CAR T-cells: A new frontier in children’s leukemia care


CAR T-cell therapy can give new hope to children with certain types of acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is a type of blood cancer, and is the most common form of cancer diagnosed in children. Most children with ALL respond well to traditional chemotherapy.

But there are few treatment options for children who don’t respond to chemotherapy or whose cancer comes back multiple times. In these cases, fewer than half survive after additional rounds of traditional treatment.

Children with leukemia deserve better, which is why my team of researchers at UT Southwestern and Children’s Health in Dallas were part of a landmark clinical trial for CAR T-cell therapy, a new treatment for pediatric ALL patients.

In July 2017, members of the Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee unanimously recommended that the FDA approve this CAR T-cell therapy, called tisagenlecleucel or CTL019, to treat ALL. The FDA approved tisagenlecleucel in August 2017. We are truly encouraged by the results of this study for children with relapsed ALL and their families.

Leading the way on the next stage of pediatric leukemia care

This clinical trial was open at 25 sites across the world. Just 13 academic institutions in the United States participated, and ours was the only trial site in the region. I had previously worked with the team of researchers at the University of Pennsylvania and Children’s Hospital of Philadelphia that first studied CAR T-cell therapy. Since joining the faculty at UT Southwestern, I’ve continued to work on this as one of the study’s lead investigators.

We are in discussions with Novartis to be one of about 30 sites nationwide that can offer this treatment to children. The number of CTL019 certified treatment centers will be limited because the care a pediatric cancer patient requires before and after treatment calls for a team of specially trained nurses, oncologists, intensive care physicians, pharmacists, and more. That level of care is available only in an academic medical setting like UT Southwestern and Children’s Medical Center, the flagship hospital of Children’s Health.

Patients who receive CAR T-cell therapy are at risk for potentially serious side effects that must be managed by a team of specialists who understand what this therapy involves. Because CAR T-cell therapy is such a new treatment – doctors first treated a child with it in 2012 – we don’t yet know the extent of its long-term effects. Patients have to be closely monitored on an ongoing basis. Our experience as part of the trial and our expert team of pediatric cancer professionals make us a logical site for this type of complex care.

What is CAR T-cell therapy, and how does it work?

CAR T-cell therapy is a form of immunotherapy, which uses the body’s own immune cells to target and destroy cancer cells. Specifically, we’re working with a type of immune cells known as T-cells that normally help fight viral infections and attack cells that may become cancerous. When patients get cancer, their tumor cells have learned to avoid detection by the immune system.

The most common type of ALL affects B-cells, which are another type of cell in the immune system. This therapy re-engineers T-cells to hunt down and fight the cancerous B-cells that cause ALL.

The process starts when our partners at Carter BloodCare draw a blood sample to gather a child’s T-cells. We send this sample to a lab run by the treatment’s manufacturer and study sponsor, Novartis.

The lab then re-engineers the patient’s T-cells to be able to recognize a specific protein on the outside of B-cells called CD19. This is done with a virus into which special genes have been inserted to “teach” the T-cells to recognize the CD19 protein. These T-cells then make special receptors called chimeric antigen receptors, or CARs. Then we give the modified CAR T-cells back to the patient. In our study, we found that in most patients these T-cells were able to hunt down the cancer cells and achieve remission, which means that we couldn’t find any cancer cells remaining.

What are the benefits and risks of CAR T-cell therapy?

One of the main benefits of CAR T-cell therapy is its effectiveness compared to traditional treatments in children whose ALL has come back. Of the children enrolled in our study, 83 percent of those treated with CAR T-cell therapy have gone into remission. That’s a huge increase from the 25 to 50 percent remission rate we typically see with traditional treatments.

In addition, CAR T-cell therapy avoids some of the side effects of chemotherapy medications. Chemotherapy medications are toxic to all fast-growing cells in the body – not just cancer cells. CAR T-cell therapy doesn’t carry these types of side effects.

However, CAR T-cell therapy isn’t for everyone and can cause other side effects that can be severe. Children who receive this treatment are at risk for a condition called cytokine release syndrome. This extreme reaction of the immune system happens because the amped-up T-cells treat leukemia cells like an infection. Children can develop symptoms that include:

  • High fever
  • Difficulty breathing
  • Low blood pressure
  • Liver or kidney problems
  • Confusion and inability to speak

These problems tend to appear within the first month after a child receives the treatment, and patients need to be treated in the hospital until these symptoms resolve.

Children who receive this therapy also develop a condition called B-cell aplasia. Because the CAR T-cells target all B-cells, including normal B-cells, children who receive this therapy have a lack of B-cells in their immune systems after treatment. That means they can’t make antibodies to fight off infections. We can give these patients a treatment called IVIG, or intravenous immunoglobulin, which consists of antibodies from other people. This boosts their immune systems and reduces their risk of infections.

Dealing with these side effects is one of the reasons why it’s so important for children to receive this therapy in an academic medical center like ours. Our team has the experience and resources to address these complications quickly and effectively.

Is CAR T-cell therapy right for my child?

Currently, only children whose ALL has not responded or has relapsed after multiple treatments can receive CAR T-cell therapy. Chemotherapy is still the best approach for children who are newly diagnosed with ALL. Standard chemotherapy is very effective, curing this type of leukemia in 85 to 90 percent of children.

For those whose leukemia comes back after chemotherapy, CAR T-cell therapy might provide new hope. I’m looking forward to sharing the benefits of CAR T-cell therapy with children throughout North Texas and beyond. We have a chance to change the way this type of leukemia is treated, in addition to studying the therapy’s potential benefits for other forms of cancer in the future.