CAR-T 세포치료 후 CRS와 ICANS의 진단 및 관리

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1. Cytokine Releasing Syndrome (CRS)

CRS는 면역치료 후 면역효과세포의 과활성화로 인한 염증성 사이토카인(IL-6, IL-1, IFN-gamma, TNF-alpha 등) 방출로 발생하는 질환입니다. 발열, 저혈압, 빈맥, 저산소증, 다발장기부전, 심부정맥, 심정지, 심부전, 모세혈관누출증후군(흉수, 폐부종 등)을 특징으로 합니다. 주입 후 2-3일 이내 발생하여 7-8일 지속되며 최대 10-15일까지 가능합니다. 치료의 근간은 tocilizumab(항-IL6R 단클론항체)과 코르티코스테로이드이며, Grade에 따라 관리합니다.
2. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)

ICANS는 면역치료 후 중추신경계를 침범하는 신경독성 증후군으로, 뇌병증, 섬망, 실어증, 무기력, 두통, 진전, 근간대경련, 어지러움, 운동기능장애, 운동실조, 수면장애, 불안, 초조, 정신병 증상(환각), 경련, 뇌부종 등을 나타냅니다. 주입 후 4-10일에 발생하여 14-17일 지속되며 1개월 이후 늦게 나타나기도 합니다. 치료의 근간은 코르티코스테로이드(덱사메타손)이며, 동반 CRS가 있을 때만 tocilizumab을 투여합니다.
3. CRS 등급별 관리 및 치료

CRS는 쇼크, 산소요구량, tocilizumab 반응에 따라 Grade 1-4로 분류됩니다. Grade 1은 정맥수액 공급과 광범위 항생제 투여, Grade 2는 tocilizumab 투약(8mg/kg Q8, 최대 4회)과 덱사메타손 시작, Grade 3는 ICU 입실 및 tocilizumab과 덱사메타손(10mg Q6) 투여, Grade 4는 ICU 입실 및 스테로이드 펄스 치료(MPD 1g/day for 3 days)를 시행합니다. 모든 등급에서 기본적으로 정맥수액 공급, 패혈증 선별, 장기독성 관리를 수행합니다.
4. ICANS 등급별 관리 및 치료

ICANS는 의식수준, ICE 점수, 경련, 운동기능, 뇌압상승/뇌부종의 5가지 지표로 Grade 1-4를 판정합니다. Grade 1은 보존적 치료와 수액 공급, Grade 2는 덱사메타손(10mg) 투약 후 반응 확인, Grade 3는 ICU 전실과 덱사메타손(10mg Q6) 투여, Grade 4는 기관삽관 고려 및 스테로이드 펄스 치료를 시행합니다. 동반 CRS가 있을 때 tocilizumab을 투여하며, 대부분 가역적입니다.

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1. Cytokine Releasing Syndrome (CRS)

Cytokine Releasing Syndrome represents a critical challenge in modern immunotherapy, particularly with CAR-T cell therapies. CRS occurs when immune effector cells release excessive cytokines, triggering a systemic inflammatory cascade. This syndrome can range from mild symptoms like fever and malaise to life-threatening conditions including hypotension, respiratory distress, and multi-organ dysfunction. Understanding CRS pathophysiology is essential for clinicians administering cellular immunotherapies. The syndrome's unpredictable nature and variable severity necessitate comprehensive patient monitoring protocols and rapid intervention capabilities. Early recognition of CRS symptoms and prompt management with cytokine-targeting agents like tocilizumab have significantly improved patient outcomes. However, the balance between controlling CRS while maintaining therapeutic efficacy remains a complex clinical challenge requiring individualized treatment approaches.
2. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)

ICANS represents a distinct and potentially devastating complication of cellular immunotherapy that affects the central nervous system. Unlike CRS, which is primarily systemic, ICANS manifests through neurological symptoms ranging from confusion and tremors to seizures and cerebral edema. The syndrome's mechanisms involve blood-brain barrier disruption, immune cell infiltration, and cytokine-mediated neuroinflammation. ICANS poses unique diagnostic and therapeutic challenges due to the complexity of CNS pathology and the difficulty in distinguishing it from other neurological complications. The unpredictable onset and severity of ICANS, sometimes occurring independently of CRS, underscore the need for specialized neurological monitoring. Current management strategies, including corticosteroids and supportive care, have improved outcomes, but long-term neurological sequelae remain a concern requiring further investigation and refined treatment protocols.
3. CRS 등급별 관리 및 치료

Grade-based management of CRS provides a structured framework for clinical decision-making in immunotherapy-related complications. Grade 1 CRS typically requires supportive care with antipyretics and close monitoring, while Grade 2 may necessitate cytokine-targeting interventions like tocilizumab. Grade 3-4 CRS demands aggressive management including high-dose corticosteroids, vasopressor support, and intensive care monitoring. This tiered approach enables clinicians to escalate interventions proportionally to symptom severity while avoiding unnecessary aggressive treatment in mild cases. However, the grading system's limitations include subjective assessment criteria and variable institutional interpretations. Standardized protocols across institutions would improve consistency in CRS management. The challenge lies in predicting which patients will progress to severe CRS and implementing preventive strategies. Integration of biomarkers and early warning systems could enhance the precision of grade-based management, ultimately improving patient safety and therapeutic outcomes.
4. ICANS 등급별 관리 및 치료

Grade-based management of ICANS requires specialized neurological expertise and differs significantly from CRS management. Grade 1 ICANS involves mild cognitive symptoms managed with supportive care and monitoring, while Grade 2 includes moderate symptoms potentially requiring corticosteroids. Grade 3-4 ICANS represents medical emergencies with severe neurological dysfunction necessitating intensive care, high-dose corticosteroids, and seizure prophylaxis. The challenge in ICANS grading lies in the subjective nature of neurological assessments and the difficulty in distinguishing ICANS from other CNS complications. Standardized neurological evaluation tools and objective biomarkers would improve diagnostic accuracy and treatment consistency. Current management focuses on reducing neuroinflammation while preserving therapeutic efficacy, a delicate balance requiring careful clinical judgment. The lack of specific ICANS-targeted therapies compared to CRS management represents a significant gap in treatment options. Future research should focus on developing targeted interventions for ICANS while establishing more objective grading criteria and management protocols.