When Filippo Milano, MD, PhD, left his home in Italy in 2008 to further specialize in allogeneic transplantation in Seattle, it was supposed to be short-term. He would just stay long enough to learn how to conduct blood and marrow transplants, or BMTs, a procedure E. Donnall Thomas, MD, pioneered at Fred Hutch Cancer Center in the 1970s.
“The plan was to stay for six months,” said Milano, a Fred Hutch hematologist-oncologist and clinical researcher. “It’s now been 17 years.”
What happened during those first few months at Fred Hutch?
“I became very passionate about research,” he said. That research was cord blood transplant, an alternative to the traditional bone marrow transplant for which Thomas won the Nobel Prize in 1990.
Thomas’ innovative “immune system transplants” have helped more than a million patients with leukemia and other blood cancers around the world. But bone or stem cell transplants require a genetically compatible donor, a daunting task for those with mixed ethnic heritage due to a lower number of available matches on national donor registries.
“Cord blood transplants are perfect for patients who don’t have a conventional donor — a matched sibling or a relative,” said Milano, who now serves as the director of the Fred Hutch Cord Blood Transplant Program. “We use stem cells from the umbilical cord, which is considered medical waste once a child is born. These stem cells are naïve — they haven’t yet adapted in response to their environment — so we don’t need to match them as we do with other transplants. Cord blood definitely expands the pool of donors for our patients.”
Now, a donor and devotee of this innovative transplantation method has stepped up to help expand the program even more by establishing an Endowed Chair in Cord Blood Research with Milano as the first recipient.
“I’m very grateful to Fred Hutch and Dr. Colleen Delaney [former head of the program] for the opportunity they gave me back in 2008. I’m forever grateful for that support,” he said. “And now, with this endowed chair, I feel even more gratitude. I feel a lot of responsibility, too. I used to go to bed always thinking about ways to get money for research to help more people. Now, I feel a different type of pressure. Now, I need to deliver even more.”
What does he plan on doing with this new funding?
“This money will allow me to do what I think is very critical — enhancing our personalized medicine,” he said. “We are learning more and more that some stem cell sources are good for one thing, some for something else. I want to keep bringing these novel approaches to patients. I want to keep using cord blood and other stem cell sources. It’s all about innovation and bridging the gap.”
Fred Hutch President and Director Thomas J. Lynch, Jr., MD, lauded Milano for his dedication as well as his vision of making stem cell transplants available to all who need them. Lynch holds the Raisbeck Endowed Chair.
“Dr. Milano is an incredibly gifted researcher and clinician who has truly expanded our ability to provide a donor for every patient who needs a transplant,” he said. “Since he came to Fred Hutch 17 years ago, Dr. Milano has worked to establish cord blood transplant as a viable and successful alternative to traditional autologous or allogeneic bone marrow transplant. For those who are ethnically diverse and don’t have many other options, it is truly leading edge, lifesaving science.”
First conducted in 1989, cord blood transplants are still somewhat new to the transplant scene, but they pack no less of a punch. Not only do the naïve stem cells in cord blood offer “a donor for everyone,” but the outcomes are every bit as good as other types of transplants.
Milano’s research — and that of others’ — shows there are even advantages to cord blood transplant, often referred to as CBT.
In 2016, Milano, Delaney and colleagues analyzed the outcomes of nearly 600 stem cell transplant patients — 140 of whom received cord blood — publishing their results in the New England Journal of Medicine.
Normally, about 30-40% of patients relapse after transplant, with relapse more common in those with minimal residual disease, where patients planning to get a transplant still have a small amount of cancer cells present in their body prior to starting the process. Findings from the study showed cord blood transplants worked better for patients at high risk of relapse.
According to the results, after four years of follow-up, “the rate of survival was 71% in the cord-blood group, 63% in the HLA-matched group [where the donor’s and recipient’s human leukocyte antigen or HLA genes were well matched] and 49% in the HLA-mismatched group.”
“Patients going into transplant with minimal residual disease can have very dismal outcomes,” Milano said. “But our cord-blood outcomes are outstanding. And we’re expanding access and equity for our patients. Cord blood is available in the public banks and it can be used immediately, say if a patient loses their donor at the last minute. It’s rapidly available for urgent transplant. We save so many lives because of this.”
Still, any kind of stem cell transplant — whether derived from a patient’s marrow (autologous), a donor’s marrow (allogeneic), a patient’s own blood (peripheral) or from donated cord blood — can be a rigorous regimen that can come with grueling side effects, some long term.
It’s crucial to let people with blood cancers know there are additional options, Milano said.
“The message I want to send to people with these cancers is ‘Even if you don’t have a conventional donor, we’ve got you. We’re going to take care of you,’” he said. “I’m here for the patients without a match and I’m happy I can fill that gap.”
