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Flu May Trigger Childhood Leukemia

Kids who get the flu may suffer a very rare side effect: childhood leukemia, a new study suggests.

The study shows that just a few months after two especially severe flu outbreaks in the U.K. there were sharp peaks in cases of acute lymphoblastic leukemia (ALL), a form of childhood leukemia.

This is not proof that flu causes any kind of cancer in children, stresses study leader Michael Murphy, MD, director of Oxford University's Childhood Cancer Research Group. But the findings support theories that flu and other infectious diseases might play a role in the ongoing slow-but-steady increase in ALL.

"There has been a long, slow increase in a certain kind of childhood leukemia that hasn't been seen for other types of leukemia," Murphy tells WebMD. "We need to figure out what is causing this. The observations about flu, we think, will encourage further investigation into whether that very common childhood phenomenon -- contact with infections -- is a determinant of rare cases of childhood leukemia."

Leukemia is cancer of the white blood cells. Childhood leukemia is a collection of different diseases with different causes. ALL is the largest subgroup of childhood leukemia, and common ALL (cALL) is most frequent. It's most likely to occur between ages 1 to 6 years, and peaks at age 2-3.

Scientists don't know what causes cALL, but they think it must be a combination of several things. One leading theory comes from leukemia researcher Mel Greaves of London's Institute of Cancer Research.

The 'Two-Hit' Theory

Greaves theorizes that it takes two "hits" for a child to get cALL. The first hit is some unknown thing -- a genetic predisposition, for example, or some toxic encounter before or shortly after birth. The second hit is an infection that hits an unusually vulnerable child in an unusual way.

"It is all a bit murky," Murphy says. "Greaves suggests that what might be happening is that something stimulates a child's immune system at an inappropriate time -- later than it should or when the immune system is unprimed and sensitive. In any case, there are these rare exceptions to the rule when you get a disordered response to a particular stimulus."

Might that "second-hit" stimulus be flu? Murphy's team looked at all cases of childhood leukemia in the U.K. from 1974 to 2000. Unlike other childhood leukemias, ALL steadily increased over this time. That, Murphy says, could be hit No. 1.

Flu Epidemics and Leukemia

During the period, there were two sharp upswings in ALL. One was in 1976; the other was in 1990. In both years -- just a few months before each of these peaks -- there were flu epidemics in the U.K. There were no other flu epidemics, and no similar ALL peaks, in any other year.

"We wonder whether there may be a cause-and-effect relationship here," Murphy says.

It's not an outlandish theory, says Hanna Khoury, MD, director of the leukemia program at Winship Cancer Center at Emory University in Atlanta.

Khoury notes that a virus called HTLV-1 directly causes a kind of leukemia. And Burkett's lymphoma can be triggered by reactivation of latent Epstein-Barr virus infection. Moreover, previous studies have shown a seasonal variation in ALL cases, with more cases seen in the winter months that include flu season.

"Do we know flu virus causes leukemia? No," Khoury says. "We don't know what causes ALL. … But this study may open new investigations looking at the role viruses play, especially influenza virus."

Khoury notes that even if flu viruses do play a role in ALL, it’s a rare event. Lots of kids get the flu every year. But only five out of every 100,000 children get ALL.

By Daniel J. DeNoon, reviewed by Louise Chang, MD

SOURCES: Kroll, M.E. Journal of the National Cancer Institute, March 15, 2006; vol 98: pp 417-420. Michael Murphy, MD, director, Childhood Cancer Research Group, Oxford University, England. Hanna Khoury, MD, director of the leukemia program at Winship Cancer Center, Emory University, Atlanta.