IF 1.5

血液科学(英文) Pub Date : 2024-10-01 DOI: 10.1097/BS9.0000000000000208

Yun Dai, Fengyan Jin

引用次数: 0

Pre-transplantation levels of lysine (K)-specific methyltransferase 2A (KMT2A) partial tandem duplications can predict relapse of acute myeloid leukemia patients following haploidentical donor hematopoietic stem cell transplantation. 移植前赖氨酸（K）特异性甲基转移酶2A（KMT2A）部分串联重复水平可预测单倍体供体造血干细胞移植后急性髓性白血病患者的复发情况。

IF 1.5

血液科学(英文) Pub Date : 2024-09-25 eCollection Date: 2024-10-01 DOI: 10.1097/BS9.0000000000000207

Dao-Xing Deng, Xiao-Hang Ma, Ze-Hua Wu, Xiao-Hui Zhang, Lan-Ping Xu, Yu Wang, Chen-Hua Yan, Huan Chen, Yu-Hong Chen, Wei Han, Feng-Rong Wang, Jing-Zhi Wang, Xiao-Jun Huang, Xiao-Su Zhao, Xiao-Dong Mo

{"title":"Pre-transplantation levels of lysine (K)-specific methyltransferase 2A (KMT2A) partial tandem duplications can predict relapse of acute myeloid leukemia patients following haploidentical donor hematopoietic stem cell transplantation.","authors":"Dao-Xing Deng, Xiao-Hang Ma, Ze-Hua Wu, Xiao-Hui Zhang, Lan-Ping Xu, Yu Wang, Chen-Hua Yan, Huan Chen, Yu-Hong Chen, Wei Han, Feng-Rong Wang, Jing-Zhi Wang, Xiao-Jun Huang, Xiao-Su Zhao, Xiao-Dong Mo","doi":"10.1097/BS9.0000000000000207","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000207","url":null,"abstract":"We aimed to identify dynamic changes of lysine (K)-specific methyltransferase 2A partial tandem duplications (KMT2A-PTD) before and after haploidentical donor hematopoietic stem cell transplantation (HID HSCT) and explore the prognostic value of pre-transplantation levels of KMT2A-PTD in acute myeloid leukemia (AML) receiving HID HSCT. Consecutive 64 AML patients with KMT2A-PTD positivity at diagnosis receiving HID HSCT were included in this study. Patients with KMT2A-PTD ≥1% before HSCT had a slower decrease of KMT2A-PTD after HID HSCT. Patients with KMT2A-PTD ≥1% before HID HSCT had a higher cumulative incidence of relapse (36.4%, 95% confidence interval [CI]: 6.3%-66.5%) at 2 years after HSCT than those with KMT2A-PTD <1% (7.5%, 95% CI: 0.3%-14.7%, P = .010). In multivariable analysis, KMT2A-PTD ≥1% before HID HSCT was the only independent risk factor for relapse (hazard ratio [HR]: 4.90; 95% CI: 1.22-19.59; P = .025). Thus, pre-transplantation levels of KMT2A-PTD could predict relapse in AML patients following HID HSCT.","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":"6 4","pages":"e00207"},"PeriodicalIF":1.5,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333528","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}

引用次数: 0

Targeting HMGCS1 restores chemotherapy sensitivity in acute myeloid leukemia. 靶向 HMGCS1 可恢复急性髓性白血病的化疗敏感性。

IF 1.5

血液科学(英文) Pub Date : 2024-07-10 eCollection Date: 2024-07-01 DOI: 10.1097/BS9.0000000000000192

Cheng Zhou, Jue Li, Xiaofan Sun, Liang Zhao, Huien Zhan, Hui Liang, Peng Fang, Tuo Zhang, Qiongzhi He, Juan Du, Hui Zeng

