Ex Vivo Perfusion Expands Pool of Lung Transplants

SAN FRANCISCO – Additional research continues to show good outcomes with a new process that allows successful transplant of lungs that might otherwise be deemed unacceptable.

Researchers at the Organ Regeneration Laboratory at the University of Toronto evaluated and repaired 58 donor lungs over 4-6 hours in a process called normothermic ex vivo lung perfusion (EVLP). In all, 50 of these lungs were successfully transplanted into patients, for a final utilization rate of 86%, Dr. Marcelo Cypel reported at the annual meeting of the American Association for Thoracic Surgery.

The current study builds on a previous report on initial experience with EVLP from the same research team (N. Engl. J. Med. 2011;364:1431-40).

"As we all know, one of the major problems in doing lung transplantation is the organ shortage and the low utilization rates. Only 17% of the lungs from brain death donors and 2% of the lungs from cardiac death donors are used currently," Dr. Cypel said. EVLP lungs accounted for 20% of the transplantations at Toronto General Hospital in 2011.

The EVLP lungs came from 32 brain death donors and 26 cardiac death donors. Dr. Cypel and his colleagues compared the outcomes of these EVLP procedures to another 253 conventional lung transplantations performed at their institution from September 2008 to December 2011.

EVLP patients received a significantly higher percentage of lungs from cardiac death donors, which are generally considered less desirable than lungs from brain death donors. They also received a higher percentage of high-risk lungs from brain death donors (PaO₂/FIO₂ below 300 mm Hg) and more lungs with chest x-ray abnormalities, such as signs of pulmonary edema, compared with the conventional group.

"Donor lungs in the EVLP group were significantly more injured at baseline, however, the outcomes were comparable," said Dr. Cypel, a member of the surgical faculty in the Division of Thoracic Surgery at Toronto General Hospital University Health Network.

For example, posttransplant survival at 1 year was 86% for the EVLP group and 87% for the traditional transplant group in this retrospective study; at 3 years these rates dropped to 70% and 72%. There were no significant differences in survival for patients who received lungs from brain death or cardiac death donors.

Other findings included no significant difference in the rate of primary graft grade 3 dysfunction at 72 hours between groups according to International Society for Heart and Lung Transplantation criteria. The EVLP patients had a trend toward a decreased length of hospital stay, compared with conventional transplant recipients, Dr. Cypel said.

"Again, you and your colleagues have demonstrated the safety and efficacy of using EVLP in the transplantation of lungs that previously would not have been used by your group," said study discussant Dr. R. Duane Davis, director of transplant services at Duke University Health System in Durham, N.C. "Using this technology, we may be able to start applying lung transplant more practically for societal needs."

Dr. Davis asked Dr. Cypel how surgeons at Toronto General Hospital achieved an 86% EVLP utilization rate compared with the 54% rate observed in the U.S. trial and comparable rates in the United Kingdom and elsewhere.

"Our experience with the procedure and extensive laboratory research prior to starting the clinical trial" explain the difference, Dr. Cypel replied. Donor selection criteria also could play a role.

"The important thing is it is taking some of the adventure out of lung transplantation," study coauthor Dr. Shaf Keshavjee said during a separate presentation at the meeting. "Ex vivo lung perfusion is clinically feasible. We can we do a long-term perfusion of lungs outside the body without injuring them. It is possible to keep lung 12 hours outside the body and normothermic."

"We are developing ways to figure out which lungs need a fix and to target treatment to lungs that need treatment," said Dr. Keshavjee, director of the Toronto Lung Transplant program and chair of the Division of Thoracic Surgery at the University of Toronto. Examples include resolution of pulmonary edema and infections through EVLP. Treating infected lungs with lavage and high-dose antibiotics may one day make these organs acceptable for transplantation, even in cases of pneumonia.

The goal is to double or triple the overall number of lung transplants using the EVLP technique in the United States, said Dr. Davis. EVLP comprises 20% of transplants in Toronto, but the overall transplant volume has not increased.

EVLP has allowed the overall number of 100 transplants or so per year in Toronto to remain steady at the same time that organ donation rates have decreased, Dr. Cypel responded.

"The major contribution of EVLP will not be for the large transplant centers like Duke or Toronto, which already use 40% of the organs and for whom a marginal increase is not that large," Dr. Cypel said. "Look at the majority of lung transplant centers that use 10% or less of the offered lungs; that is where we can have a major impact by increasing the number of organs available."

Vitrolife supported the clinical trial. Dr. Cypel and Dr. Keshavjee reported no other relevant disclosures. Dr. Davis said he received research support from Vitrolife for a U.S. study.