Outreach and awareness are a big part of this, said Sarah Mahan, a clinical research coordinator who's worked in the Cord Blood Transplant Program for two years. “We want to really expand our program and the ways that we can impact and better patient lives,” she said.
Toward that end, the Cord Blood Transplant Program currently has three directives:
“We’re trying to consolidate all of that and make connections to expand our program’s impact,” Mahan said. “We really need to raise awareness so we can continue our research.”
Mahan and team are currently planning what they hope will become an annual event, the Seattle Celebration of Cord Blood, in collaboration with Bloodworks Northwest and the National Cord Blood Network.
“As a main transplant center for cord blood in the U.S., we're very excited for the opportunity to partner with the National Cord Blood Network to host this event,” she said.
Fred Hutch’s Blood and Marrow Transplantation Program, which performs 400-plus BMTs every year, helps patients through the whole process, including lifelong post-transplant care through the Long-Term Follow-Up (LTFU) Program. These patients can also opt in to the LTFU research program, which investigates complications like graft-vs.-host-disease, or GVHD, a common chronic side effect.
Some transplant effects are unexpectedly beneficial, however, such as the graft-vs.-leukemia effect Milano has encountered in CBTs. He plans to use some of the new funding to investigate why exactly T cells in cord blood recognize and eliminate residual leukemia cells after transplant.
“We definitely need to pair any clinical research or trials with basic research on this,” he said. [Fred Hutch’s Basic Research Division is where foundational discoveries often take place.] “We need to understand why things work this way or that way. We need to understand the graft-versus-leukemia effect better to reduce relapse. We have hints, but not a definitive answer. I want to explore it more and collaborate with others.”
Last December at the annual American Society of Hematology (ASH) meeting, Milano presented findings from a Phase 2 trial of 14 patients with acute AML who went through CBT using a cryopreserved non-HLA-matched expanded progenitor cell product to enhance the graft versus leukemia effect.
Results showed successful transplants in all, with no transplanted-related mortality and no cases of chronic GVHD.
“We had 100% survival and zero percent grade 3 or 4 GVHD,” he said. “I don’t think in my life I’ve ever run a clinical trial better than that.”
Currently, Milano is conducting a Phase 2 clinical trial testing out a CBT that pairs one unit of cord blood with another unit derived from between six and nine people. One drawback of CBT is the small number of stem cells that cord blood contains. This means the stem cells need more time to repopulate the immune system, leaving patients vulnerable to infection in the meantime.
Milano and his team are trying to curb both the threat of opportunistic infections (which strike while patients are severely immunocompromised) and cancer relapse.
“My hypothesis is that the interaction between multiple people and the matched cord unit enhances the cord blood effect and that’s why we’re not seeing relapse,” he said. “It’s working. So far, so good.”
In the meantime, Milano is pursuing another passion and potential cure for patients: gene therapy.
“I’m currently coordinating, along with Dr. Hans-Peter Kiem, a group to bring gene therapy to Fred Hutch for those with sickle cell disease,” he said. “The FDA has approved two products for sickle cell and I’m actively working to bring those products here so we can treat out sickle cell patients within the next few months.”
For Milano, it’s “always about finding opportunities for others.”
Cord Blood Day
5-7 pm | Arnold Building
FRED HUTCH
1100 Fairview Ave. N., Seattle, WA
Please join us for a night of food, fun and scientific presentations to celebrate the achievements of cord blood. This event will include perspectives from patients, donors, clinicians, and researchers who have been impacted by cord blood in and around the Seattle area.
Currently, there are 46 endowed chairs at Fred Hutch, all of which allow donors to partner with scientists and clinicians to provide sustained, flexible support for forward-looking research.
These endowments are a cornerstone of the Campaign for Fred Hutch, which is bringing together the community to raise $3 billion to radically increase the pace and scale of innovation. This endowed chair is one of 25 endowed chairs supported by matching funds from the Anniversary Challenge.
Milano said he is particularly grateful for the endowed chair funding as relying on grants can be challenging.
“I could barely speak English when I came to Fred Hutch in 2008 and am so grateful for the opportunity I got at that time,” he said. “It can be difficult to get funding to keep the research going but Fred Hutch perpetuated the program and believed in what I was doing, and we were able to keep the cord blood program alive. So now, I want to give back to the U.S. and to Fred Hutch.”
Diane Mapes is a senior editor and writer at Fred Hutch Cancer Center, who's written for NBC News, TODAY, CNN, MSN, Seattle Magazine and other publications. A breast cancer survivor and patient advocate, you can reach her at dmapes@fredhutch.org or doublewhammied.com / @double_whammied / @doublewhammied.bsky.social. Just diagnosed and need information and resources? Visit our Patient Care page.
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