Acute lymphoblastic leukemia (ALL) is the most common form of childhood leukemia. Usually we can cure ALL with chemotherapy, but sometimes that fails. When patients would reach that point, it used to be that the outlook for them was not very good.

T cell hacking

Then a new treatment was developed that uses the patient’s own immune system to fight the cancer in their blood. T cells (white blood cells that attack infections) from the patient’s own body are reprogrammed to create armies of cancer-fighting cells. In many cases, this therapy achieves complete and even lasting remission of the leukemia.

It’s amazing to see children who were desperately sick before undergoing the treatment go back to school and their normal lives.  The treatment — called chimeric antigen receptor (CAR) T therapy — has saved many lives and will save many more when it is fully approved and made more widely available.

Emerging side effects

But, as so often happens in cancer therapy, the treatment has side effects.  The T cells that attack the cancer can be very aggressive.  They release substances called cytokines that urgently signal to other white cells to come and join the fight.  The reinforcements release even more cytokines, and sometimes the body’s reaction can get out of hand. 

This cytokine release syndrome (“cytokine storm”) often causes fever and flu-like symptoms. In severe cases, especially when the patient has a great deal of cancer for the T cells to attack, the patient can go into shock, with low blood pressure; internal organs become swollen. The patient is given medication and sometimes has to go on a ventilator. For a short time, the cure can seem nearly worse than the disease.

“... we’re able to more precisely manage the toxicities that may occur from these very powerful treatments.”

Fine-tuning with tech

Researchers collaborating across several institutions looked for a solution to this serious reaction. Since pediatricians believe in prevention, we wanted to deal with this problem before it really got rolling. Like weather forecasters, we needed ways to predict and hopefully avoid the coming storm.

First we analyzed a myriad of cytokines and the levels of these cytokines in patients, pediatric patients with ALL, and some adults as well. Next, the cytokine profiles were used to develop predictive model algorithms, which were then tested in a separate group of pediatric patients. The predictive models worked and we were able to use a single blood test after CAR T cells are given to pick out patients who are highly likely to suffer from severe cytokine release syndrome.

Future applications

Those who fit the profile of being likely to have severe cytokine release syndrome can be promptly treated, hopefully heading off a serious, potentially life-threatening problem. Knowing which cytokines matter also has allowed us to treat cytokine release syndrome using very targeted drugs that were developed for completely different conditions. On the other hand, those who seem unlikely to develop cytokine release syndrome can avoid unnecessary treatment and maybe even extra days in the hospital. Having this information is an advantage all around.

This approach of using cytokines as a biomarker is an exciting aspect of precision medicine to assess possible reactions to these emerging immunotherapy cancer treatments. Modern medicine is making incredible strides in detecting and treating disease, including cancer. By bringing together biochemistry and some serious math, we’re able to more precisely manage the toxicities that may occur from very these powerful treatments. All this is to the benefit of patients who would otherwise have few or no options.