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Every CAR T-cell treatment made from your own cells starts with leukapheresis: over a few hours, blood is taken from a vein, a machine keeps the white cells it needs, and the rest is returned. The date is booked with the manufacturer. Where possible it is done before more chemotherapy, which can weaken the T cells, and some recent treatments need a gap before collection.
EBMT/JACIE 2019: book leukapheresis only once the manufacturer has confirmed a manufacturing slot. Any approved leukapheresis device may be used; the procedure resembles unmobilised collection for donor lymphocytes or photopheresis, and no device-specific protocol has been issued by device or CAR T-cell manufacturers. Sites must be qualified by the manufacturer; FACT-JACIE accreditation confirms a quality system. Collection is possible with absolute lymphocyte counts as low as 0.1 x 10^9/L, but manufacturing success is likelier above 0.5 x 10^9/L. Where disease allows, collect before salvage chemotherapy, because cumulative chemotherapy harms T-cell quality, and respect washout periods after recent treatments (EBMT Table 4, not read). Prior blinatumomab does not rule out anti-CD19 CAR T. Infectious disease markers are tested on the day of collection; sterility and cell counts (white cells, haematocrit, CD3+, viable CD45+) are reasonable quality control. Fresh products are kept at 2 to 8 degrees until shipped; one manufacturer (Novartis) requires on-site cryopreservation and accepts cells collected within the preceding 18 months.
SITC 2020 (LE: 4): prior allogeneic transplant, bispecific T-cell engagers or anti-CD19 or other antibodies do not exclude CAR T-cell therapy if the target antigen is still expressed. Bridging therapy starts only after collection (see the bridging protocol).
Why: Manufacturing capacity is limited, and collected cells must go straight into a booked production run.
“Confirmation of an agreed manufacturing slot is therefore mandatory prior to deciding on a date for apheresis.”
Why: The more chemotherapy a person has had, the poorer the T cells tend to be.
“Depending on the disease burden, it may be possible to arrange for leukapheresis before starting salvage chemotherapy to treat disease relapse.”
Why: Collection works at lower counts, but making the product is more likely to succeed with more lymphocytes.
“Although apheresis can be performed in patients with absolute lymphocyte counts as low as 0.1×109/L, the likelihood of reaching the target number of autologous lymphocytes and successfully manufacturing the drug product is higher in individuals with absolute lymphocyte counts exceeding 0.5×109/L.”
Why: Recent treatment can reduce the number and fitness of the T cells collected.
“In addition, the choice of salvage therapy (chemotherapy, serotherapy and radiotherapy) may adversely affect subsequent attempts at leukapheresis and washout periods need to be considered.”
Why: These treatments do not stop CAR T cells working if the target is still there.
“Patients who have previously undergone allo-HSCT, bispecific T cell engager (BiTE) therapy, anti-CD19 monoclonal antibody (mAb) therapy, and mAbs against other targets (eg, rituximab) may be treated with CAR T cells, provided the patient’s disease still expresses the target antigen”
Why: Regulations require the markers, and a contaminated or poor product cannot be manufactured.
“In addition to testing for infectious disease markers in peripheral blood samples on the day of collection, reasonable quality control should include sterility testing as well as some hemocytometric parameters (white blood cell count, hematocrit, CD3+, and viable CD45+ counts).”
Why: Each manufacturer sets how the cells must travel; one requires freezing at the collection centre.
“The other commercial manufacturers will collect fresh apheresis product packed in their own specified shipping containers. Until shipping, these apheresis products are stored refrigerated (2-8°C).”
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.
EBMT/JACIE 2019 is the only guideline on collection read in full and is the basis here; it is ungraded and says no apheresis-specific protocol has been proposed by device or CAR T-cell manufacturers. Its points are practical and uncontested in the sources read: confirm the manufacturing slot, collect before further chemotherapy where possible, aim for a lymphocyte count above 0.5 x 10^9/L, observe washout periods, and follow each manufacturer's handling requirements. The European 2022 update, a 2022 guidance drawn from tisagenlecleucel manufacturing and a French SFGM-TC consensus could be read only as abstracts. Accreditation (FACT-JACIE) and manufacturer site qualification govern the detail.
EBMT and JACIE, Haematologica 2020 · EBMT, JACIE and EHA, Annals of Oncology 2022 · Cytotherapy (International Society for Cell and Gene Therapy journal) 2022 · Société francophone de greffe de moelle et de thérapie cellulaire, Bulletin du Cancer 2021
Where it differs: Recommendations on timing, location, vascular access in small patients, T-cell yield, contaminating cells, washout periods and adverse events at collection, based on tisagenlecleucel trial and real-world manufacturing.
Evidence: Experience-based review; only the abstract was read, so its specific recommendations are not given here.
Cytotherapy (International Society for Cell and Gene Therapy journal) 2022
Where it differs: Collecting and cryopreserving mononuclear cells in advance from selected patients at high risk of relapse, before CAR T-cell therapy is needed.
Evidence: Named by EBMT as under debate; no evidence cited.
| Recommendation | Grade, as printed | Source |
|---|---|---|
| EBMT/JACIE 2019 recommendations | not graded (consensus) | EBMT and JACIE, Haematologica 2020 |
| Prior allogeneic transplant, BiTE or antibody therapy is not a bar if the target is expressed | LE: 4 | SITC, Journal for ImmunoTherapy of Cancer 2020 |
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