Loading
Low blood counts are the commonest side effect of CAR T-cell therapy. Most recover within weeks, but in some people counts stay low for months, raising infection risk. Teams check counts often, give growth factor injections, transfusions and infection-preventing tablets, and look at the bone marrow if counts stay low after about a month. Some need their own stored stem cells.
EHA/EBMT 2023 named immune effector cell-associated haematotoxicity (ICAHT) and graded it by depth and duration of neutropenia, separately for early (day 0 to 30) and late (after day +30) cytopenia; it also set out risk factors, the pre-infusion CAR-HEMATOTOX score and recommendations on growth factors, prophylaxis, transfusion, autologous stem cell boost and allogeneic transplant. Only its abstract could be read. ASTCT's 2026 consensus grading update also addresses ICAHT (abstract only).
SITC 2020 (LE: 4 unless stated): for cytopenias in the first 28 days, follow blood counts without marrow biopsy; for cytopenias beyond 28 days, bone marrow aspirate and biopsy with viral studies; consider holding G-CSF until day 14 or CRS has resolved; consider growth factors for ANC under 500 per microlitre after day 28; no GM-CSF in the CRS window (LE: 5); antibacterial and antifungal prophylaxis for all with persistent neutropenia. The Haematologica 2025 review (Beyar-Katz, Rejeski, Shouval): watch and wait for early cytopenias; irradiated red cells and platelets because of fludarabine exposure; red cell threshold 7 to 8 g/dL; platelets at 10 or below (20 with bleeding, fever or infection); thrombopoietin receptor agonists for persistent thrombocytopenia (retrospective data only); autologous CD34+ boost for G-CSF-refractory ICAHT, with 70 to 100% neutrophil recovery in retrospective series, and allogeneic transplant as a last option. No prospective or randomised trial of any ICAHT treatment exists.
Why: Knowing who is at high risk lets the team plan growth factors, back-up stem cells or a gentler conditioning regimen.
“The use of the recently introduced and widely applied CAR-HEMATOTOX score, evaluating these parameters, allows for early identification of patients at high risk of developing ICAHT.”
Why: A shared grading lets teams compare and decide when to escalate.
“For the grading of ICAHT, a classification system based on depth and duration of neutropenia was developed for early (day 0-30) and late (after day +30) cytopenia.”
Why: Early low counts are expected after lymphodepletion and often recover on their own.
“For cytopenias occurring within the first 28 days after IEC infusion, a bone marrow biopsy may not be indicated—complete blood counts with differential may be adequate for follow-up”
Why: Relapse, infection of the marrow or a new marrow disorder can each cause low counts and need different treatment.
“For cytopenias persisting >28 days after IEC infusion, bone marrow biopsy and bone marrow aspiration should be performed in addition to the standard work-up to assess response and cellularity, including assessment of viral pathogens”
Why: Growth factor during peak CAR T-cell expansion was feared to worsen cytokine release syndrome.
“To avoid interaction with the peak CRS risk and CART expansion period, consider holding growth factors until day 14 from infusion of CAR T cells or once CRS has resolved”
Why: Growth factor shortens severe neutropenia; GM-CSF in particular may aggravate CRS.
“For persistent neutropenia (ANC<500 cells/µL) after day 28 following CAR T cell infusion, growth factors should be considered”
Why: Long neutropenia is when serious bacterial and fungal infections happen.
“All patients who develop persistent neutropenia should have antibacterial and antifungal prophylaxis.”
Why: Fludarabine in the lymphodepletion raises the risk of transfusion-associated graft-versus-host disease.
“Blood products are typically administered based on a patient’s blood counts, and it is imperative that red blood cells and platelets be irradiated, in part because of the prior exposure to fludarabine, which can increase the risk of transfusion-associated graft-versus-host disease (Table 3).”
Why: These drugs stimulate platelet production; the evidence is retrospective and uncontrolled.
“Thrombopoietin receptor agonists, such as eltrombopag and romiplostim, are potential treatment options for patients with persistent thrombocytopenia after CAR T-cell therapy, as they stimulate platelet production and may reduce transfusion dependence.”
Why: In retrospective series most patients recovered neutrophils within one to three weeks of a boost, without conditioning.
“For patients with G-CSF-refractory and persistent ICAHT, an autologous stem cell boost is emerging as a promising therapeutic option.”
Why: It can restore blood production but carries its own serious risks.
“In cases in which autologous stem cells are not available, allogeneic SCT may be considered, although this option is typically reserved for patients who have exhausted other treatment options and are not critically ill.”
