New treatment in clinical trial at Cleveland Clinic may vastly increase number of donor lungs



CLEVELAND, Ohio-- In a lab at the Cleveland Clinic, underneath what looks like an oversized plastic cake dome, a pair of human lungs sit, tethered to tubes and hoses.

Disembodied, the pinkish-yellow organs rise and fall to the rhythm of a mechanical ventilator.

They are among the 80 percent of donated lungs deemed unsuitable for transplant -- damaged or infected or simply waterlogged from prolonged resuscitation attempts -- a situation that has led to a chronic shortage of suitable organs and a steady waiting list.

But if the transformation process this set of lungs is about to undergo is approved by the FDA in the next year, the waiting list for a lung transplant could become a thing of the past.

So here they sit, hooked up to a mini heart-lung machine, undergoing an experimental rehabilitation.

A proprietary solution shoots through a hose and into the waiting organs, while a ventilator mechanically fills them with oxygen through another tube. The process takes about two hours.

KENNETH_MCCURRY_13705557.JPGDr. Kenneth McCurry, Program and Surgical Director of lung and heart-lung transplantation at the Cleveland Clinic.  

When it's done, about 75 percent of these "untransplantable" lungs are fit for donation -- functioning just as well as lungs that don't require the treatment, said Dr. Kenneth McCurry, program and surgical director of lung and heart-lung transplantation at the Cleveland Clinic, which is one of several institutions testing the system in a clinical trial.

"Some are even better," he said.

"This is an exciting technology that is likely going to revolutionize lung transplant," said Dr. Kevin Chan, the chairman of the United Network for Organ Sharing and Organ Procurement and Transplantation Networks' lung subcommittee, and medical director of lung transplant at University of Michigan Health System.

"It's moving quickly," said Chan.

The Clinic has used the system, called XVIVO (for ex vivo, meaning outside the body), on 16 sets of lungs so far.

McCurry and his team aren't yet transplanting the rehabbed lungs into waiting recipients, though, because the solution they're using, called Steen after the Swedish doctor who invented it, is not yet approved by the Food and Drug Administration.

In June, XVIVO's parent company, Vitrolife, applied to the FDA for approval of the solution. The FDA's stamp of approval, which may come as early as the end of the year, would allow researchers at the Clinic and other U.S. centers to start transplanting lungs treated using the XVIVO system.

The system is, however, already approved by the European Medicines Agency for use in several European countries, and in Canada by Health Canada, where Toronto's University Health Network (UHN)/University of Toronto pioneered the use of the XVIVO system and has been successfully recovering and transplanting lungs since 2008.

Patients who received lungs transplanted after the XVIVO treatment at Toronto's UHN did just as well as traditional lung transplant patients in terms of 30-day mortality, ICU and hospital stay, and length of time on mechanical ventilation. The research team there has transplanted 75 patients using the system.

"The results are even superior to standard donor lungs," said Dr. Shaf Keshavjee, director of the Toronto lung transplant program at the University of Toronto. "Now we have almost three-year follow-up on some of those patients."

The Clinic's McCurry thinks that his team, which performs between 100 and 125 lung transplants a year, already one of the largest programs in the country, could increase its transplant volume by 50 percent to 100 percent using the XVIVO system.

Lung transplants recipients are most commonly people with severe COPD (chronic obstructive pulmonary disease), a progressive disease that makes it difficult to breathe. Patients with cystic fibrosis, idiopathic pulmonary fibrosis (a rare disease that causes thickening, stiffening and scarring of lung tissue) and pulmonary hypertension (an increased pressure in the pulmonary arteries) also often need transplants.

In 2012 so far 1,822 lung transplants were performed in the United States, according to UNOS, and there are 1,624 people on the waiting list for a transplant.

"The mortality rate for people waiting for lung transplant is still quite significant," McCurry said. Two hundred and forty people died waiting for a lung in 2010, according to UNOS.

Changes to transplant waiting list requirements now bump the most severe cases to the top of the list, and improvements in technology have increased the amount of time donated lungs can be stored before transplant, both significantly reducing wait times.

Still, the vast majority of donated lungs are deemed unsuitable for transplant because they are somehow damaged.

"Lungs are one of two organs, the other being the intestine, that are exposed to the external environment," said McCurry. "So there's a risk of aspiration and pneumonia, and other types of infections are reasonably common in donors."

"The lungs are more fragile than the other organs," Chan said, and flushing the body with fluid, a technique that preserves other solid organs like the kidneys and liver for transplant, can flood and damage the lungs.

The main reason donated lungs are turned down is fluid accumulation, McCurry said. The solution used in the XVIVO system works by pulling that excess water out, drying the lungs and restoring lost function.

After infusing the solution, the researchers can ventilate the lungs and measure how well they absorb oxygen. Lungs rehabbed using the proprietary solution and the XVIVO system will be able to be used at other centers for transplant after they're treated.

McCurry believes the XVIVO system may be the perfect way to deliver other treatments to donor lungs, too. He hopes his team may one day be able to use the platform to deliver antibiotics or to treat donated lungs to make it easier for patients to receive them.

Rejection is a big problem for lung transplant recipients, and nationally, five-year survival rates after transplant are only about 53 percent.

"We might be able to change the lung in some way so that the recipient's immune system might respond to it less vigorously, thereby decreasing the risk of rejection," McCurry said.

A vastly expanded donor pool may also mean that more people who wouldn't traditionally be offered a transplant -- the really high-risk patients, for example -- will be able to get one.

"This could have a huge impact on lung transplantation," Chan said. "Part of our job now is to ensure that this technology is available to the people that need it and that the donors are allocated equitably."

And the technology may be a boon to patients on other transplant waiting lists, as well.

"I think in the big picture it's a real transformational change in how we do transplantation," said Keshavjee, who believes the XVIVO method represents a paradigm change in his field.

Traditionally, donor organs are cooled to slow down the deterioration process, then rushed to a patient. Their function can only be assessed after the transplant, he said, but XVIVO "will allow us to assess organ function, prepare the organs for transplant and, in time to come, all organs can be improved and enhanced before being transplanted -- not just lungs."

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