A disabled form of the virus that causes AIDS has been used for the first time in a child as a treatment for Acute Lymphoblastic Leukemia (ALL).
Emily "Emma" Whitehead, a 7-year-old girl from Philipsburg, Pennsylvania was diagnosed with ALL in 2010. She received standard chemotherapy treatments, but in October 2011, her cancer returned.
Children who receive the standard chemotherapy treatments for two-years after being diagnosed with ALL, have an eighty-five percent chance of becoming cancer free. Emma however was among the 15 percent of children whose cancer is resistant to even the most extreme chemotherapy regiments. Her parents, Kari and Tom Whitehead, desperate to do whatever they could to save their daughter, decided to seek out advise from Dr. Rheingold, an Oncology specialist at the Children’s Hospital of Philadelphia (CHOP) Cancer Center.
After speaking with the family and examining Emma, Dr. Rheingold agreed with Emma's initial oncologist's suggestion of trying one more round of more intense chemotherapy. When that round also failed, Kari and Tom took their daughter back to CHOP and at Dr. Rheigngold's suggestion, enrolled Emma in a cutting edge clinical trial called CTL019.
CTL019 is an experimental T-cell therapy used in adult patients with chronic lymphocytic leukemia (CLL) and patients with ALL and B cell non-Hodgkin lymphoma (NHL). The treatment genetically modifies the patients T-cells, a form of white blood cells key to the body's immune system. The modification allows the protein within the cells to recognize and bind to the CD19 molecule, a B cell in blood. According to the New York Times, this process is done by using a disabled form of the virus that causes AIDS. By using the disabled virus, the T-cells were "reprogrammed" to kill cancer cells.
The body's T-cells cannot detect cancerous B cells on their own. By binding the cells to CD19, and thus genetically modifying the cells, they are then able to not only detect the cancer, but attach directly to the cancer cells and destroy them.
In a process called adoptive T-cell transfer, or adoptive immunotherapy, the T-cells are removed from the patient through a process similar to blood donation. The cells are then modified using a disabled form of the HIV virus, lentivirus. The infectious portion of lentivirus is removed in the laboratory, leaving a "carcass" of the virus remaining. This process eliminates the risk of viral infection according to Michael Kalos, director of the Translational and Correlative Studies Laboratory in Penn’s Perelman School of Medicine. Once the cells are reprogrammed they are injected back into the patient's body.
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Emma sits with her mother, father and doctor after her T-cells were removed.
Dr. Stephen Grupp, a pediatric oncologist at CHOP, explained that researchers put a new gene into the T-cells by using the gutted virus. That gene is incorporated into the actual DNA of the T-cell and the gene produces a new protein that doesn't exist in nature.
Kalos went on to say:
“So instead of trying to stimulate or trigger a rare cell in somebody’s body by a vaccine, you give them the end product of that, which is a billion cells that are engineered to recognize what you want them to recognize.”Emma's Treatment
A few short days after the T cells were injected back into Emma, she developed chills and a high fever, which according to doctors, is a sign that the treatment was working. The reaction is known as cytokine-release syndrome, also called "shake and bake" by many oncologists. Steroids were administered to Emma but did nothing to ease the symptoms. Her temperature spiked up to 105, her blood pressure was dropping and, unconscious and swollen almost beyond recognition, she was put on a ventilator. On April 24, 2012 her family was told that she had a 1 in 1,000 chance of surviving the night.
Her family and doctors refused to give up despite the grim prognosis. Dr. Stephan Gruppa ordered a battery of blood tests which showed that Emma's levels of one of the cytokines, known as interleukin-6, had spiked to a thousandfold of what is considered normal. Using a drug typically given to rheumatoid arthritis patients, Emma's condition improved rapidly. Nearly overnight, her breathing improved, her fever dropped and her blood pressure was back to normal.
On May 2, 2012, a week after Emma's family gathered at her bedside to say goodbye, she woke up. Doctors ordered a Minimal Residual Disease report, which can locate one leukemia cell in 10,000-100,000 cells. The report came back negative for cancer.
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Emma resting after receiving the genetically altered T-cells.
On June 1st, Emma returned home to signs which read “We Believe” and “Welcome Home Emily” in her yard. Beverly Fahr, a family friend who helped organize the homecoming celebration, told Centre Daily Times:
“Emily’s been an inspiration for the entire town. For me, it just makes me proud to see how the community has come together. Tom and Kari sharing (their story) with the community ... we all just share the sense that we've all been part of it.”
Because the research is still in the early stages, it is unknown if patients will need to receive the modified T-cells throughout their life. There is also uncertainty surrounding the effects of the altered T-cells on the body long term. Because the cells destroy healthy B-cells as well as cancerous ones, patients are vulnerable to certain types of infections. Emma and others receiving the treatment may require regular treatments of immune globulins to prevent illnesses. Even if Emma does require periodic T-cell treatment and/or immune globulins, it was a risk worth taking. Emma is now back at school, receiving good grades and enjoying her passion for reading. Her father told the New York Times:
“It’s time for her to be a kid again and get her childhood back.”