SAN FRANCISCO – Additional research continues to show good outcomes with a new process that allows successful transplant of lungs that might otherwise be deemed unacceptable.

Researchers at the Organ Regeneration Laboratory at the University of Toronto evaluated and repaired 58 donor lungs over 4-6 hours in a process called normothermic ex vivo lung perfusion (EVLP). In all, 50 of these lungs were successfully transplanted into patients, for a final utilization rate of 86%, Dr. Marcelo Cypel reported at the annual meeting of the American Association for Thoracic Surgery.

The current study builds on a previous report on initial experience with EVLP from the same research team (N. Engl. J. Med. 2011;364:1431-40).

"As we all know, one of the major problems in doing lung transplantation is the organ shortage and the low utilization rates. Only 17% of the lungs from brain death donors and 2% of the lungs from cardiac death donors are used currently," Dr. Cypel said. EVLP lungs accounted for 20% of the transplantations at Toronto General Hospital in 2011.

The EVLP lungs came from 32 brain death donors and 26 cardiac death donors. Dr. Cypel and his colleagues compared the outcomes of these EVLP procedures to another 253 conventional lung transplantations performed at their institution from September 2008 to December 2011.

EVLP patients received a significantly higher percentage of lungs from cardiac death donors, which are generally considered less desirable than lungs from brain death donors. They also received a higher percentage of high-risk lungs from brain death donors (PaO₂/FIO₂ below 300 mm Hg) and more lungs with chest x-ray abnormalities, such as signs of pulmonary edema, compared with the conventional group.

"Donor lungs in the EVLP group were significantly more injured at baseline, however, the outcomes were comparable," said Dr. Cypel, a member of the surgical faculty in the Division of Thoracic Surgery at Toronto General Hospital University Health Network.

For example, posttransplant survival at 1 year was 86% for the EVLP group and 87% for the traditional transplant group in this retrospective study; at 3 years these rates dropped to 70% and 72%. There were no significant differences in survival for patients who received lungs from brain death or cardiac death donors.

Other findings included no significant difference in the rate of primary graft grade 3 dysfunction at 72 hours between groups according to International Society for Heart and Lung Transplantation criteria. The EVLP patients had a trend toward a decreased length of hospital stay, compared with conventional transplant recipients, Dr. Cypel said.

"Again, you and your colleagues have demonstrated the safety and efficacy of using EVLP in the transplantation of lungs that previously would not have been used by your group," said study discussant Dr. R. Duane Davis, director of transplant services at Duke University Health System in Durham, N.C. "Using this technology, we may be able to start applying lung transplant more practically for societal needs."

Dr. Davis asked Dr. Cypel how surgeons at Toronto General Hospital achieved an 86% EVLP utilization rate compared with the 54% rate observed in the U.S. trial and comparable rates in the United Kingdom and elsewhere.

"Our experience with the procedure and extensive laboratory research prior to starting the clinical trial" explain the difference, Dr. Cypel replied. Donor selection criteria also could play a role.

"The important thing is it is taking some of the adventure out of lung transplantation," study coauthor Dr. Shaf Keshavjee said during a separate presentation at the meeting. "Ex vivo lung perfusion is clinically feasible. We can we do a long-term perfusion of lungs outside the body without injuring them. It is possible to keep lung 12 hours outside the body and normothermic."

"We are developing ways to figure out which lungs need a fix and to target treatment to lungs that need treatment," said Dr. Keshavjee, director of the Toronto Lung Transplant program and chair of the Division of Thoracic Surgery at the University of Toronto. Examples include resolution of pulmonary edema and infections through EVLP. Treating infected lungs with lavage and high-dose antibiotics may one day make these organs acceptable for transplantation, even in cases of pneumonia.

The goal is to double or triple the overall number of lung transplants using the EVLP technique in the United States, said Dr. Davis. EVLP comprises 20% of transplants in Toronto, but the overall transplant volume has not increased.

EVLP has allowed the overall number of 100 transplants or so per year in Toronto to remain steady at the same time that organ donation rates have decreased, Dr. Cypel responded.

"The major contribution of EVLP will not be for the large transplant centers like Duke or Toronto, which already use 40% of the organs and for whom a marginal increase is not that large," Dr. Cypel said. "Look at the majority of lung transplant centers that use 10% or less of the offered lungs; that is where we can have a major impact by increasing the number of organs available."

Vitrolife supported the clinical trial. Dr. Cypel and Dr. Keshavjee reported no other relevant disclosures. Dr. Davis said he received research support from Vitrolife for a U.S. study.

