# IEC-HS after CAR T-cell therapy: recognition and stepwise treatment

Source: https://onco.cc/protocols/iec-hs-management/  
OnCo record `iec-hs-management` (Protocol). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Rarely after CAR T-cell therapy the immune system stays switched on after cytokine release syndrome has settled, and starts damaging the blood, liver and clotting (IEC-HS). It shows as very high ferritin, falling blood counts, low clotting proteins and liver test changes. It is treated with anakinra and steroids, adding other drugs if it worsens, while infection and relapse are ruled out.

## Summary

ASTCT 2023 named and defined IEC-HS: a hyperinflammatory syndrome with features of macrophage activation or HLH, attributable to immune effector cell therapy, with new or worsening cytopenias, hyperferritinaemia, coagulopathy with hypofibrinogenaemia and/or transaminitis. It usually follows CRS and appears as CRS resolves; it is a diagnosis of exclusion, and a substantially raised (more than twice the upper limit or baseline) or rapidly rising ferritin is a prerequisite. Fever is deliberately not a criterion, to keep it distinct from CRS. Grading (Table 2) follows CTCAE 'immune system disorder, other', grade 1 to 5.

Treatment (expert opinion, Figure 3 and Table 3): start before life-threatening complications with anakinra (adults 100 to 200 mg subcutaneous or intravenous every 6 to 12 hours) with or without corticosteroids (adults dexamethasone 10 to 40 mg daily), allowing about 48 hours to judge effect before adding agents; ruxolitinib second line, dose-reduced with azoles or renal impairment; for refractory life-threatening disease, etoposide 50 to 100 mg/m2 once (not HLH-94 induction doses), or emapalumab where IFN-gamma is high (debated). Tocilizumab is discouraged for IEC-HS without CRS. Supportive: daily blood count, PT/PTT and fibrinogen, daily renal and liver tests, fibrinogen replacement, transfusion, cautious G-CSF, infectious disease input and prophylaxis matched to the immunosuppression. SITC 2020 (LE: 4): cryoprecipitate for delayed hypofibrinogenaemia, anakinra and steroids for late tocilizumab-refractory HLH/MAS-like toxicity, etoposide only as a last resort.

## Fields

- Kind: Protocol
- Last checked: 2026-11-11
- Also known as: IEC-HS; immune effector cell-associated HLH-like syndrome; carHLH; HLH/MAS after CAR T; macrophage activation syndrome after CAR T; MAS-L
- Tags: protocol; cell-therapy; car-t; acute-oncology

## Connected records

- protocols: [Cytokine release syndrome after CAR T-cell therapy: ASTCT grading, tocilizumab and steroids](https://onco.cc/protocols/crs-grading-and-management/), [ICANS after CAR T-cell therapy: ICE score, ASTCT grading, steroids and seizure management](https://onco.cc/protocols/icans-grading-and-management/), [Infection screening, prophylaxis and immunoglobulin replacement around CAR T-cell therapy](https://onco.cc/protocols/car-t-infection-prevention/), [Prolonged low blood counts after CAR T-cell therapy (ICAHT): grading, work-up and treatment](https://onco.cc/protocols/icaht-prolonged-cytopenia/)
- technologies: [CAR-T cell therapy](https://onco.cc/technologies/car-t/)
- drugs: [Dexamethasone](https://onco.cc/drugs/dexamethasone/), [Emapalumab](https://onco.cc/drugs/emapalumab/), [Etoposide](https://onco.cc/drugs/etoposide/), [Methylprednisolone](https://onco.cc/drugs/methylprednisolone/), [Ruxolitinib](https://onco.cc/drugs/ruxolitinib/)
- institutions: [Society for Immunotherapy of Cancer](https://onco.cc/institutions/sitc/)
- terms: [Cytokine release syndrome (CRS)](https://onco.cc/terms/crs/), [Cytopenias and myelosuppression](https://onco.cc/terms/cytopenias/)

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