Hemophagocytic Lymphohistiocytosis (HLH): Byron’s Story
Meet Byron
Little Byron already has a big personality. The natural charmer is all smiles, despite facing serious medical challenges in his first year of life.
“He’s got his long list of girlfriends at Children’s Mercy,” Byron's mom, Kimberlie, laughed. “He’s just a happy-go-lucky little person.”
At 7 weeks old, Byron came down with a fever. To be safe, Kimberlie and Byron’s dad, Alex, followed their pediatrician’s protocol: When his temperature hit 100.4 degrees Fahrenheit, they took Byron to the Children’s Mercy Emergency Department.
They expected to find out he had a virus and be sent home. But Byron’s blood work came back abnormal, and imaging showed issues with his liver.
Kimberlie and Alex were shocked; Byron had been fine, other than the fever. Now he was getting sicker and needed more support. He was admitted to the Pediatric Intensive Care Unit (PICU) for stabilization and more tests. The PICU team quickly reached out to J. Allyson Hays, MD, Director, Histiocytosis Program, for a consult.
“When kids have fever and low blood counts, many times it is due to an infection,” said Dr. Hays. “However, if they don't bounce back, it's important to consider other diagnoses like hemophagocytic lymphohistiocytosis (HLH).”
An unexpected rare-disease diagnosis
Byron’s labs — especially his high ferritin levels — supported an HLH diagnosis. HLH is a rare disease that impacts the immune system, turning white blood cells against red.
“HLH is when red blood cells are being engulfed, being eaten, in the bone marrow,” explained Dr. Hays.
Secondary HLH is acquired from an infection (like Epstein-Barr virus), an impaired immune system or cancer. But primary HLH is inherited.
“Given that he was so young, there was a high suspicion that this was the inherited kind of HLH,” said Dr. Hays. Secondary HLH can sometimes go away on its own, but the only treatment for primary HLH is a bone marrow transplant.
Dr. Hays ordered genetic testing right away, but it would take weeks to confirm Byron had inherited HLH. In the meantime, Dr. Hays referred Byron to the Blood and Marrow Transplant (BMT) team. They started the donor matching process in case his genetic tests came back positive.
Treatment strategy: Close cooperation
There is a tight collaboration between the multidisciplinary Histiocytosis and BMT teams. “Our offices are literally across the hall from each other; they’re knocking on my door and vice versa,” said Dr. Hays. The teams worked together to develop Byron’s treatment plan.
“HLH is an underlying immune dysregulation where the immune system doesn’t have the off switch,” said BMT physician Ibrahim Ahmed, MD, MBBCh. “As long as this switch is built into the code of the immune cells, it’s going to reactivate again.
“The role of Dr. Hays and the Histiocytosis team is to switch off this fire, control the environment and give the body time to heal. Conditioning chemotherapy kills the immune system. Then we replace the stem cells, the seeds for the future immune cells and blood products.”
Byron stayed at Children’s Mercy for two weeks to get stabilized, place a central line and start chemotherapy. He continued outpatient chemotherapy at home to complete the 8-week plan.
“There’s no rapid test to say, ‘Yes, HLH is for sure what’s going on,’” said Kimberlie. “We were putting a lot of faith in Dr. Hays. Which I totally would again, 10 times over. She is a phenomenal person.”
“The goal is to try to send him to transplant when he’s as heathy as possible,” said Dr. Hays. “He’s healthier when he goes in, and healthier when he comes out.”
As expected, Byron’s genetic testing showed he had inherited HLH. There are multiple genes associated with the disorder. Byron had two mutations, which is unusual: One copy of the PRF1 gene, which encodes perforin, was abnormal. Alone, that would make him an HLH carrier (like both of his parents) but not give him HLH. But both copies of his UNC13D gene, which makes a protein called Munc13-4, were also abnormal.
“When there’s an infected cell, the body calls in reinforcements to surround it,” explained Dr. Hays. “With the perforin mutation, Byron wasn’t able to poke a hole in the infected cell, and then with the UNC13D mutation, the detergents that are supposed to kill the infection aren’t packaged correctly.”
Byron needed a new immune system — quickly.
A new “birthday”
Fortunately, Byron’s BMT team was able to find a bone marrow match for him within weeks. They scheduled Byron’s bone marrow transplant for late February.
“This is our son’s new chance at life,” said Kimberlie. “This is his new birthday.”
To counteract the big emotions of the day, Byron’s big sister, Addison, then 2 years old, entertained everyone with a dance party during the transplant. (Addison’s testing showed she doesn’t have or carry HLH.) Afterward, the family settled in for a five-week hospital stay as they waited to see if Byron’s new immune system would take over.
Within eight days, they saw proof of engraftment: The donor stem cells started making healthy new blood cells. “I remember I called my husband: ‘There are cells!’” said Kimberlie.
As spring started, Byron and his family went home to start their new life together. He was on immunosuppression drugs, and the team tracked his chimerism, or the ratio of donor to original immune cells. The ideal is 100%, but a “mixed chimer” can be tolerable and healthy.
"We like to see that a very strong engraftment that’s stable,” said Dr. Ahmed. “It can take up to a year for the immune system to fully recover and reconstitute.”
The early months post-transplant were a blur for Byron’s family, with up to four visits a week to Children’s Mercy for bloodwork and therapy. But by the summer, Byron was hitting developmental milestones, graduating from feeding therapy and starting to wean off the immunosuppressants. He had his central line removed, and his appointments are now monthly.
“Post-transplant care is evidence-based, but it’s also an art,” said Dr. Ahmed. “It’s a journey.”
The BMT team has taken over Byron’s regular follow-up care, but Dr. Hays still drops by to see Byron when he comes in for his appointments. When he’s 5, he’ll switch to annual check-ups. He’ll also be followed by the Survive and Thrive Clinic to monitor for any late chemotherapy effects and teach him to advocate for his health as he gets older.
Kimberlie is excited to be able to take Byron to the swimming pool this summer and spend time together as a family doing the little, everyday things. They are planning a trip to celebrate his first “transplant-versary” next February.
HLH treatment is a team effort
Both Dr. Hays and Dr. Ahmed emphasized how many people helped care for Byron: Transplant coordinators, nutritionists, psychologists, psychotherapists, child life specialists, nurse practitioners, in- and outpatient nurses and more.
“Dr. Ahmed and his whole team have done a phenomenal job,” said Dr. Hays. “The PICU engaged all the right people to get to his diagnosis quickly. He came to chemotherapy and transplant not as sick and with not as much organ damage — his body tolerated it a lot better.”
“In our program, we consider the families and patients part of the team, too,” said Dr. Ahmed. “It's a learning curve. Byron’s parents are awesome at understanding what needs to be done. They’re coping very well with a lot of changes, the anticipation, the weight, the progress of things.”
Kimberlie said she had help coping: The best decision she made was talking to Family Therapy during Byron’s hospital stays. “As a parent, you want to be the tough one,” said Kimberlie, “But there are times where it's like, ‘I can't keep doing this. I need help.’”
She also said that Byron’s care teams became like a second family. “Enjoy that time and appreciate those people,” Kimberlie encouraged other Children’s Mercy families. “I actually really miss seeing them. It’s hard at the time, but when you look back, you’re going to forever be grateful for those people.”
And they are grateful for Byron. “He’s so cute; he entered all our hearts quite easily,” said Dr. Ahmed. “He has all the keys!”