Filippo Milano, MD, PhD
Studies show that only about one-third of patients with acute myeloid leukemia who have detectable amounts of cancer cells in their blood at the time of allogeneic hematopoietic cell transplantation will be alive 3 years later, compared with nearly three-quarters of those patients without minimal residual disease.1 To find a more effective treatment and better outcome for these patients, Filippo Milano, MD, PhD, and colleagues launched a study to investigate whether an alternative stem cell donor source found in umbilical cord blood is a viable option for patients lacking a traditional donor match.
Dr. Milano, Associate Director of the Cord Blood Transplant Program at Fred Hutchinson Cancer Research Center in Seattle, and colleagues reviewed the outcomes of 582 patients with acute myeloid or lymphoid leukemia or myelodysplastic syndrome who had received a first allogeneic hematopoietic cell transplant from an unrelated donor at the cancer center. The sources of donor stem cells were procured from cord blood, bone marrow, or peripheral blood.
Their study results show that survival with hematopoietic cell transplantation from unrelated cord blood donors was at least as good as that with human leukocyte antigen (HLA)-matched unrelated donors and better than that with HLA-mismatched unrelated donors in high-risk patients with acute leukemia or myelodysplastic syndrome.2
Because stem cells in the umbilical cord are less developed than adult stem cells, they don’t have to be “matched” as stringently to a patient’s HLA type, explained Dr. Milano. Although transplanted umbilical cord blood can be used to treat or cure more than 80 diseases, including leukemia—the most commonly treated disease—and inherited diseases of red blood cells, the immune system, and certain metabolic abnormalities,3 only about 35,000 cord blood stem cell transplants from unrelated donors have been performed worldwide. In the United States, more than half of all stem cell transplants from unrelated donors in children use cord blood.4
AN ASPIRING PROFESSIONAL soccer player growing up in his native Italy, an injury caused Dr. Milano to jettison a career in sports and pursue a career in his other passion: medicine. After completing his medical education and training in hematology in Rome, Dr. Milano traveled to the Fred Hutchinson Cancer Center’s Cord Blood Transplant Program in 2008 with the intention of spending 6 months in the United States to gain experience in cord blood transplantation procedures and complete a fellowship program in hematology at the University of Washington. But an opportunity to join the cancer center’s cord blood transplantation program and coach in the National Premier Soccer League proved too difficult to resist, and he now calls Seattle home.
Medicine and sports are not Dr. Milano’s only talents. When he is not in the clinic or on the soccer field, he can be found cooking dinner for his patients. “I grew up with the culture of food, and for Italians, food means more than just preparing meals; it’s sharing an experience with people,” said Dr. Milano. “Sharing a meal is a way to take care of people, both physically and emotionally, and it makes me feel very good. Being a good doctor entails more than just prescribing drugs; it entails becoming part of a patient’s life. Cooking for my patients is an emotional experience, because oncologists don’t always have good news about their patients and to see my patients enjoying a meal I’ve prepared is very rewarding.”
The ASCO Post talked with Dr. Milano, who also holds the positions of Assistant Professor at the University of Washington School of Medicine and Assistant Member of the Fred Hutchinson Cancer Research Center, about the results of his study; the advantages of cord blood transplantation compared with allogeneic bone marrow transplantation in high-risk patients with leukemia; and the importance of mentoring the next generation of scientists.
In your study of cord blood transplantation in patients with leukemia who have minimal residual disease but are at high risk of relapse after transplant, survival from unrelated cord blood donors was at least as good as that with HLA-matched unrelated donor stem cells and better than that with HLA-mismatched unrelated donor stem cells. Were you surprised by the study’s findings?
Yes, absolutely. When we started thinking about this project, we were trying to compare our institution’s outcomes between cord blood transplantation and HLA-matched and HLA-mismatched unrelated donor stem cell allogeneic transplantation. We knew that although our patients were doing well, they were not doing so well when it came to overall survival. So, we were surprised to see in those patients with minimal residual disease that the result was better from cord blood donor stem cells than HLA-mismatched unrelated donor stem cells, and it suggested better outcome in overall survival when compared with HLA-matched unrelated donor stem cells. And that brings up an important point: With cord blood donor stem cells, the donor is available anytime.
Determining the Best Treatment Option
Based on your study results, is it more advantageous to use cord blood stem cells than HLA-matched or HLA-mismatched donor cells in high-risk patients with leukemia?
