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A few days before CAR T cells are given, a short course of chemotherapy, usually fludarabine and cyclophosphamide, lowers your own white cells to make room for the CAR T cells to grow. The team first checks that your CAR T cells are ready and that you have no uncontrolled infection. The doses and timing follow the instructions for your product.
EBMT/JACIE 2019: lymphodepletion favours CAR T-cell expansion and persistence; fludarabine-cyclophosphamide is the most widely used regimen, usually over 3 to 5 days before infusion, with admission unless the centre has a safe outpatient pathway. If more than about 3 weeks pass between lymphodepletion and infusion and the white count is above 1.0 x 10^9/L, consider repeating it (SITC 2020: consider after 4 weeks). Infections must be treated and controlled first; SITC 2020 does not give lymphodepletion while a suspected fungal infection is uncontrolled.
The regimen and dose come from each product's label. YESCARTA (axicabtagene ciloleucel, US label revised 07/2026): cyclophosphamide 500 mg/m2 and fludarabine 30 mg/m2 intravenously on days 5, 4 and 3 before infusion. KYMRIAH (tisagenlecleucel, revised 6/2025): for adult DLBCL and follicular lymphoma, fludarabine 25 mg/m2 and cyclophosphamide 250 mg/m2 daily for 3 days, with bendamustine 90 mg/m2 for 2 days as the alternative after grade 4 haemorrhagic cystitis or cyclophosphamide resistance, and lymphodepletion may be omitted if the white count is under 1 x 10^9/L in the week before; for children and young adults with B-ALL, fludarabine 30 mg/m2 for 4 days and cyclophosphamide 500 mg/m2 for 2 days. Both labels: confirm the product is available before starting; no live vaccines for at least 6 weeks before lymphodepletion.
Why: Lymphodepletion without a product to follow leaves the person with low counts and no treatment.
“Confirm availability of YESCARTA prior to starting the lymphodepleting regimen.”
Why: Lymphodepletion and the cytokine surge after CAR T cells make an existing infection much worse.
“If a fungal infection is suspected, lymphodepleting chemotherapy should not be administered until appropriate antifungals have been initiated and fungal infection is controlled.”
Why: Live vaccines can cause infection when the immune system is suppressed.
“Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during YESCARTA treatment, and until immune recovery following treatment with YESCARTA.”
Why: This combination gave better CAR T-cell persistence and disease control than older regimens.
“Fludarabine-cyclophosphamide is the most widely used LD conditioning regimen.”
Why: Each product was tested with its own regimen, and the doses differ between products.
“Administer a lymphodepleting chemotherapy regimen of cyclophosphamide 500 mg/m2 intravenously and fludarabine 30 mg/m2 intravenously on the fifth, fourth, and third day before infusion of YESCARTA.”
Why: Close monitoring and good hydration are needed during these days.
“If the center does not have established policies and infrastructure to allow for safe outpatient-based administration, hospitalization is recommended during this period to ensure close monitoring and optimal hydration.”
Why: These raise the risk of severe cytokine release syndrome and other harm.
“Delay the infusion of KYMRIAH if a patient has unresolved serious adverse reactions (including pulmonary reactions, cardiac reactions, or hypotension) from preceding chemotherapies, active uncontrolled infection, active graft versus host disease (GVHD), or worsening of leukemia burden following lymphodepleting chemotherapy”
Why: Once the person's own lymphocytes come back, the CAR T cells lose the space they need to expand.
“If there is a long delay (in general, more than 3 weeks) between completing LD conditioning and the subsequent CAR T-cell infusion, and the white blood cell count is >1.0×109/L, then consideration should be given to re-treating the patient with LD chemotherapy prior to administration of the CAR T cells.”
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.
For the regimen and dose, the product's own label is the authority, and labels differ (fludarabine 30 mg/m2 with cyclophosphamide 500 mg/m2 for three days for axicabtagene ciloleucel; fludarabine 25 mg/m2 with cyclophosphamide 250 mg/m2 for three days, or bendamustine, for tisagenlecleucel in lymphoma). For the checks around it, EBMT/JACIE 2019 and SITC 2020 agree: control infection first, confirm the product, monitor closely, and consider repeating lymphodepletion after a long delay. They differ slightly on that delay: EBMT says more than 3 weeks with a white count above 1.0 x 10^9/L; SITC says consider repeating after 4 weeks. Neither is graded on this point. The 2022 EBMT/JACIE/EHA update was read only as an abstract.
Kite Pharma; US Food and Drug Administration 2026 · Novartis; US Food and Drug Administration 2025 · EBMT and JACIE, Haematologica 2020 · SITC, Journal for ImmunoTherapy of Cancer 2020 · EBMT, JACIE and EHA, Annals of Oncology 2022
Where it differs: Bendamustine 90 mg/m2 daily for 2 days when a patient had grade 4 haemorrhagic cystitis with cyclophosphamide or shows resistance to a cyclophosphamide regimen.
Evidence: Label instruction; in the pivotal DLBCL trial 22 of 107 patients given lymphodepletion received bendamustine.
Where it differs: Lymphodepletion may be omitted if the white count is under 1 x 10^9/L within a week before infusion.
Evidence: Label instruction, reflecting trial eligibility.
Where it differs: Considers repeating lymphodepletion after a delay of 4 weeks, without a white count threshold.
Evidence: Panel recommendation without a level of evidence.
| Recommendation | Grade, as printed | Source |
|---|---|---|
| EBMT/JACIE 2019 recommendations | not graded (consensus) | EBMT and JACIE, Haematologica 2020 |
| Regimen and dose | product label (regulatory instruction) | Kite Pharma; US Food and Drug Administration 2026 |
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