Gene Therapy Helps 2 Babies Fight Type of Leukemia

WEDNESDAY, Jan. 25, 2017 (HealthDay News) -- Two infants with an advanced form of leukemia are in remission after treatment with genetically tweaked immune system cells, British researchers report.

Both babies had run out of treatment options for their cancer, known as B-cell acute lymphoblastic leukemia, or ALL. But, after treatment with genetically altered T-cells -- a type of immune system cell -- both went into remission.

The babies are now "at home and doing well," said Dr. Waseem Qasim, one of the doctors reporting on the cases.

They will still have to be monitored for "some time," said Qasim, a professor of cell and gene therapy at University College London.

Small trials are under way, he said, to see if the therapy can be more widely applied.

ALL is a cancer of the white blood cells that strikes roughly 6,000 U.S. adults and children each year, according to the American Cancer Society. The cancer progresses quickly, and doctors usually treat it with multiple chemotherapy drugs.

Among children with ALL, more than 80 percent are cured with intensive chemo, according to the U.S. National Cancer Institute.

Unfortunately, infants often have a "poor response" to their initial chemo, said Dr. Kevin Curran, a pediatric oncologist at Memorial Sloan Kettering Cancer Center in New York City.

So researchers at Sloan Kettering and a few other centers have been testing a new treatment known as CAR T-cell therapy.

It involves taking T-cells from the patient, then genetically altering them to be "armed" with chimeric antigen receptors, or CARs. That allows the T-cells to recognize and attack ALL cells once they are infused back into the patient's blood.

Several studies have shown the approach can work -- winning complete remissions in some patients who'd run out of treatment options.

"The first hurdle was to show that this works," said Curran, who was not involved in the new study.

But there are other hurdles, he pointed out. With babies, in particular, one issue is that they may not have enough healthy T-cells to collect.

So Qasim's team sought a way around that. Instead of using T-cells from the two babies, they used cells from a healthy donor, then genetically fine-tuned them to be "universal" CAR T-cells.

The cells were altered both to fight the babies' ALL and to minimize the risk of the donor cells causing a dangerous immune reaction called graft-versus-host disease.

After receiving the T-cell therapy, one baby did develop graft-versus-host disease. But it was limited to the skin and responded to treatment, according to the study authors.

Both babies went into remission within 28 days of receiving their T-cell infusion. From there, both were able to undergo chemo and a bone marrow transplant. That wiped out the babies' existing immune system -- including the donor T-cells -- and replaced it with a healthy one.

According to Qasim, the babies have remained leukemia-free for 10 and 16 months, and are being closely monitored.

Qasim and his colleagues report on the two cases in the Jan. 25 online issue of Science Translational Medicine.

Curran called the results "fantastic," but also cautioned that they are based on only two patients. So larger studies are clearly necessary, he said.

Still, part of what's promising, according to Curran, is the use of "universal" T-cells. Harvesting cells from individual patients, then genetically engineering them, is a time-consuming and labor-intensive process.

If, instead, scientists could create a "bank" of universal T-cells, that could make the treatment more feasible, Curran said.

Qasim agreed that "off-the-shelf" T-cells could offer a practical advantage.

"Having cells premanufactured and ready to use would have obvious advantages in terms of scheduling and coordinating with other treatments," he said.

A lot of work remains, however, before that can happen.

Researchers are still sorting out the potential safety issues with CAR T-cell therapy in general, Curran said. There is a risk of "toxicities," he noted -- including a side effect called cytokine-release syndrome, which causes severe fever and a drop in blood pressure.

And in one trial of adult patients, several died from brain swelling. The U.S. Food and Drug Administration temporarily halted that study last year.

More information

The U.S. National Cancer Institute has more on CAR T-cell therapy.

SOURCES: Waseem Qasim, M.D., Ph.D., professor, cell and gene therapy, University College London, England; Kevin Curran, M.D., pediatric oncologist, Memorial Sloan Kettering Cancer Center, New York City; Jan. 25, 2017, Science Translational Medicine, online