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SAN ANTONIO -- A novel, experimental tandem lung and bone marrow transplant has been a feasible and effective treatment for patients with terminal lung disease who also had primary immunodeficiencies or evidence of bone marrow failure, researchers reported here.

So far, seven patients with end-stage lung disease have been treated with the experimental protocol, which involves bilateral lung transplant followed by bone marrow transplant from the cadaver lung donor, according to the technique's pioneers, bone marrow transplant physician Paul Szabolcs, MD, of Children's Hospital Pittsburgh, and pulmonologist and researcher John McDyer, MD, of the University of Pittsburgh Medical Center (UPMC).

McDyer is scheduled to deliver a talk about the tandem transplant protocol and patient outcomes on Wednesday at CHEST 2018, the American College of Chest Physicians annual meeting.

"There are many primary immune deficiencies and many of them can affect the lungs and lead to end-stage lung disease," McDyer told MedPage Today in a recent interview. "Historically, there has been a huge resistance in the lung community to transplant these patients. Because of this underlying immune deficiency they are thought to be poor candidates for life-long immune suppression."

The first tandem lung-bone marrow transplant was performed by Szabolcs in 2009 at Duke University Medical Center in Durham, North Carolina. The patient was a teenager with a combined immune deficiency disorder. She received bone marrow harvested from her lung donor 4 months after her bilateral lung transplant. The bone marrow fully engrafted and today her immune system is normal.

"Sixteen months after she received the bone marrow, she was weaned off all immunosuppression," McDyer said. "She was 17-years-old when she had her transplants, and she is 8 years out now. She graduated college and got married. She is cured."

Four patients have now received the tandem transplant protocol at UPMC, and a fifth has had her lung transplant and will soon have her bone marrow transplant, McDyer said.

Three transplants were performed in patients with primary immunodeficiencies and end-stage-lung disease. The patients included a girl, age 14 years, with IL-7R deficiency, a female, age 39, with Common Variable Immunodeficiency (CVID), and a male, age 38, with Severe Combined Immunodeficiency (SCID).

Two of the three patients successfully engrafted donor bone marrow. The teenage girl has been off all immunosuppression therapy for over a year. The male patient failed to engraft the donor bone marrow, but was doing well 16 months post-lung transplant.

A fourth patient (male, age 20) with interstitial lung disease and myelodysplastic syndrome with monosomy 7 and short telomeres had very advanced lung disease, bone marrow failure, and myelodysplastic syndrome when referred to UPMC by St. Jude Medical Center in Fullerton, California.

"On the morning we found lungs for him, his platelet count was 16,000 and he was also neutropenic," McDyer said. "It was a rough surgery and post-op, but he went home on room air and his lung function continues to improve. He got his bone marrow transplant in July and he's fully engrafted."

Pulmonologist Marie Budev, DO, MPH, who directs the Cleveland Clinic Lung Transplant and Heart and Lung Transplant Program, told MedPage Today that the tandem lung-bone marrow transplant may be an especially promising protocol for interstitial pulmonary fibrosis patients with telomere mutations, as their disease course often involves anemia, liver cirrhosis, and other complications in addition to fibrosis.

"What if instead of putting these patients on tons of immunosuppression, which will only make their anemia worse, we could routinely do bone marrow transplants and make these drugs unnecessary?" she said. "This would be revolutionary."

Budev said the protocol could eventually be used in an even larger population of lung transplant patients to allow them to avoid life-long immunosuppression.

For now, McDyer said that it will be used only in the sickest patients with end-stage lung disease and bone marrow irregularities who have no other treatment options.

"What we are talking about at this stage is salvage transplants for patients with immune deficiency, or patients with advanced bone marrow abnormalities. These are patients that nobody else would transplant," he said.

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