Stem cell transplant candidates, like singles in search of a spouse, are hoping to find their perfect match. But, just as many husbands and wives find happiness without checking off each other’s every box, a new scientific study has demonstrated transplant success for a wider group of blood cancer patients when an exact match is unavailable.
The study, involving researchers at City of Hope® and other cancer centers, shows that a drug—used to reduce severe side effects in stem cell transplants involving related donors—may also provide similar protection in peripheral stem cell transplants involving mismatched, unrelated donors, thereby increasing the potential for successful outcomes.
The study also used more tolerable regimens (reduced-intensity conditioning) of chemotherapy and radiation therapy to kill cancer cells in each patient’s blood prior to them receiving hematopoietic cell transplant (HCT). This may provide hope for older patients and those in poor health, who otherwise may not qualify for a stem cell transplant because of the toll it may take on them.
Finally, by reducing how closely the match between the patient and donor must be, the study expanded treatment for underserved groups, such as Black people and other minorities, who have a much harder time finding suitable matches within the national donor registry. If the studied therapy is adapted, it may also mean reduced wait times for patients because there will be a higher likelihood of finding an acceptable, but mismatched, donor in the pool sooner.
“This innovative approach can greatly expand the patient access to safe and effective stem cell transplantation,” says Monzr M. Al Malki, MD, who led the study and presented its findings in May at a Chicago conference of the American Society of Clinical Oncology (ASCO). Dr. Al Malki is Director of the Unrelated BMT (Bone Marrow Transplant) Donor Program and the Haploidentical (Half-Match) Transplant Program at City of Hope National Medical Center in Duarte, California.
The study involved unrelated donor (allogeneic) stem cell transplants using the drug cyclophosphamide post-transplant (PTCy) to reduce the severity graft-versus-host disease (HVGD), a potentially life-threatening complication that may occur in stem cell transplants.
“Fully matched donors remain the golden standard of care in patients undergoing allogeneic transplantation regardless of other factors, but patients who have no fully matched donor among their siblings or in the registry could be a perfect candidate for this type of therapy,” Dr. Al Malki says.
NMDP (previously known as the National Marrow Donor Program or Be the Match) says that up to 70 percent of patients needing an HCT stem cell transplant do not have a fully matched family donor and must rely on the donor registry. However, depending on a patient’s ethnic background, the chance of finding a suitable match on the registry ranges from a low of 29 percent to 79 percent.
In this article, we will examine:
- How are stem cell donors identified?
- What is PTCy-based GVHD prophylaxis?
- The future of stem cell transplants
If you’ve been diagnosed with a blood cancer, such as lymphoma or leukemia, and want to get a second opinion of your diagnosis or treatment options, call us or chat online with a member of our team.
How are stem cell donors identified?
Stem cell transplants are used to treat blood cancers (hematological malignancies), including certain lymphomas, leukemias and multiple myeloma. The transplants may be autologous, using the patient’s own stem cells, or allogeneic, using stem cells from a donor, either related or unrelated. Autologous transplants are performed, when possible, with the stem cells harvested from the patient’s blood, multiplied in the lab and then returned to the patient following chemotherapy and radiation therapy that kills all the other blood cells in the body.
Allogeneic transplants may come from a related donor, or an unrelated donor through the NMDP. In either case, chances are low that the donor will be a perfect match. In determining a match, doctors look for a donor whose blood proteins (called human leukocyte antigens or HLA), are very similar to the patient’s needing a transplant. In the study, researchers looked at eight different markers on the blood proteins. These markers are, in effect, a personal “code” for each patient, Dr. Al Malki says.
The study tested the study’s drug regimen on patients who were receiving stem cells from donors who matched between five and seven of the eight selected markers.
Being able to have treatment success with donors who match fewer of a patient’s markers also increases the ability to find suitable donors for a larger number of transplant candidates.
“Ethnically diverse patients have significant challenges in finding fully matched donors, not only due to being underrepresented in the registry, but also due to the complexity of their HLA system,” Dr. Al Malki says.
The researchers estimated a 99 percent chance that a donor could be found for wide groups of patients needing transplants if the stem cell matched as few as five of the eight markers. That match capability may also increase the number of transplants involving younger donors, whose stem cells are thought to be more effective in transplants.
What is PTCy-based GVHD prophylaxis?
When a patient receives a transplant, doctors monitor to make sure the body doesn’t reject the foreign cells. One particular form of this immune reaction is called graft-versus-host disease (GVHD).
“Transplants using mismatched unrelated donors have always been historically difficult due to the higher incidence of graft-versus-host-disease,” Dr. Al Malki says.
When performing stem cell transplants from related donors, doctors have used cyclophosphamide as a prophylaxis to suppress the immune response. The new study looked at the use of cyclophosphamide post-transplant in cases involving partially matched unrelated donors.
A previous study published in 2022 reported favorably on the use of cyclophosphamide from a partially matched, unrelated donor. The new study involved 70 high-risk patients with advanced blood cancers, who received transplants involving peripheral stem cells, which are ones floating in the bloodstream that are much easier to collect than those in bone marrow. Half of the patients were people of color.
“In this study, we have included only patients who have no fully matched donor, trying to address their access to HCT,” Dr. Al Malki says. “This has allowed us to enrich the study with patients with diverse backgrounds. This study does not only reflect the diversity of patients we see in the clinic and in the U.S. population, but also addresses the group of patients who will benefit the most from such innovations in treatment.”
The study included patients with acute myeloid leukemia, myelodysplastic syndromes (MDS), acute lymphocytic leukemia (ALL) and other blood cancers.
It found that the portion of patients having severe GVHD after receiving transplants under the study regimen was about 10 percent, Dr. Al Malki says, which is the same as for matched donor transplants. “This highlights the safety profile for this approach and hopefully the reflection on improvement in the overall survival of those patients,” he says.
Researchers reported an overall survival rate close to 80 percent a year following transplant.
The future of stem cell transplants
The study used reduced-intensity conditioning to kill off cancerous blood cells prior to a patient receiving a transplant. The success of this more tolerable regimen of chemotherapy and radiation, as opposed to high-dose treatments that kill all blood cells, “depends on the graft-versus-tumor (GVT) effect of the donor stem cells,” according to the Lymphoma & Leukemia Society.
“The goal is to have the donor stem cells take up residence in the recipient’s marrow and produce white blood cells that will attack the patient’s remaining cancerous blood cells,” the society says.
Prior studies using other forms of GVHD prophylaxis have “shown that mild GVHD could be associated with lower relapse of disease, confirming the association between GVHD and GVT,” Dr. Al Malki says. Whether this is also true of cyclophosphamide is still under study, he says.
The research is now part of an ongoing Phase 2 study, involving about 300 patients at medical centers across the country, looking at a more intense regimen prior to transplantation, ASCO reports. Researchers will also be looking at how best to use cyclophosphamide—including the way it is delivered, how to combine it with other treatments, and how to further reduce any toxicity.
As Dr. Al Malki reported, the study’s findings “could expand access to a potentially life-saving therapy.”
If you’ve been diagnosed with a blood cancer, such as lymphoma or leukemia, and want to get a second opinion of your diagnosis or treatment options, call us or chat online with a member of our team.
