DURHAM -- The stop at Duke Medical Center was supposed to be a quick checkup, a side trip as the Burbach family headed from their home in Georgia to Myrtle Beach for vacation.
But when doctors saw 15-year-old Laura Margaret Burbach toting oxygen and appearing wan - scary on a 4-foot, 5-inch teenager who weighed less than 60 pounds - they suggested the family instead check her into the hospital.
Laura Margaret's lungs were shot. A casualty of repeated infections her faulty immune system failed to vanquish, her lungs were no longer capable of keeping her alive.
Arriving at Duke in June, the Burbachs - David, Sarah and Laura Margaret - were supposed to initiate the process of getting Laura Margaret a bone marrow or cord blood transplant. Either was a risky but fairly common procedure to replace her deficient immune-fighting blood cells with those from a healthy donor.
With her respiratory system in such sorry shape, however, Laura Margaret also needed new lungs.
That sort of double transplant had never been undertaken, or at least never chronicled in medical literature. But without both transplants, Laura Margaret would die.
"I really think it was her only chance," said Dr. David Zaas, the pulmonologist who coordinated her care.
With no playbook to guide them, the Duke team began to plan. They needed approvals from federal authorities and their own institutional watchdog, and faced long statistical odds to find organs that both fit and matched Laura Margaret's own failing body.
But as each new specialist and caregiver joined the team to save Laura Margaret, the will to succeed only grew. A peppy, pink-loving high school cheerleader, Laura Margaret was 48 pounds of determination and grit.
"She's maybe the most inspiring patient I've ever had," said Dr. Paul Szabolcs, a pediatric bone marrow specialist.
Eager to save Laura Margaret, they might inch medicine ahead by setting the foundation for a new approach that could help many others.
'She has it, too'
Before she was 2, Laura Margaret lost her big brother.
Michael Burbach was continually sick, born with an immune deficiency disease. Commonly known as "bubble boy disease," the condition was made famous in a 1970s TV movie about a Texas boy who grew up in a plastic bubble to prevent exposure to infections.
Often inherited, immune deficiency disorders are actually an array of diseases in which the immune system lacks two key weapons - T cells and B cells - causing children to fall prey to opportunistic infections. Before immune cell transplants, most babies with severe forms of the disease died as toddlers.
Michael's diagnosis was made just as Laura Margaret was born, on Oct.13, 1993. Sarah Burbach said the diagnosis came with the hope that Laura Margaret might one day be able to donate bone marrow and save her brother.
Her blood test six months later, however, brought horrible news: "They called to say, 'No, she's not a match, and Sarah, she has it, too.' I still remember that day vividly."
But David Burbach was a sufficient match for his son. So the family pursued bone marrow transplants at Duke, which has become one of the world's top treatment centers for immune deficiency diseases, curing more than 100 children with transplants.
Michael had two transplants at Duke, but neither worked. He died just shy of his 4th birthday.
Heartbroken, the Burbachs kept a close watch on Laura Margaret's health, keeping her home if they knew some bug was going around. But they also strived to create a normal childhood for their little girl.
"We didn't choose for her to live that kind of a life - in a bubble," Sarah Burbach said.
A way of life
Laura Margaret thrived. Growing up in Madison, Ga. - a small town east of Atlanta - she took piano and voice lessons, and acted in local theater productions.
At Morgan County High School, she was a member of the student council and became a cheerleader - one of the featherweight girls at the top of pyramids who gets somersaulted into the air. She had sleepovers, got her learner's permit to drive, excelled in school with challenging Advanced Placement classes.
"Even if I wasn't going to have a long life, I was going to have a real life," Laura Margaret said.
But her achievements were made in spite of endless infections that took a huge toll. Her lungs, in particular, bore the brunt.
"It was just another facet of our lives," Laura Margaret said. "Most people wake up and take a shower and go to school. I would wake up and run IVs, and do my breathing treatment, and then shower and go to school."
Her high school principal, Mark Wilson, said Laura Margaret has long inspired her classmates, and the entire community. Last fall for the homecoming football game, the crowd released pink balloons in her honor, sharing the scene via her ever-present computer link.
"There are people in the world who seem like they have extra time - they can get more done than anyone else. Laura Margaret is one of those people," Wilson said, ticking off a list of the teenager's accomplishments. "It's amazing all she does, and she has these challenges."
Her health declined sharply last spring, when she began needing oxygen to breathe. Even still, the family never considered that Laura Margaret's lungs had deteriorated so badly. Still gearing up for a bone marrow or cord blood transplant at Duke, the family planned a quick visit in June to meet doctors and lay the groundwork before vacationing in Myrtle Beach.
Their travel plans abruptly changed.
