When it comes to a still-mysterious condition known as Castleman disease, David Fajgenbaum, a professor of hematology/oncology at the University of Pennsylvania's Perelman School of Medicine, is more than an advocate or a physician/scientist: He is also a patient.
Addressing a team of volunteers for the Castleman Disease Collaborative Network (CDCN), Fajgenbaum quickly details on a white board what is known about CD, a group of poorly understood inflammatory disorders that can vary from a single enlarged lymph node to life-threatening multiple organ failure.
The network, founded by the 31-year-old Fajgenbaum and Frits van Rhee of the University of Arkansas, has two goals: to uncover how the disease works and to establish a global network to improve biomedical research.
"We need to understand what it is that happens to the immune system and why it does what it does," Fajgenbaum said. "We want to know what drives the disease and ideally identify a drug that already exists that targets one of these subtypes."
Castleman disease was first identified in 1954 by Benjamin Castleman of Harvard University. There are approximately 5,000 to 6,000 new cases per year of CD in the United States, about the same number as amyotrophic lateral sclerosis, also known as Lou Gehrig's disease.
In CD, the body's immune system becomes activated and releases inflammatory proteins - among them interleukin-6 - that can shut down the liver, kidneys, and bone marrow. The disease can occur in a single lymph node (unicentric) or multiple lymph nodes (multicentric). MCD (multicentric Castleman disease) can be caused by infection with human herpesvirus 8, or it can occur for idiopathic, or unknown, reasons.
In August 2010, while in medical school, Fajgenbaum was diagnosed with idiopathic multicentric Castleman disease. This subtype has a five-year survival rate of 65 percent, which is nearly as deadly as the average for all cancers combined. While similar to lymphoma, the disease is not a cancer.
In the summer before Fajgenbaum's first year of college, his mother was diagnosed with brain cancer. After she died, her grieving son decided to devote his career to cancer research. He also created a group for other mourning students called National Students of AMF Support Network, which would give him valuable experience for his later work with the Castleman network.
After his graduation from Georgetown University in 2007, Fajgenbaum won an All Britain fellowship to study for a master's degree in public health at Oxford University. After medical school at Penn, he earned an M.B.A. from Wharton.
During his third year of medical training at Penn, suffering from enlarged lymph nodes, fatigue, and night sweats, Fajgenbaum went to the emergency room, where he was told that his kidneys and bone marrow "weren't working right." Subsequently, he had a retinal hemorrhage, which temporarily blinded him in one eye. He gained 70 pounds of fluid when his liver stopped working.
"No one knew what was wrong," said Fajgenbaum, who had always been healthy and fit - he was a quarterback as an undergraduate at Georgetown.
He spent seven weeks in the hospital. During a second relapse, a lymph node biopsy confirmed a diagnosis of CD. Over the next few years he returned to the hospital several times with organ failure. During one visit, he gathered friends to say a final goodbye; at another, he received last rites.
After a year's medical leave, Fajgenbaum finished his third year of medical school and suffered yet another relapse. This time he and his father, also a medical doctor, traveled to Little Rock to speak with van Rhee, the most prominent expert on the disease. Van Rhee gave Fajgenbaum an intense course of chemotherapy to put the disease in remission.
All this time, Fajgenbaum had questions.
"We know the immune system is activated in this disease, but why? Which immune cells are to blame? There was no answer to basic questions," he said. "And no one was working together. Researchers were using different terminologies. They were not sharing information. They had no idea whether they were talking about the same subtype of the disease."
Fajgenbaum wanted to find better ways to connect scientists, to decide which issues demand the most urgent investigation, and to fund researchers.
"Usually, foundations raise money and then distribute the money to researchers based on what they want to investigate," Fajgenbaum said. "But in this case we didn't know how the disease works, and it was urgent that we figure that out."
So he and Arthur Rubenstein, a retired Penn dean who was setting up a new orphan disease program at Penn, went to work.
"We identified all the top researchers on the disease around the world and connected them, developing a network of over 300 physicians," Fajgenbaum said. "Then we used the community to figure out what top people should be on a 28-member scientific advisory board. And then, through crowdsourcing and leveraging expertise of our members, we tried to figure out not what an individual wanted to work on but what the community thought needed to be done in research."
Fajgenbaum and his associates published a new model on the workings of idiopathic multicentric Castleman disease in the medical journal Blood. He recruited experts to launch four high-impact studies and completed plans for a global patient registry to help improve care and accelerate research. Their latest project is to raise $225,000 for a large study to "identify potential diagnostic tests, better understand what causes the intense immune response, uncover which immune cells cause the problems, and understand how we can stop the disease."
Fajgenbaum recently accepted an award from the rare-disease patient advocacy organization Global Genes for his work on the disease.
"My job is that of a quarterback," he said. "I find people way smarter than me, and I try to prioritize what needs to be done. Who is the best person in the world to do this study? What is the best area to study?
"We are not only deciding what to do but providing help to drive it forward," he said.
Fajgenbaum, who is on a series of immunosuppressant medications, passed the critical five-year mark in August. His remission periods are stretching longer, from an initial 4½ months to his current 21 months.
"I respond to really big challenges by saying, 'What can I do about it? Whom can I bring on board? Can I work all night, all day, all weekend to solve it?' "
He takes a breath.
"With the work we've done over the past three years, we're light-years ahead of where we were."
And with that, a smaller white board tucked under his arm like a football, he vanishes into his office, back to work.
'Quest for Cure' Gala on Friday
On Friday, the Castleman Disease Collaborative Network (CDCN) will host the "Quest for a Cure" Gala at Penn Medicine's new Jordan Medical Education Center.
The gala will cap a two-day meeting of 20 world experts on Castleman disease, who will gather here to establish the first international criterion for diagnosing the disease. Without such information, diagnostic delays have resulted in patient suffering and even death.
At the gala, David Fajgenbaum will present
a brief talk on the CDCN's approach to transform
CD research over the last three years and how this approach might apply to other rare diseases.
For more information on the event and to buy tickets, go to http://www.cdcn.org/quest.