Treatment response, survival, safety, and predictive factors to chimeric antigen receptor T cell therapy in Chinese relapsed or refractory B cell acute lymphoblast leukemia patients.

Abstract:

:This study aimed to evaluate treatment response, survival, safety profiles, and predictive factors to chimeric antigen receptor T cell (CAR-T) therapy in Chinese patients with relapsed or refractory B cell acute lymphoblast leukemia (R/R B-ALL). 39R/R B-ALL patients who underwent CAR-T therapy were included. Baseline data were collected from patients' electronic medical records. Patients' peripheral bloods, bone marrow aspirates, and biopsies were obtained for routine examination, and treatment response and survival profiles as well as adverse events were evaluated. The rates of complete remission (CR), CR with minimal residual disease (MRD) negative/positive, and bridging to hematopoietic stem-cell transplantation (HSCT) were 92.3%, 76.9%, 15.4%, and 43.6%, respectively. The median event-free survival (EFS) was 11.6 months (95% confidence interval (CI): 4.0-19.2 months) and median overall survival (OS) was 14.0 months (95% CI: 10.9-17.1 months). Bridging to HSCT independently predicted better EFS and OS, while high bone marrow blasts level independently predicted worse EFS. The incidence of cytokine release syndrome (CRS) was 97.4%, and refractory disease as well as decreased white blood cell independently predicted higher risk of severe CRS. Other common adverse events included hematologic toxicities (grade I: 5.1%, grade II: 7.7%, grade III: 17.9%, grade IV: 69.2%), neurotoxicity (28.2%), infection (38.5%), and admission for intensive care unit (10.3%). In conclusion, CAR-T therapy presents with promising treatment response, survival and safety profiles, and higher disease burden predicts worse survival as well as increased risk of severe CRS in Chinese R/R B-ALL patients.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Li L,Liu J,Xu M,Yu H,Lv C,Cao F,Wang Z,Fu Y,Zhang M,Meng H,Zhang X,Kang L,Zhang Z,Li J,Feng J,Lian X,Yu L,Zhou J

doi

10.1038/s41419-020-2388-1

subject

Has Abstract

pub_date

2020-03-30 00:00:00

pages

207

issue

3

issn

2041-4889

pii

10.1038/s41419-020-2388-1

journal_volume

11

pub_type

杂志文章
  • Prolyl isomerase Pin1: a promoter of cancer and a target for therapy.

    abstract::Pin1 is the only known peptidyl-prolyl cis-trans isomerase (PPIase) that specifically recognizes and isomerizes the phosphorylated Serine/Threonine-Proline (pSer/Thr-Pro) motif. The Pin1-mediated structural transformation posttranslationally regulates the biofunctions of multiple proteins. Pin1 is involved in many cel...

    journal_title:Cell death & disease

    pub_type: 杂志文章,评审

    doi:10.1038/s41419-018-0844-y

    authors: Chen Y,Wu YR,Yang HY,Li XZ,Jie MM,Hu CJ,Wu YY,Yang SM,Yang YB

    更新日期:2018-08-29 00:00:00

  • Expression of ETS1 in gastric epithelial cells positively regulate inflammatory response in Helicobacter pylori-associated gastritis.

    abstract::Gastric epithelial cells (GECs) provide the first point of contact of the host by Helicobacter pylori (H. pylori), and the interaction between H. pylori and GECs plays a critical role in H. pylori-associated diseases. Aberrant expression of transcription factors (TFs) contributes to the pathogenesis of inflammatory di...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2705-8

    authors: Teng Y,Cang B,Mao F,Chen W,Cheng P,Peng L,Luo P,Lu D,You N,Zou Q,Zhuang Y

    更新日期:2020-07-01 00:00:00

  • Effect of hydroxychloroquine and characterization of autophagy in a mouse model of endometriosis.

    abstract::In endometriosis, the increased survival potential of shed endometrial cells (which normally undergo anoikis) is suggested to promote lesion development. One mechanism that may alter anoikis is autophagy. Using an autophagic flux inhibitor hydroxychloroquine (HCQ), we identified that it reduces the in vitro survival c...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2015.361

    authors: Ruiz A,Rockfield S,Taran N,Haller E,Engelman RW,Flores I,Panina-Bordignon P,Nanjundan M

    更新日期:2016-01-14 00:00:00

  • Hepatocyte caveolin-1 modulates metabolic gene profiles and functions in non-alcoholic fatty liver disease.

