To begin therapy, T-cells are harvested from the patient by leukapheresis, whereby whole blood is removed from the patient, mononuclear cells (including T-cells) are separated, and the remaining blood components are returned to circulation.

The patient undergoes clinical examination at least 1 day prior to the apheresis procedure to determine whether the collection can be obtained peripherally or whether the patient will require a central venous catheter. If a central venous catheter is required, it is usually placed the morning of the collection and removed after the procedure.

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Patients are instructed to inform the apheresis nurse about any symptoms during the procedure. The most common side effect during apheresis is citrate toxicity, which can cause paresthesia, flushed sensation, nausea, and vomiting; it is caused by citrate binding to calcium in the patient’s blood in the apheresis tubing during collection.11 Oral calcium carbonate (TUMS) usually alleviates symptoms associated with citrate toxicity; however, a calcium infusion is occasionally needed.

After apheresis, the T-cells are sent to a manufacturing facility at University of Pennsylvania or one designed for Good Manufacturing Practice-grade production of CTL019 cells. The T-cells are activated on antibody-coated beads then transfected with a lentivirus engineered to incorporate the genetic material encoding the CAR, producing CAR expression on the T-cell surface and the generation of CTL019 cells. The CTL019 cells are allowed to multiply until a quantity sufficient to initiate treatment has developed; this typically takes approximately 3 to 4 weeks.

The patient undergoes lymphodepleting chemotherapy prior to infusing the CTL019 cells to facilitate their expansion after infusion. A review of lymphodepleting chemotherapy and its potential side effects is conducted, and patients must recover from all chemotherapy-related toxicities before the CTL019 infusion. Additional pretreatment medications include acetaminophen and diphenhydramine/H1 antihistamines. Steroids, however, are not administered as part of the preinfusion medication regimen. 

The reprogrammed T cells have the potential to expand postinfusion, generating additional CTL019 cells programmed to hunt CD19-positive tumor cells. This expansion appears to be necessary for the treatment’s antitumor activity. Lympholytic and immunosuppressive agents may diminish CAR T-cell expansion, thereby reducing its antitumor efficacy. Therefore, avoiding these agents is recommended; steroids should also be avoided. Therapeutic or higher doses of steroids should be stopped more than 72 hours prior to infusion of CTL019 cells, as they might affect the CAR T-cell activity. Patients may not receive steroids during and after CTL019 therapy unless they develop severe cytokine release syndrome (CRS) or steroid therapy is clinically indicated.