Finding the Match

By Sara Bondell - May 27, 2021

Imagine being told you have blood cancer and need a stem cell transplant to save your life. Now imagine being told the chances of finding a donor are slim because of your race.

That’s what happened to Michael Signil when he was diagnosed with non-Hodgkin’s lymphoma at age 30. While he was responding well to chemotherapy, a transplant was his only shot at a cure. But as a Black man, his chance of finding a donor on the national registry was low.

“It’s discouraging to see that there was no match,” said Signil. “I looked it up online, and if I didn’t find a match and have the transplant, I could only survive about 10 more years with chemotherapy.”

White donors dominate the National Marrow Donor Program. Whites of European descent have a 75% chance of finding an optimal donor, while Blacks have just a 16% chance. Hispanics and Latinos have about a 50% chance of finding a match.

Patients like Signil who can’t find a match with a family member or unrelated donor can seek alternative donor types. One option is a haploidentical transplant, which comes from a related donor who is a half match.

Nelli Bejanyan, MD, Blood and Marrow Transplant and Cellular Immunotherapy
Nelli Bejanyan, MD, Blood and Marrow Transplant and Cellular Immunotherapy

This unequal access to donors on the bone marrow registry represents a major health care disparity. The Blood and Marrow Transplant and Cellular Immunotherapy Program at Moffitt Cancer Center has received funding through an internal initiative to promote research that addresses the unmet needs of minority populations to launch two clinical trials to improve the success of haploidentical transplants.

“We are hopeful that by optimizing the haploidentical transplant platform it brings us closer to where we are with fully matched transplant outcomes,” said Nelli Bejanyan, MD, a medical oncologist in the program and the lead investigator in both studies.

The ultimate goal: Nearly every patient who needs a stem cell transplant will have a donor, regardless of race and ethnicity.

Half match
Many patients with blood cancers or disorders require allogeneic stem cell transplants, which involve transferring the stem cells from a healthy person into a patient’s body after high-intensity chemotherapy and radiation. The donated stem cells can come from either a related or unrelated donor.

Human leukocyte antigen, or HLA, matching is used to match patients and donors for transplant. It’s more complex than just matching blood type—it’s more like a fingerprint—and the goal is to match 8/8 different HLA markers. Since HLA types are inherited, siblings sometimes make good matches. Each full sibling has a 25% chance of being a full match. As most patients have more than one sibling, approximately 30% of patients have at least one matched sibling. If a family member isn’t a match, patients turn to the bone marrow registry.

Joseph Pidala, MD, PhD, Blood and Marrow Transplant and Cellular Immunotherapy Program
Joseph Pidala, MD, PhD, Blood and Marrow Transplant and Cellular Immunotherapy Program

While you can match with a donor from a different race, it is less likely. “There are many things that determine whether we can find a suitable donor, but one of the dominant issues is race and ethnicity,” said Joseph Pidala, MD, PhD, a medical oncologist in Moffitt’s Blood and Marrow Transplant and Cellular Immunotherapy Program.

When Signil was told he needed a transplant, the majority of his family members not only wanted to be tested to see if they were a match, but also donate to the registry. However, they couldn’t find any donation centers in Michael’s mother’s native country of Bermuda.

“It seems like no Caribbean islands have access. No African countries have access,” said his mother, Belinda Signil. “These are places with large minority populations and it feels like if you are Black or African American you are butted out.”

Michael Signil poses with his mother, Belinda.
Michael Signil poses with his mother, Belinda.

If a family member or unrelated donor from the registry aren’t an option, doctors look to other donor types to facilitate stem cell transplant, including mismatched unrelated donors, umbilical cord blood or related haploidentical donors. “Racial and ethnic minorities have to rely on these often because they can’t find that ideal fully matched unrelated donor,” said Pidala.

Everyone is a half match with a parent, son or daughter, and there’s a 50% chance a sibling is a half match, so haploidentical transplants drastically improve a chance for an appropriate match.

Michael’s brother, Sean, and his father were both suitable half matches, but Sean was a better match because of his age. Sean not only donated enough stem cells for his brother’s transplant, but also extra that can be frozen and used for Michael in the future if needed.

