For months, doctors in Michigan had been searching for a bone marrow donor for a 68-year-old African American patient. She had been treated for acute myeloid leukemia once before, but the fast-growing blood cancer came back. A bone marrow transplant, in which healthy donor stem cells replace a patient’s unhealthy marrow, was her best chance at survival.
A donor must have closely matched genes for human leukocyte antigens, or HLA, to be considered compatible. “The issue is that it is difficult to find a fully matched donor for minorities,” says Muneer Abidi, an oncologist at Henry Ford Hospital in Detroit, who led the patient’s care.
The team turned to Ossium Health, a San Francisco–based biotech startup that is collecting bone marrow from recently deceased organ donors, cryopreserving it, and building a bank of frozen bone marrow. The company’s aim is to create an “off-the-shelf” treatment that can be readily deployed for patients who desperately need a transplant.
The company had opened an early-stage clinical trial to test the approach in patients with blood cancers. Abidi’s patient didn’t technically qualify for the study because of her age, but she was able to get the transplant through an expanded access program Ossium set up. The company identified a close match in their bank and shipped the frozen cells to the hospital.
Once thawed, Abidi and his team infused the cells into the woman on June 27. A few weeks later, the newly transplanted cells had started to grow and make healthy blood cells—a key milestone. In September, Ossium announced that the transplant had been successful. It was the company’s first attempted deceased donor transplant, and likely the first time a cancer patient had received preserved stem cells from a cadaver.
“If her leukemia doesn’t relapse and she doesn’t have very severe complications, this is a curative treatment option for her,” Abidi says. The patient has suffered some expected post-transplant complications, but has since been discharged from the hospital. Doctors continue to monitor her health.
Bone marrow is the machinery responsible for making nearly all of the body’s blood cells. Stem cells in the marrow give rise to new blood cells. But if the bone marrow malfunctions, those stem cells can form abnormal blood cells, causing cancer. During a bone marrow transplant, doctors infuse the donor stem cells from the marrow into the recipient’s bloodstream. “These cells are smart enough, they know where to go,” Abidi says. “They travel from the circulation into the bone marrow and then, over a period of time, regenerate and restart the blood production process.”
Sometimes siblings are able to be donors, but 70 percent of patients who need a transplant don’t have a donor match in their family. In those cases, doctors in the US turn to unrelated donors who have joined NMDP (formerly the National Marrow Donor Program) or other stem cell registries. Depending on a patient’s ethnic background, the chance of finding a full match through NMDP can vary widely. Black or African American patients face the toughest odds, with just a 29 percent chance of finding a full match, because the registry isn’t diverse enough.
Collecting donor stem cells used to require surgically removing marrow from a bone, usually in the hip or sternum, with a needle and syringe. Now, donors can take a drug that releases stem cells from the marrow and sends them to the bloodstream, where the cells can be collected by a machine in a process called apheresis. This has become the preferred way to collect stem cells because it is safer, less painful, and doesn’t require anesthesia. It can also yield more stem cells than the older needle-harvesting method.
If a matched donor can’t be found, stem cells can sometimes come from cord blood, which is collected from the umbilical cord and placenta after a baby is born, then frozen and stored in a cord blood bank. Cord blood transplants have been more common in children, since most adult patients need more cells than are contained in a single cord.
A “match” is the number of HLA genes that any two people have in common. The closer the match, the lower the risk of graft-versus-host disease, a common complication of transplants in which the donor cells recognize the recipient’s body as foreign and attack them. A fully matched donor is one with an HLA score of 8/8, but in recent years, partially matched donors that range from 4/8 to 7/8 are becoming more common thanks to a repurposed drug called cyclophosphamide that reduces the chance of graft-versus-host disease. Given three to four days after transplant, it’s leading to outcomes comparable to fully matched transplants.
For African American and Black patients, their chances of finding a donor jump from 29 percent with an 8/8 match to as high as 84 percent with a 7/8 match. Yet, for a small number of patients, a donor is still elusive.
“Today’s ecosystem is based around living volunteers,” Ossium’s CEO and cofounder, Kevin Caldwell, says. While the US organ donor system has existed for decades, bone marrow has never been regularly collected from those deceased donors in the same way that hearts, lungs, kidneys, and livers have. Nobody had come up with an efficient way of obtaining the cells from deceased donors or cryopreserving them at scale so they can be stored until needed.
“Unlike a solid organ, you can’t just transplant bone marrow into the nearest person who is roughly the right size who needs it,” Caldwell says. “You really have to have a close genetic match between the donor and the recipient.”
The new method of stem cell harvesting, via apheresis, doesn’t work well in deceased people because it relies on blood pressure. Based on previous research conducted at the University of Pittsburgh and Johns Hopkins University, Ossium developed a way to extract bone marrow from the spinal column, a part of the body that typically went unused. The company has partnered with US organ procurement organizations to recover spinal columns from cadavers and ship them to the company’s facility in Indianapolis. There, bone marrow is extracted and cryopreserved in liquid nitrogen vapor at about –190 degrees Celsius.
Caldwell says Ossium has “processed thousands of donors” since the company was founded in 2016. (The exact number of donors in the bank is proprietary, he says.) Ossium’s frozen bone marrow has now been given to three people in total, including the Michigan woman, with a fourth transplant scheduled soon.
Robert Negrin, a professor of medicine at Stanford University and vice president of the American Society of Hematology, calls the transplants an “important milestone,” but whether the technique will be useful for cancer patients remains to be seen. “We have other options that work pretty well,” he says, referring to partially matched donor transplants and cord blood transplants. “But there are always situations that could fall through the cracks.”
Negrin sees potential for deceased donor bone marrow transplants to help organ transplant patients, who currently must take immunosuppressive drugs for the rest of their lives to avoid their immune system attacking the new organ. But because immune cells originate in the bone marrow, if they could receive a marrow transplant from the same donor, Negrin says patients could—in theory—go off immunosuppressive drugs.
Steven Devine, chief medical officer of NMDP, says one potential advantage of Ossium’s product is that it could reduce wait times for patients whose disease is so advanced that they need a transplant right away. NMDP has partnered with Ossium to run its early phase clinical trial.
However, there’s some evidence that the freezing process can decrease the quality of stem cells and may slightly increase the risk of cancer relapse, so Devine says Ossium’s approach may be more suitable for other types of patients, such as those with sickle cell disease, for whom bone marrow transplants can be a cure. “Ultimately, the value and the demand will be determined by clinical research,” he says.
Ossium will also need a very large, very diverse donor pool in order to provide matches that donor registries don’t already have. But Abidi is confident that deceased donor bone marrow transplants could open up a significant treatment option for minorities. “Once this becomes standard of care,” Abidi says, “this is going to be a game changer.”
