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Dome - When the match is half full

May 2011

When the match is half full

Date: May 20, 2011

Richard Jones
Richard Jones and colleagues use an unexpected protocol to push beyond previous treatment boundaries for patients who need a bone marrow transplant.

For years, bone marrow transplants have proven their mettle as a remarkably effective way to treat—even cure—certain types of cancers and genetic diseases.

But there’s a reason that bone marrow or stem cell transplants haven’t been available to all the patients they could save: The healthy donor tissue needed for the transplants has had to closely match the patient’s tissue. Absent that match, the body’s immune response gears up to reject the new tissue, or the new healthy tissue can attack the recipient in graft-versus-host disease, or GVHD.

Complicating the situation even further, finding a proper match could take months, which is time that most patients who need a transplant don’t have.

Today, however, new research at Hopkins is making it possible to transplant tissue that isn’t a close match, without launching the potentially deadly side effects that would have been a risk just years ago.

“Now,” says Richard Jones, director of the Bone Marrow Transplant Program, “patients up to age 75 have nearly a 100 percent chance of finding a match.”

In the past, donor and patient tissue had to have in common all 10 of the human leukocyte antigens that indicate the likelihood of tissue rejection or GVHD.

But even in siblings, there’s only a 30 percent chance that all these protein markers will match. And though millions of potential marrow donors have signed on with international registries, the chance that a patient of northern European descent, for example, will find at least one nearly complete donor match is still only about 50 percent to 60 percent. For some ethnic groups, the odds are much lower.

Using immunosuppressant drugs to stave off the recipient’s immune response has allowed physicians to transplant tissue from donors with as few as half the protein markers being a match. The problem has been that this approach leaves already vulnerable patients immunocompromised and at serious risk for other illnesses.

To get around this conundrum, Jones and his Hopkins colleagues have put a new spin on the well-established practice of administering the anticancer drug cyclophosphamide in high doses before a transplant. “Cyclophosphamide,” says Jones, “has been the most commonly given drug before bone marrow transplants because it has a powerful antitumor effect, and it is also a powerful immunosuppressant.”

What’s different about the Hopkins approach, he says, is that “now we also give cyclophosphamide after the transplant.”

Although Jones admits that doing so is very counterintuitive, he explains that it takes advantage of the time when the T-cells lining up to attack the mismatched tissue are especially vulnerable. And not only does posttransplant administration of cyclophosphamide target the problem T-cells, it doesn’t wipe out whole immune system in the process.

Hopkins oncologists have now completed about 250 of these half-matched transplants, including, says Jones, about 65 last year alone—“the most anywhere in the world.”

And not only is the approach helping patients with blood cancers and genetic diseases, it’s also produced encouraging signs for all varieties of organ transplants. Testing on that front is still in the early stages, Jones says, “but I think it’s fair to say it looks very promising.”