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Research & Innovation
It starts with a Q:
For the latest cutting-edge research, innovative collaborations and remarkable discoveries in child health, read stories from across all our areas of study in Q: Advances and Answers in Pediatric Health.
The CAR-T Cell Therapy Process: What to Expect
Our top-ranked hematology, oncology, blood and marrow transplant and cellular therapy programs are national leaders in new and advanced treatments for pediatric cancers and blood diseases.
Our team of pediatric experts will support you throughout your CAR-T cell therapy process. We've compiled these resources as a quick reference for before, during or after a CAR-T cell infusion.
What are CAR-T cells?
Chimeric antigen receptor (CAR) T cells are a recently approved therapy that uses a patient's own immune cells (called T cells) to attack their cancer cells. The cells that are used come from the patient, are genetically modified and then infused back into the patient to try to cure their cancer.
At Children's Hospital Colorado, we currently offer the commercially available FDA-approved KYMRIAH® product, as well as novel CAR-T cells that are part of clinical trials designed to improve CAR-T cell efficacy.
The main goal of the CAR-T cell infusion is to cure certain types of leukemia such as acute lymphoblastic leukemia. The CAR-T cells target a specific protein on the surface of acute lymphoblastic leukemia cells called CD19. Because this cell surface marker is also on normal B cells, both normal and the leukemic B cells are killed, but other normal tissues are not usually affected.
How does CAR-T cell therapy work?
During the procedure, blood is drawn from a patient, the immune cells are sorted and the immune cells (called T cells) are collected. Next, using a non-contagious virus, the T cells are genetically engineered to make a protein (i.e. the chimeric antigen receptor, or CAR) on the cell surface that recognizes certain types of cancer cells.
These engineered CAR-T cells are then infused back into the patient, where the CARs can recognize and attach to specific proteins on the surface of cancer cells. When the CAR attaches to the cancer cell, it triggers the T cells to kill the cancer cell.
How are blood T cells collected?
The T cells that are used to make CAR-T cells are collected from the patient's peripheral blood, a process called leukapheresis. The patient will have a large IV, a central line or a PICC line (a thin, flexible IV tube) placed in their arm or chest. Then, an apheresis machine collects the T cells and returns the other blood cells back into the body. This happens in the specialized stem cell apheresis center, the Blood Donor Center, as an outpatient visit and takes about 5 to 8 hours over the course of 1 to 5 days. The length of time depends on how many stem cells are needed and how easy it is to get that amount.
After all the cells are collected each day, they are sent to the laboratory where the T cells will be exposed to a non-contagious virus that causes the cells to make a protein that recognizes CD19 on leukemia cells.
The donor is awake and able to talk during the whole collection.
Consultation before CAR-T cells: You will meet with your child's cellular therapy doctor to discuss the disease and how appropriate a CAR-T cell infusion is for treating it. You will discuss potential risks and benefits of CAR-T cells versus no CAR-T cells, and you may discuss your preparative regimen (the low-dose chemotherapy given prior to a CAR-T cell infusion).
If you and the cellular therapy physician decide to proceed, your child will have a central line or PICC line surgically inserted into a large vein in the chest or arm. The central line is placed for the administration of preparative regimen chemotherapies, the CAR-T cells and any medications or fluids you may need after your CAR-T cell infusion.
Conditioning regimen: Several days prior to your child's transplant, they will receive low-dose chemotherapy; this is called the preparative or conditioning regimen. The conditioning regimen is designed to make room in the blood for the CAR-T cells so that they are not crowded out by normal immune cells. The conditioning regimen will take place in the hospital or in an outpatient clinic over several days.
The chemotherapy drugs will be given through the central line. During this time, your child may have side effects from the preparative regimen including nausea, vomiting and diarrhea. To counteract the side effects, your BMT team will give anti-nausea medicines. Your cellular therapy team will review the common side effects of your child’s preparative regimen with you before it begins.
CAR-T cell infusion ("day 0"): Engineered T cells will be infused into the patient using their central line. The bag of cells to be infused often looks like a small platelet transfusion. Before the infusion, patients are given acetaminophen (Tylenol) and diphenhydramine (Benadryl) to prevent any immediate reactions to the infusion.
Shortly after the CAR-T cells are developed in the laboratory, they are frozen to allow for storage, if needed. The frozen CAR-T cells will be thawed shortly before they are infused. These cells are frozen using a special preservative called dimethyl sulfoxide (DMSO) that prevents the cells from breaking during the freezing process. DMSO can cause a distinct smell during and after infusion and may cause some short-term side effects such as high blood pressure.
Immunosuppressive therapy: CAR-T cells allow the immune system to recognize and kill cancer cells. Therefore, it is very important that patients who receive CAR-T cells do not receive any immunosuppressive medicines, including steroids, after their infusion.
Recovery from CAR-T cell infusion
When the infusion is done, the CAR-T cells can immediately start to find and kill any leukemia cells that might be hiding out. Reactions immediately after the infusion are rare. However, as the T cells grow and multiply in the patient's body, there can be some reactions that require closely monitoring. For that reason, the patient will need to stay close to Children's Colorado for the first 30 days, as required by the U.S. Food and Drug Administration.
During this time, we will monitor for:
- Tumor lysis syndrome: changes to electrolyte levels, usually when there is a lot of leukemia or many B cells present
- Fever: low-dose chemotherapy will cause your child's counts to drop, so they may need to be admitted to determine whether the fever is due to infection or a side effect of the CAR-T cells.
- Neurological changes: how you talk and write (i.e., your handwriting) as well as your ability to coordinate your movements
- Low IgG: normal B cells, which create an immune protein called immunoglobulin (IgG), become very low after a CAR-T cell infusion. You may need supplemental IV infusions of IgG (called IVIG) every month.
Side effects of a CAR-T cell infusion
Infections: Even though we give our CAR-T cell patients preventative antibiotics, infections still happen. We will monitor your child for a fever and other signs of infection. If your child has a fever, we will draw blood cultures and we may prescribe or change antibiotics. With some infections, we may get X-rays, CT scans or other special tests to figure out the cause.
Hospitalization: Usually, your child will get their low-dose chemotherapy and CAR-T cell infusion in the outpatient clinic. However, some patients may need to be admitted for their infusion and may require longer hospitalization for close monitoring.
Cytokine release syndrome (CRS): CRS is caused by a large rapid release of inflammatory proteins, called cytokines, from immune cells when they encounter the CD19 cells (leukemia cells or B cells). The release of these cytokines may lead to fever, changes in heart rate or blood pressure, flu-like symptoms, trouble breathing, headache and changes in speech or neurological function. Often, the reaction is mild but it can sometimes be life-threatening. If the patient has signs or symptoms of CRS, they will be admitted for close monitoring and may need IV fluids, antibiotics and other medications.
CAR-T cell late side effects: There are few known late effects after CAR-T cells, given that this therapy is relatively new. Late effects of CAR-T cell infusions can be from chemo, the CAR-T cells, CRS, therapy associated with the original illness or any combination of these. As with any cancer therapy, CAR-T cell therapy will include monitoring of the emotional, medical and physical well-being of the patient and family. Regardless of what your child may need, we are here to help.
After the patient’s immune system and any short-term transplant complications are resolved, the patient will be followed in our HOPE Survivorship clinic.