Gene Therapy May Provide Hope for Patients with Advanced Leukemia

Margaret Dayhoff-Brannigan, Cancer Prevention and Treatment Fund

Acute Lymphoblastic Leukemia (ALL) is difficult to treat in children and adults. The most effective treatment is a stem cell transplant, but for patients whose cancer comes back after stem cell treatments, or who cannot be treated with a stem cell transplant, there are very few other options.

A study published in the prestigious New England Journal of Medicine in October 2014 tested a new treatment on terminally ill patients, 78% of whom survived at least 6 months.1

What is Acute Lymphoblastic Leukemia?

ALL is a cancer of the blood and bone marrow. It is the most common form of leukemia in children. In a healthy person, blood consists of red blood cells which carry oxygen and nutrients, platelets that help wounds to heal, and white blood cells which help the body fight infection. These different types of cells are made from stems cells in the bone marrow. In a patient with ALL, there are too many abnormal white blood cells that do not work properly to fight infections. These patients do not have enough red blood cells and platelets, and that can cause anemia or excessive bleeding. 2

Treatment Options

Currently there are four treatment options for ALL patients. Chemotherapy is a common cancer treatment that uses drugs to kill cancer cells. Radiation therapy is a treatment for cancer that uses x-rays or other forms of radiation to kill cancer cells. Targeted therapy uses very specific drugs or substances to identify and attack only cancer cells without causing harm to normal cells. Chemotherapy with stem cell transplant combines chemotherapy (and sometimes radiation) to kill cancer causing stem cells in the body, and then replaces them with a donors stem cells.2 How successful the treatment is usually depends on how old the person is when they are diagnosed and the amount of white blood cells the person has. ALL has a cure rate of 80-90% in childhood cases, but only about 40% in adults. Approximately 1,170 adults and 270 children die of ALL each year.3

Two Promising New Treatment for Patients with Relapsed ALL

There are two promising new treatments, but more research is needed before doctors will know more about which patients are most likely to benefit and before these treatments will be widely available.

Researchers at two hospitals in Philadelphia used an experimental treatment for ALL on 25 children and 5 adults.1 The children were seen at Children’s Hospital of Philadelphia by Dr. Shannon Maude and Dr. Stephan Grupp and their colleagues. The adult patients were treated at the University of Pennsylvania School of Medicine under the care of Dr. Noelle Frey. These patients all had relapsed several times or had failed to respond to any treatment. All had only a few weeks or months to live. The scientists took blood from each patient and separated out the white blood cells. These cancerous white blood cells were then genetically modified so that they could recognize and attack the diseased cells that cause the leukemia. The genetically modified cells were then put back in the patient using a blood transfusion.

One month after the treatment, 27 of the 30 patients were in remission. However, as the study continued, 7 of the 27 had a relapse, anywhere from 6 weeks to 8.5 months after treatment. More relapses are expected as the study continues.

Overall, 78% of the patients in the study were still alive 6 months after treatment, which was much longer than would have been expected without the gene therapy.1 When the results were written up for publication, one patient had survived two years after therapy. However, approximately half the patients had received the treatment less than 7 months earlier (some as little as 1-2 months earlier), making it impossible to calculate the average number of months of survival for the 30 patients.

Although patients were selected for the study if they were not eligible for stem cell transplant, several became eligible after gene therapy improved their health, and successfully underwent stem cell transplants or another treatment. However, the patient who has survived for two years did so without additional treatment.

We expect that a subsequent publication will give 2-year follow-up data for all 30 patients.

A different and also successful treatment for patients with relapsed or untreatable ALL was published recently by a different group of scientists at the Memorial Sloan-Kettering Cancer Center in New York City. They used a similar method to modify the genes in the patients’ white blood cells. However, this treatment was only effective at giving patients a short period of remission while they were waiting for a stem cell transplant. None of the patients in this study could be cured without also receiving a stem cell transplant.4 In contrast, the treatment studied by doctors in Philadelphia is the first to offer the possibility of a long reprieve or even possibly a cure in patients who had very little time left to live.


  1. Maude, S. L., Frey, N., Shaw, P. A., et al. (2014). Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med 371, 1507-17.  
  2. General Information About Childhood Acute Lymphoblastic Leukemia. National Cancer Institute June 5, 2014. Available at: Accessed Oct 24, 2014.  
  3. T-Cell Therapy Puts Leukemia Patients in Extended Remission. The New York Times Oct 15, 2014. Available at: – story-continues-1. Accessed Oct 24, 2014.  
  4. Davila, M. L., Riviere, I., Wang, X., et al. (2014). Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med 6, 224ra25.