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Chimeric antigen receptor-modified T cells (CAR-T) have become an effective treatment for refractory and relapsed B-cell non-Hodgkin’s lymphoma (NHL).
Under this background, it is imperative to standardize the clinical treatment of its side effects.
.
The Biotherapeutics Committee of the Chinese Research Hospital Association organized experts to compile the "Expert Consensus on the Clinical Management of CAR-T Cells Treating NHL Toxic Side Effects", which aims to provide clinicians with a more standardized identification and treatment of CAR-T treatment of NHL-related side effects The disposal principles and exploratory disposal recommendations.
This consensus mainly introduces 4 parts of CAR-T-related toxic and side effects, including cytokine release syndrome (CRS), CAR-T-related encephalopathy syndrome, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, and other adverse events (Bone marrow suppression, infection, B-cell deficiency/hypogammaglobulinemia, tumor lysis syndrome, allergic reaction, abnormal proliferation of CAR-T cells, etc.
).
In the past, we have summarized the CRS (please click for details: CRS of CAR-T cytotoxic side effects | CAR-T cell treatment of NHL toxic side effects clinical management expert consensus).
In this issue, the editor summarizes CAR-T-related encephalopathy syndromes as follows for the reference of readers.
CAR-T Cell-related Encephalopathy Syndrome (CAR-T Cell-related Encephalopathy Syndrome, CRES) refers to neurological dysfunction and related pathological changes that occur after CAR-T cell therapy.
Immune effector cell-associated neurotoxicity syndrome (ICANS) refers to the pathological process and dysfunction of the central nervous system caused by the activation or response of T cells or endogenous immune effector cells after immunotherapy or secondary to infusion.
Compared with CRES, the definition of ICANS is broader, and it also includes neurological abnormalities secondary to other immunotherapy (such as specific CD3-CD19 diabodies, PD-1 antibodies, etc.
).The pathogenesis of CRES is still unclear.
Factors such as high cytokine levels, high tumor burden, abnormal blood-brain barrier function, the structure of CAR-T, and the expression of CD19 in intracranial vascular tissue may be related to the occurrence of CRES.
The incidence of CRES in lymphoma patients is 20% to 60%, mainly occurring within 8 weeks after CAR-T cell reinfusion, with a median duration of 4 to 6 days.
The main clinical manifestations include headache, delirium, cognitive impairment, muscle tremor, ataxia, language impairment, nerve palsy, sensory impairment, lethargy, seizures, etc.
Secondary cerebral edema is an important cause of neurotoxic death.
Differential diagnosis of CRES CRES occurs after CAR-T cell reinfusion.
Most patients also have thrombocytopenia, which must be differentiated from cerebral hemorrhage.
After CAR-T cell reinfusion, the coagulation function is abnormal, and there is also the risk of thrombosis.
It should also be distinguished from cerebral infarction.
Past medical history and head MRI can rule out and differentiate CRES from cerebral hemorrhage/cerebral infarction.
CRES is also easily confused with epileptic seizures, but most patients with epilepsy have a history of cerebrovascular accidents and seizures.
There may also be CRES combined with epilepsy, and we should also be vigilant.
For CRES combined with epilepsy, the treatment should be based on CRES treatment, which can also take into account the treatment of epilepsy.
According to the recommendations, control of grand epilepsy, and hormonal therapy can be given at the same time.
CRES classification and clinical treatment The CRES treatment process includes classification of the diagnosis and severity of CRES based on the CARTOX-10 nervous system scoring system (Table 1) and clinical manifestations (Table 2); then the corresponding clinical treatment is carried out according to the CRES classification ( table 3).
Table 1 CARTOX-10 Nervous System Scoring System
Table 2 CRES grading standards Table 3 CRES grading clinical treatment This article is excerpted from the Biotherapeutics Committee of the Chinese Research Hospital Association.
Expert consensus on clinical management of the toxic and side effects of CAR T cell treatment of NHL[J].
Journal of Translational Medicine, 2021, 10( 1):1-11.
