# Blood counts that do not come back after CAR-T: ICAHT

Source: https://onco.cc/technologies/rejuv-tx-prolonged-cytopenias/  
OnCo record `rejuv-tx-prolonged-cytopenias` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

After CAR-T the blood counts often take much longer to recover than after ordinary chemotherapy, and in some people they dip again weeks later after appearing to have recovered. Since 2023 this has had a name, ICAHT, and an agreed grading system, which matters because it means it is measured and reported rather than described loosely.

## Summary

Haematological toxicity is the commonest adverse event after CAR-T therapy and the one that lasts longest. In 2023 the European Society for Blood and Marrow Transplantation and the European Hematology Association convened an international panel of 36 CAR-T experts and published a consensus grading system and best practice recommendations, naming the entity immune effector cell-associated haematotoxicity, or ICAHT. The panel's own account of why it was needed is that a worldwide survey had shown considerable heterogeneity in practice patterns.

The grading system is built on the depth and duration of neutropenia and distinguishes early ICAHT, from day 0 to day 30, from late ICAHT, after day plus 30. That split is the clinically important observation: haematopoietic reconstitution after CAR-T does not follow the pattern of chemotherapy-associated myelosuppression. Counts can recover and then fall again, a biphasic course that is characteristic and is why a normal count at day 28 is not the end of the matter. The consensus also provides recommendations on risk factors, on pre-infusion scoring systems including the CAR-HEMATOTOX score, and on diagnostic work-up, with a section on identifying haemophagocytosis in the context of severe haematotoxicity.

Why it happens is not fully understood and the field says so. A review in 2024 concluded that the underlying pathophysiology remains poorly understood, and that translational studies from the preceding three years suggest CAR-T-induced inflammation and baseline haematopoietic function are key contributors to prolonged cytopenia. In other words: how much marrow reserve a person arrives with, worn down by prior lines of chemotherapy, and how much inflammation the CAR-T cells generate, together explain much of what follows. The CAR-HEMATOTOX score, calculated before infusion, exists to identify people at high risk in advance so that risk-based interventions can be planned.

Management, in the consensus panel's own framing, covers growth factor support, anti-infective prophylaxis, transfusions, autologous haematopoietic stem cell boost and allogeneic transplantation. Granulocyte colony-stimulating factor is the mainstay. For people refractory to it, a stem cell boost using previously cryopreserved autologous cells is available where such cells were stored, which is one reason storage decisions made before CAR-T matter later. Anti-infective prophylaxis follows the neutropenia rather than the calendar.

The clinical consequence that makes this worth a record of its own is that ICAHT drives infection, transfusion dependence, prolonged hospital stay and a share of non-relapse mortality. The grading system does not treat anything; what it does is make the problem countable, comparable between centres and reportable in trials, which is the precondition for anything else. A second paper from the same group describes an automated computational implementation of the grading criteria, benchmarked manually and computationally in two independent cohorts totalling 1,251 patients, because manual grading proved time-consuming and subject to error.

No grade is attached to this record: it describes a complication and its grading, not an intervention to recommend or warn against. The interventions it names, growth factor support and stem cell boost, rest on consensus recommendation rather than on randomised evidence in this setting, which the panel states.

## Fields

- Kind: Technology
- Status: established
- Last checked: 2026-10-02
- Also known as: ICAHT; immune effector cell-associated haematotoxicity; prolonged cytopenia after CAR-T; CAR-HEMATOTOX
- Tags: rejuvenation; survivorship; transplant; cell-therapy; cytopenias
- Principle: CAR-T therapy injures haematopoiesis by two routes that are not the direct cytotoxicity of lymphodepletion. Systemic inflammation, driven by the expanding CAR-T cells and by cytokine release syndrome, suppresses the marrow niche and skews progenitors; and the baseline haematopoietic reserve of a heavily pretreated patient, often with clonal haematopoiesis, is low to begin with. Because inflammation waxes and wanes with CAR-T expansion, recovery is biphasic rather than monotonic.
- Since: 2023
- Strengths: A published consensus grading system, so the problem is measured the same way across centres; Separates early from late events, which reflects the biphasic course rather than hiding it; A validated pre-infusion risk score, CAR-HEMATOTOX, allows planning before treatment; An automated implementation of the grading exists, benchmarked in 1,251 patients
- Limitations: Pathophysiology is incompletely understood, as the field states; Management recommendations rest on consensus rather than randomised evidence; Stem cell boost needs cryopreserved cells that may not have been stored; The grading system measures the problem; it does not shorten it

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Cytopenia
- Rejeski et al., Immune effector cell-associated hematotoxicity: EHA/EBMT consensus grading and best practice recommendations (Blood 2023): https://doi.org/10.1182/blood.2023020578
- Rejeski et al., Immune effector cell-associated haematotoxicity after CAR T-cell therapy: from mechanism to management (Lancet Haematol 2024): https://doi.org/10.1016/S2352-3026(24)00077-2
- Development and validation of an automated computational approach to grade immune effector cell-associated hematotoxicity (Bone Marrow Transplant 2024): https://doi.org/10.1038/s41409-024-02278-3
- Immune effector cell-associated hematotoxicity: mechanisms, clinical manifestations, and management strategies (Haematologica 2025): https://doi.org/10.3324/haematol.2024.286027
- Hill et al., Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy (Blood 2018): https://doi.org/10.1182/blood-2017-07-793760

## Connected records

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- fronts: [Recovery & Rejuvenation](https://onco.cc/fronts/rejuvenation/), [Supportive Care & Survivorship](https://onco.cc/fronts/supportive-care/)
- terms: [Cytokine release syndrome (CRS)](https://onco.cc/terms/crs/), [Cytopenias and myelosuppression](https://onco.cc/terms/cytopenias/), [Late effects and survivorship toxicity](https://onco.cc/terms/late-effects/)
- bottlenecks: [Survivorship and late effects are neglected](https://onco.cc/bottlenecks/b-survivorship/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)

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