A proposal for improving cord blood transplants

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Roughly one in five hematopoietic stem cell transplants performed to treat blood disorders such as leukemia uses cord blood instead of the traditional bone marrow. Cord blood – harvested from umbilical cords shortly after birth – could be used more often if more of it were available. Nearly 14 million people worldwide have volunteered to donate their bone marrow, while the number of cord blood units available for transplant is just over 380,000.

Dutch researchers may have found a partial solution. In an article published in this week’s edition of Proceedings of the National Academy of Sciences, they propose that a relatively simple change in the way donors are matched with recipients could expand the number of optimal matches by up to eighteenfold.

When patients need a bone marrow or cord blood transplant, they are matched with donors who share as many human leukocyte antigens (HLAs) as possible. The immune system checks these proteins to tell whether a cell belongs in the body or is foreign, so the closer the match, the greater the chance the transplant will take.

The researchers examined 1,121 patients who received a unit of cord blood from the New York Blood Center National Cord Blood Program. Only 62, or 6%, got blood that was HLA-matched. The remaining 1,059 patients got mismatched blood.

But by coincidence, 79, or 7%, got blood that was matched in another way – according to noninherited maternal antigens, or NIMAs. These are proteins that patients were exposed to from their mothers before they were born. As a result, the researchers speculated that patients with NIMA matches would tolerate their transplants better and have higher survival rates.

They were right.

Three years after their transplants, patients who didn’t have an HLA match but got NIMA-matched cord blood were 40% less likely to have died than patients who didn’t have either kind of match, according to the study. For the sake of comparison, patients who had an HLA match were 60% less likely to have died than patients without either kind of match.

The difference was especially pronounced in patients who were at least 10 years old. Compared with patients with no match, those with an HLA match were 70% less likely to have died and those with a NIMA match were 60% less likely to have passed away, the study found.

NIMA-matched blood had other benefits too. The transplants engrafted faster than in unmatched patients, and the incidence of graft-versus-host disease was lower. The benefits were greatest for patients who were expected to have the worst outcomes, the researchers reported.

The Dutch scientists said they intend to start using NIMA status to matching patients with cord blood and will track the results to see if these trends hold up. They urged others to do so as well.

Allowing patients to substitute one HLA-matched antigen for a NIMA-matched antigen would boost the number of possible matches by a factor of six, and allowing two substitutions would theoretically boost it as much as 18 times. The team calculated that even a sixfold increase in potential matches was the equivalent of increasing the number of cord blood units available for transplant to more than 2 million.

“Although much work lies ahead, our findings justify changing the match algorithm for CB [cord blood] transplants,” they wrote.

-- Karen Kaplan