UF researchers evaluate transfusion treatment for bone marrow transplant patients

May 16, 2001

GAINESVILLE, Fla.—The nation’s blood supply is a precious commodity. But the gift of life is in limited stock, and what exists comes at a price — millions of dollars in annual health-care costs. Patients themselves may pay a physical fee, as repeated transfusions increase their risk of infection or allergic reactions.

Now University of Florida researchers have found there is no danger in waiting longer than usual to administer a certain type of transfusion to cancer patients who have undergone bone marrow transplantation — a discovery that may decrease demands on blood reserves and reduce transfusion-related side effects. They presented their findings May 12 at the annual meeting of the American Society of Clinical Oncology in San Francisco.

Each year, an estimated 40,000 people worldwide undergo bone marrow transplant. The high doses of chemotherapy and radiation these patients receive wreak havoc on platelets — particles manufactured in bone marrow that help blood clot — rendering them prone to potentially lethal complications if platelet levels drop too low. Almost all patients who undergo bone marrow transplant experience some gastrointestinal or urinary tract bleeding, though usually mild. But 10 percent to 20 percent of patients develop major bleeding.

Once platelets dwindle to a certain number, it’s standard practice for doctors to administer platelet transfusions as a preventive measure. Recent studies in leukemia patients who did not undergo transplantation have shown it’s safe to hold off on the transfusions until platelet levels creep even lower. Whether the same could be done for bone marrow transplant patients, who receive more aggressive doses of chemotherapy and radiation and thus are more susceptible to bleeding, hadn’t yet been shown.

“We concluded that either strategy — transfusing at a lower threshold or at the traditional higher one — is safe,” said Dr. John Wingard, a professor of medicine at UF’s College of Medicine and the UF Shands Cancer Center.
“There are times when the number of available blood products is limited in the community. This reassures us we can safely wait to administer a transfusion at the lower threshold without compromising our patients’ well-being.”

The earlier leukemia studies suggested the number of transfusions could be slashed by a third.

“We were hoping we’d duplicate those findings,” he said. “Fewer transfusions would mean less likelihood that patients would get an infection, develop antibodies against platelets or suffer other adverse reactions. Unfortunately, we found we were not able to save on the number of transfusions in these patients.”

The 159 patients in the UF study mostly had leukemia or other cancers of the bone marrow and blood, though some had solid tumors, said Dr. Marc Zumberg, a clinical assistant professor of medicine in the division of hematology and oncology at UF’s College of Medicine and the UF Shands Cancer Center.

Patients were randomly divided into two groups: those who received preventive transfusions when their platelet counts dropped below 20,000 per microliter or those who received transfusions when counts declined to 10,000 per microliter. Platelets normally number in the hundreds of thousands.

At both thresholds, the incidence of bleeding was similar; the group transfused at the 10,000 level did not experience more complications than those transfused at the 20,000 level. However, the group transfused at the lower threshold did not receive fewer transfusions overall. On average, participants in both groups were given about 10 transfusions in the two to three months they received treatment.

“We’re still trying to clarify the reasons, but it seems when bleeding recently occurred there tended to be more transfusions than we expected given if you were in the group that got transfusions at the lower threshold,” Wingard said. “Physicians appeared to be somewhat less confident about delaying transfusions when platelet levels were very low and the patient had experienced recent bleeding, or when the patient had a recent acute illness. Clinicians seemed less comfortable letting platelet levels remain that low.”

In addition, some of the patients in the 10,000 group had their platelet counts checked in the evening, when they were more likely to be lower, possibly elevating their chances of receiving additional transfusions, Zumberg said. Other analyses indicate patients who were receiving a medication to treat fungal infections also were more likely to receive more platelets. There was a trend toward more use of this medicine in the 10,000 arm of the study, Zumberg said, and it is well known that patients receiving the drug are more likely to need platelet transfusions.

“I think a more restrictive strategy of transfusing at a lower threshold is reasonable,” Zumberg said. “We are going to readdress what we will do in our own transplant unit. In a larger study we may be able to show that we can reduce the number of platelet transfusions, or we may need to stratify thresholds based on the type of bone marrow transplant patients receive, because (certain transplant patients) are at lower risk for bleeding.”

Dr. Edmund K. Waller, director of the Bone Marrow & Stem Cell Transplant Center at Emory University Hospital, said he currently uses a platelet threshold of 10,000 for hospitalized patients.

“It’s nice to have a randomized study in transplant patients that supports that,” he said. “These kinds of randomized studies are critically important to providing a scientific basis for medical practice.”