The Sweet Success of Suppression (So Far)
Date: June 28, 2013
On the day of the transplant, Brendan Marrocco’s new hands and forearm came to him courtesy of a donor’s kind family and extraordinary surgery. But what lets Marrocco keep his limbs is no less of a phenomenon. The young man underwent a program of “immune modulation” during and around the time of his surgery that not only lowers rejection risk but also cuts down suppressive medication. The approach overturns the status quo.
“The protocol we use to safeguard these composite tissue grafts is unique,” says transplant surgeon Gerald Brandacher. Developed by the Johns Hopkins team, it has two goals: Keep patients from rejecting complex transplants. Let patients enjoy a near-normal quality of life.
Hands are targets for rejection, Brandacher says, with their skin and blood vessels bringing “an immunological challenge.” Of necessity, then, standard tactics for hand allograft recipients have included a conservative, lifetime cocktail of three highly immunosuppressive drugs. Toxicity and infection, however, are a constant concern.
Marrocco’s treatment underscores the difference. On transplant day, under the new protocol, he received both antibodies and a single immunosuppressant, tacrolimus, to lessen his potential scorched-earth immune response to the graft. Two weeks later, he was infused with donor bone marrow.
“It’s not a bone marrow transplant, where you replace the recipient’s immune system,” Brandacher says. In Marrocco’s case, the goal was to set a fine balance between recipient and donor immune cells. In ways not well understood, the injection reprograms immune response. Recipients’ T cells newly tolerate donor tissue as well as their own. The beauty of that? Marrocco should need only mild medication for life, and steroids only rarely.