New research led by John Wagner, Jr., M.D., director of the Pediatric Blood and Marrow Transplantation program at the University of Minnesota and a researcher in the Masonic Cancer Center, University of Minnesota, has established a new standard of care for children who suffer from acute myeloid leukemia (AML).
In a recent paper in the New England Journal of Medicine, Wagner and his coworkers compared clinical outcomes in children who suffered from acute leukemia and myelodysplastic syndrome who received transplants of either one unit or two units of partially matched cord blood. This large study was conducted at multiple sites across the United States, between December 2006 and February 2012. Coordinating the study was the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) in collaboration with the Pediatric Blood and Marrow Transplant Consortium and the Children’s Oncology Group.
Umbilical cord blood provides a wonderfully rich source of blood-forming stem cells, and has been demonstrated to benefit many diseases of the blood or bone marrow, as in the case of leukemia and myelodysplasia, or bone marrow failure syndromes, hemoglobinopathies, inherited immune deficiencies and certain metabolic diseases. For leukemia patients cord blood offers several advantages since there is no need for strict tissue-type matching (human leukocyte antigen or HLA matching) or for a prolonged search for a suitable donor.
Wagner and others discovered that the survival rates of children who received either one or two units of umbilical cord blood were about the same, but, overall, their recorded survival rates were better than those reported in prior published reports. These higher survival rates, therefore, represent a new standard of care for pediatric patients, for whom there is often an adequate single cord blood unit, and for adults for usually require double units, since a single unit with an adequate number of blood-forming stem cells simply may not exist at time.
“Based on promising early studies using two cord blood units in adults for whom one unit is often not sufficient, we designed this study in order to determine if the higher number of blood forming stem cells in two cord blood units might improve survival,” explained Wagner. “What we found, however, was that both treatment arms performed very well with similar rates of white blood cell recovery and survival.”
Children with blood cancers who receive transfusions of umbilical cord blood show quantifiable clinical benefits even though the blood may not match their own tissue types. The reason stems from the immaturity of cord blood stem cells and their ability to suppress rejection from the immune system. This is an important aspect of umbilical cord blood transplants, since patients who cannot find a matched unrelated donor also benefit from cord blood transplants. However, cord collection from the placenta after birth often results in a limited number of blood-forming stem cells, which decreases the potential benefits of cord blood. The “double UCB approach” was pioneered at the University of Minnesota as a strategy to overcome this inherent limitation in the use of umbilical cord blood.
Despite the similarities in survival rates between children who received one unit or two units of cord blood, some differences were noted. Children transplanted with a single cord unit had faster recovery rates for platelets and lower risks of Graft Versus Host Disease; a condition in which the transplanted donor blood immune cells attack the patient’s body, which causes several complications.
“This is helpful news for physicians considering the best treatment options for their patients,” said Joanne Kurtzberg, M.D., chief scientific officer of the Robertson Clinical and Translational Cell Therapy Program, director of the Pediatric Blood and Marrow Transplant Program, co-director of the Stem Cell Laboratory and director of the Carolinas Cord Blood Bank at Duke University Medical Center. “We found children who have a cord blood unit with an adequate number of cells do not benefit from receiving two units. This reduces the cost of a cord blood transplant for the majority of pediatric patients needing the procedure. However, for larger children without an adequately dosed single cord blood unit, using two units will provide access to a potentially life-saving transplant.”
“The involvement of multiple research partners was instrumental to the success of the study completion,” added Dennis Confer, M.D., chief medical officer for the National Marrow Donor Program® (NMDP)/Be The Match® and associate scientific director for CIBMTR. “This trial is a testament to the importance of the BMT CTN and the collaboration of partners like the Children’s Oncology Group.”
Mary Horowitz, M.D., M.S., chief scientific director of CIBMTR and professor of medicine at the Medical College of Wisconsin, concurred. “Because of this tremendous collaboration, we were able to expand the scale of this research to multiple transplant centers across the United States and Canada. And the results will undoubtedly improve clinical practice, and most importantly, patient outcomes.”
Interestingly, in this study, patients who received cord blood with significant HLA mismatches showed no detrimental effects on their outcomes. Future studies will examine a closer look at how the HLA match within the cord blood unit impacts outcomes for patients, particularly those within minority populations.