Photo by Todd McNaught
Some children with an aggressive form of leukemia whose cancer returns after a stem-cell transplant can be cured with a second transplant, according to new findings from the Clinical Research Division.
In a study of 25 children with acute myeloid leukemia who relapsed after a first transplant, Dr. Soheil Meshinchi and colleagues found that nearly half of those who underwent a second transplant from a tissue-matched donor were still alive after 10 years.
The prognosis was best for children who received the second transplant in remission and those who were transplanted six or more months after the first transplant. Survival rates also were better for children whose initial transplant involved transfusion of their own stem cells that had been treated to remove cancerous cells-a procedure known as an autologous transplant-compared to those who were first transplanted with cells from a tissue-matched donor.
Not all children who relapse after transplant for AML will survive long enough to undergo a second transplant. But based on their findings, the researchers recommend that those who do and who also meet certain other criteria be considered for the procedure.
"Pediatric AML is a very difficult disease to treat, and patients who relapse after transplant typically have a very poor prognosis," said Meshinchi, an associate in clinical research in Radich's lab and a pediatric oncologist. "The existing treatments for patients who have relapsed after an initial transplant do very little to improve long-term survival. The fact that there is currently no viable option for treating this group of patients suggests that a second transplant should be considered for children who meet the criteria that we've found to be associated with a favorable outcome."
The results are published in the November issue of Biology of Blood and Marrow Transplantation. Coauthors included Drs. Wendy Leisenring, Paul Carpenter, Ann Woolfrey, Eric Sievers, Jerry Radich and Jean Sanders.
Leukemia is the most common childhood cancer, and nearly one quarter of cases are AML. Children with AML typically are treated either with intensive chemotherapy or, if they have a tissue-matched sibling or parent, with a procedure known as an allogeneic stem-cell transplantation. About half of children treated with chemotherapy survive, and survival rates for those who receive transplants are only somewhat better. In contrast, the survival rate for acute lymphoblastic leukemia-the most common childhood leukemia-is greater than 80 percent.
Allogeneic stem-cell transplantation involves first destroying the patient's diseased bone marrow and immune system with high doses of radiation and chemotherapy. The marrow and immune systems are reconstituted with a transfusion of stem cells from a sibling or unrelated donor with compatible tissue type. Some children for whom matched donors cannot be found are treated with an autologous transplant, although because it offers no survival advantage compared to chemotherapy alone, the procedure is less commonly used. Second transplants often cause complications that lead to transplant failure and poor survival rates. But in an earlier Fred Hutchinson study of adult and pediatric leukemia patients who received a second transplant, the researchers found that children experienced fewer treatment side effects than older patients and also had a greater than 40 percent chance of survival after the second procedure.
Based on these results, Meshinchi and colleagues examined the outcome of 25 pediatric AML patients, ages 1 to 17, who received a second stem-cell transplant. Eleven of the patients had received autologous transplants as their primary therapy and 14 received transplants from tissue-matched donors. The preparative regimen for all first transplants involved treatment with the drugs busulfan and cyclophosphamide. All second transplants were from donors and involved total body irradiation and cyclophosphamide as the preparative regimen.
Ten years after the second transplant, 48 percent of the children were still alive and free of their cancer. Children were more than seven times as likely to have a good outcome if their disease had been brought into remission with chemotherapy or radiation prior to second transplant than if they were not in remission. Children who had second transplants performed less than six months after the first were nearly five times as likely to relapse as those who had a second transplant six or more months after a first transplant.
"A second transplant would not suitable for every pediatric AML patient who relapses," Meshinchi said. "Children who experienced significant toxic side effects from their first transplant would not be good candidates. But for those who have matched donors and other favorable characteristics, a second transplant should be considered."