Stem Cell Breakthrough Offers New Hope to Cancer Patients

For some people with blood cancers who need a stem cell transplant, finding a donor who is an excellent match can mean the difference between life and death.

Unfortunately, even though there are more than 40 million potential donors in the national registry, finding a perfect match isn’t always possible, especially in underrepresented racial and ethnic groups.

But a new approach using an old chemotherapy drug, cyclophosphamide, is is opening up new possibilities for people with cancers like leukemia, lymphoma, and multiple myeloma. Researchers have found that by administering the drug several days after transplantation, people receiving blood stem cells from unrelated, partially matched donors can have survival rates comparable with those who received exactly matched cells.

The interim results from the ACCESS trial will be presented as an oral abstract on May 31 at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

“This innovative approach can greatly expand patient access to safe and effective stem cell transplant, regardless of matching degree with the donor,” says lead coauthor Monzr M. Al Malki, MD, a hematologist and oncologist and director of the Unrelated Donor BMT program at City of Hope, a cancer research and treatment organization with locations across the United States.

That’s exciting because it means more patients will be able to receive this potentially life-extending therapy, says Dr. Al Malki.

Many Black, Hispanic, and Latino People With Cancer Can’t Find a Stem Cell Donor Match

Donor compatibility is determined by a set of protein markers on blood cells called HLAs (human leukocyte antigens), says David Miklos, MD, a professor of medicine and chief of Stanford BMT and Cell Therapy Program at Stanford Medicine in California. Stanford was one of the medical sites of the trial, though Dr. Miklos is not a coauthor of the research.

Since stem cell transplants began over 50 years ago, the gold standard has been finding a close relative, usually a sibling. But even then, the chance that a sibling is a fully matched donor is 25 percent, and the chance of a partial sibling match is 50 percent — leaving many people without a suitable donor.

While close to 4 in 5 white people could find a registry match through the National Bone Marrow Registry, fewer than 3 in 10 Black individuals and fewer than half of Latino and Hispanic people could.

Why was an exact match needed? Anything less increased the likelihood of a graft failure, as well as graft-versus-host disease — meaning the transplanted cells attack the patient’s own, which can cause serious or even fatal complications, explains Miklos.

The Drug That Transformed Stem Cell Transplants

About a decade ago, researchers started using cyclophosphamide to destroy the parts of a person’s immune system that would reject the transplant. That breakthrough allowed researchers to not only have better outcomes in fully matched donors, it also opened the door for successful transplants between people who were only partial matches.

More recently, researchers have been studying the effectiveness of cyclophosphamide in transplants from partially matched donors who are unrelated. In a study published in June 2021, investigators found the drug yielded high survival rates in 80 people receiving bone marrow transplants from partially matched, unrelated donors.

High Survival Rate in Mismatched Donors

The new study looked at cyclophosphamide treatment in patients receiving peripheral blood stem cell transplantation — meaning healthy stem cells are harvested from a donor’s bloodstream, and then administered via infusion to the person with cancer.

Blood stem cell transplantation has largely replaced bone marrow transplantation, according to researchers. It’s an easier way of collecting stem cells from donors, and it’s a little safer, because donors don’t need to be under anesthesia as they would in bone marrow transplantation, says Al Malki.

For this part of the study, the researchers examined data from 70 adults who were 65 years old on average, all with advanced blood cancers. Participants received a “reduced-intensity” conditioning regimen to somewhat suppress their immune system to prepare them for transplantation, followed by an infusion stem cells from unrelated, partially matched donors.

The researchers reported an overall high survival rate of 79 percent at one year — which is comparable to survival rates seen with fully matched donors.

The main side effect or risk of transplantation is graft-versus-host disease, says Al Malki. After one year, 51 percent of participants were free of the disease and had not relapsed, which is also comparable to what would be seen with fully matched donors, he says.

New Findings Mean That ‘All Patients Have Donors’ Now

Historically, barriers in access to transplant have existed due to the low availability of matched, related sibling donors, as well as the substantial variance of matched, unrelated donor availability, especially for patients with diverse ancestry, says study coauthor Steven M. Devine, MD, chief medical officer of NMDP (formerly known as the National Marrow Donor Program and Be The Match).

“These findings advance our ability to offer more options to patients without a fully matched donor, many of whom are ethnically diverse and have been underserved in receiving potentially lifesaving cell therapy,” says Dr. Devine.

These findings are incredibly important and critical in the effort to improve existing inequities, says Miklos.

“In the past, we could not bring some patients forward to receive this lifesaving therapy because they didn’t have a compatible donor, but with the new approach of using post-transplant cyclophosphamide, all patients have donors now,” he says.