{"title":"Targeting HMGCS1 restores chemotherapy sensitivity in acute myeloid leukemia.","authors":"Cheng Zhou, Jue Li, Xiaofan Sun, Liang Zhao, Huien Zhan, Hui Liang, Peng Fang, Tuo Zhang, Qiongzhi He, Juan Du, Hui Zeng","doi":"10.1097/BS9.0000000000000192","DOIUrl":"10.1097/BS9.0000000000000192","url":null,"abstract":"Acute myeloid leukemia (AML) is a common hematological malignancy with overall poor prognosis. Exploring novel targets is urgent and necessary to improve the clinical outcome of relapsed and refractory (RR) AML patients. Through clinical specimens, animal models and cell-level studies, we explored the specific mechanism of 3-hydroxy-3-methylglutaryl coenzyme A synthase 1 (HMGCS1) in AML and the mechanism of targeting HMGCS1 to attenuate cell proliferation, increase chemotherapy sensitivity and improve the occurrence and development of AML. Here, we reveal that HMGCS1 is overexpressed in RR patients and negatively related to overall survival (OS). Knocking out HMGCS1 in AML cells attenuated cell proliferation and increased chemotherapy sensitivity, while stable overexpression of HMGCS1 had the opposite effects. Mechanistically, we identified that knockout of HMGCS1 suppressed mitogen-activated protein kinase (MAPK) pathway activity, while overexpression of HMGCS1 could remarkably enhance the pathway. U0126, a MEK1 inhibitor, offset the effects of HMGCS1 overexpression, indicating that HMGCS1 promotes RR AML through the MAPK pathway. Further, we verified that hymeglusin, a specific inhibitor of HMGCS1, decreases cell growth both in AML cell lines and primary bone marrow cells of AML patients. Furthermore, combination of hymeglusin and the common chemotherapeutic drug cytarabine and adriamycin (ADR) had synergistic toxic effects on AML cells. Our study demonstrates the important role of HMGCS1 in AML, and targeting this protein is promising for the treatment of RR AML.","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":"6 3","pages":"e00192"},"PeriodicalIF":1.5,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11239175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592251","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}

引用次数: 0

Serum albumin is associated with the inherent property of acute myeloid leukemia and correlates with patient outcomes. 血清白蛋白与急性髓性白血病的固有特性有关，并与患者的预后相关。

血液科学(英文) Pub Date : 2024-05-10 eCollection Date: 2024-04-01 DOI: 10.1097/BS9.0000000000000189

Jiayuan Chen, Yan Hui, Yujia Zhai, Miao Yang, Xue Zhang, Yingchang Mi, Jianxiang Wang, Hui Wei

{"title":"Serum albumin is associated with the inherent property of acute myeloid leukemia and correlates with patient outcomes.","authors":"Jiayuan Chen, Yan Hui, Yujia Zhai, Miao Yang, Xue Zhang, Yingchang Mi, Jianxiang Wang, Hui Wei","doi":"10.1097/BS9.0000000000000189","DOIUrl":"10.1097/BS9.0000000000000189","url":null,"abstract":"An accurate prognostic model for acute myeloid leukemia (AML) can guide personalized treatment. In our prospective cohort of 591 patients newly diagnosed with AML, we evaluated the prognostic significance of serum albumin levels. We recognized baseline serum albumin as a prognostic factor by univariate Cox regression analysis (albumin-high vs albumin-low: overall survival [OS]: hazard ratio [HR]: 0.679, 95% confidence interval [CI]: 0.529-0.870, P = .002; cumulative incidence of relapse [CIR]: HR: 0.705, 95% CI: 0.530-0.938, P = .017) and multivariate Cox regression analysis (OS: HR per g/L: 0.966, 95% CI: 0.940-0.993, P = .014; CIR: HR per g/L: 0.959, 95% CI: 0.927-0.993, P = .017). In the subgroup analysis, serum albumin was prognostic significant in patients who received intermediate-dose cytarabine combined with daunorubicin and omacetaxine mepesuccinate induction (albumin-high vs albumin-low: OS: HR: 0.585, 95% CI: 0.397-0.863, P = .007; CIR: HR: 0.551, 95% CI: 0.353-0.861, P = .009) rather than those receiving conventional-dose induction regimens. In addition, the impact of baseline serum albumin level was evident in patients with intermediate European LeukemiaNet risk (albumin-high vs albumin-low: OS: HR: 0.617, 95% CI: 0.424-0.896, P = .011; CIR: HR: 0.617, 95% CI: 0.388-0.979, P = .040). Gene set enrichment analysis revealed that leukemia stem cell signatures were enriched in patients with low serum albumin levels. Our study suggested that baseline serum albumin level was associated with the inherent properties of AML and correlated with patient outcomes.","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":"6 2","pages":"e00189"},"PeriodicalIF":0.0,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11090624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140917215","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}

