Umbilical cord blood stem cells build new blood supply faster after lab expansion

A new technique for expanding blood stem cells from umbilical cords in the lab before transplanting them into a patient reduces the perilous time it takes for the new blood supply to take hold.

Cord blood transplants provide a source of blood stem cells to cancer patients who need a transplant after high-dose chemotherapy for leukemia, lymphoma and other malignancies but cannot find a matched donor.

This is particularly true for people of Latino, African or Asian heritage, who are underrepresented in the bone marrow donor pool, which makes it hard to find a matched blood stem cell donor.

"Pre-transplant cord blood expansion on mesenchymal precursor cells could become the new standard of care if our findings are confirmed in a randomized clinical trial," said Elizabeth Shpall, M.D., professor in the Department of Stem Cell Transplantation and Cellular Therapy. She is principal investigator of an early stage clinical trial and senior author of a paper published this week in the New England Journal of Medicine.

Umbilical cords provide amuch lower dose of cells than those given by a matched donor whose stem cells are taken from the bone marrow or circulating blood. The result: slower establishment of the new blood supply, particularly white cells (neutrophils) and platelets, exposing patients to greater risk of infection and bleeding.

Shpall and colleagues show how expanding one of the two cords on a bed of supportive in the lab increases the number of cells transplanted and the speed of establishment (engraftment) of white cells and platelets for the patient over those who get the usual unexpanded double cord transplant.

This approach, growing the cells on a bed of mesenchymal cell precursors available off the shelf from the Australian company Mesoblast, Limited, could be a major step forward for cord blood transplants.

Central findings comparing 31 expanded cord patients and 80 historical controls showed:

• A median 14-fold increase in total cells transplanted and a 40-fold increase in CD34+ cells crucial to engraftment.

• Median time to neutrophil engraftment of 15 days, compared to 24 for controls.
• Median time of platelet engraftment of 42 days, compared with 49 for controls.
• Cumulative neutrophil engraftment rate of 88% at 26 days, compared with 53% in control cases.
• Cumulative platelet engraftment rate of 71% at 60 days, compared with 31% in controls.
• 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% of the expanded cord blood group compared with 24% among controls.

Mesoblast's mesenchymal precursor cells are now being formally evaluated in a prospective, randomized Phase 3 trial led by Shpall in 15 centers 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.

Additional information

About donor and cord blood stem cell transplants:

National Marrow Donor Program/Be the Match

MD Anderson news release