More Chemotherapy May Help after Initial Treatment for Childhood Leukemia Fails

Adapted from the NCI Cancer Bulletin.

A small percentage of children diagnosed with acute lymphoblastic leukemia (ALL) responds poorly to initial chemotherapy. When this initial treatment, called induction therapy, fails to induce a complete clinical remission, most leukemia experts would recommend an allogeneic stem cell transplant. However, a new study suggests that at least some of these children may do better if they receive additional chemotherapy rather than a stem cell transplant.

Reporting their findings in the April 12, 2012, New England Journal of Medicine, the researchers noted that doctors can cure 8 in 10 children newly diagnosed with ALL. But certain subgroups of patients tend to do worse than others. For instance, patients whose cancers do not go into complete clinical remission after 4 to 6 weeks of induction therapy are at high risk for poor outcomes.

To determine the optimal treatment for these patients, the researchers analyzed data on more than 44,000 children who participated in ALL clinical trials around the world. Of these children, 1,041 had cancers that responded poorly to induction therapy. Most of these patients went on to have a stem cell transplant, but some received only additional chemotherapy.

A subset of the children whose cancers did not respond to induction therapy unexpectedly showed better long-term survival with chemotherapy alone than with stem cell transplantation. These children were younger than age 6, had precursor B-cell ALL rather than T-cell ALL, and had no other high-risk clinical or genetic features.

More than 70 percent of the children in the subgroup that received additional chemotherapy rather than a stem cell transplant survived at least 10 years, which was more than twice the survival rate of the entire group of patients who did not respond to induction therapy.

“This study tells us that the failure of induction therapy should no longer be considered an automatic indication for a bone marrow transplant,” said co-author Ching-Hon Pui, M.D., chair of the St. Jude Children’s Research Hospital department of oncology. “[But]a 72 percent survival rate is still not acceptable, and we need to find better ways to treat these patients,” he added.

The study also demonstrates “the power of large collaborative efforts to discover important new insights into disease,” said Karen Rabin, M.D., of Baylor College of Medicine, who wrote an accompanying editorial. The benefit of chemotherapy for these patients emerged only after 14 research groups on three continents combined their results.