    abstract::Caveolin-1 (CAV1) is a crucial regulator of lipid accumulation and metabolism. Previous studies have shown that global Cav1 deficiency affects lipid metabolism and hepatic steatosis. We aimed to analyze the consequences of hepatocyte-specific Cav1 knockout under healthy conditions and upon non-alcoholic fatty liver di...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2295-5

    authors: Han M,Piorońska W,Wang S,Nwosu ZC,Sticht C,Wang S,Gao Y,Ebert MP,Dooley S,Meyer C

    更新日期:2020-02-06 00:00:00

  • miR-195 targets cyclin D3 and survivin to modulate the tumorigenesis of non-small cell lung cancer.

    abstract::miR-195 has recently been reported to function as a tumor suppressor in various cancers, including non-small cell lung cancer (NSCLC). However, the mechanisms by which miR-195 represses the tumorigenesis of NSCLC cells are not fully understood. We performed a high-throughput screen using an miRNA mimic library and con...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-017-0219-9

    authors: Yu X,Zhang Y,Cavazos D,Ma X,Zhao Z,Du L,Pertsemlidis A

    更新日期:2018-02-07 00:00:00

  • Aquaporin 3 maintains the stemness of CD133+ hepatocellular carcinoma cells by activating STAT3.

    abstract::An increasing interest in liver cancer stemness arises owing to its aggressive behavior and poor prognosis. CD133, a widely known liver cancer stem cell marker, plays critical roles in the maintenance of liver cancer stemness. Thus, exploring the regulatory mechanism of CD133 expression is significant. In the present ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1712-0

    authors: Wang Y,Wu G,Fu X,Xu S,Wang T,Zhang Q,Yang Y

    更新日期:2019-06-13 00:00:00

  • Knockout of Atg5 delays the maturation and reduces the survival of adult-generated neurons in the hippocampus.

    abstract::Autophagy is an evolutionarily conserved lysosomal degradation pathway that plays important roles in cell maintenance, expansion and differentiation. Removal of genes essential for autophagy from embryonic neural stem and precursor cells reduces the survival and inhibits neuronal differentiation of adult-generated neu...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2015.406

    authors: Xi Y,Dhaliwal JS,Ceizar M,Vaculik M,Kumar KL,Lagace DC

    更新日期:2016-03-03 00:00:00

  • DDX5-targeting fully human monoclonal autoantibody inhibits proliferation and promotes differentiation of acute promyelocytic leukemia cells by increasing ROS production.

    abstract::Acute promyelocytic leukemia (APL) therapy involves the compounds cytotoxic to both malignant tumor and normal cells. Relapsed APL is resistant to subsequent chemotherapy. Novel agents are in need to kill APL cells selectively with minimal toxicity. DDX5 has been recognized to be a novel target to suppress acute myelo...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-02759-5

    authors: Wu J,You YQ,Ma YX,Kang YH,Wu T,Wu XJ,Hu XX,Meng QH,Huang Y,Zhang N,Pan XB

    更新日期:2020-07-20 00:00:00

  • Eicosapentaenoic acid attenuates dexamethasome-induced apoptosis by inducing adaptive autophagy via GPR120 in murine bone marrow-derived mesenchymal stem cells.

    abstract::Long-term use of glucocorticoids is a widespread clinical problem, which currently has no effective solution other than discontinuing the use. Eicosapentaenoic acid (EPA), an omega-3 long chain polyunsaturated fatty acid (n-3 PUFA), which is largely contained in fish or fish oil, has been reported to promote cell viab...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2016.144

    authors: Gao B,Han YH,Wang L,Lin YJ,Sun Z,Lu WG,Hu YQ,Li JQ,Lin XS,Liu BH,Jie Q,Yang L,Luo ZJ

    更新日期:2016-05-26 00:00:00

  • Chloride channels are necessary for full platelet phosphatidylserine exposure and procoagulant activity.

    abstract::Platelets enhance thrombin generation at sites of vascular injury by exposing phosphatidylserine during necrosis-like cell death. Anoctamin 6 (Ano6) is required for Ca(2+)-dependent phosphatidylserine exposure and is defective in patients with Scott syndrome, a rare bleeding disorder. Ano6 may also form Cl(-) channels...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.495

    authors: Harper MT,Poole AW

    更新日期:2013-12-19 00:00:00

  • Preclinical screening of histone deacetylase inhibitors combined with ABT-737, rhTRAIL/MD5-1 or 5-azacytidine using syngeneic Vk*MYC multiple myeloma.