SAN FRANCISCO – Additional research continues to show good outcomes with a new process that allows successful transplant of lungs that might otherwise be deemed unacceptable.

Researchers at the Organ Regeneration Laboratory at the University of Toronto evaluated and repaired 58 donor lungs over 4-6 hours in a process called normothermic ex vivo lung perfusion (EVLP). In all, 50 of these lungs were successfully transplanted into patients, for a final utilization rate of 86%, Dr. Marcelo Cypel reported at the annual meeting of the American Association for Thoracic Surgery.

The current study builds on a previous report on initial experience with EVLP from the same research team (N. Engl. J. Med. 2011;364:1431-40).

"As we all know, one of the major problems in doing lung transplantation is the organ shortage and the low utilization rates. Only 17% of the lungs from brain death donors and 2% of the lungs from cardiac death donors are used currently," Dr. Cypel said. EVLP lungs accounted for 20% of the transplantations at Toronto General Hospital in 2011.

The EVLP lungs came from 32 brain death donors and 26 cardiac death donors. Dr. Cypel and his colleagues compared the outcomes of these EVLP procedures to another 253 conventional lung transplantations performed at their institution from September 2008 to December 2011.

EVLP patients received a significantly higher percentage of lungs from cardiac death donors, which are generally considered less desirable than lungs from brain death donors. They also received a higher percentage of high-risk lungs from brain death donors (PaO₂/FIO₂ below 300 mm Hg) and more lungs with chest x-ray abnormalities, such as signs of pulmonary edema, compared with the conventional group.

"Donor lungs in the EVLP group were significantly more injured at baseline, however, the outcomes were comparable," said Dr. Cypel, a member of the surgical faculty in the Division of Thoracic Surgery at Toronto General Hospital University Health Network.

For example, posttransplant survival at 1 year was 86% for the EVLP group and 87% for the traditional transplant group in this retrospective study; at 3 years these rates dropped to 70% and 72%. There were no significant differences in survival for patients who received lungs from brain death or cardiac death donors.

Other findings included no significant difference in the rate of primary graft grade 3 dysfunction at 72 hours between groups according to International Society for Heart and Lung Transplantation criteria. The EVLP patients had a trend toward a decreased length of hospital stay, compared with conventional transplant recipients, Dr. Cypel said.

"Again, you and your colleagues have demonstrated the safety and efficacy of using EVLP in the transplantation of lungs that previously would not have been used by your group," said study discussant Dr. R. Duane Davis, director of transplant services at Duke University Health System in Durham, N.C. "Using this technology, we may be able to start applying lung transplant more practically for societal needs."

Dr. Davis asked Dr. Cypel how surgeons at Toronto General Hospital achieved an 86% EVLP utilization rate compared with the 54% rate observed in the U.S. trial and comparable rates in the United Kingdom and elsewhere.

"Our experience with the procedure and extensive laboratory research prior to starting the clinical trial" explain the difference, Dr. Cypel replied. Donor selection criteria also could play a role.

"The important thing is it is taking some of the adventure out of lung transplantation," study coauthor Dr. Shaf Keshavjee said during a separate presentation at the meeting. "Ex vivo lung perfusion is clinically feasible. We can we do a long-term perfusion of lungs outside the body without injuring them. It is possible to keep lung 12 hours outside the body and normothermic."

"We are developing ways to figure out which lungs need a fix and to target treatment to lungs that need treatment," said Dr. Keshavjee, director of the Toronto Lung Transplant program and chair of the Division of Thoracic Surgery at the University of Toronto. Examples include resolution of pulmonary edema and infections through EVLP. Treating infected lungs with lavage and high-dose antibiotics may one day make these organs acceptable for transplantation, even in cases of pneumonia.

The goal is to double or triple the overall number of lung transplants using the EVLP technique in the United States, said Dr. Davis. EVLP comprises 20% of transplants in Toronto, but the overall transplant volume has not increased.

EVLP has allowed the overall number of 100 transplants or so per year in Toronto to remain steady at the same time that organ donation rates have decreased, Dr. Cypel responded.

"The major contribution of EVLP will not be for the large transplant centers like Duke or Toronto, which already use 40% of the organs and for whom a marginal increase is not that large," Dr. Cypel said. "Look at the majority of lung transplant centers that use 10% or less of the offered lungs; that is where we can have a major impact by increasing the number of organs available."

Vitrolife supported the clinical trial. Dr. Cypel and Dr. Keshavjee reported no other relevant disclosures. Dr. Davis said he received research support from Vitrolife for a U.S. study.