High protein levels associated with remission and survival in patients with blood-borne cancers
GAINESVILLE, Fla. — Call it the immune system’s version of urban combat.
University of Florida researchers have identified a protein linked to remission in patients who have undergone bone marrow transplantation for blood-borne cancers such as leukemia or lymphoma. Known as interleukin-12, or IL-12, the protein’s role in the body’s hunt for insurgent cancer cells has yet to be fully defined, but study findings presented at today’s meeting of the American Society of Hematology in San Diego show patients with high levels soon after transplantation were twice as likely to survive as those with low levels. The protein also may give doctors the ability to accurately assess a cancer patient’s long-term prognosis a mere week after bone marrow transplantation.
Until now, doctors have had no reliable way of determining patients’ chances of relapse or death in the long run. Typically they do their best to estimate prognosis by looking at how well the bone marrow donor and recipient are matched, the kind of cancer the patient has and how well treatments prior to the transplant have controlled the disease.
“What we found was patients with high levels of IL-12 in the blood after transplantation did quite well after transplantation in the way of less cancer relapse and improved survival after transplantation, suggesting that IL-12 is important in the fight against cancer,” said Dr. Vijay Reddy, an assistant professor of hematology and oncology at UF’s College of Medicine who also is affiliated with the UF Shands Cancer Center.
In addition, patients with high levels of IL-12 experienced no increase in adverse effects after transplantation, such as graft-vs.-host disease, in which transplanted cells — the graft — don’t discern between healthy tissues and cancer and attack both. The findings suggest the protein could someday be used to rev up the immune system to more effectively fight cancer, Reddy said.
The results also build on related research UF scientists published earlier this year on dendritic cells, the captains of the immune system that normally initiate the body’s response to infection or disease, ordering a molecular army of soldierlike cells to the front lines. When dendritic cells are produced in large enough numbers after blood stem cell transplantation, they appear to launch the body’s fight against the return of blood-borne cancers without attacking a patient’s healthy tissues. These cells are believed to generate IL-12.
“By looking at IL-12, we’re able to identify how the immune system is functioning,” said Reddy, adding that researchers eventually hope to evaluate whether the protein could someday be used to strengthen the immune system’s anticancer response.
Each year, an estimated 30,000 patients undergo a bone marrow or peripheral blood stem cell transplant for a diagnosis of leukemia or another blood disease. Both types of transplantation aim to restore patients’ blood stem cell counts after their own stem cells have been wiped out by high-dose chemotherapy or radiation therapy used to treat cancer. After they are infused into the bloodstream, stem cells take up residence in the bone marrow, where they give rise to the immune system’s infection-fighting white blood cells, red blood cells or platelets.
UF researchers studied 120 cancer patients who received a bone marrow transplant. In the first week after the procedure, 46 patients had low levels of IL-12, 49 patients had medium levels and 25 patients had high levels. Those with high levels were less likely to relapse and were more likely to survive if they did than patients with lower levels. At 500 days post-transplant, 49 percent of those in the low-level group had relapsed, compared with only 23 percent in the high-level group. Those with high IL-12 levels also were more likely to survive without ever relapsing at all and experienced no increase in transplant-related side effects.
The data suggest the need for further studies aimed at determining whether administering IL-12 to cancer patients could help prevent relapse after bone marrow transplantation, Reddy said.
“The concept of a cancer vaccine is to boost the immune system as one would for chickenpox or measles in trying to prevent those diseases,” he said. “In the future, we hope to be able to challenge the immune system so it can recognize cancer before it’s full-blown and be able to fight it — to be able to treat cancer with the immune system itself.”
The research is part of an ongoing quest to identify cells that, when transplanted into a cancer patient, will not attack the body yet will recognize residual cancer cells and target them, a beneficial phenomenon known as graft-vs.-leukemia, Reddy said.
“Dr. Reddy’s results represent a shift in the way people think about outcomes after transplant,” said Dr. Kenneth R. Cooke, an assistant professor of pediatrics at the University of Michigan Cancer Center. “Most people up to this point think more about the cells in the stem cell graft, particularly lymphocytes, and their role in both graft-vs.-host disease and graft-vs.-leukemia. Dr. Reddy’s group is showing that a particular cytokine (protein) level correlates with outcome. What is most intriguing is that Dr. Reddy is measuring levels within the first week of transplantation and correlating these results with outcome down the road, specifically the risk of relapse and death. If you think about it, this can be very important. If you could measure these levels right away and predict with some certainty what a patient’s outcome will be, this opens the door for early intervention if things are not looking promising early on.”
Cooke cautioned, however, that it’s too soon to know whether high levels of IL-12 are merely associated with good outcomes or are truly the direct cause of them.
“IL-12 may be a sentinel of something else that’s really going on,” he said. “Thus, there is still work to be done to ascertain the precise role of IL-12 in improving outcomes after bone marrow transplantation.”