For organs kept alive before transplant, tantalizing possibilities

For Robin Larocca, her lungs ravaged by a rare disease, the options were disappearing quickly.

In three months, her doctors said, she would be too sick for the transplant she needed to save her life. In a year or so, she would likely be dead.

There appeared to be no available match, particularly because Larocca needed a double transplant rather than the more common single lung.

Then doctors at the Hospital of the University of Pennsylvania offered her a chance to be in a clinical trial of a process that allows surgeons to better assess and eventually, perhaps, fix an organ that otherwise would have been rejected. She didn't hesitate.

"I didn't feel there was any other choice," said Larocca, who lives in Jackson Township, N.J. "I wanted to extend my life and give my daughter a better quality of life."

The process is called perfusion. Derived from the Latin perfusionem ("a pouring over"), it means the delivery of oxygenated blood to the tissues of the body.

Normally, they are inside. But donor kidneys have been perfused before transplant since the 1960s. Surgeons started experimenting with small numbers of other organs about a decade ago.

Pumping blood or a synthetic solution through them for several hours allows time to run tests rather than discarding an organ because of the mere possibility of a problem. It also opens up all sorts of futuristic medical ideas.

At Penn, a pair of donor lungs spent time in a Swedish-made XVIVO Perfusion System machine before being transplanted into Larocca in February 2013. Today, at 48, she is managing a deli after decades of being too ill to work.

Edward Cantu performed HUP's first such lung transplant in 2012. He hopes that the process could eventually shorten waiting lists for lungs and other major organs, most of which are rejected as unsuitable by surgeons who must make an immediate decision.

In one case, Cantu said, surgeons used perfusion to assess and transplant a lung from a homicide victim who had been shot in the other lung; normally it would have been rejected. In Larocca's case, there was a possibility that the donor had lung cancer, so the organs had to be tested to make sure they were cancer-free.

The United Network of Organ Sharing, which oversees the nation's transplant system, estimates that an average of 22 people a day die while awaiting a transplant. More than 20 percent of patients awaiting a lung transplant die waiting.

Perfusion of lungs, hearts and livers isn't yet widespread enough to have significantly affected organ supply - about 400 for lung transplants worldwide so far - but "the potential is dramatic, it's real and it's not very far off," said David Klassen, the network's chief medical officer.

"Any time you open up a new potential source of organs that are safe for transplant, it's big news," said Cantu. The number of transplants at Penn increased significantly the first year that perfusion was used despite an actual decline in the number of available organs.

Patients like Larocca are on course to match the five-year survival rate for conventional lung transplants, Cantu said, currently 50 percent.

Doctors at HUP expect to start perfusing livers within six months, said Abraham Shaked, director of the Penn Transplant Institute, and hearts in two to five years.

Temple University Hospital is planning to use lung perfusion for a transplant as soon as an appropriate donor organ can be found. Temple also expects to eventually use perfusion in heart transplants, said transplant surgeon Suresh Keshavamurthy.

Hahnemann University Hospital is on schedule to start transplanting livers using perfusion next year. David J. Reich, transplant chief at Hahnemann, said surgeons there are testing the use of an experimental cell line during perfusion to stimulate growth and reduce inflammation.

Shaked describes the three elements of perfusion in transplant surgery as "preserve, assess, and repair."

The Food and Drug Administration allows lungs to be preserved through perfusion for up to six hours (longer for some other organs), giving physicians more time for evaluation. They can do a bronchoscopy on a damaged lung, for example, inserting a tube to get a closer look at the air passages.

But it is the possibilities for "repair" that has transplant surgeons excited.

If an infection is found, for example, the lung might be injected with a dose of antibiotics far higher than the body could tolerate if it had to pass through the liver and kidneys, wiping out the infection in hours - before the lung is actually transplanted.

Currently, recipients and donors must have compatible blood types, severely limiting suitable matches. If perfusion could be used to make organs O-positive, the one blood type that is accepted by all others, it would essentially create universal donors.

"You could genetically alter organs," Klassen adds, so that the recipient's immune system doesn't see them as alien - reducing or perhaps at some point eliminating the lifetime need for powerful immunosuppressant drugs.

At perfusion's most distant frontiers, said Cantu, associate surgical director of lung transplantation at Penn, a group at Harvard is experimenting with "decellulizing" lungs in rats and repopulating the framework of a lung with stem cells in order to regenerate an entire new organ.

"This is the holy grail," Cantu said, quickly adding that it's probably at least a decade away in humans. "You'd have a new lung that's basically you. There would be no immunosuppression.

"It's an incredibly exciting time in lung transplants, in all transplants, really."

Where does perfusion go from here?

"That's the big question," said Howard Nathan, president and CEO of Gift of Life, the organ transplant network for Eastern Pennsylvania, South Jersey and Delaware. "Can it be a routine procedure? "

Perfusion can increase the supply of available organs, but Nathan still stresses the potential of low-tech - getting more donors simply by working with hospitals' personnel, intensive care units and trauma centers.

"It's a multi-pronged effort," said Hahnemann's Reich. "We need more advocacy. We're working on all those fronts."

As exciting as the technical advances are, the spread of organ perfusion will be determined by economics as well as by science. Each kind of organ requires a different perfusion machine.

Several companies make the machines, and the price presumably will come down over time. Currently, however, a lung perfusion machine costs about $250,000 and supplies can add up to $40,000 to the cost of a single transplant.

For Robin Larocca, the details of perfusion aren't what is important. She no longer has to tote a tank of oxygen around the house or on errands. She has the energy to work.

One of her biggest struggles is trying to compose a thank-you note to the donor's family, to be forwarded anonymously by Gift of Life.

"It's a hard letter to write," she says. "When it comes time to put it on paper, the words just don't flow."