Immunotherapy is a new and exciting type of treatment for children whose leukemia does not respond to conventional treatments. Immunotherapy alters the immune system—a network of organs and cells that help protect against infection and disease. The immune system keeps track of all substances normally found in the body, and any cells identified as foreign are attacked. However, the immune system doesn’t always recognize cancer cells as foreign. Immunotherapies alter the immune system so it can correctly identify and kill cancerous cells. This is done in many ways, including use of monoclonal antibodies, cancer vaccines, and immune checkpoint inhibitors. But these types of immunotherapy are used primarily for adults with cancer.

In 2017, the FDA approved a type of immunotherapy for children and teens with B-cell leukemia who relapsed or whose leukemia didn’t respond to initial therapy. This treatment, called chimeric antigen receptor (CAR) T-cell therapy, involves collecting T cells, genetically altering them, and then returning them to the child’s bloodstream to attack the cancerous B cells.

Process of CAR T-cell therapy

The first step in CAR T-cell therapy is collecting T cells via a process called leukapheresis. Blood is withdrawn from the body, T cells are removed, and the blood is reinfused back into the child or teen. The T cells are sent to a manufacturing facility to be genetically engineered to attack cancerous B cells. The number of reengineered cells (called CAR T cells) is then increased at the manufacturing plant. During the few weeks while this is happening, the child is usually given chemotherapy to stop disease progression. When millions of new T cells are available, they are frozen and sent to the hospital to be thawed and infused into the child or teen.

When we were accepted into the CAR-T trial, our son had to be weaned off his GVHD [graft-versus-host disease] drugs before they could collect his T cells. This was risky, but he was 17 and was willing to take the chance in hopes of a cure. After they collected and manufactured the T cells, but before they could infuse them, our son relapsed in the CNS again. This dramatically increased the risk of the procedure. The consent was brutal because of all of the possible complications, including death. My son asked the doctor, “If I die, will you still learn something from this?” The doctor said, “You are here so we can do our best to save your life.” And we decided to go ahead.

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Infusion day. Magic gold was 60 cc of CAR-T cells infused through Mitchell’s PICC line. After we went back to the hotel he developed a fever, so he was admitted. On Day 7, he started developing neurological symptoms—irritable, slurring words. Within 24 hours, he was unresponsive and moved up to the ICU. He was in a coma for five days. My husband and I worried about brain damage and talked about the wisdom of trying this trial. Then, we just decided to give up that burden and accept whatever happened. Two hours later, he opened his eyes and tried to talk. He started talking like a 2 year old, but gradually he improved, and within two weeks was emotionally and physically back. It was a huge success, and within two months, Mitchell was starting his senior year of high school, from which he graduated with honors (after front-line treatment, relapse, transplant, relapse, and then CAR T-cell clinical trial). He is in college, doing well, but still coping with side effects from the transplant. We were so incredibly lucky.

Side effects of CAR T-cell therapy

Three side effects may occur shortly after infusion of CAR T cells. These include:

• Cytokine release syndrome, sometimes called the cytokine storm: When the immune system is activated by the CAR T cells, a large number of proteins called cytokines are released, which can result in high fevers, low blood pressure, pain, or poor lung oxygenation. Less common side effects of the cytokine storm are brain swelling, delirium, confusion, or seizures. These symptoms most often occur in the first week after infusion of the T cells.
• B-cell aplasia (few or no B cells): The reengineered T cells kill not only cancerous B cells but also healthy B cells. Because B cells help guard against infection, IV immunoglobulin is given monthly to boost immune function. It is not yet known how long these infusions are needed.
• Tumor lysis syndrome: This metabolic complication occurs when a large number of cancer cells are destroyed in a short amount of time. This rare side effect can occur up to two weeks after infusion of the modified T cells.

The consent process was hard because the known side effects were very scary and the unknowns were even scarier. They took my 14-year-old son’s T cells, did the manufacturing magic, and gave him back 10% of them on Day 1 and 30% more the following day. He had what is called the cytokine storm, but a milder version than many of the other kids had. He had a low fever, mild discomfort, and was a little confused for a few days.

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Last Wednesday, February 17, Justin had a bone marrow biopsy and spinal tap performed on the one-year anniversary of receiving his modified T cells. The initial results were good but we had to wait until this Monday to get the official word that NO Minimal Residual Disease was found! This is the longest Justin has ever been in remission and we are thrilled! Mentally, Justin is trying to wrap his head around it all. He is doing well in school and last night signed up to take the SAT, so life marches on. As happy as I am, my joy is tempered by the struggles many of our friends in our pediatric cancer family are still enduring. Survivor guilt is very real. While I know they are happy for us, there still has to be a moment of “Damn, why didn’t CAR-T work for my kid?” or “Why didn’t my kid survive?” My heart aches with every relapse, my heart breaks with every death. In our own quiet way we’ve been supporting various charities and specific individuals and are prayerfully considering what else we can do and how best to share our resources. Please keep these children in your prayers: Logan, Patrick, Valeria, Brooke, and Adam. And comfort for Kelly as her sweet boy Kevin earned his angel wings last week.

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My 4-year-old son relapsed soon after he started maintenance for his high-risk ALL and then two months after his transplant. The doctor called my husband (he’s calmer than I am) to say he had relapsed. The second relapse was the first time our son had ever seen his father cry. He told his friends, “My dad was crying. He came home to tell me my cancer was back.” We’d gone from a very bad situation to a grim situation. They started weaning him off cyclosporine, and our transplant doctor came to talk with us about a Phase I immunotherapy trial in another city. It was called the CART-19 trial and it involved collecting T cells, genetically modifying the T cells to attack the cancer cells, and then infusing them back into your child. Our son was patient #21. We stayed near the hospital in an apartment for six weeks, and went to the hospital weekly for labs. Four weeks after the infusion while we were out trick-or-treating, we got a call saying, “It worked, no more leukemia.” I started shouting, “His cancer is gone, his cancer is gone.” The woman at the door started crying and then offered us a beer. We went home the next day. That was 3 ½ years ago and he’s doing great.

It is not known how long remissions after this therapy will last in children and teens. Some of the earliest recipients are now many years out and doing well, but others relapsed yet again. Much long-term follow up is needed to learn more about the effectiveness of the treatment over time as well as the potential long-term side effects.