    abstract::Multiple myeloma (MM) is an incurable malignancy with an unmet need for innovative treatment options. Histone deacetylase inhibitors (HDACi) are a new class of anticancer agent that have demonstrated activity in hematological malignancies. Here, we investigated the efficacy and safety of HDACi (vorinostat, panobinosta...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.306

    authors: Matthews GM,Lefebure M,Doyle MA,Shortt J,Ellul J,Chesi M,Banks KM,Vidacs E,Faulkner D,Atadja P,Bergsagel PL,Johnstone RW

    更新日期:2013-09-12 00:00:00

  • High-fat diet feeding and palmitic acid increase CRC growth in β2AR-dependent manner.

    abstract::Epidemiology studies indicate that consumption of high-fat diet (HFD) is directly associated with the development of colorectal cancer (CRC). However, the exact component in HFD and the mechanism underlying its effect on CRC growth remained unclear. Our study shows that HFD feeding increases β2AR expression in the xen...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1958-6

    authors: Fatima S,Hu X,Huang C,Zhang W,Cai J,Huang M,Gong RH,Chen M,Ho AHM,Su T,Wong HLX,Bian Z,Kwan HY

    更新日期:2019-09-26 00:00:00

  • The regulatory mechanism and biological significance of the Snail-miR590-VEGFR-NRP1 axis in the angiogenesis, growth and metastasis of gastric cancer.

    abstract::Vascular endothelial growth factor receptor (VEGFR) and neuropilins (NRPs), a co-receptor of VEGF, play a key role in the formation and development of blood vessels and in tumour growth and metastasis. However, whether VEGFR1/2 and NRP1 are regulated by the same upstream mechanism is unclear, especially in gastric can...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2428-x

    authors: Mei B,Chen J,Yang N,Peng Y

    更新日期:2020-04-17 00:00:00

  • ELABELA attenuates deoxycorticosterone acetate/salt-induced hypertension and renal injury by inhibition of NADPH oxidase/ROS/NLRP3 inflammasome pathway.

    abstract::ELABELA (ELA), a 32-residue hormone peptide abundantly expressed in adult kidneys, has been identified as a novel endogenous ligand for APJ/Apelin receptor. The aim of this study was to investigate the role of ELA in deoxycorticosterone acetate (DOCA)/salt-induced hypertension and further explore the underlying mechan...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-02912-0

    authors: Chen Z,Wu C,Liu Y,Li H,Zhu Y,Huang C,Lin H,Qiao Q,Huang M,Zhu Q,Wang L

    更新日期:2020-08-22 00:00:00

  • miR-182-5p and miR-378a-3p regulate ferroptosis in I/R-induced renal injury.

    abstract::Renal tubular cell death is the key factor of the pathogenesis of ischemia/reperfusion (I/R) kidney injury. Ferroptosis is a type of regulated cell death (RCD) found in various diseases. However, the underlying molecular mechanisms related to ferroptosis in renal I/R injury remain unclear. In the present study, we inv...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-03135-z

    authors: Ding C,Ding X,Zheng J,Wang B,Li Y,Xiang H,Dou M,Qiao Y,Tian P,Xue W

    更新日期:2020-10-28 00:00:00

  • Manganese superoxide dismutase promotes anoikis resistance and tumor metastasis.

    abstract::Normal cells require adhesion to extracellular matrix for survival. Cell detachment causes a drastic increase in reactive oxygen species (ROS) that promotes anoikis. In the present study, we observed that upon detachment from matrix, human mammary epithelial cells strongly upregulate manganese superoxide dismutase (Mn...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.20

    authors: Kamarajugadda S,Cai Q,Chen H,Nayak S,Zhu J,He M,Jin Y,Zhang Y,Ai L,Martin SS,Tan M,Lu J

    更新日期:2013-02-21 00:00:00

  • miRNA let-7e targeting MMP9 is involved in adipose-derived stem cell differentiation toward epithelia.

    abstract::miRNA let-7e is involved in stem cell differentiation, and metalloproteinases are among its potential target genes. We hypothesized that the inhibitory action of let-7e on regulation of MMP9 expression could represent a crucial mechanism during differentiation of adipose-derived stem cells (ASCs). ASCs were differenti...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.2

    authors: Ventayol M,Viñas JL,Sola A,Jung M,Brüne B,Pi F,Mastora C,Hotter G

    更新日期:2014-02-06 00:00:00

  • Consequences of blunting the mevalonate pathway in cancer identified by a pluri-omics approach.

