New test could discern serious condition early after bone marrow transplant

Protein level in blood reveals graft-versus-host disease, may indicate severity of this complication

A new blood test can discern whether a skin rash signals a high-risk complication or just a minor nuisance in people who have undergone a bone marrow transplant, researchers report in the Jan. 6 Science Translational Medicine. The test may also identify early on which patients face long odds and need aggressive treatment for the complication.

TELLTALE BIOMARKER Skin cells from people who underwent a bone marrow transplant show excess elafin protein (orange) in a person with graft-versus-host disease (right) compared with a person without the complication. Increased elafin levels in the blood may indicate who has GVHD and predict its severity. James Ferrara/University of Michigan

As if marrow transplant recipients don’t have enough problems, some patients also develop graft-versus-host disease. In this condition the newly transplanted, or grafted, bone marrow cells attack tissues in the body.

In most cases of GVHD, the patient breaks out in a rash, although the complication can also strike the liver and intestines. Unfortunately, it’s not always apparent whether a rash signifies GVHD or a milder reaction. A skin biopsy can tell them apart, but it’s time-consuming and requires tissue sampling. A blood test could optimize diagnosis and management of GVHD, but there is currently no reliable blood test that discerns GVHD from an innocuous rash.

Doctors treat GVHD with steroids, and many administer these strong drugs if any rash appears without waiting for biopsy results since controlling GVHD early can keep it from getting out of control, says coauthor and pediatric hematologist James Ferrara of the University of Michigan in Ann Arbor. Roughly half of deaths related to marrow transplants stem from GVHD or its complications, he notes, so there is pressure to keep it under control.

Ferrara and a team of researchers measured the amounts of 66 proteins in the blood of transplant patients, some of whom had rashes that biopsies showed were GVHD. In these patients, a protein called elafin showed up at concentrations three times greater than in people who did not have GVHD.

The researchers then compared 20 other marrow recipients. All had rashes that appeared about a month after transplant, but biopsies had shown that 10 patients had GVHD and 10 patients were experiencing a reaction to antibiotics. Those with GVHD had nearly four times as much elafin circulating in their blood as did the others. The outer skin of GVHD patients also showed elevated elafin concentrations.

Blood samples from 492 people who underwent a marrow transplant between 2000 and 2008 confirmed these results. The scientists then tracked the progress of 159 patients within this group who had skin-rash GVHD. Those with lower blood elafin levels when GVHD was diagnosed were 71 percent more likely to be alive five years after transplant than those with higher levels. The scientists adjusted for factors such as age and how closely the donor’s marrow matched the recipient’s.

Elafin concentrations might be a tip-off for the potential severity of skin-rash GVHD, says Joseph Antin, a hematologic oncologist at Harvard Medical School and the Dana-Farber Cancer Institute in Boston. “It gives you a heads up on who may get into trouble. If this is the tip of the iceberg, then presumably I could treat them more aggressively than I would have.”

Bone marrow transplant is typically a last-resort measure for people with leukemia, lymphoma or other illnesses. The procedure requires radiation or chemotherapy, or both, to wipe out the patient’s bone marrow cells, which are replaced by blood stem cells from a donor’s marrow or gleaned from the donor’s blood. These stem cells form the basis for new blood cells, both white and red, and platelets in the recipient.

But the new white blood cells, which are immune cells, sometimes mutiny within their new body, and that’s GVHD. Steroids that suppress immunity can contain GVHD, but these drugs carry side effects and weaken an already-depleted immune system — leaving a patient vulnerable to infection.

“I believe this biomarker will be used when we’re not clear what the diagnosis is,” Ferrara says. He also hopes that elafin levels and possibly other biomarkers in the blood will improve GVHD treatment to the point of making bone marrow transplant more accessible. Some people, especially those with sickle cell disease, could benefit from a transplant but don’t want to risk the complications.

More Stories from Science News on Health & Medicine