The patient's disease status at the time of transplant was the major predictive factor.
Prognostic factors that affect the outcomes of unrelated bone marrow transplants in children with acute myeloid leukemia (AML) are not well understood. A recent study suggests that patients who receive a bone marrow transplant during remission have superior outcomes compared with those who undergo transplantation during relapse or active disease.
“There is not much information about outcomes seen in pediatric patients with AML across multiple institutions to assess risk factors in different groups,” explained lead author Nancy Bunin, MD, professor of pediatrics and director of blood and marrow transplant at the Children’s Hospital of Philadelphia, Pennsylvania. Dr. Bunin said this information is important because it allows oncologists to counsel families and determine when the risks of a bone marrow transplant outweigh expected benefits.
The researchers studied a registry of 286 patients aged ≤18 years who received unrelated donor bone marrow transplants facilitated by the National Donor Marrow Program. At time of transplantation, 142 had AML in second complete remission, 90 had relapsed AML, and 36 had primary induction failure. All the patients had received bone marrow grafts from an unrelated donor following a myeloablative conditioning regimen.
Investigators concluded that the patient’s disease status at the time of transplant was the major predictive factor on outcomes, including rate of AML recurrence and period of overall survival and leukemia-free survival (LFS). Children in complete remission at the time of transplantation had the highest 5-year LFS probabilities, at 45%, compared with 20% for those with relapsed disease and 12% for children with primary induction failure. Risk of acute—but not chronic—graft-versus-host disease was lower in patients with T-cell depleted marrow, and T-cell depletion was not associated with higher levels of leukemia recurrence.
“Not surprisingly we discovered that the results are best when patients are in second remission, and 45% of these patients were in remission at 5 years,” said Dr. Bunin. “Those who were transplanted in relapse did not do as well, but 20% were in remission at 5 years. Those who did extremely poorly were those never in remission and I think there could be some thought given about not taking these patients to transplant.” Dr. Bunin believes there are multiple reasons why those in second remission appear to have the best prognosis following bone marrow transplantation; one is that rates of relapse are lower for patients in remission. “Another consideration is the amount of disease,” she said and explained that “if you go into transplant with least amount disease possible or minimal residual leukemia, your risk of relapse is less and risk of transplant mortality is lowered.”
Kamar Godder, MD, MPH, chair of the Division of Pediatric Hematology/Oncology and professor of pediatrics at Virginia Commonwealth
University School of Medicine in Richmond noted that this is the first sizable study of its kind in this patient population. She described the study as useful even though it relied on registry data.
Dr. Godder noted, however, that it is unclear how researchers chose to eliminate survivors in adjusting for the lack of data on deceased patients and expressed concern that it may have introduced bias. “Prior to 2002, there was no consent obtained to collect the data, so they had to go back and ask surviving patients or parents [and] legal guardians,” she noted. “They decided not to request consent from those who had died, meaning they had a higher proportion of those who had passed away. The way they adjusted for this may be a concern for bias.” She also noted that the registry had no data on the severity of chronic graft-versus-host disease or the performance status of survivors.
The numbers, however, convey the important clinical message that emerges from this study. “The bottom line is that 45% of the patients who go through transplant with an unrelated donor in second remission will survive for 5 years,” said Dr. Godder. “This tells physicians to not play around with their patients in remission, send them directly to transplant. Don’t hold them forever, because that is not going to make them better.”
The other important finding from this study is that there may be reason for some optimism when subjecting those patients who do not respond well to medical treatment to a bone marrow transplant. “We know that patients who are not in remission are not going to do that well,” said Dr. Godder. “On the other hand, they were able to rescue about 20% of the patients who otherwise would have been dead.”
J Clin Oncol
Bunin NJ, et al. Unrelated donor bone marrow transplantation for children with acute myeloid leukemia beyond first remission or refractory to chemotherapy. . 2008;26(26):4326-4332.
Kurt Ullman is a freelance health and medical writer based out of Indianapolis.