How care is usually carried out, read from the guidelines and standards cited. Your own team's protocol and their judgement come first; this page is for understanding it, not for doing it yourself.
The EHA/EBMT 2023 consensus is the reference for grading and managing ICAHT, but only its abstract could be read, so its recommendations are not reproduced step by step here. The steps rest on SITC 2020 (graded LE: 4 and LE: 5) and on a 2025 review co-written by the EHA/EBMT consensus's first author, which describes the same toolkit (CAR-HEMATOTOX, grading by depth and duration, G-CSF, transfusion, thrombopoietin receptor agonists, autologous boost, allogeneic transplant). The sources disagree on the timing of G-CSF: SITC 2020 says consider holding it until day 14 or until CRS has resolved; the 2025 review describes G-CSF from day +2 for high-risk patients and cites retrospective data that early G-CSF did not increase CRS progression. EBMT/JACIE 2019 notes that about a third of patients have neutropenia beyond day 30 and that growth factor support may be indicated early.
European Hematology Association and EBMT, Blood 2023 · SITC, Journal for ImmunoTherapy of Cancer 2020 · Haematologica 2025 · EBMT and JACIE, Haematologica 2020
Where it differs: Starts G-CSF on day +2 after infusion when CAR-HEMATOTOX predicts high risk, rather than holding it until day 14 or CRS resolution.
Evidence: Retrospective: in 197 patients given prophylactic G-CSF or pegylated G-CSF, progression from grade 1 CRS to higher grades did not increase, and neutrophil recovery was faster. A myeloma series found more CRS with cumulative G-CSF above 1,500 micrograms or more than 5 days.
Where it differs: Uses bendamustine, described as less myelosuppressive in some cases, for patients at high risk of ICAHT.
Evidence: Described as an option by the review; no comparative trial is cited for ICAHT outcomes.
Where it differs: Collects and stores haematopoietic stem cells before CAR T-cell therapy in patients at significant risk, so a boost is possible later.
Evidence: Number needed to treat and cost-effectiveness unknown; a worldwide survey found a boost available in under 30% of patients, or not at all for 61% of responders.
Where it differs: Prednisone 0.5 mg/kg/day for prolonged cytopenia, mainly after CAR T cells for B-cell ALL, when G-CSF fails.
Evidence: Described by the review as very circumstantial; one small series of 17 patients.
| Recommendation | Grade, as printed | Source |
|---|---|---|
| No marrow biopsy needed for cytopenias in the first 28 days | LE: 4 | SITC, Journal for ImmunoTherapy of Cancer 2020 |
| Marrow aspirate and biopsy with viral studies for cytopenias beyond 28 days | LE: 4 | SITC, Journal for ImmunoTherapy of Cancer 2020 |
| Growth factors for ANC below 500 after day 28 | LE: 4 | SITC, Journal for ImmunoTherapy of Cancer 2020 |
| No GM-CSF until the CRS risk period is over “If growth factors are administered, GM-CSF is not recommended until the risk period for CRS is over (usually 2 weeks) (LE: 5).” | LE: 5 | SITC, Journal for ImmunoTherapy of Cancer 2020 |
| Evidence base for ICAHT treatments overall “There are no prospective or randomized clinical trials specifically focused on ICAHT therapeutic approaches, and current recommendations are largely based on expert opinion.” | expert opinion | Haematologica 2025 |
Shares Infection screening, prophylaxis and immunoglobulin replacement around CAR T-cell therapy, CAR-T cell therapy and the tags protocol, cell-therapy, car-t.
Shares CAR-T cell therapy and the tags protocol, cell-therapy, car-t.
Shares IEC-HS after CAR T-cell therapy: recognition and stepwise treatment, Infection screening, prophylaxis and immunoglobulin replacement around CAR T-cell therapy, Cytokine release syndrome after CAR T-cell therapy: ASTCT grading, tocilizumab and steroids, Society for Immunotherapy of Cancer and the tags protocol, cell-therapy, car-t.
Shares CAR-T cell therapy and the tags protocol, cell-therapy, car-t.
Shares Infection screening, prophylaxis and immunoglobulin replacement around CAR T-cell therapy, Cytokine release syndrome after CAR T-cell therapy: ASTCT grading, tocilizumab and steroids and the tags protocol, cell-therapy.
Shares CAR-T cell therapy and the tags cell-therapy, car-t.
Shares CAR-T cell therapy and the tags cell-therapy, car-t.
Shares CAR-T cell therapy and the tags cell-therapy, car-t.