CRS, ICANS 치료 및 간호중재

문서 내 토픽

1. Cytokine Releasing Syndrome (CRS)

면역치료 후 내인성 또는 주입된 T세포 및 기타 면역 효과 세포의 활성화로 인한 과도한 면역 반응. 염증성 사이토카인(IL-6, IL-1, IFN-gamma, TNF-alpha) 방출로 내피 손상 및 모세혈관 누출 발생. 발열, 저혈압, 빈맥, 저산소증, 오한, 심장/간/신장 기능 부전, 심방세동, 심실빈맥, 심정지, 심부전, 모세혈관 누출 증후군(흉수, 폐부종) 등의 증상. 주입 후 2-3일 이내 발생하여 7-8일 지속, 10-15일까지 가능. 치료는 tocilizumab(항-IL6R 단클론항체)과 코르티코스테로이드 기반.
2. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)

면역치료 후 T세포 및 기타 면역 효과 세포 활성화로 인한 중추신경계 병리 과정. 뇌병증, 섬망, 실어증, 무기력, 두통, 진전, 근간대경련, 어지러움, 운동 기능 장애, 운동실조, 수면 장애, 불안, 초조, 정신병 증상(환각), 경련, 뇌부종 등 발생. 주입 후 4-10일에 발생하여 14-17일 지속, 한 달 이후 늦은 발병도 가능. CRS와 연관되어 CRS 발현 2-4일 이내 증상 발생 가능. 치료는 코르티코스테로이드(덱사메타손, 메틸프레드니솔론) 기반.
3. CRS 등급 및 치료 관리

Grade 1: 체온 ≥38.0°C, IV 수액 공급, 광범위 항생제 고려. Grade 2: 저혈압(MAP≤65) 또는 산소 6L 이하, tocilizumab 투약(8mg/kg Q8, 최대 4회). Grade 3: 저혈압(MAP≤65) 또는 산소 6L 이상, ICU 입실, tocilizumab 및 스테로이드(Dexa 10mg Q6) 시작. Grade 4: 저혈압 또는 CPAP/BIPAP/기관삽관 필요, ICU 입실, 24시간 내 반응 없으면 스테로이드 펄스(MPD 1g/day 3일) 고려.
4. ICANS 등급 및 치료 관리

Grade 1: 자발적 각성, ICE 7-9, 경련/운동기능/뇌압상승 없음, 보존적 치료 및 수액 공급. Grade 2: 음성 반응, ICE 3-6, Dexa 10mg 투약 후 반응 확인, 호전 없으면 Q6 간격 투약. Grade 3: 접촉 반응, ICE 0-2, 임상 경련 있음, Dexa 10mg Q6, 3일 간격 신경영상 검사. Grade 4: 강한 자극에만 반응/무반응, ICE 0, 생명 위협적 경련, 편마비/하반신마비, 뇌부종, MPD 1g/day 3일 투약.

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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 response. This syndrome can range from mild symptoms like fever and fatigue to severe manifestations including hypotension, organ dysfunction, and potentially fatal outcomes. Understanding CRS pathophysiology is essential for clinicians administering cellular immunotherapies. The syndrome's unpredictability necessitates careful patient monitoring and preparedness for rapid intervention. Early recognition of CRS symptoms and prompt management with cytokine-blocking agents like tocilizumab have significantly improved patient safety. However, the balance between controlling CRS and maintaining therapeutic efficacy remains challenging. Better predictive biomarkers could help identify high-risk patients before treatment initiation, allowing for preventive strategies and personalized management approaches.
2. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)

ICANS represents a distinct and serious 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 mechanism involves immune cell infiltration and cytokine-mediated inflammation in the brain. ICANS can occur independently or concurrently with CRS, complicating clinical management. The syndrome's variable presentation and potential for rapid deterioration make early detection crucial. Current understanding of ICANS pathophysiology remains incomplete, hindering development of targeted preventive strategies. Management typically involves supportive care and immunosuppression, but optimal treatment protocols are still evolving. The neurological nature of ICANS demands specialized monitoring and expertise, requiring collaboration between oncologists and neurologists. Future research should focus on identifying reliable biomarkers and developing neuroprotective strategies to minimize this serious adverse effect.
3. CRS 등급 및 치료 관리

CRS grading systems provide essential frameworks for standardizing severity assessment and guiding treatment decisions. The Lee grading system and CTCAE criteria offer structured approaches to classify CRS from grade 1 (mild) to grade 4 (life-threatening). Appropriate grading enables consistent communication among healthcare providers and facilitates clinical decision-making. Management strategies should be proportionate to severity: mild cases may require supportive care alone, while severe CRS necessitates aggressive intervention with tocilizumab and corticosteroids. The timing of intervention is critical—early recognition and treatment prevent progression to severe disease. However, excessive immunosuppression may compromise therapeutic efficacy. Clinicians must balance CRS control with maintaining anti-tumor immunity. Standardized management protocols based on grading systems have improved outcomes significantly. Ongoing refinement of these grading systems and treatment algorithms, incorporating emerging biomarkers and clinical experience, will further optimize patient safety while preserving therapeutic benefits of cellular immunotherapies.
4. ICANS 등급 및 치료 관리

ICANS grading systems, such as the CTCAE neurotoxicity criteria adapted for ICANS, are essential for standardizing assessment and guiding clinical management. Grading ranges from mild cognitive effects (grade 1) to severe neurological complications including seizures and cerebral edema (grade 4). Accurate grading requires careful neurological examination and sometimes neuroimaging, making assessment more complex than CRS evaluation. Management is primarily supportive, focusing on seizure prophylaxis, cerebral edema control, and symptomatic treatment. Corticosteroids are commonly used, though evidence for optimal dosing and duration remains limited. Unlike CRS, specific cytokine-blocking agents have limited proven efficacy for ICANS. The lack of targeted treatments underscores the importance of prevention and early intervention. Multidisciplinary approaches involving oncologists, neurologists, and intensive care specialists improve outcomes. Current management relies heavily on clinical judgment and experience rather than evidence-based protocols. Future development of ICANS-specific grading systems and targeted therapeutic interventions is urgently needed to better protect patients from this serious neurological complication.