Historically, haploidentical transplants came with in an increased risk for graft-versus-host- disease (GVHD), where the immune cells from the donor attack the patient’s healthy tissues. However, in the early 2000s oncologists developed a new GVHD prevention approach using a chemotherapy agent called cyclophosphamide. When given after a haploidentical transplant, this treatment reduces the chance of GVHD.

While this new chemotherapy regimen made the risk for GVHD after a haploidentical transplant comparable to that of a matched donor transplant, haploidentical transplants can still carry a slightly higher risk of cancer recurrence.

“Minorities suffer the most because they don’t have enough options available in terms of donors and then their outcomes are not as good,” said Bejanyan.

‘Find the sweet spot’
The first haploidentical transplant trial focuses on reducing the risk of GVHD. The standard protocol for haploidentical transplants includes a cocktail of chemotherapy and immune blocking medicines to prevent GVHD. One of those drugs, tacrolimus, can cause harsh side effects such as kidney damage and tremors.

Moffitt’s study switched tacrolimus with a different immunosuppressive drug called sirolimus. Almost 60% of those enrolled on the trial were minority patients, and not only did they experience less side effects, but also the new drug combination resulted in a decrease in the risk of GVHD from 40% to the historical benchmark of 20%.

The results are so promising that Moffitt now uses the new GVHD prevention regimen as the standard platform for all haploidentical transplants.

“The trial impacted patients. It clearly provided benefits in terms of preventing GVHD, but it also clearly provided minority patients access to timely stem cell transplant,” said Pidala.

Michael is enrolled in the second haploidentical transplant trial, which aims to optimize the transplant chemotherapy regimen to reduce the risk of blood cancer recurrence after transplant.

"I thought this trial is my best shot at beating this thing. If I did the safe route, maybe it wouldn’t have worked. This was my Hail Mary pass, going for the gold."

- Michael Signil

“I thought this trial is my best shot at beating this thing,” he said. “If I did the safe route, maybe it wouldn’t have worked. This was my Hail Mary pass, going for the gold.”

Prior to transplant, patients undergo what is called conditioning chemotherapy, which includes two drugs combined with radiation.

Hany Elmariah, MD, Blood and Marrow Transplant and Cellular Immunotherapy Program
Hany Elmariah, MD, Blood and Marrow Transplant and Cellular Immunotherapy Program

“The risk of blood cancer recurrence depends very strongly on the chemotherapy given prior to the transplant,” said Hany Elmariah, MD, a medical oncologist in the Blood and Marrow Transplant and Cellular Immunotherapy Program and lead investigator of the trial. More intense chemotherapy results in a low risk of relapse, but a high risk of toxicity and mortality. Less intense chemotherapy lowers that risk of toxicity, but carries a higher risk of recurrence.

“We are hoping to find a sweet spot that best balances the risks of toxicity and recurrence, ultimately to improve the overall likelihood for cure,” said Elmariah.

To find that sweet spot, the trial provides a new regimen of chemotherapy and radiation. While the trial is still open, initial results show the new protocol could have a positive effect on recurrence rates. 

Both trials demonstrate Moffitt’s mission to increase minority participation in clinical trials and that the studies can be successful. The results also not only benefit minority patients, but also older and sicker patients of all races in need of transplants who may not tolerate the harsh transplant process.

“When you have a patient who is a minority, you expect it’s very likely they will end up getting a haploidentical transplant,” said Elmariah. “So, having trials aimed at optimizing haploidentical transplants is inherently going to be beneficial to racial minorities.”

Making the future better
Because of alternative donor sources such as haploidentical transplants, the goal moving forward is to continue to optimize all types of transplants to combat complications and reduce risk of disease recurrence.

More than six months since his transplant, Michael is cancer free. He hopes his participation in the clinical trial will someday help others.

Michael Signil hopes his participation in a clinical trial can help other patients from minority populations.
Michael Signil hopes his participation in a clinical trial can help other patients from minority populations.

“It was a great thing to be a part of,” he said. “It was a hard thing to go through, but I am happy I can make the future better for someone else.”

Michael and his family are still pushing to bring awareness and donation opportunities to minority communities around the world, and hope his story will help bridge the health care inequality gap.

“Historically speaking, medical professionals and minorities don’t have a good track record. The average African American is not so keen to participate in anything that says the word ‘trial,’” said Belinda. “The fact my son is a success story will hopefully inspire others to go to the doctor and be more trusting.”

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Sara Bondell Medical Science Writer More Articles


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