Cancer patients receiving bone marrow transplants at University of Colorado Hospital are the first in the region to benefit from a proven technology that wipes out pathogens in blood platelets. UCH took its first delivery of treated platelets, which are vital to blood clotting, from the Bonfils Blood Center in Denver on July 25.
Call it a zapper of microscopic bugs, including Zika, dengue, chikungunya, hepatitis B and C, West Nile, E. coli, Salmonella, Staph, Listeria, and many others known and otherwise. The Intercept process also stops lymphocytes – a type of white blood cell – that can attack organs in stem cell transplant recipients and cause graft-versus-host disease.
Long time coming
The technology, while remarkable, is far from experimental. The U.S. Food and Drug Administration first approved the Cerus Intercept for platelet as well as plasma donations in December 2014 – 12 years after the Intercept earned the CE Mark in Europe. In March, the agency followed up with the platelet-in-plasma approval that Bonfils and UCH were waiting for.
Bonfils has been tracking the technology for years and has been working with Cerus on an experimental basis since 2013, said Crystal Stanley, Bonfils’ production manager. Mary Berg, MD, UCH’s medical director of Transfusion Services, also has been following the technology for years. For one thing, recent FDA guidance suggests it may allow hospitals to store platelets longer prior to transfusion if they’re treated with Intercept. But Berg has been interested for an even more important reason.
“I’ve seen bacterial contamination in platelets and I’ve seen people die from it, so I’ve seen how horrible it can be,” she said.
None of those deaths were at UCH, she said. But the impact of such infections at other places has reached far beyond patients and their loved ones. Berg related her knowledge of a case in which bacteria introduced via a platelet unit killed a teenage patient. The nurse who had administered the transfusion quit her job, Berg said.
“She couldn’t hang another platelet bag,” she said.
Platelets are the most infection-prone of blood products. The apheresis process (which separates the platelets from other blood components, which flow back to the donor) evicts infection-fighting white blood cells. And for good reason: White blood cells can cause a variety of problems, from febrile transfusion reactions to graft-versus-host disease. Second, platelets are stored at room temperature, which is unique among blood products.
“Platelets stored in plasma are a great culture medium for bacteria,” Berg said. “They just have a party – they’re happy to grow.”
The same holds for other pathogens. What’s good for them is bad for patients, particularly those with suppressed immune systems recovering from intense chemotherapy. Anywhere from 1 in 1,500 to 1 in 5,000 platelet units is contaminated with bacteria, depending on the estimate; for patients receiving more than one unit, the risk rises accordingly.
And so Bonfils has followed strict procedures to minimize that risk. Tests for known viruses such as HIV and hepatitis B and C happen on “day zero,” just after the donor unplugs. The platelets then wait a day post-draw for bacterial screening.
The result is that UCH and the dozens of other Colorado hospitals to whom Bonfils delivers blood products don’t receive platelet units until day two or day three post-draw. Given that contamination risk rises with time, a platelet unit’s shelf life is a maximum of five days under the current regimen, and the FDA is leaning toward cutting that to four days, Berg said.
“Managing our platelet inventory is a real challenge,” Berg said, “and if we have to throw them away on day four, it’s going to make it even worse.”
The Cerus Intercept could change that. In recent guidance, the FDA said platelets repeat-tested with a bacterial test called Verax PGD or units treated with the Cerus Intercept could be kept for a full seven days, Berg said.
How it works
The Intercept system would seem fantastical if it didn’t actually exist. Bathe mustard-colored units of platelets in a tailored form of psoralen – a plant-derived compound found in citrus fruit and celery – expose it to a precise, gentle dose of ultraviolet-A light for approximately five minutes, and about every living cell or semi-living virus is permanently disabled. Filter out the synthetic psoralen to trace levels and the platelet unit is ready to go.
The synthetic psoralen, called amotosalen, penetrates cell walls and nuclei, glomming onto DNA and RNA. The UV light triggers a chemical reaction that in essence welds amotosalen bars willy-nilly between and among DNA and RNA strands, thwarting replication. Platelets, which don’t contain DNA, are immune to such interference.
There’s a premium for such platelet units — $135 on top of the industry-standard $550 for an untreated bag.
The benefits go beyond patient safety, though. Patients receiving the Intercept units seem to have fewer complications, not just with respect to infections, but also in terms of febrile transfusion reactions, in which patients spike a fever when transfused. When that happens, clinicians stop the transfusion.
“So you end up wasting that product,” Berg said. “To have fewer transfusion reactions means cost savings to the hospital.”
Intercept units also need no irradiation, a standard process to kill white blood cells lingering in platelet units. Irradiation is standard for platelets destined for transplant patients. UCH irradiates its own platelet units delivered from Bonfils, but Bonfils does it for many hospitals.
Patient safety, not to mention peace of mind, is Intercept’s biggest draw. It’s as much about dealing with familiar scourges as emerging ones such as Zika, Berg said.
“With this type of pathogen inactivation technology, we don’t have to worry about the next virus,” she said.