If you encounter copyright issues, please contact to delete.
Poke "read the original text" and we will make progress together
Under this background, it is imperative to standardize the clinical treatment of its side effects.
.
The Biotherapeutics Committee of the Chinese Research Hospital Association organized experts to compile the "Expert Consensus on the Clinical Management of CAR-T Cells Treating NHL Toxic Side Effects", which aims to provide clinicians with a more standardized identification and treatment of CAR-T treatment of NHL-related side effects The disposal principles and exploratory disposal recommendations.
This consensus mainly introduces 4 parts of CAR-T-related toxic and side effects, including cytokine release syndrome (CRS), CAR-T-related encephalopathy syndrome, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, and other adverse events (Bone marrow suppression, infection, B-cell deficiency/hypogammaglobulinemia, tumor lysis syndrome, allergic reaction, abnormal proliferation of CAR-T cells, etc.
).
In the past, we have summarized the CRS (please click for details: CRS of CAR-T cytotoxic side effects | CAR-T cell treatment of NHL toxic side effects clinical management expert consensus).
In this issue, the editor summarizes CAR-T-related encephalopathy syndromes as follows for the reference of readers.
CAR-T Cell-related Encephalopathy Syndrome (CAR-T Cell-related Encephalopathy Syndrome, CRES) refers to neurological dysfunction and related pathological changes that occur after CAR-T cell therapy.
Immune effector cell-associated neurotoxicity syndrome (ICANS) refers to the pathological process and dysfunction of the central nervous system caused by the activation or response of T cells or endogenous immune effector cells after immunotherapy or secondary to infusion.
Compared with CRES, the definition of ICANS is broader, and it also includes neurological abnormalities secondary to other immunotherapy (such as specific CD3-CD19 diabodies, PD-1 antibodies, etc.
).The pathogenesis of CRES is still unclear.
Factors such as high cytokine levels, high tumor burden, abnormal blood-brain barrier function, the structure of CAR-T, and the expression of CD19 in intracranial vascular tissue may be related to the occurrence of CRES.
The incidence of CRES in lymphoma patients is 20% to 60%, mainly occurring within 8 weeks after CAR-T cell reinfusion, with a median duration of 4 to 6 days.
The main clinical manifestations include headache, delirium, cognitive impairment, muscle tremor, ataxia, language impairment, nerve palsy, sensory impairment, lethargy, seizures, etc.
Secondary cerebral edema is an important cause of neurotoxic death.
Differential diagnosis of CRES CRES occurs after CAR-T cell reinfusion.
Most patients also have thrombocytopenia, which must be differentiated from cerebral hemorrhage.
After CAR-T cell reinfusion, the coagulation function is abnormal, and there is also the risk of thrombosis.
It should also be distinguished from cerebral infarction.
Past medical history and head MRI can rule out and differentiate CRES from cerebral hemorrhage/cerebral infarction.
CRES is also easily confused with epileptic seizures, but most patients with epilepsy have a history of cerebrovascular accidents and seizures.
There may also be CRES combined with epilepsy, and we should also be vigilant.
For CRES combined with epilepsy, the treatment should be based on CRES treatment, which can also take into account the treatment of epilepsy.
According to the recommendations, control of grand epilepsy, and hormonal therapy can be given at the same time.
CRES classification and clinical treatment The CRES treatment process includes classification of the diagnosis and severity of CRES based on the CARTOX-10 nervous system scoring system (Table 1) and clinical manifestations (Table 2); then the corresponding clinical treatment is carried out according to the CRES classification ( table 3).
Table 1 CARTOX-10 Nervous System Scoring System
Table 2 CRES grading standards Table 3 CRES grading clinical treatment This article is excerpted from the Biotherapeutics Committee of the Chinese Research Hospital Association.
Expert consensus on clinical management of the toxic and side effects of CAR T cell treatment of NHL[J].
Journal of Translational Medicine, 2021, 10( 1):1-11.
If you encounter copyright issues, please contact to delete.
Poke "read the original text" and we will make progress together