Gorham-Stout disease: 12 years, two patients and one innovation

Dan and Alex, a few weeks after Alex's surgery
Dan and Alex, a few weeks after Alex’s surgery for Gorham-Stout disease (Photo Susanne Malloy)

On a snowy Saturday in January, two mothers sat sipping tea and conversing about their sons. It was an ordinary scene, but the women’s conversation was far from ordinary.
The scariest thing a doctor can tell you is ‘I don’t know. I’ve never seen this before.’ To find two doctors who treated this before and then to see Dan doing so well is tremendously gratifying. ~ Susanne Malloy

Susanne’s son Alexander Malloy, 14, had been recently diagnosed with Gorham-Stout disease. Gorham-Stout, also referred to as “vanishing-bone” disease, triggers a process that destroys bones and typically affects a single area like the shoulder, jaw hip, rib or spine.

“It was shocking,” recalls Susanne. An MRI earlier that week, prompted by a worsening of her son’s mild scoliosis, had shown Alex was missing bones in his spine and likely had Gorham-Stout.

After the MRI, Alex’s orthopedic surgeon, Dr. Lawrence Karlin, reassured Susanne and her husband Tom that Boston Children’s Hospital would have a plan for their son.

As Susanne and Tom digested the diagnosis, she began thinking Gorham-Stout, a rare bone disease of the lymphatic system reported in about 300 patients, sounded familiar. “I can’t have heard of it before,” she told herself.

The feeling persisted, so she called a friend, who said, “That sounds like Dan Ventresca.”

Twelve years earlier, Dan, who lived a few streets away from the Malloys in Hingham, Massachusetts, had been diagnosed with the same disease. Like Alex, Dan’s disease was located in his spine. Susanne’s friend called Dan’s mother.

Gorham-Stout: A connection

Within minutes, Sheila Ventresca invited Susanne to her home.

“It was so hard to find hope. To hear about Dan and how well he is doing now really helped us get through this,” says Susanne.

Like Alex, Dan is an avid athlete, enthusiastic hockey player and received care at Boston Children’s. But the similarities end there.

“My story reads more like ‘War and Peace’,” jokes Dan.

Gorham-Stout: Then

During his junior year of high school, in 2004, Dan started experiencing back pain that seemed like muscle spasms. After a few months, it became clear that Dan’s pain was more than a routine muscle spasm, and his doctor ordered an MRI scan. It showed what looked like a growth. He needed a specialist.

Alex, around the time of Dan's diagnosis
Alex, around the time of Dan’s diagnosis

“Through luck and good fortune I wound up at Boston Children’s and got connected with Dr. Hedequist,” says Dan.

Dan was admitted right away. Dr. Daniel Hedequist, an orthopedic surgeon in the Boston Children’s Orthopedic Center, and team formulated a game plan for the teen.

“The goal of Gorham-Stout treatment has always been to stabilize the disease. The disease is characterized by lengthy periods of stability followed by sudden bone loss,” explains Dr. Cameron Trenor, director of clinical research in the Boston Children’s Vascular Anomalies Center. In Dan’s case, the disease had eaten away at part of his spine, so he needed spinal fusion surgery to stabilize his spine.

The first step was medical treatment — interferon — to interrupt the lymphatic process destroying Dan’s spine, and bisphosphonates, which can slow bone loss over time.

One challenge treating patients with Gorham-Stout disease located in the spine is secure placement of hardware to stabilize the spine. It’s an exceptionally tricky surgery because as the disease progresses, it destroys the vertebra surrounding the fusion hardware. The hardware then loses its anchor.

After several weeks of inpatient medical treatment, Hedequist scheduled Dan’s spinal fusion surgery.

“I think my surgery was complex and messy,” says Dan.

Hedequist agrees. Dan’s chest kept filling with chyle, a milky-fluid which is a combination of lymph and fats carried by the lymphatic system. If chyle isn’t controlled and drained during surgery it can lead to respiratory distress and possibly death. Fortunately, Dan’s team controlled his complications, and he slowly regained strength during his one-month post-surgical hospital stay.

Contact sports were off limits for the hockey-loving Dan after his spinal fusion, so he switched to golf and pitching, playing on the Hingham High School teams during his senior year.

Dan on the pitching mound after his surgery
Dan on the pitching mound after his surgery

Gorham-Stout: Now

Fast forward 12 years.

