Thanks to recent advances, it is now possible — and frequently advisable — to perform an allogeneic (or “from a donor”) stem cell transplant to treat leukemia, even when no perfectly matched donor can be found.
This opens a hopeful door for patients who thought they were out of options.
While leukemia and other blood cancers may respond to chemotherapy (and there's growing promise in the areas of immunotherapy and targeted therapy), in many cases a transplant of healthy stem cells from a donor is the only realistic path to a cure.
A New Gold Standard
The gold standard for transplants has always involved finding a close relative, usually a sibling, with all of his or her blood proteins (known as HLA markers) identical to the patient's.
But that happens only 30% of the time; 70% must look elsewhere.
Since 1987, “elsewhere” has been the National Bone Marrow Registry. With more than 25 million people signed up and tested, a 100% matched, unrelated donor can often be found.
But it's not inevitable.
Ethnicity plays a role. Most Europeans have a better than 50-50 chance of finding a match on the registry. The odds drop to 3 in 10 for people of Hispanic origin, and 4 out of 5 African Americans won't find a “perfect” match.
Anything less than an exact match increases the likelihood of graft failure as well as graft-versus-host disease (GVHD), when the transplanted cells attack the patient, causing serious, even fatal complications.
Over the last decade, however, a third option has emerged.
It's called a haploidentical, or half-matched transplant, and once again it involves a close relative, but this time only half of the donor's HLA markers need to align with the patient's.
But why is “half” suddenly enough?
Because, in effect, it's the “better” half.
“With an unrelated donor,” explains Al Malki, “all you're really matching is the 'tips' of the mountains,” focusing on HLA while ignoring all other genetic differences between donor and patient, differences that could conceivably affect the success of the transplant.
“But when the donor is Mom or Dad, you're matching the whole mountain,” a much more preferable scenario, at least in theory.
Monzr Al Malki, M.D.
Early attempts at haploidentical transplants fared poorly because doctors tried the same anti-GVHD strategy they were using in 100% unrelated matches — administering drugs like cyclosporine after the transplant to suppress the immune system — and it didn't work. “The outcomes used to be miserable,” Al Malki recalled.
So a switch was made.
“Now we use the chemo drug cyclophosphamide to kill angry lymphocytes [white blood cells] so they can't attack,” he explained. This change helped bring down graft failure and GVHD levels dramatically.
Is it a permanent solution?
Long-term results won't be known for some time, but a growing number of trials and studies are showing positive results.
Most recently, Al Malki presented the findings of the largest study thus far, stretching over 13 years and comparing 1,000 patients with acute lymphoblastic leukemia who received transplants from matched unrelated donors, with 500 recipients of haploidentical transplants. Both groups displayed statistically equal rates of overall survival, relapse and “nonrelapse mortality.” And the haplo group showed lower rates of GVHD.
More Donors, More Options
City of Hope doctors have performed more than 250 haploidentical transplants in the last five years. The haploidentical procedures are becoming more common and popular, especially when you factor in the additional benefits of receiving a transplant from within your family.
Because HLA markers are inherited, every parent is automatically a haploidentical match for his or her child, and vice versa. Every brother or sister has a 50% chance of being a haplo match for a sibling.
“What that means,” Al Malki said, “is that every patient now has an average of 3.5 viable donors in his own family.” This makes an enormous difference in terms of time and expense. It can take several months and significant resources to track down an unrelated 100% matched donor, possibly from halfway around the world, collect the donor’s cells and complete the transplant process.
“But your relatives are right there in the room with you,” Al Malki said, pointing out that transplants from family members can take as little as two to three weeks.
What's more, haploidentical success rates are likely to keep improving. Clinical trials now underway are looking at better ways to prevent GVHD by “depleting” donor cells before they're transplanted, so they lack the ability or inclination to attack the patient.
Bottom line, the haploidentical option means a potential cure is now available to virtually every patient, because the lack of a donor is no longer an issue. Al Malki and others believe haploidentical transplants could eventually become a standard of care.
“Haploidentical transplants are faster, easier and cheaper.” he said. “This is the future.”
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April 24, 2019 | By
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