引用次数: 0

The RTK-RAS signaling pathway is enriched in patients with rare acute myeloid leukemia harboring t(16;21)(p11;q22)/FUS::ERG. 在携带t（16;21）(p11;q22)/FUS::ERG的罕见急性髓性白血病患者中，RTK-RAS信号通路富集。

血液科学(英文) Pub Date : 2024-05-10 eCollection Date: 2024-04-01 DOI: 10.1097/BS9.0000000000000188

Anli Lai, Wenbing Liu, Hui Wei, Ying Wang, Dong Lin, Chunlin Zhou, Bingcheng Liu, Runxia Gu, Yan Li, Shuning Wei, Benfa Gong, Kaiqi Liu, Xiaoyuan Gong, Yuntao Liu, Guangji Zhang, Junping Zhang, Yingchang Mi, Jianxiang Wang, Shaowei Qiu

{"title":"The RTK-RAS signaling pathway is enriched in patients with rare acute myeloid leukemia harboring t(16;21)(p11;q22)/FUS::ERG.","authors":"Anli Lai, Wenbing Liu, Hui Wei, Ying Wang, Dong Lin, Chunlin Zhou, Bingcheng Liu, Runxia Gu, Yan Li, Shuning Wei, Benfa Gong, Kaiqi Liu, Xiaoyuan Gong, Yuntao Liu, Guangji Zhang, Junping Zhang, Yingchang Mi, Jianxiang Wang, Shaowei Qiu","doi":"10.1097/BS9.0000000000000188","DOIUrl":"10.1097/BS9.0000000000000188","url":null,"abstract":"Acute myeloid leukemia (AML) with t(16;21)(p11;q22)/FUS::ERG is a rare AML subtype associated with poor prognosis. However, its clinical and molecular features remain poorly defined. We determined the clinicopathological, genomic, and transcriptomic characteristics and outcomes of patients with AML harboring FUS::ERG at our center. Thirty-six AML patients harboring FUS::ERG were identified, with an incidence rate of 0.3%. These patients were characterized by high lactate dehydrogenase levels (median: 838.5 U/L), elevated bone marrow blast counts (median: 71.5%), and a CD56-positive immunophenotype (94.3%). Notably, we found that RTK-RAS GTPase (RAS) pathway genes, including NRAS (33%) and PTPN11 (24%), were frequently mutated in this subtype. Transcriptome analysis revealed enrichment of the phosphatidylinositol-3-kinase-Akt (PI3K-Akt), mitogen-activated protein kinase (MAPK), and RAS signaling pathways and upregulation of BCL2, the target of venetoclax, in FUS::ERG AML compared to RUNX1::RUNX1T1 AML, a more common AML subtype with good prognosis. The median event-free survival in patients with FUS::ERG AML was 11.9 (95% confidence interval [CI]: 9.0-not available [NA]) months and the median overall survival was 18.2 (95% CI: 12.4-NA) months. Allogeneic hematopoietic stem cell transplantation failed to improve outcomes. Overall, the high incidence of RTK-RAS pathway mutations and high expression of BCL2 may indicate promising therapeutic targets in this high-risk AML subset.","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":"6 2","pages":"e00188"},"PeriodicalIF":0.0,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11090622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140917132","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}

引用次数: 0

Early megakaryocyte lineage-committed progenitors in adult mouse bone marrow. 成年小鼠骨髓中的早期巨核细胞系定向祖细胞

血液科学(英文) Pub Date : 2024-05-07 eCollection Date: 2024-04-01 DOI: 10.1097/BS9.0000000000000187

Zixian Liu, Jinhong Wang, Yao Ma, Miner Xie, Peng Wu, Sen Zhang, Xiaofang Wang, Fang Dong, Hui Cheng, Ping Zhu, Mingzhe Han, Hideo Ema