    abstract::We have previously shown that the combination of statins and taxanes was a powerful trigger of HGT-1 human gastric cancer cells' apoptosis1. Importantly, several genes involved in the "Central carbon metabolism pathway in cancer", as reported in the Kyoto Encyclopedia of Genes and Genomes, were either up- (ACLY, ERBB2...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-018-0761-0

    authors: Goulitquer S,Croyal M,Lalande J,Royer AL,Guitton Y,Arzur D,Durand S,Le Jossic-Corcos C,Bouchereau A,Potin P,Akoka S,Antignac JP,Krempf M,Ferchaud-Roucher V,Giraudeau P,Corcos L

    更新日期:2018-07-03 00:00:00

  • Excitotoxic cell death induces delayed proliferation of endogenous neuroprogenitor cells in organotypic slice cultures of the rat spinal cord.

    abstract::The aim of the present report was to investigate whether, in the mammalian spinal cord, cell death induced by transient excitotoxic stress could trigger activation and proliferation of endogenous neuroprogenitor cells as a potential source of a lesion repair process and the underlying time course. Because it is diffic...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2013.431

    authors: Mazzone GL,Mladinic M,Nistri A

    更新日期:2013-10-31 00:00:00

  • Prolyl hydroxylase 2 silencing enhances the paracrine effects of mesenchymal stem cells on necrotizing enterocolitis in an NF-κB-dependent mechanism.

    abstract::Treatment options for necrotizing enterocolitis (NEC) remain inadequate. Here we examined if and how prolyl hydroxylase 2 (PHD2) silencing enhances the paracrine effects of bone-marrow-derived mesenchymal stem cells (BM-MSCs) on NEC. In this study, BM-MSCs were transduced with lentiviruses containing GFP (GFP-MSC) or ...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2378-3

    authors: Chen H,Zhang H,Zheng Y,Min X,Luo Y,Zhou W,Ma F,Li J,Lu Q,Zhang C,Cai H,Sha W

    更新日期:2020-03-16 00:00:00

  • MicroRNA-302 induces proliferation and inhibits oxidant-induced cell death in human adipose tissue-derived mesenchymal stem cells.

    abstract::Mesenchymal stem cells (MSCs) are a heterogeneous population of cells that proliferate in vitro as plastic-adherent cells, have a fibroblast-like morphology, form colonies in vitro and can differentiate into bone, cartilage and fat cells. The abundance, ease and repeatable access to subcutaneous adipose tissue and the...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2014.344

    authors: Kim JY,Shin KK,Lee AL,Kim YS,Park HJ,Park YK,Bae YC,Jung JS

    更新日期:2014-08-21 00:00:00

  • Sirt3 suppresses calcium oxalate-induced renal tubular epithelial cell injury via modification of FoxO3a-mediated autophagy.

    abstract::High oxalic acid and calcium oxalate (CaOx)-induced renal tubular epithelial cell (TEC) injury plays a key role in nephrolithiasis. However, the mechanism remains unknown. Gene array analysis of the mice nephrolithiasis model indicated significant downregulation of sirtuin 3 (Sirt3) and activation of mitogen-activated...

    journal_title:Cell death & disease

    pub_type: 杂志文章,收录出版

    doi:10.1038/s41419-018-1169-6

    authors: Peng Y,Yang C,Shi X,Li L,Dong H,Liu C,Fang Z,Wang Z,Ming S,Liu M,Xie B,Gao X,Sun Y

    更新日期:2019-01-15 00:00:00

  • miR-6086 inhibits ovarian cancer angiogenesis by downregulating the OC2/VEGFA/EGFL6 axis.

    abstract::miRNAs have emerged as a pivotal component of gene regulatory networks, mediating cytokines secretion, cell cycle, and differentiation regulation. However, how miRNAs collaborate with transcription factors and downstream effector proteins that determine the fate of ovarian cancer cells remains to be understood, especi...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2501-5

    authors: Wu B,Zhang L,Yu Y,Lu T,Zhang Y,Zhu W,Song Q,Lv C,Guo J,Tian Y,Deng N

    更新日期:2020-05-11 00:00:00

  • The lncRNA TP73-AS1 is linked to aggressiveness in glioblastoma and promotes temozolomide resistance in glioblastoma cancer stem cells.

