Nearly anyone can receive a bone marrow transplant through the Fred Hutch Bone Marrow Transplant Program at Seattle Cancer Care Alliance (SCCA) — even without an optimally HLA-matched donor — because of new sources of stem cells and new methods for making these cells work safely and effectively. Lack of a matched donor is no longer a major limitation.
Researchers at Fred Hutch were instrumental in developing new options like minimally mismatched, haploidentical and cord blood transplants. They continue to improve techniques to ensure even better transplant access and outcomes for diverse patients.
Transplants with matched unrelated donors
At one time, only 30 percent of those who needed a transplant could find a suitable match (based on HLA typing)—because they had a matched sibling available to donate. That left 70 percent with no chance at a transplant at all.
Donors helping strangers
Over time, advances in the field allowed another 30 to 35 percent to find a match among unrelated donors who volunteered to help someone in need.
- This option has its roots at Fred Hutch, the first place that had an unrelated donor program — a list of about 200 people, including Fred Hutch employees, willing to donate to a stranger.
- The Fred Hutch program eventually developed into the National Marrow Donor Program, which operates Be The Match, the world’s largest and most diverse marrow registry.
What if the match isn't perfect?
Many of those without an “optimal,” or perfect, HLA match, either from a sibling or from the registry of volunteer donors, can now have a transplant using cells from a “minimally mismatched” donor.
- An optimal match usually means matching on 8 out of 8 HLA markers.
- A minimal mismatch is usually defined as matching on 7 out of 8 markers.
Using new methods to limit potential complications, many more patients can have a minimally mismatched transplant that improves their chance for survival.
Newer options to help nearly every patient
Even when patients expand the search outside their family to all registered donors worldwide, it can be difficult to find a suitable match. Until recently, about 35 to 40 percent of people who needed a transplant still had no match.
Today, practically all of our patients find a donor, thanks to two additional sources of donor cells: haploidentical (half-matched) family members and cord blood. These new options mean patients no longer need to delay transplantation while waiting for a perfect or near-perfect match.
An HLA-haploidentical donor is a half-match for the recipient.
- Parents are always a half-match for their children and vice versa.
- Siblings have a 50 percent chance of being a half-match for each other. (They have a 25 percent chance of being a perfect match and a 25 percent chance of not matching at all.)
Like transplants with minimally mismatched donors, haploidentical transplants are not ideal, but they allow many patients to find a suitable donor and proceed quickly with a potentially life-saving transplant.
Cord blood transplants
Cord blood for transplants is collected at the time of a baby’s birth, if the mother volunteers, with no risk to the baby or mother. After the umbilical cord is cut, a needle is inserted into the vein of the umbilical cord, and the leftover blood from the placenta and umbilical cord is withdrawn and stored for future use.
The blood-forming stem cells from cord blood are more versatile than those from bone marrow or peripheral blood when used for a transplant, simply because the immune cells in cord blood are naïve.
- They aren’t yet educated against foreign invaders, such as bacteria and viruses, so there’s less risk of an adverse interaction between the transplanted cells and the recipient’s tissues.
- The donor and recipient don’t need to be such a close match for the transplant to be successful. A match in 4 out of 6 HLA markers in cord blood is usually considered acceptable.
- Cord blood donors can be identified for most people in need of a transplant, even if no other suitable match can be found.
Improving transplant outcomes
Many centers across the country are finding that outcomes of transplants using haploidentical or cord blood donors are very similar to outcomes of transplants using matched donors.
The rates of acute or chronic graft-versus-host disease (GVHD) are less than or similar to the rates with matched donors using current protocols. GVHD results when an incomplete match between the donor and recipient causes the donor immune system to attack the recipient’s (host’s) tissues.
Preventing GVHD in haploidentical transplants
Haploidentical transplants rely on advances in drug therapies to prevent GVHD.
- One preventive therapy uses a high dose of the chemotherapy drug cyclophosphamide given on days three and four post-transplant, followed by standard immunosuppressive treatments starting on day five.
- This protocol may seem counterintuitive because high-dose chemotherapy is typically given earlier in the transplant process, during the conditioning phase (to destroy the malfunctioning cells in the recipient’s body).
- Doctors have found that giving cyclophosphamide after a haploidentical transplant helps prevent GVHD because cyclophosphamide kills certain donor immune cells (T-cells) that would otherwise cause GVHD.
Combining and expanding units of cord blood
For cord blood transplants, SCCA doctors now routinely combine two units of cord blood (from different donors) to extend this option to adults.
- Each unit of cord blood has a very limited number of stem cells. So cord blood transplants were once used only in pediatric patients — who, because of their smaller size, don’t need to receive as many stem cells as adults do.
- By combining units of cord blood, we can now treat many adults this way.
Still, it takes longer to restore blood counts after a transplant with cord blood than with marrow or peripheral blood from an adult. That’s why Fred Hutch’s Colleen Delaney, MD, developed a technique that expands the number of cells in a unit of cord blood 150-fold.
- Dr. Delaney is working on increasing the number of cells further to treat adults more effectively.
- Studies show that expanding one of the two units of cord blood in the lab before transplant increases the rate of post-transplant engraftment (when the recipient’s body resumes producing blood cells and develops an immune system again).
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