Every morning, Brenna Hasselmann, now 20, gets up and runs for 3 miles. Every single step is a gift.

Brenna Eighteen months ago, when Brenna first came to Children’s Hospital of Philadelphia (CHOP), she was struggling to breathe. For the prior nine years, she had been battling kaposiform lymphangiomatosis (KLA), an extremely rare condition in which the lymphatic vessels develop abnormally, expanding and invading surrounding tissue, bones and organs and wreaking havoc.

In Brenna’s case, the lymphatic vessels around her lungs and heart leaked so much excess fluid, she could barely function. Walking was difficult. When she tried to sleep, she felt like she was drowning.

At the Jill and Mark Fishman Center for Lymphatic Disorders, center Director Yoav Dori, MD, PhD, performed a dynamic contrast MR lymphangiography (DCMRL) to see the status of her KLA. Lymphatic fluid “was where it was not supposed to go,” Brenna says. Dr. Dori is candid: “It was a mess. It was as if liters and liters of fluid were poured on her lungs.”

Interventional techniques, such as plugging the leaks, wouldn’t work; the damage was too profound.

Looking for unconventional treatments

Some KLA patients have found relief with medications originally developed for other diseases. Brenna was already on one medication, rapamycin, an immunosuppressant that also slows down the growth of certain cells. Dr. Dori and oncologist Jessica Foster, MD, decided to try adding vincristine, a chemotherapy drug that stops cancer cells from multiplying. The hope was it would halt Brenna’s KLA progression. It was paired with prednisone, a steroid, to decrease inflammation and also slow the accumulation of fluid.

“Because I’d been on steroids many times before, I was prepared for my face to swell, but I wasn’t prepared for losing my hair, muscle atrophy, insomnia and debilitating anxiety,” Brenna says. 

She had started her freshman year at Virginia Tech in the fall of 2018, but after one month, needed to withdraw. Her body was failing, and she feared that catching the slightest cold would “be the end of me. I truly did not think I would live to see 2019,” she says.

It was also crushing emotionally. Her medical condition meant she couldn’t keep pace with her peers and that create low self esteem and a feeling of worthlessness.

She returned home to New Jersey to wait. And hope.

About the same time, Dr. Foster had seen a journal article on genetic testing for patients with KLA that showed a specific genetic mutation. This mutation has also been found in certain tumors, and the protein pathway it affects is well studied in oncology. A different cancer drug, trametinib, an MEK inhibitor used to treat metastatic melanoma, had been effective in blocking the mutated protein pathway in tumors, which happened to be the same protein pathway that triggers the abnormal growth in KLA patients.

Dr. Dori took biopsies of the lymph fluid in the lung region and from lymph nodes in her groin for genetic testing. While waiting on the genetic test results, Brenna began taking trametinib on Feb. 15, 2019. “We were so worried about her, we didn’t feel we could wait for the results,” Dr. Foster says.

Correcting the chain of proteins

While it ended up Brenna did not have the specific gene mutation that paper mentioned, the mutation she did have was in the same chain of proteins that was reported and was susceptible to MEK inhibition. This chain of proteins eventually tells the lymph vessels what to do — and in Brenna’s case, those signals were out of whack, causing the malformations.

“Think of it like a factory that isn’t working right,” Dr. Dori says. “It’s overproducing and all the products are defective. Her lymph vessels were defective.”

The one small pill of trametinib Brenna takes each day — about a quarter of the cancer-fighting dose — gets her “factory” back to making proper lymph vessels.

“There was a tremendous difference. It was just crazy,” Brenna says. Within a month, Brenna felt better than she had in nearly a decade. “As soon as I started feeling better, I was eager to be active,” she says.

She started jogging in February. By March, she began to train more seriously.

From ‘I can’t breathe’ to running a 5K

Brenna running outside In July, she ran a 5K race, finishing in 29 minutes, 55 seconds. 

When Dr. Dori performed another DCMRL, the difference was shocking. The liters and liters of excess fluid were gone. The interconnected, invasive lymph vessels had remodeled themselves and are behaving normally. To her doctors’ knowledge, Brenna is the first KLA patient in the world who has been treated with trametinib, and they shared her success through a case study article in the journal EMBO Molecular Medicine.

“From the vascular anomaly perspective, there’s never before been a drug that completely remodels the lymphatic channels,” Dr. Dori says. “It gives a lot of hope for the future for children with these conditions. It changes everything we understand about lung disease — that the body can remodel itself in a month or two. New lymphatics channels are created, and the old, dilatated ones disappear.”

Three-way collaboration: Lymphatics, Genetics, Oncology

Brenna is the second CHOP lymphatics patient who arrived in severely compromised health and, through the collaboration of Lymphatics, Genetics and Oncology, was restore to health. Several additional children, with different conditions, are also benefiting from this unique three-way collaboration.

Brenna smiling “You have to think past the vascular problem, to the cause,” Dr. Dori says. “If we can find the genetic cause and there’s a drug that resolves it, we can make some diseases go away. We need genetics to identify the cause of the channel problem and oncology to identify the chemotherapy drugs to treat the abnormal growth.”

“All of the boundaries between departments go away,” Dr. Foster says. “That’s the great thing about CHOP. We foster discovery.”

Dr. Foster manages Brenna’s ongoing treatment, including keeping an eye out for side effects, which so far have been minimal. Her prognosis is so strong, they were able to reduce her medication dose by half.

For Brenna, the benefits have been remarkable.

“After struggling to breathe just walking up stairs, I honestly can’t believe I’m in the same body,” she says. “It’s so bizarre not having to worry about my lungs or chronic pain anymore. I’m a whole new person.”

Next frontier: A degree in biology

Brenna is back in school, attending a community college in New Jersey, with an eye toward transferring to a four-year university in the Philadelphia area. Her major: biology with an eye toward a career in health.

“I know my experiences will help me empathize with my patients because I’ve been in their position,” she says. “I aspire to be as great as the staff at CHOP.”

“I’m so grateful for Dr. Foster, Dr. Dori and everyone at CHOP,” she adds.

They gave me my life back. Now I have a future.

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