutations drive ALL relapse through influencing PRPS1/2 hexamer stability. Ultra-deep sequencing was performed to identify <i>PRPS2</i> mutations in ALL samples. The effects of <i>PRPS2</i> mutations on cell survival, cell apoptosis, and drug resistance were evaluated. In vitro PRPS2 enzyme activity and ADP/GDP feedback inhibition of PRPS enzyme activity were assessed. Purine metabolites were analyzed by ultra-performance liquid-chromatography tandem mass spectrometry (UPLC-MS/MS). Integrating sequencing data with clinical information, we identified <i>PRPS2</i> mutations only in relapsed childhood ALL with thiopurine therapy. Functional <i>PRPS2</i> mutations mediated purine metabolism specifically on thiopurine treatment by influencing PRPS1/2 hexamer stability, leading to reduced nucleotide feedback inhibition of PRPS activity and enhanced thiopurine resistance. The 3-amino acid V103-G104-E105, the key difference between PRPS1 and PRPS2, insertion in PRPS2 caused severe steric clash to the interface of PRPS hexamer, leading to its low enzyme activity. In addition, we demonstrated that PRPS2 P173R increased thiopurine resistance in xenograft models. Our work describes a novel mechanism by which PRPS2 mutants drive childhood ALL relapse and highlights PRPS2 mutations as biomarkers for relapsed childhood ALL.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1f/5b/bs9-5-39.PMC9891442.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10661692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1097/BS9.0000000000000146
[This corrects the article DOI: 10.1097/BS9.0000000000000115.].
[这更正了文章DOI: 10.1097/BS9.0000000000000115.]。
{"title":"Erratum: Assessment of humoral immunity and nutritionally essential trace elements in steady-state sickle cell disease Nigerian children before and after Prevenar 13 pneumococcal vaccination.","authors":"","doi":"10.1097/BS9.0000000000000146","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000146","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1097/BS9.0000000000000115.].</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9891438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10717127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1097/BS9.0000000000000138
Thomas Schiestel
To The Editor
{"title":"Acquired hemophilia associated with vedolizumab in a patient with hemorrhagic rectocolitis.","authors":"Thomas Schiestel","doi":"10.1097/BS9.0000000000000138","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000138","url":null,"abstract":"To The Editor","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9891452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10717135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1097/BS9.0000000000000142
Qishan Hao, Yang Song, Qiuyun Fang, Yani Lin, Long Chen, Xiaodan Wang, Ping Zhang, Zhe Wang, Xiaoyuan Gong, Kaiqi Liu, Qinghua Li, Zheng Tian, Min Wang, Jianxiang Wang, Yingchang Mi
Methotrexate (MTX) has an antitumor effect when used for the treatment of acute lymphoblastic leukemia (ALL). This study aims at evaluating the associations between 14 polymorphisms of six genes involved in MTX metabolism with serum MTX concentration and toxicity accompanying high-dose MTX. Polymorphisms in 183 Chinese patients with ALL were analyzed using TaqMan single nucleotide polymorphism genotyping assay. The serum MTX concentration was determined using homogeneous enzyme immunoassay. MTX-related toxicities were also evaluated. Renal toxicity was significantly associated with higher serum MTX concentrations at 24, 48, and 72 hours, and MTX elimination delay (P = 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively), whereas SLCO1B1 rs4149056 was associated with serum MTX concentrations at 48 and 72 hours, and MTX elimination delay in candidate polymorphisms (P = 0.014, P = 0.019, and P = 0.007, respectively). SLC19A1 rs2838958 and rs3788200 were associated with serum MTX concentrations at 24 hours (P = 0.016, P = 0.043, respectively). MTRR rs1801394 was associated with serum MTX concentrations at 72 hours (P = 0.045). Neutropenia was related to SLC19A1 rs4149056 (odds ratio [OR]: 3.172, 95% confidence interval [CI]: 1.310-7.681, P = 0.011). Hepatotoxicity was associated with ABCC2 rs2273697 (OR: 3.494, 95% CI: 1.236-9.873, P = 0.018) and MTRR rs1801394 (OR: 0.231, 95% CI: 0.084-0.632, P = 0.004). Polymorphisms of SLCO1B1, SLC19A1, ABCC2, and MTRR genes help predict higher risk of increased MTX levels or MTX-related toxicities in adult ALL patients.
{"title":"Effects of genetic polymorphisms on methotrexate levels and toxicity in Chinese patients with acute lymphoblastic leukemia.","authors":"Qishan Hao, Yang Song, Qiuyun Fang, Yani Lin, Long Chen, Xiaodan Wang, Ping Zhang, Zhe Wang, Xiaoyuan Gong, Kaiqi Liu, Qinghua Li, Zheng Tian, Min Wang, Jianxiang Wang, Yingchang Mi","doi":"10.1097/BS9.0000000000000142","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000142","url":null,"abstract":"<p><p>Methotrexate (MTX) has an antitumor effect when used for the treatment of acute lymphoblastic leukemia (ALL). This study aims at evaluating the associations between 14 polymorphisms of six genes involved in MTX metabolism with serum MTX concentration and toxicity accompanying high-dose MTX. Polymorphisms in 183 Chinese patients with ALL were analyzed using TaqMan single nucleotide polymorphism genotyping assay. The serum MTX concentration was determined using homogeneous enzyme immunoassay. MTX-related toxicities were also evaluated. Renal toxicity was significantly associated with higher serum MTX concentrations at 24, 48, and 72 hours, and MTX elimination delay (<i>P</i> = 0.001, <i>P</i> < 0.001, <i>P</i> < 0.001, and <i>P</i> < 0.001, respectively), whereas <i>SLCO1B1</i> rs4149056 was associated with serum MTX concentrations at 48 and 72 hours, and MTX elimination delay in candidate polymorphisms (<i>P</i> = 0.014, <i>P</i> = 0.019, and <i>P</i> = 0.007, respectively). <i>SLC19A1</i> rs2838958 and rs3788200 were associated with serum MTX concentrations at 24 hours (<i>P</i> = 0.016, <i>P</i> = 0.043, respectively). <i>MTRR</i> rs1801394 was associated with serum MTX concentrations at 72 hours (<i>P</i> = 0.045). Neutropenia was related to <i>SLC19A1</i> rs4149056 (odds ratio [OR]: 3.172, 95% confidence interval [CI]: 1.310-7.681, <i>P</i> = 0.011). Hepatotoxicity was associated with <i>ABCC2</i> rs2273697 (OR: 3.494, 95% CI: 1.236-9.873, <i>P</i> = 0.018) and <i>MTRR</i> rs1801394 (OR: 0.231, 95% CI: 0.084-0.632, <i>P</i> = 0.004). Polymorphisms of <i>SLCO1B1, SLC19A1, ABCC2</i>, and <i>MTRR</i> genes help predict higher risk of increased MTX levels or MTX-related toxicities in adult ALL patients.</p>","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9891445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10661697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-27eCollection Date: 2023-01-01DOI: 10.1097/BS9.0000000000000147
Brian Eyden, Xiaochen Wang
,
{"title":"The eighth International Forum on Stem Cells: virtual meeting, October 20-21, 2022.","authors":"Brian Eyden, Xiaochen Wang","doi":"10.1097/BS9.0000000000000147","DOIUrl":"10.1097/BS9.0000000000000147","url":null,"abstract":",","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10653338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46010084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}