{"title":"Early megakaryocyte lineage-committed progenitors in adult mouse bone marrow.","authors":"Zixian Liu, Jinhong Wang, Yao Ma, Miner Xie, Peng Wu, Sen Zhang, Xiaofang Wang, Fang Dong, Hui Cheng, Ping Zhu, Mingzhe Han, Hideo Ema","doi":"10.1097/BS9.0000000000000187","DOIUrl":"10.1097/BS9.0000000000000187","url":null,"abstract":"Hematopoietic stem cells (HSCs) have been considered to progressively lose their self-renewal and differentiation potentials prior to the commitment to each blood lineage. However, recent studies have suggested that megakaryocyte progenitors (MkPs) are generated at the level of HSCs. In this study, we newly identified early megakaryocyte lineage-committed progenitors (MgPs) mainly in CD201-CD48- cells and CD48+ cells separated from the CD150+CD34-Kit+Sca-1+Lin- HSC population of the bone marrow in adult mice. Single-cell colony assay and single-cell transplantation showed that MgPs, unlike platelet-biased HSCs, had little repopulating potential in vivo, but formed larger megakaryocyte colonies in vitro (on average 8 megakaryocytes per colony) than did previously reported MkPs. Single-cell RNA sequencing supported that HSCs give rise to MkPs through MgPs along a Mk differentiation pathway. Single-cell reverse transcription polymerase chain reaction (RT-PCR) analysis showed that MgPs expressed Mk-related genes, but were transcriptionally heterogenous. Clonal culture of HSCs suggested that MgPs are not direct progeny of HSCs. We propose a differentiation model in which HSCs give rise to MgPs which then give rise to MkPs, supporting a classic model in which Mk-lineage commitment takes place at a late stage of differentiation.","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":"6 2","pages":"e00187"},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11078525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140890630","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}

引用次数: 0

Investigation of the relationship between coagulation parameters and mortality in COVID-19 infection. 研究 COVID-19 感染者凝血参数与死亡率之间的关系。

血液科学(英文) Pub Date : 2024-04-30 eCollection Date: 2024-04-01 DOI: 10.1097/BS9.0000000000000191

Fatih Ikiz, Ahmet Ak

{"title":"Investigation of the relationship between coagulation parameters and mortality in COVID-19 infection.","authors":"Fatih Ikiz, Ahmet Ak","doi":"10.1097/BS9.0000000000000191","DOIUrl":"https://doi.org/10.1097/BS9.0000000000000191","url":null,"abstract":"This study, which included patients over the age of 18 who were diagnosed with coronavirus disease 2019 (COVID-19) in the emergency clinic, aims to determine the relationship between coagulation parameters and mortality. Epidemiologic data such as age, gender, medical history, vital parameters at emergency department admission, clinical findings, coagulation parameters such as d-dimer, prothrombin time (PT), active partial thromboplastin time (aPTT), international normalized ration (INR), fibrinogen, and platelet were evaluated. Patients with positive computerized tomography (CT) findings and positive polymerase chain reaction (PCR) together were included in the study. It was revealed that d-dimer, fibrinogen, INR, and PT values were higher in the elderly group. It was shown that there was a significant relationship between hospitalization days (ward or intensive care unit) and d-dimer levels. It was observed that d-dimer, fibrinogen elevation was significantly associated with prognosis by increasing mortality, and that platelet and aPTT values were also associated with prognosis and were lower in the mortality group. On the other hand, in receiver operating characteristic (ROC) analysis, the sensitivity and specificity data were 80.3%/80.0% for d-dimer, 70.5%/72.2% for fibrinogen, 58.2%/59.4% for aPTT, and 59.7%/59.2% for platelet, respectively. The overall classification success was 88.6% and mortality prediction success was 37.7% in the regression model of some coagulation parameters (d-dimer, fibrinogen, aPTT, and platelet) which were effective on prognosis. In conclusion, it was determined that d-dimer, fibrinogen, aPTT, and platelet parameters were directly associated with mortality and when these coagulation parameters were used together with the clinical, vital, and demographic data of the patients, the success of mortality prediction increased significantly.","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":"6 2","pages":"e00191"},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874254","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}

引用次数: 0

COVID-19 in immunocompromised patients after hematopoietic stem cell transplantation: a pilot study. 造血干细胞移植后免疫功能低下患者的 COVID-19：一项试点研究。

