by Jordan Wilkerson
figures by Nicholas Lue
Desimond Viray is a Californian in his early ‘30s. He works in IT support for Jelly Belly Candy Company and lives with his wife and four children. Ten years ago, he was diagnosed with a rare form of blood cancer, chronic myelogenous leukemia (CML).
Each year, nearly 9000 new cases of CML arise in the U.S. While Viray — and many other patients with blood diseases — have several treatment options, the best chance of a cure is usually through either a stem cell or bone marrow transplant. In fact, over 12,000 patients each year are in need of transplants like these to cure life-threatening ailments like the various forms of leukemia and lymphoma.
For years, Viray has been trying to obtain this potentially life-saving treatment. His biggest obstacle? He’s Filipino American.
The Ancestry Obstacle for a Donor Match
In the U.S., racial minorities are much less likely to find a suitable blood stem cell donor than White Americans (Figure 1). Patients are more likely to find a stem cell match from donors of similar ethnicity, and much fewer non-White Americans have signed up as possible donors in The National Marrow Donor Program’s, or NMDP’s, Be The Match registry (Figure 2).
Viray and his wife have been spreading his story on social media to raise awareness of this disparity. Last year, his story caught the eye of representatives of the Asian American Donor Program (AADP), who now provide a more elevated platform for his message. AADP, which works in partnership with NMDP, aims to mitigate the very obstacle that Viray now faces. The subset was founded in 1989, just a few years after NMDP was established in 1986. At the time, the registry only had around 120 potential Asian/Pacific Islander donors. Several Asian leukemia patients consequently went without transplant, eventually dying from their cancers. One of them was only 9 months old.
“AADP started with the effort of helping Asian communities,” explains Shanna Singh, the Senior Community Engagement Representative for AADP. Since then, the program’s scope has broadened. “Although we focus on Asian donors, if we get an African American patient, for example, who wants to campaign or get help from us, we work with African American communities for that,” she says. AADP now registers around 8000 potential donors each year. In 2018, 55 of those people donated. Although most of the cases are related to leukemia or lymphoma, Singh states there are over 100 other blood diseases that could be cured with a stem cell or bone marrow transplant.
Still, Viray has not found a suitable match since his diagnosis a decade ago. Instead, he has been undergoing chemotherapy — in the form of pills he takes daily.
The medication that leukemia patients take without a transplant must be strong enough to kill cancerous white blood cells yet mild enough to not wipe out the healthy ones, which are necessary to maintain a functioning immune system. This balanced approach often leaves residual cancer cells lingering in the patient’s marrow, which can become drug resistant as the cancer mutates.
The years of cancer medication has taken a toll on Viray. So far, he has been on four different medications: Gleevec, Sprycel, Bosiluf, and, most recently, Tasigna.
“Every time I take new medication, I get worried about what the possible side effects would be. Usually, I have a hard time tolerating those side effects,” Viray says. The most common side effects he has faced are headaches and fatigue.
A year ago, though, he experienced a rare but jarringly dangerous side effect of Sprycel. Viray’s heart started failing. His daughter found him unconscious at home one day, and he was admitted to the hospital soon after.
“I could’ve had a heart attack at any moment,” he says. “It pretty much almost took my life.”
Cleaning the Immune System’s Slate and Starting Anew
A more assured approach to rid the body of blood cancer is to increase the strength of chemotherapy, killing the blood stem cells indiscriminately and entirely. This tactic of complete annihilation better ensures complete cancer remission. But by killing all of the healthy cells, too, it would also fatally cripple the immune system, i.e. white blood cells.
That’s where the transplant comes in. A donor’s stem cells are injected into the patient usually a few months after the mass destruction caused by the heightened chemotherapy. Because the blood stem cells can split and grow into healthy white blood cells, the donor’s cells effectively set the foundation for a new, healthy immune system.
People usually donate their blood stem cells that have leaked from the bone marrow into the blood stream. In some cases – such as when the patient’s condition is particularly unstable –, a stem cell transplant may not be sufficient. Instead, they might need a bone marrow transplant. According to Singh, marrow extract from the donor’s hip contains a sample of the donor’s mature immune system rather than just the infant stages that stem cells would provide.
Ethnicity, an Essential Element for Blood Stem Cells
The transplant’s goal to grow a new immune system is why ethnicity matters. The immune system, even when crippled, is on the constant hunt for foreign invaders such as bacteria. Your immune system checks whether a cell it encounters is yours — and thus safe — by examining the specific proteins that festoon the cell’s outer surface. In the context of stem cell and bone marrow transplants, if too many of these surface proteins look unfamiliar to the patient’s immune system, the donor’s cells are destroyed.
The particular proteins that are displayed on someone’s blood cells are determined by that person’s genetic makeup. Those proteins are referred to as human leukocyte antigen (HLA) markers. For leukemia patients like Viray, this means that in order to trick the immune system into accepting a donor’s stem cells, the donor must have HLA markers very similar to theirs (Figure 3).
Like all genes, we inherit these markers from our parents. If someone has a similar ancestral background to you, their HLA markers are more likely to be close enough that your immune system will treat their stem cells as if they were yours.
For a successful transplant, it’s essential that the HLA markers match as closely as possible. So while the AADP broadly caters to ‘Asian Americans,’ the donor and patient’s race must match much more closely than that to ensure a high chance of a successful transplant. “It’s really important to break it down as specifically as you can in order to find the best match. It’s not always that you’re going to match with someone in your ethnic background,” Singh says, but “chances are that you are.”
Viray’s best bet for a donor is, therefore, another person with Filipino ancestry. Yet, only 0.5% of the national registry is comprised of Filipino Americans (Figure 2). Someone with a mixed racial background faces even more troubling odds. And while family members are an obvious candidate for any patient seeking a donor, Be the Match reports that only 30% of patients find a suitable donor among their relatives.
Today, Viray is still looking for a potential donor with help from AADP. Though his relatively stable condition is keeping him hopeful, “it’s very important that I start now,” he says. “There are a lot of contingencies even after finding a suitable donor that 100% matches. It’s not guaranteed. That’s why it’s important that we do this search for a donor even if it’s going to take 10-20 years. We’re trying to get more people involved and not just for me. For other patients, too.”
To register as a donor with AADP, just text the code ‘AADP’ to the number 61474. You can still register even if you are not a citizen as long as you plan to stay in the U.S. for next 3-5 years.
Jordan Wilkerson is a Ph.D. student in the Chemistry and Chemical Biology program at Harvard University.
Nicholas Lue is a third-year PhD student in the Chemical Biology program at Harvard University. You can find him on Twitter as @nicklue8.