Researchers have discovered a new reason why some patients with cancer are able to fight infections associated with chemotherapy treatment, while many others have life-threatening difficulties in overcoming these bacterial attacks.

Their findings reported in Lancet (Vol. 358, No. 9281: 614-618; 637-638) offer the possibility that, in the future, physicians will be able to screen patients to select those most at risk for chemotherapy-related infections, and offer them preventive treatments.

In the first study, British researchers found that those children especially prone to such infection had smaller amounts of a key immune system protein when compared to children who did not suffer excess infections.

That protein, called mannose-binding lectin (MBL), helps activate the immune system at the first sign of infection, and also assists in digestion of bacterial invaders. Patients whose mutated genes produce too little mannose-binding lectin are at risk of complications such as fatal bouts of pneumonia.

Those mutations are quite common in the general population, the researchers say. One-third of people have a single mutation that reduces the level of MBL protein, and 12% have several mutations that produce even less.

“Having those particular genes usually doesn’t make a difference in healthy individuals, but becomes important if they need chemotherapy to treat cancer,” Alan Ezekowitz, MBChB, Dphil, Harvard University pediatrician and immunologist, tells ACS News Today.

“We now have a new way of thinking about how we can prevent their increased risk of infection,” says Ezekowitz, who wrote a commentary on the studies for the Lancet.

A normal side effect of chemotherapy treatment, especially in patients with blood cell cancers, is “neutropenia,” a loss of infection-fighting white blood cells which increases a patient’s risk of developing serious infections. Such infections are responsible for the majority of chemotherapy-related deaths in certain types of childhood and adult leukemia.

But physicians have never been able to tell which cancer patients are most at risk for infection-related complications, and have been able to do little to prevent or treat these infections aside from using antibiotics and injections of certain bone marrow stimulants to increase the production of white blood cells.

In a second study in the same issue of Lancet (pp. 637-638), Danish researchers grouped 54 patients being treated for blood cancers according to whether they had serious infections after chemotherapy treatments. They found consistently lower amounts of MBL protein in the group that had the most infections.

In the larger British study, which looked at 100 children, most of whom were being treated for leukemia, researchers discovered that the amount of MBL protein a child had in their blood correlated with the number of days he or she suffered from a fever brought on by an infection. Children with two copies of a the normal gene had almost twice as much MBL protein in their blood, and infection-induced fevers that lasted fewer days than children who had one or two mutated genes.

Several drugs now exist that boost white blood cell counts in patients, and other so-called “MBL replacement therapies” are being developed. But before physicians begin to screen protein levels in patients, studies need to be conducted that test whether such drugs adequately boost MBL and prevent infections, immunologist Nigel Klein, PhD, leader of the British study, said in an interview.

Klein adds that further research on the protein may offer tantalizing clues in how to improve treatment in other diseases. He reported in his study that “the notion that MBL is able to modulate disease progression in various clinical settings — for example, HIV infection, rheumatoid arthritis, and cystic fibrosis — is gaining support.”

In the meantime, the work on MBL and chemotherapy-induced infections may soon offer a “real clinical advantage” to patients, Herman Kattlove, MD, a medical oncologist and editor at the American Cancer Society, tells ACS News Today.

“If you know in advance that a patient will be susceptible to infection, you may be able to offer treatment a day or two after starting chemotherapy, to prevent the onset or reduce duration of an infection,” Kattlove says.

Editor’s note: R. Alan B. Ezekowitz, author of the commentary, has a financial interest in NatImmune, a biotech company that produces recombinant MBL for therapy against infections in susceptible patients.

Jens C. Jensenius and Steffen Thiel, authors of the Danish study, are cofounders of NatImmune, and they have shares in the company. Their research received no support from NatImmune.