Dan, now a healthy 28-year-old managing his disease, hears about Alex and checks in to wish Alex good luck before the younger teen’s spinal fusion surgery.

Hedequist, encountering another teen athlete with Gorham-Stout disease confined to his spine, prepares Susanne and Tom, telling them their son would go to the ICU after surgery, might stay in the hospital for a few weeks and would likely be sidelined from sports for a few months.

Dr. Dan Hedequist with Alex
Dr. Dan Hedequist with Alex (Photo Susanne Malloy)

But the younger hockey-loving Hingham teen differed from Dan in one key way.

Since Dan’s diagnosis in 2004, specialists in the Boston Children’s Vascular Anomalies Center had consulted on more than 50 patients with Gorham-Stout, and, in 2012, started offering families sirolimus, a new medical treatment option.

“Without sirolimus treatment, operating on the affected area is like cutting into a wet sponge filled with chyle,” explains Trenor. The fluid also creates a post-operative infection risk. (These complications accounted for Dan’s lengthy post-operative recovery.) Sirolimus appears to lessen chyle within the tissues around involved bones, making for a cleaner operation and a much lower infection risk. “We’ve used sirolimus in patients with other lymphatic disorders, and it’s been successful and very well-tolerated,” Trenor continues.

Trenor reviewed the medical options with the Malloys. Though interferon has been used in more patients, it requires daily injections. Sirolimus, which has been used successfully in fewer patients, is a twice-daily pill. Both medications are paired with bisphosphonates to slow bone loss.

After discussing treatment options with Trenor and reviewing recent clinical trial results, Susanne and Tom opted for sirolimus treatment for their son. Trenor was confident the treatment would be effective but wasn’t sure how fast Alex would respond to the drug.

“The known side effects of sirolimus seemed minimal, and we knew interferon was an option if Alex did not respond to sirolimus, but thankfully he responded very well and very quickly to sirolimus treatment. Plus, he hasn’t had any side effects,” says Susanne.

If diagnosed early enough, patients are less likely to need surgery when they are treated with sirolimus. Alex, who was the first Boston Children’s patient to have surgery after initial treatment with sirolimus, needed surgery because his disease had progressed prior to diagnosis. “Alex’s surgery was shockingly positive. Gorham-Stout is not the same disease with this treatment,” says Trenor.

Hedequist agrees. “When I did Alex’s spinal fusion, I asked for another biopsy to check the diagnosis. There was no chyle at all,” says Hedequist. “This medication is a game-changer for surgery.”

Though sirolimus has a fairly quick effect on the lymphatic process that destroys bone, rebuilding bone may take two to three years. Patients with Gorham-Stout are monitored over time with MRI scans to characterize the whole disease process: bone loss and re-growth and lymph involvement.

Gorham-Stout: What’s next

Dan and Alex at the 2016 Eversource Walk for Boston Children’s

Alex, in contrast to Dan, spent three nights in the hospital. Six weeks after his surgery, Hedequist gave him the green light to return to non-contact sports.

“We thought it would be a long time before he could play again,” says Susanne.

Alex is mulling his options, pondering baseball, golf, crew and lacrosse.

His parents are reflecting on their good fortune. “The scariest thing a doctor can tell you is ‘I don’t know. I’ve never seen this before.’ To find two doctors who treated this before and then to see Dan doing so well is tremendously gratifying,” says Susanne.

On the research side, Trenor and his colleagues in the Vascular Anomalies Center continue to study Gorham-Stout, sirolimus and other new treatment options. As for patient care, Trenor, Hedequist and other specialists are forging ahead with a new model for treatment.

“Treatment is a collaboration between medicine and surgery. Patients treated with sirolimus are less likely to need surgery,” says Trenor. Hedequist adds, “If patients can be diagnosed and treated with sirolimus early in the disease process, medication can prevent collapse of the spine, so surgery may be unnecessary. If surgery is needed, medical treatment reduces risks associated with chyle.”

Dan, an avid golfer, manages his disease medically; visiting specialists at Tufts Medical Center every few months for ongoing bisphosphonate infusions and MRI scans to monitor his disease.

Alex will follow a similar treatment plan at Boston Children’s. As Alex’s disease stabilizes, Trenor expects to take him off treatment and re-initiate therapy as needed if his bone loss recurs.

Learn more about the Boston Children’s Vascular Anomalies Center.