Donated umbilical cord blood establishes a new blood supply in patients more quickly after transplantation when it is first expanded in the lab on a bed of cells that mimics conditions in the bone marrow, researchers report in the December 13 edition of the New England Journal of Medicine.

The phase 1/2 study led by scientists at The University of Texas MD Anderson Cancer Centre, addresses the main difficulty with using umbilical cord blood stem cells to replace the blood supply of patients who have had theirs destroyed by chemotherapy or radiation to treat leukaemia, lymphoma and other blood-based diseases.

“You get fewer cells – blood stem cells, immune cells – from two umbilical cords than you do by collecting from a donor’s bone marrow or peripheral blood,” said senior author Elizabeth Shpall, professor in MD Anderson’s Department of Stem Cell Transplantation and Cellular Therapy. That lengthens the time between infusion of the cord blood cells and establishment, or engraftment, of the new blood supply. “It’s a high-risk time, patients don’t have white blood cells to fight infection, they don’t have platelets to keep them from bleeding,” Shpall added.

By taking blood from one of the two donated umbilical cords and growing it in the laboratory on a bed of mesenchymal precursor cells, the researchers greatly increased the number of cells transplanted, reduced recovery time and increased the proportion of patients whose new blood became established.

“Expansion achieved a median 12-fold increase in total cells transplanted and a 40-fold increase in the number of CD34+ cells, which are crucial for engraftment,” Shpall said. “This led to faster engraftment of white blood cells and platelets, which we believe enhances patient safety.”

"Pre-transplant cord blood expansion on mesenchymal stromal cells could become the new standard of care if our findings are confirmed in a randomized clinical trial,” Shpall said. Shpall notes that readily available mesenchymal precursor cells provided by Australian regenerative medicine company Mesoblast Limited reduced the time it takes to expand the cord blood cells from more than a month to a few weeks.

Australian scientist and study co-author Paul Simmons, executive vice president for research at Mesoblast, led the research team that originally identified mesenchymal precursor cells and discovered a way to extract mesenchymal cells from the bone marrow for use in other settings.  

Only about 25 per cent of those needing a blood stem cell transplant have a matching donor – the ideal situation for a transplant. Double-cord blood transplant is one of the main options for the rest, which includes a higher proportion of those with African, Asian or Latino heritage, who are underrepresented among blood stem cell donors.

Patients who receive peripheral blood from a matched donor, the main method used in blood stem cell transplants, on average have their infection-fighting white blood cells (neutrophils) engraft in 11 days and their platelets in 13 days. For a double-cord blood transplant, the same cells engraft in 26 days and 53 days, respectively.

“That isn’t good enough,” said Shpall, who also directs MD Anderson’s Cord Blood Bank. She and other researchers have long sought optimal ways to expand cord blood. The key cells are blood stem cells, which can differentiate into any type blood cell – platelets, white cells or red cells.

In 31 high-risk patients, the team expanded blood cells from one of the two cords transplanted. They compared outcomes to 80 cases of standard double-cord blood transplant reported to the Center for International Blood and Marrow Transplantation.
The study’s composite endpoint of neutrophil engraftment within 26 days, platelet engraftment within 60 days and survival at 100 days was reached by 63 percent of the expanded cord blood group compared with 24 percent among controls.

“Cord blood transplant patients often need platelet transfusions for months,” de Lima said. “Most of the control group did not start making their own platelets, while in the study group, 70 per cent of patients engrafted within 60 days.” “From patients’ perspective, these are things you want to see going forward: less bleeding, less infection, fewer trips to hospital and less dependence on transfusions,” de Lima said.
Mesoblast's mesenchymal precursor cells are now being formally evaluated in a prospective, randomized Phase 3 trial led by Shpall in 15 centres that will compare 120 patients who receive one expanded and one regular cord blood transplant to 120 others who get the standard double cord transplant.