Early Blood Signal May Predict Chemo Risk

'Microbe sensor' seems to prevent treatment-related immune trouble

FRIDAY, Aug. 24, 2001 (HealthDayNews) -- The strength of the body's earliest, bred-in-the-bone response to infection may signal which cancer patients are likely to suffer serious immune complications from chemotherapy.

Two new studies show that variations in a blood protein called MBL can predict how bad infections will be during drug treatment for leukemia and other cancers. Both studies appear this week in the journal, The Lancet, and together they suggest that giving MBL to patients might ease their risk of serious infection, experts say.

Infections are a major and potentially life-threatening problem for people with leukemia and other cancers who undergo drug treatment that suppresses the immune system, leaving it particularly vulnerable to hostile microbes. For example, 65 percent of children who die of myeloid leukemia succumb to chemotherapy-related infections.

MBL, or mannose-binding lectin, is like the point man for the immune response, a sort of molecular hand to the ground that picks up the first signs of an attack.

The protein is genetically programmed to identify a vast library of invaders, from bacteria and yeast to viruses, including herpes and HIV, which causes AIDS. In the first minutes or hours of an infection, MBL triggers a basic part of the inflammatory response called the complement system.

Researchers have identified at least seven genetic variations on the MBL theme, which appear to determine how much of the protein people carry in their blood.

In one study, Dr. Nigel Klein and colleagues at the Institute of Child Health in London sought to learn whether the MBL genes of cancer patients influenced their ability to fight off chemotherapy-related infections, known as febrile neutropenic episodes. Neutrophils are blood cells that fight invading organisms, and neutropenia occurs when they are markedly suppressed.

The researchers followed 100 children, ages 1 month to 17 years, who were being treated for various cancers, though almost all involved blood malignancies. About 40 percent of the children had the most common genetic form of MBL, called A/A, which generated the highest levels of the protein, while the rest fell into three other categories that produced less of the molecule.

Children with the most MBL were still vulnerable to the bouts of fever and low neutrophil counts that mark these infections, the researchers say. But they had an average of two episodes over the six-month study period compared with three among those with mutations in the protein.

Those with high MBL also had much shorter bouts of infection, 10 days vs. more than 20 days, than children with less of the molecule.

While baseline MBL may be important, the protein's response to infection could be the key factor in fighting off infection. "It's not just your absolute level that counts, because the protein increases when you need it," says Klein. MBL concentrations in children with the normal gene surged during infection while those with the mutations could muster only a weak response, he says.

The study was too small and too short to figure out whether greater MBL concentrations are linked to a better prognosis, Klein says. However, of the four children admitted to the intensive care unit, only one had the normal MBL gene, and both of the two who died had low levels of the protein.

In the second study, Danish researchers say they found that before chemotherapy begins, low levels of MBL can predict how likely adult leukemia patients were to have severe infections. Compared with 100 healthy people, MBL concentrations in the 54 cancer patients didn't vary a great deal. But the eight patients who developed clinically important infections had much less of the molecule than those who did not suffer such complications.

The researchers speculate that giving cancer patients MBL before they start chemotherapy or during treatment might help prevent serious infections. Two of the authors have founded a company, NatImmune, which is trying to make therapeutic MBL, but the firm did not fund the studies.

Klein says MBL may prove a "quite important" addition to cancer treatment for both children and adults who are particularly vulnerable to chemotherapy-related infection. The rise of drug-resistant bacteria makes the need for a useful immune-boosting agents even more pressing, he says.

"Replacement therapy is a tantalizing possibility," writes Dr. Alan Ezekowitz, a pediatrician at Massachusetts General Hospital in Boston, in an editorial accompanying the journal articles. Ezekowitz says the two papers "herald a new era of defining [infection] risk" for patients undergoing chemotherapy, and that MBL may be only one of many "microbial sensors" that can be exploited.

Ezekowitz says he has a financial stake in NatImmune.

What To Do: To find out more about chemotherapy-related infections, visit the National Cancer Institute. For more on leukemia, try the Leukemia and Lymphoma Society or the Leukemia Research Foundation.

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