IF 1.5

血液科学(英文) Pub Date : 2024-01-25 eCollection Date: 2024-04-01 DOI: 10.1097/BS9.0000000000000183

Zilu Zhang, Jingtao Huang, Luxiang Wang, Zengkai Pan, Jiayu Huang, Chuanhe Jiang, Sujiang Zhang, Su Li, Xiaoxia Hu

{"title":"COVID-19 in immunocompromised patients after hematopoietic stem cell transplantation: a pilot study.","authors":"Zilu Zhang, Jingtao Huang, Luxiang Wang, Zengkai Pan, Jiayu Huang, Chuanhe Jiang, Sujiang Zhang, Su Li, Xiaoxia Hu","doi":"10.1097/BS9.0000000000000183","DOIUrl":"10.1097/BS9.0000000000000183","url":null,"abstract":"Data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients at early stage of immune reconstitution after hematopoietic stem cell transplantation (HSCT) are limited. In the present study, we retrospectively investigated the incidence and clinical features of SARS-CoV-2 infection in patients who underwent HSCT in 2022. Patients (allo-HSCT, n = 80; auto-HSCT, n = 37) were consecutively included in the study. The SARS-CoV-2 infection rate was 59.8%, and the median interval of HSCT to coronavirus disease 2019 (COVID-19) was 4.8 (range: 0.5-12) months. Most patients were categorized as mild (41.4%) or moderate (38.6%), and 20% as severe/critical. No deaths were attributable to COVID-19. Further analysis showed that lower circulating CD8+ T-cell counts and calcineurin inhibitor administration increased the risk of SARS-CoV-2 infection. Exposure to rituximab significantly increased the probability of severe or critical COVID-19 compared with that of mild/moderate illness (P < .001). In the multivariate analysis, rituximab use was associated with severe COVID-19. Additionally, COVID-19 had no significant effect on immune reconstitution. Furthermore, it was found that Epstein-Barr virus infection and rituximab administration possibly increase the risk of developing severe illness. Our study provides preliminary insights into the effect of SARS-CoV-2 on immune reconstitution and the outcomes of allo-HSCT recipients.","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":"6 2","pages":"e00183"},"PeriodicalIF":1.5,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10817160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139572399","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}

引用次数: 0

Sequential treatment escalation improves survival in patients with Waldenstrom macroglobulinemia. 循序渐进的治疗可提高瓦尔登斯特罗姆巨球蛋白血症患者的生存率。

血液科学(英文) Pub Date : 2024-01-17 eCollection Date: 2024-01-01 DOI: 10.1097/BS9.0000000000000179

Ying Yu, Wenjie Xiong, Tingyu Wang, Yuting Yan, Rui Lyu, Qi Wang, Wei Liu, Gang An, Weiwei Sui, Yan Xu, Wenyang Huang, Dehui Zou, Jianxiang Wang, Lugui Qiu, Shuhua Yi

{"title":"Sequential treatment escalation improves survival in patients with Waldenstrom macroglobulinemia.","authors":"Ying Yu, Wenjie Xiong, Tingyu Wang, Yuting Yan, Rui Lyu, Qi Wang, Wei Liu, Gang An, Weiwei Sui, Yan Xu, Wenyang Huang, Dehui Zou, Jianxiang Wang, Lugui Qiu, Shuhua Yi","doi":"10.1097/BS9.0000000000000179","DOIUrl":"10.1097/BS9.0000000000000179","url":null,"abstract":"Waldenstrom macroglobulinemia (WM) is a type of incurable, indolent B-cell lymphoma that is prone to relapse. Over time, treatment strategies have progressed from cytotoxic drugs to rituximab (R)- or bortezomib (V)-based regimens, and have now entered into an era of Bruton tyrosine kinase inhibitor (BTKi)-based regimens. However, the optimal treatment for the relapsed patients is still unclear. Herein, we analyzed the outcomes of the first- and second-line therapies in 377 patients with WM to illustrate the optimal choices for second-line therapy. After a median follow-up of 45.4 months, 89 patients received second-line therapy, and 53 patients were evaluated for response. The major response rates (MRR) of first- and second-line treatment were 65.1% and 67.9% (P = 0.678). The median progression-free survival (PFS) for the second-line therapy (PFS2) was shorter than that for the first-line therapy (PFS1) (56.3 vs 40.7 months, P = 0.03). However, PFS2 in targeted drugs group (R-/V-/BTKi-based regimens) was comparable to PFS1 (60.7 months vs 44.7 months, respectively, P = 0.21). Regarding second-line therapy, patients who underwent sequential treatment escalation-such as transitioning from cytotoxic drugs to R-/V-/BTKi-based regimens or from R-/V-based to BTKi-based regimens (escalation group) -had higher MRR (80.6% vs 47.1%, respectively, P = 0.023) and longer PFS2 (50.4 vs 23.5 months, respectively, P < 0.001) compared to the non-escalation group. Patients in the escalation group also had longer post-relapse overall survival compared with the non-escalation group (median, 50.4 vs 23.5 months, respectively, P = 0.039). Our findings indicate that sequential treatment escalation may improve the survival of patients with WM.","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":"6 1","pages":"e00179"},"PeriodicalIF":0.0,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10796142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139492810","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}

