Leukemia in 2015: What's New?
Doug Olson, 68, of Pipersville, Pennsylvania, kept his chronic lymphocytic leukemia as low-key as he could. A scientist who developed medical diagnostic instruments, he only told co-workers about his cancer on a need-to-know basis. For the first six years, his treatment consisted of watchful waiting.
But Olson's blood counts gradually got worse, and he eventually needed chemotherapy. With each round of chemo, spread out over several years, his remissions grew shorter. By 2010, half of his bone marrow consisted of cancer cells. Opportunistic infections took hold of his body as his immune system weakened. Olson was told he needed a bone-marrow transplant, or he would likely only have two years left to live.
Blood-Cell Cancer
Last year, nearly 53,000 Americans were diagnosed with leukemia, according to the National Cancer Institute. Leukemia is a malignancy of the blood-forming cells. Blood is made up of red blood cells, platelets and infection-fighting white blood cells. In leukemia, the bone marrow makes abnormal white blood cells, which keep reproducing and crowding out normal blood cells. Patients with leukemia are vulnerable to bleeding, infection, fatigue and other symptoms. Leukemia can spread throughout the body.
The disease is classed in two ways. The first is how quickly it progresses: whether the disease is chronic or acute. Leukemia is also grouped by the type of white blood cell affected: either lymphoid cells of the immune system, or myelogenous cells of the bone marrow. Chronic lymphocytic leukemia, the type Olson has, is the most common chronic leukemia in adults.
Pioneering Treatment
Olson hoped to avoid a bone-marrow transplant. He'd recently connected with oncology researcher David Porter, who told him about an experimental treatment he was involved with at the University of Pennsylvania.
In September 2010, Olson became one of the first patients to undergo experimental chimeric antigen receptor T-cell therapy. Also known as CAR T-cell therapy, it's been designated by the Food and Drug Administration as a breakthrough treatment for leukemia. It's now in phase 2 clinical trials.
Olson received the outpatient treatment through an IV infusion. At first, he didn't experience any effects, good or bad. Two weeks later, he developed chills and other flu-like symptoms.
Porter eventually came to him with good news: The treatment was proving effective. Olson becomes emotional when he recalls learning: "They can't find a cancer cell anywhere. It's not in your bone marrow; it's not in your blood. It's gone."
Kids and Leukemia
Next door to the Hospital of the University of Pennsylvania is the Children's Hospital of Philadelphia. Shannon Maude, an attending physician in pediatric oncology at CHOP and assistant professor of pediatrics at the university's Perelman School of Medicine, divides her time between seeing sick kids and conducting research.
Acute lymphoblastic leukemia, or ALL, is the most common form of leukemia in kids and the most common childhood cancer. "Over the last 10 to 15 years, we've seen an improvement, such that for the majority of children with ALL, there's close to 90 percent chance of them being cured," Maude says.
Initially, Maude says, children have symptoms such as pain, bruising and fever that alert their pediatricians. If blood test results raise concern, that's when children come to the oncology clinic, where they undergo a bone marrow procedure, so the team can perform a biopsy to make the leukemia diagnosis.
"When we have those results back, we meet with the family," Maude says. "Usually with the parent separate from the child if the child is young. If the child is older or a teenager and can understand, then we talk to them as well about what's going on."
Standard Treatment
"Patients with ALL can be quite sick initially," Maude says. It's a long therapy, she says, with treatment averaging 2.5 to 3.5 years, mostly on an outpatient basis. "The initial period is very intense and obviously a trying time for the families of these kids," Maude says.
Child life specialists and other hospital services are there to help kids and families cope, and every effort is made to disrupt kids' lives as little as possible. "As [children] get past the initial intense part, they're often going back to school or interacting with their friends and so can carry on a relatively normal life," Maude says.
Chemotherapy is given in phases. Induction, the early phase, is meant to reduce leukemia cells in the bone marrow as much as possible. Consolidation is next, to target any remaining leukemia cells. Intensification may require hospitalization for side effects. Maintenance involves less-intense courses of chemo given monthly during outpatient visits.
Short-term side effects include hair loss, mouth sores, nausea and vomiting, and increased risk of infection. Patients might need strong antibiotic or antifungal medications to treat infections. They may require transfusions as blood counts drop. Some leukemia patients undergo radiation treatments.
When it comes to stem cell or bone marrow transplant, recommendations "depend on the type of leukemia and the response to therapy," Shannon says. "For children with ALL, the standard therapy is typically chemotherapy alone. Transplant is considered for patients who have a poor response to therapy and patients who relapse."
Unfortunately, Maude says, for children who relapse, cure rates haven't improved as much as for others. But "that's started to change," she says. "We have more options for children who relapse."
CAR T-cell therapy is one. With the experimental treatment, "CHOP and Penn very closely collaborate," she says. "It's the exact same therapy at both places."
"Living Drug"
Maude explains how the treatment works. "T-cells are very important cells in the immune system that do a good job of clearing out infections, like bacteria and viruses," she says. However, "they don't recognize [cancer cells] as being foreign." In CAR T-cell therapy, scientists reprogram the cells "to see leukemia as something that needs to be killed," Maude says.
The process starts with apheresis, a procedure used to remove T-cells from the patient. In the lab, the cells undergo gene transfer, in which they're bioengineered along with a piece of DNA also engineered in the lab and returned to the patient's body, where they now fight cancer cells.
"The T-cells will then regrow many times inside the body, probably a thousand times or more," Maude says. "It's what some people have called a living drug, because the T-cells can actually stick around for months, or in some cases, even years."
But CAR T-cell therapy can cause severe side effects when given. Cytokine-release syndrome happens when the T-cells growing in the body stimulate an immune process that causes very high fevers. "In some cases, [patients] get very sick to where they require medicines to help with their blood pressure," Maude says, "or in some cases, they require help with their breathing." A drug called tocilizumab can help.
The CHOP study, with results released in October in the New England Journal of Medicine and at the December meeting of the American Society of Hematology, has reported on 39 young people with ALL who've been treated with CAR T-cell therapy, "We've seen 90 percent of these patients initially go into remission a month after the therapy," Maude says. For those still being followed, she says, "at six months, approximately 70 percent of them remain in remission."
The Leukemia and Lymphoma Society has been funding the CAR T-cell research for nearly two decades, to create the therapy in the laboratory and move it into clinical trials, says Andrea Greif, the society's director of communications.
The clinical study was partially funded by the drug company Novartis, which is helping to commercialize the work by supporting clinical trials and developing the manufacturing process, and it will work with the FDA as the regulatory process goes forward, Greif says.
Breakthroughs: Not Overnight
For patients with CLL, the response rate to CAR T-cell therapy is lower. Olson is one of the fortunate 50 percent who did achieve remission, Greif says.
Clinical trials at Memorial Sloan Kettering Cancer Center and the National Cancer Institute have shown similar results.
Other innovative therapies are also in the works, Greif says. Last year, the FDA granted the drug Ibrutinib breakthrough status for certain CLL patients. And blinatumomab was approved to treat patients with an uncommon form of ALL.
Olson is still closely monitored, and he receives IV immunoglobulin replacement therapy because the T-cell treatment eliminated antibody-producing cells that help fight infections. But he's doing well. Last September, he had his four-year checkup, with no signs of leukemia found.
Lisa Esposito is a Patient Advice reporter at U.S. News. You can follow her on Twitter, connect with her on LinkedIn or email her at lesposito@usnews.com.
