“Your child has…”
In the millisecond before the word is spoken, life hangs in the balance. An inhalation of outrageous hope; an exhalation of gut-wrenching fear.
Then the word relapsed drops like a boulder onto a mother’s heart.
When doctors at a Puerto Rican hospital uttered that word to Jessica Lopez-Montanez, her son was just completing two-and-a-half years of treatment for acute lymphoblastic leukemia (ALL). Although ALL is the most common form of childhood cancer, Christopher’s battle had suddenly become decidedly uncommon, the family’s end-of-therapy celebration short-lived.
Curing the toughest cases
For children with newly diagnosed ALL, the survival rate is about 94 percent. But when the disease returns during or soon after the end of therapy, the outlook is not as rosy. Christopher’s local hospital offered few options for a child with a high-risk relapse. Fortunately, Christopher’s hometown medical team learned about a new clinical trial that had recently opened thousands of miles away in Memphis, Tennessee. This regimen combined chemotherapy with immunotherapy, a treatment that uses the immune system to help fight cancer.
The entire time that Christopher had been undergoing initial therapy in Puerto Rico, scientists at St. Jude Children’s Research Hospital had been preparing for this clinical trial—conducting research that might someday save his life.
A global resource
Jessica had heard of St. Jude long before her son ever relapsed. During his treatment, she had read books and combed the Internet for details about his disease.
“The thing is, when a mother has a son who is sick, she is always trying to search and find out what’s the best thing for him,” she says. “So I always had hope.”
When she and her family arrived in Memphis, Jessica was confident that they had found the right place.
“I had seen St. Jude on TV, but it was more than I had expected. I thought, ‘He is going to live. He is going to receive good treatment here, and he is going to be well,’” she recalls.
At St. Jude, the 10-year-old enrolled in a clinical trial created especially for children with relapsed leukemia. For years, researchers worldwide had been trying to find a way to raise survival rates for children like Christopher. But survival rates had plateaued.
“For the last 20 years, leukemia study groups around the world had tried different things,” explains Deepa Bhojwani, MD, of St. Jude Oncology. “They tried giving more intense chemotherapy; giving it in different combinations; giving chemo that hadn’t been given during front-line treatment. Everybody’s results were exactly the same: no improvement.”
Children with high-risk disease—like Christopher, whose disease relapsed during or soon after the end of treatment—had about a 30 percent survival rate. For children with standard-risk relapsed disease, the survival rate was 50 percent.
“A team of people from different areas at St. Jude came together to find an answer,” Bhojwani continues. “We knew that intensifying the chemotherapy was not the answer. We needed to add something novel to the treatment.
“That’s when we thought about combining chemo-therapy and immunotherapy in one block to attack the disease from different angles.”
Meeting the challenge
Children in the St. Jude clinical trial have either B-cell ALL (a cancer that affects white blood cells called B lymphocytes) or B-cell lymphoblastic lymphoma (a type of non-Hodgkin lymphoma). Like Christopher, participants have either relapsed or their disease has not responded to initial therapy.
A test developed at St. Jude allows clinicians to closely monitor each child’s response to treatment. That test can detect even one leukemic cell among 10,000 normal cells, called minimal residual disease, or MRD. In the St. Jude clinical trial, if MRD is discovered after any block of chemotherapy, that child receives more intensive therapy.
Children in the clinical trial receive chemotherapy as well as a monoclonal antibody that has been used mostly with lymphoma treatments in the past.
The antibody kills the leukemia cells more effectively when natural killer (NK) cells are added. The NK cells are harvested from the parent and infused into the patient. NK cells can also directly kill leukemia cells.
After that, children with standard-risk disease receive another two years of chemotherapy. Patients with high-risk disease—such as Christopher—undergo bone marrow transplants as soon as they have no evidence of MRD.
Christopher’s mom served as his NK cell donor, as well as his bone marrow donor.
“This clinical trial is a good option to get the leukemia very well controlled and, if they are high-risk, to get the children to transplant,” Bhojwani explains. “Our hope is that the kids will not relapse again.”
Throughout the process, Christopher asked questions. He read about his condition and his medications. Then he quizzed his clinical team so that he would understand each step of the process.
“I used to draw leukemia cells and explain to him about leukemia and its treatment,” Bhojwani recalls. “Because I couldn’t speak Spanish well, our interpreter would explain to him what I was saying as I drew the cells and described the mechanisms. I was impressed with how inquisitive Christopher was and how much he understood about the mechanisms involved in leukemia treatment.”
The St. Jude clinical trial takes a unique approach to treating children who have relapsed ALL and lymphoma.
“This therapy is novel, and it has the potential to really improve outcomes,” Bhojwani says. “This combo regimen has not been done anywhere else.”
The exceptional supportive care at St. Jude enables children undergoing treatment to receive preventive antibiotics and meticulous follow-up care to help them avoid infections. The transplant team consists of individuals who have years of experience in performing high-risk transplants, especially haploidentical, or half-matched, transplants that use parents as donors.
The clinical trial is also providing scientists with a way to better understand why some children have disease that is more resistant to treatment than other children and why relapsed disease is more difficult to treat.
A place of rebirth
Throughout his treatment, Christopher provided support to other children at St. Jude. “Christopher had a sense of peace and tranquility,” Jessica says. “He would share his insights with other kids that were sick. He would reassure them and encourage them to let the doctors know if they had any problems.”
After Christopher completed his transplant, he attended a special celebration.
His mom and stepdad had put their wedding plans on hold for the years that Christopher was undergoing treatment. Once the crisis was over, the couple knew the perfect time and place to say their vows: St. Jude.
“My child comes first,” Jessica explains, “so he was our sole focus for a long time. But once we found out that he was going to be okay, we wanted to be united in the place where he had been reborn—the place where he got cured from cancer.”
Abridged from Promise, Winter 2015