“There is definitely a suggestion that recipients of cord blood transplantation have a lower relapse rate than patients receiving an allogeneic transplantation.”— Filippo Milano, MD, PhD
Yes, it is. I admit I’m biased, and my study is a retrospective study, so it is not perfect from a statistical standpoint. But there is definitely a suggestion that recipients of cord blood transplantation have a lower relapse rate than patients receiving an allogeneic transplantation. There is also a suggestion that in patients with high-risk disease, cord blood transplantation may offer a better option for a cure; but we need to confirm our results in a randomized trial, and we should test other sources of stem cells, not just HLA-matched unrelated and HLA-mismatched unrelated donor cells. We need to determine what the best choice is for patients.
Advantages of Cord Blood Stem Cells
Why are stem cells from the umbilical cord effective in patients undergoing transplantation?
In our study, and in general, the umbilical cord cells are naïve, and that allows us to have a higher HLA disparity; so the stem cells don’t have to match 100% with a patient’s HLA type, giving us a big advantage because we can find a donor for every transplant patient. Furthermore, the higher grade of disparity allowed makes cord blood transplantation effective in patients with leukemia, especially patients with aggressive disease, such as those patients with minimal residual disease.
Another advantage of cord blood stem cells is they can be more universally used in African American patients, who have fewer matched unrelated donor stem cells to choose from in donor registries and who have greater variation in HLA types than white patients. If you are white, you have between a 50% and 70% chance of finding a matched donor, but if you are African American, you only have between a 16% and 19% chance.5 For minority patients, a partial HLA match is acceptable, and most minority patients can find a suitable bone marrow donor regardless of ethnicity.
Encouraging Use of Cord Blood Transplantation
Is blood cord transplantation becoming more common in the treatment of cancer and other diseases?
No, unfortunately not. It’s actually becoming less common because of the cost associated with the procedure and the expertise required to perform cord blood transplantation. In the United States, only about 10 cancer centers perform more than 10 cord blood transplants a year, and that’s why more cancer centers don’t have enough expertise in the procedure.
Another problem is many cancer centers are reluctant to change their practice of performing more traditional stem cell transplants. Everyone knows that if you have a patient with high-risk disease, cord blood might be the best stem cell source for that patient. But despite that fact, there is a lot of reluctance to abandon the more traditional sources for donor stem cells.
“Many cancer centers are reluctant to change their practice of performing more traditional stem cell transplants for donor stem cells.”— Filippo Milano, MD, PhD
Cord blood transplants also are associated with a lower risk for acquiring graft-vs-host disease— the Achilles’ heel of transplantation—because it contributes to transplant-related mortality and can affect patients’ quality of life.
We have performed more than 400 cord blood transplantations since our cord blood program launched in 2006 and have since instituted a committee of experts in the cord blood field, with the goal of determining guidelines for standardizing care for cord blood transplant recipients. The guidelines were recently published in Biology of Blood and Marrow Transplantation,6 and we hope they will encourage more cancer centers to perform cord blood transplantations in their high-risk patients.
Physician and Teacher
In addition to coaching a semiprofessional soccer team, you also mentor some of the team members interested in a career in science. Why is mentorship important to you?
I’ve been coaching the team for 3 years, and we have won the Northwest Division in the National Premier Soccer League 2 years in a row. This past year, we also qualified for the U.S. Open Cup, so the experience has been very gratifying. But I don’t forget science while I’m coaching soccer.
Some of the college players are interested in biology and other life sciences, and I follow them throughout the year mentoring them. Some of the players work in the lab with me, and I show them they can have dual goals: pursuing a career in science and playing soccer at a very high semiprofessional level.
I am living the American Dream. It is a privilege for me to take care of patients with cancer, become part of their live, and offer them emotional and caring support throughout their decision-making process and treatment. I also get to nurture the next generation of scientists. What could be better than that? ■
DISCLOSURE: Dr. Milano reported no conflicts of interest.
1. Walter RB, Buckley SA, Pagel JM, et al: Significance of minimal residual disease before myeloablative allogeneic hematopoietic cell transplantation for AML in first and second complete remission. Blood 122:1813-1821, 2013.
2. Milano F, Gooley T, Wood B, et al: Cord-blood transplantation in patients with minimal residual disease. N Engl J Med 375:944-953, 2016.
3. National Cord Blood Program: Cord Blood Q&A. Available at http://www.nationalcordbloodprogram.org/qa/what_is_ treated.html. Accessed July 26, 2017.
4. National Cord Blood Program: Cord Blood Can Save Lives. Available at http://www.nationalcordbloodprogram.org. Accessed July 26, 2017.
5. Gragert L, Eapen M, Williams E, et al: HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. N Engl J Med 371:339-348, 2014.
6. Barker JN, Kurtzberg J, Ballen K, et al: Optimal practices in unrelated donor cord blood transplantation for hematologic malignancies. Biol Blood Marrow Transplant 23:882-896, 2017.