Blood transplants may be more harmful than bone marrow transplants in pediatric leukemia patients

Results differ from adult patients, underscore need for more research

A new study has shown for the first time that transplantation of peripheral blood stem cells (PBSC) from sibling donors may be more harmful than bone marrow in pediatric leukemia patients.

Researchers from the International Bone Marrow Transplant Registry (IBMTR) found that patients undergoing PBSC transplants were more likely to die of transplant-related causes than those who underwent bone marrow transplants. It is estimated that nearly 30% of transplants from sibling donors in pediatric patients now use peripheral blood stem cells. The study and an accompanying editorial will be published November 1 in the Journal of Clinical Oncology (JCO).

“Our data support the use of bone marrow for transplantation in these patients when a matched sibling donor is available,” said Mary Eapen, MBBS, MS, Assistant Professor at the Medical College of Wisconsin and lead author of the study. “The higher rates of mortality observed after PBSC transplantation compared to bone marrow transplantation should serve as a cautionary note, and underscore the urgent need for a properly designed clinical trial to define the role, if any, of donor peripheral blood stem cell transplantation in children.”

Background

Leukemia is cancer of the bone marrow. Bone marrow transplants involve the collection from the donor of “hematopoietic” stem cells – immature cells found in the bone marrow that mature into red blood cells, white blood cells, and platelets. Doctors have traditionally treated children with leukemia using bone marrow donated from a sibling when available, or from an unrelated volunteer donor. Another approach is peripheral blood stem cell (PBSC) transplantation, in which these stem cells are collected from the donor’s blood, rather than directly from their bone marrow.

In both types of transplantation, the patient’s cancerous bone marrow is destroyed with high doses of chemotherapy or radiation. Then bone marrow or peripheral blood stem cells are given to the patient, which replaces the destroyed marrow.

In adults, peripheral blood collection has become increasingly common in recent years, because it allows donors to avoid the difficulties of bone marrow collection, such as surgery and anesthesia. Since peripheral blood transplantation has been shown to be as safe and effective as bone marrow transplantation in adults, some doctors have begun recommending use of peripheral blood transplants in pediatric patients.

Findings

Eapen and her colleagues compared the outcomes of 143 PBSC and 630 bone marrow transplants in patients with acute leukemia aged 8-20 years who were transplanted between 1995 and 2000. This analysis was performed with data reported to the International Bone Marrow Transplant Registry (IBMTR).

Despite faster recovery of blood counts, more patients who underwent PBSC transplantation died as result of transplant-related complications (26%, compared to 14% of bone marrow transplants) – especially chronic graft-versus-host disease, a potentially serious complication in which the transplanted cells attack the tissues of the recipient. Chronic graft-versus-host disease was significantly higher after PBSC transplants than after bone marrow transplants (33% vs. 19%).

Overall mortality was also higher after PBSC transplants – 57%, versus 44% after bone marrow transplants. The risk of leukemia recurrence after transplantation did not differ. These results persisted after controlling for relevant risk factors that may affect outcomes after transplantation. It is important to note that the current study addresses transplants from donors only, not “autologous” PBSC transplants, in which stem cells are taken from the patient’s own blood. This approach has been proven safe among adults and children, and is widely used.

An accompanying editorial by Donna A. Wall, MD, of the Texas Transplant Institute in San Antonio, underscored the need for a prospective study designed to assess PBSC and bone marrow transplantation in pediatric patients. “This is an unsettling finding, given that nearly 30% of transplants from sibling donors in pediatric patients now use peripheral blood grafts,” Dr. Wall said. “It very well may be that peripheral blood stem cells do not offer a benefit over bone marrow in pediatric patients. It is critical that this question be carefully studied by prospectively identifying the patients, diseases, and clinical settings in which clinical benefit is likely to be observed. Until then, patients and families need to be informed about the risks of transplant-related morbidity, including chronic graft-versus-host disease and higher risk of mortality.”