引用次数: 0

Immune checkpoint expression patterns on T cell subsets in light-chain amyloidosis: VISTA, PD-1, and TIGIT as potential therapeutic targets. 轻链淀粉样变性中 T 细胞亚群的免疫检查点表达模式：作为潜在治疗靶点的 VISTA、PD-1 和 TIGIT。

血液科学(英文) Pub Date : 2024-01-15 eCollection Date: 2024-01-01 DOI: 10.1097/BS9.0000000000000181

Jinghua Wang, Yujie Zhao, Pengjun Liao, Shuxin Huang, Youxue Huang, Shaohua Chen, Yangqiu Li, Liye Zhong

{"title":"Immune checkpoint expression patterns on T cell subsets in light-chain amyloidosis: VISTA, PD-1, and TIGIT as potential therapeutic targets.","authors":"Jinghua Wang, Yujie Zhao, Pengjun Liao, Shuxin Huang, Youxue Huang, Shaohua Chen, Yangqiu Li, Liye Zhong","doi":"10.1097/BS9.0000000000000181","DOIUrl":"10.1097/BS9.0000000000000181","url":null,"abstract":"Amyloid light chain (AL) amyloidosis is a rare plasma cell dyscrasia with dismal prognosis. This study aims to investigate the T-cell immune checkpoint expression patterns in systemic AL amyloidosis and its relationship with clinicobiological traits. We examined the frequencies of V-domain immunoglobulin suppressor of T cell activation+ (VISTA+), programmed cell death 1+ (PD-1+), T cell immunoglobulin and mucin-domain-containing-3+ (Tim-3+), T cell immunoreceptor with Ig and ITIM domains+ (TIGIT+) T cells in peripheral blood (PB) and bone marrow (BM) from 19 patients with newly diagnosed AL amyloidosis. Patients with AL amyloidosis had significantly higher percentages of VISTA+ and PD-1+ T cells in PB than healthy individuals (HIs), with no statistical differences in BM. The percentages of some double-positive T cells in PB were also considerably higher in AL amyloidosis than those in HIs. Additionally, the patients with renal involvement had more PD-1+ and TIGIT+ T cells than the patients without, and PD-1+CD3+%, PD-1+CD4+%, PD-1+Treg% were positively correlated with 24-hour proteinuria levels. Furthermore, the AL amyloidosis patients had higher counts of PD-1+ Treg in PB than multiple myeloma (MM) patients, while the MM patients had higher counts of TIGIT+ T cells than AL amyloidosis patients. Collectively, this is the first report of elevated proportions of VISTA+ and PD-1+ T cells in PB of AL amyloidosis patients, indicating an immunosuppressive milieu, and the increased PD-1+ and TIGIT+ T cells were associated with renal damage. VISTA, PD-1, and TIGIT may be potential targets for reversing T-cell exhaustion in AL amyloidosis.","PeriodicalId":67343,"journal":{"name":"血液科学(英文)","volume":"6 1","pages":"e00181"},"PeriodicalIF":0.0,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10789457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139473109","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}

引用次数: 0

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