Avoiding rejection
Doctors quickly determined Laura Margaret could never survive the toxic preparation for a bone marrow or cord blood transplant. The procedures, while life-saving, require annihilation of the immune system to allow the donated cells to establish themselves.
But doctors had another idea: transplant new lungs to solve her immediate problems, and new marrow to correct the underlying flaws of her immune system.
The combination would protect Laura Margaret against the main reason transplants fail: rejection, which occurs when the recipient's immune system attacks the new organ as a foreign invader. If Laura Margaret's new immune system came from the same donor as the lungs, it would have no cause to attack. And she wouldn't need toxic anti-rejection drugs.
"The idea that we might be able to essentially create an immune system that wouldn't react against the organ is something of the holy grail that we all hope to achieve," said Dr. R. Duane Davis, her lung transplant surgeon.
Surgeons in Boston have reported good results in kidney recipients who have received small infusions of marrow from living donors, and Davis is aware also of a case involving a living donor who gave part of a lung that coincided with a limited marrow infusion. But no one had proposed anything on the scale of what Duke doctors had in mind for Laura Margaret.
They wanted to use the lungs and marrow of an unrelated deceased donor, and do two full transplants weeks apart.
If the strategy worked, it might pave the way for similar procedures for others who need lung transplants - people such as Laura Margaret with immune disorders as well as cystic fibrosis patients - possibly extending the life of transplanted lungs that often wear out in less than 10 years.
"We thought, Why not try?" Zaas said. "Why not see what we can do?"
Moving forward, however, required both government and institutional approval. The U.S. Food and Drug Administration and Duke administrators demanded detailed plans, so the doctors met regularly to talk strategy and draft proposals.
Job one was getting Laura Margaret in shape for a lung transplant. Too frail even to qualify for a spot on the transplant list, Laura Margaret began a regimen to gain weight and strength.
Living with her mom in an apartment near Duke - her dad remained in Madison to work, driving up when he could on weekends - Laura Margaret exercised every day at the Center for Living.
On Dec. 6, she won a spot on the transplant list. But doctors doubted that a matching donor would be found quickly.
Lung donors must match recipients for blood type and be roughly the same size. Bone marrow transplants require an even finer match, based on a protein called human leukocyte antigen. The immune system uses HLA markers to identify the body's cells, so HLA must match as closely as possible to avoid sparking an immune attack.
Typically, doctors aim to match six HLA markers between donors and recipients, but the FDA approved Laura Margaret's procedure using a match of just two. Szabolcs, her bone marrow specialist, said the lower match was possible because the marrow was to undergo a special process to deplete some of the attack cells.
Even with the more generous match criteria, however, Laura Margaret had only about a 10 percent probability of landing a suitable donor.
"It was the needle in the haystack," Zaas said.
A donor appears
Incredibly, the needle appeared. Laura Margaret had been on the transplant list less than one week when the call came that she was a match for lungs and marrow from a deceased donor. And the match was even better than expected - hitting three HLA markers instead of two.
Davis and his group performed the lung transplant Dec. 16. Twenty-four hours later, Laura Margaret was out of bed and walking.
"Almost immediately I noticed a difference," she said.
On Dec. 23, she was discharged and began preparing for her bone marrow transplant. As the day approached, she was given chemotherapy and a shot of radiation to wipe out her deficient immune cells. Then on April 2, the healthy bone marrow cells of a person who died in December began flowing from an IV line into Laura Margaret's veins.
"This is your second birthday," nurse Lauren Harris said.
In the best of circumstances, the transplant cells naturally migrate to the bone marrow and begin replicating as if they had always lived there, churning out red and white blood cells in their own image. The engraftment process can take as long as a month, and on Wednesday, Szabolcs read Laura Margaret's lab results.
"Outstanding news!" he said. "Her cells are almost all donor cells."
For Laura Margaret, that means the immune deficiency syndrome she was born with may well be gone. But the next few weeks will be critical. As her new immune system takes hold, she is vulnerable to infections, since her defenses are only now building. She is also at risk of developing a condition in which the donor cells attack her body as a foreign threat. So far, however, she shows no sign of problems.
Szabolcs called her recovery remarkable, and on Thursday, he offered a gift she had dreamed of for months.
Wearing a festive top hat and a surgical mask that revealed only her eyes, Laura Margaret emerged from her hospital room into the hall of the bone marrow transplant unit where she had lived for nearly a month. Nurses, doctors, technicians, fellow patients and their families lined the hall and showered her with pink confetti to celebrate her discharge.
As the other young patients watched, some bald from chemotherapy and guarded behind paper masks, Laura Margaret fought sobs.
"I can't believe this is happening," she cried. "I was diagnosed when I was 6 months old, and I'm now 16, and I don't have immune deficiency syndrome anymore!"
And then she walked out of the hospital, trailing confetti and a legacy of hope, to resume a real life.
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