SAN FRANCISCO—Umbilical cord blood transplants provide new hope for children with leukemia and genetic diseases requiring transplantation, Joanne Kurtzberg, MD, said at the 42nd Annual Meeting of the American Society of Hematology (ASH). She reported that 53% of pediatric patients treated with cord blood transplant at Duke University are surviving.
In this single-institution study, the largest ever conducted using cord blood, 208 patients under the age of 18 received umbilical cord blood transplants from unrelated donors between 1993 and 2000 at Duke University Medical Center. Patients had hematologic malignancies, genetic disorders, immune deficiencies, and metabolic disorders, all of which were incurable without a marrow replacement. Life expectancy was less than 1 year.
The transplants were successful in 108 patients, who are alive at a median follow-up of 2.3 years, said Dr. Kurtzberg, director of the Pediatric Stem Cell Transplantation Program at Duke.
For patients with acute lymphocytic leukemia (ALL), 3-year event-free survival is 46%, while those transplanted in first remission have an event-free survival rate of 80%. ALL patients treated before the age of 1 had the best survival rates, with 22 of 25 (90%) still alive and free of disease at 3 years.
Event-free survival at 3 years was 80% in patients with chronic myelogenous leukemia (CML) in chronic or accelerated phase and 88% in patients with myelo-dysplastic syndromes.
"Diseases that in the past have been incurable can now be cured if patients are referred early for treatment with umbilical cord blood transplants from an unrelated donor," Dr. Kurtzberg said.
Transplants of cord blood, taken from a baby’s umbilical cord and the placenta, can be used successfully in patients because the HLA antigens do not need to match those of the recipient as closely as in bone marrow transplantation.
Only seven patients (3%) in the Duke study received transplants in which all six antigens matched exactly; 185 patients (89%) received cord blood transplants in which only four or five of six antigens matched (59% and 30%, respectively). Sixteen (7%) children received haplo-identical umbilical cord transplants.
Chronic GVHD Reduced
HLA disparity had no adverse effect on survival, the researchers concluded, adding that this may be due to the fact that fetal blood cells are immunologically immature and do not trigger rejection of tissue.
The rate of chronic graft-versus-host disease (GVHD) is only 9% in umbilical cord blood transplant patients vs 100% in unrelated bone marrow transplant patients, Dr. Kurtzberg said in an interview with ONI. Chronic GVHD causes significant morbidity and is responsible for half of the late deaths in the marrow transplantation population.
"This means a lot of bone marrow transplant patients are really sick and can’t have a normal quality of life," Dr. Kurtzberg said, "whereas these kids receiving cord blood have a rough first 3 months, but after that, they recover and don’t have late complications from their transplants. In pediatrics, that is our goal—we’re not looking at buying somebody a year, we’re looking at buying somebody decades."
Dr. Kurtzberg said that 95% of patients can find a two-antigen mismatched umbilical cord blood donor. Such mismatched transplant patients experience no significant differences in time to engraftment, compared with related donor transplant groups. In multivariate analysis, she said, the cell dose/kg was the only statistically significant variable predictive of a favorable outcome.
Possibilities and Options
Physicians must learn about these possibilities for children, Dr. Kurtzberg told ONI. "The family of a child who doesn’t have a bone marrow donor shouldn’t be told that there are no options," she said. "Ninety percent of the time you can find a mismatched, but suitable, cord blood donor, and the outcomes are at least comparable to those with unrelated bone marrow transplants, and may be better."