    abstract::Glioblastoma multiform (GBM) is the most common brain tumor characterized by a dismal prognosis. GBM cancer stem cells (gCSC) or tumor-initiating cells are the cell population within the tumor-driving therapy resistance and recurrence. While temozolomide (TMZ), an alkylating agent, constitutes the first-line chemother...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1477-5

    authors: Mazor G,Levin L,Picard D,Ahmadov U,Carén H,Borkhardt A,Reifenberger G,Leprivier G,Remke M,Rotblat B

    更新日期:2019-03-13 00:00:00

  • Cytochrome c oxidase deficiency accelerates mitochondrial apoptosis by activating ceramide synthase 6.

    abstract::Although numerous pathogenic changes within the mitochondrial respiratory chain (RC) have been associated with an elevated occurrence of apoptosis within the affected tissues, the mechanistic insight into how mitochondrial dysfunction initiates apoptotic cell death is still unknown. In this study, we show that the spe...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2015.62

    authors: Schüll S,Günther SD,Brodesser S,Seeger JM,Tosetti B,Wiegmann K,Pongratz C,Diaz F,Witt A,Andree M,Brinkmann K,Krönke M,Wiesner RJ,Kashkar H

    更新日期:2015-03-12 00:00:00

  • TRAIL enhances paracetamol-induced liver sinusoidal endothelial cell death in a Bim- and Bid-dependent manner.

    abstract::Paracetamol (acetaminophen, APAP) is a universally used analgesic and antipyretic agent. Considered safe at therapeutic doses, overdoses cause acute liver damage characterized by centrilobular hepatic necrosis. One of the major clinical problems of paracetamol-induced liver disease is the development of hemorrhagic al...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2012.185

    authors: Badmann A,Langsch S,Keogh A,Brunner T,Kaufmann T,Corazza N

    更新日期:2012-12-20 00:00:00

  • Induction of autophagy by spermidine is neuroprotective via inhibition of caspase 3-mediated Beclin 1 cleavage.

    abstract::Spermidine, a natural polyamine presented widely in mammalian cells, has been implicated to extend the lifespan of several model organisms by inducing autophagy. However, the effect of spermidine against neuronal damage has not yet been fully determined. In this study, neuronal cell injury was induced by treating PC12...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/cddis.2017.161

    authors: Yang Y,Chen S,Zhang Y,Lin X,Song Y,Xue Z,Qian H,Wang S,Wan G,Zheng X,Zhang L

    更新日期:2017-04-06 00:00:00

  • MicroRNA-181a-5p and microRNA-181a-3p cooperatively restrict vascular inflammation and atherosclerosis.

    abstract::MicroRNAs have emerged as important post-transcriptional regulators of gene expression and are involved in diverse diseases and cellular process. Decreased expression of miR-181a has been observed in the patients with coronary artery disease, but its function and mechanism in atherogenesis is not clear. This study was...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1599-9

    authors: Su Y,Yuan J,Zhang F,Lei Q,Zhang T,Li K,Guo J,Hong Y,Bu G,Lv X,Liang S,Ou J,Zhou J,Luo B,Shang J

    更新日期:2019-05-07 00:00:00

  • DJ-1 modulates the unfolded protein response and cell death via upregulation of ATF4 following ER stress.

    abstract::The unfolded protein response (UPR) triggered by endoplasmic reticulum (ER) stress is a feature of many neurodegenerative diseases including Alzheimer's disease, Huntington's disease and Parkinson's disease (PD). Although the vast majority of PD is sporadic, mutations in a number of genes including PARK7 which encodes...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-019-1354-2

    authors: Yang J,Kim KS,Iyirhiaro GO,Marcogliese PC,Callaghan SM,Qu D,Kim WJ,Slack RS,Park DS

    更新日期:2019-02-12 00:00:00

  • Long noncoding RNA lncARSR confers resistance to Adriamycin and promotes osteosarcoma progression.

    abstract::One of the significant challenges for chemotherapy is the appearance of resistance to compounds. Although several signaling pathways have been implicated in the development of Adriamycin (ADM) resistance, mechanisms involved in ADM-resistant osteosarcoma progression remain unknown. The present study attempted to illus...

    journal_title:Cell death & disease

    pub_type: 杂志文章

    doi:10.1038/s41419-020-2573-2

    authors: Shen P,Cheng Y

    更新日期:2020-05-13 00:00:00