Gene signature identifies leukemia patients who should avoid transplants

An international team of researchers led by scientists at Dana-Farber Cancer Institute in Boston have used a gene test to identify certain patients with adult T-cell acute lymphoblastic leukemia (ALL) who can be successfully treated with chemotherapy alone and should not be subjected to the rigors of bone marrow transplants.

Adolfo Ferrando, MD, PhD, and A. Thomas Look, MD, of Dana-Farber, along with collaborators from several institutions in the United States and Israel, found that these patients survived for at least three years after being treated with intensive chemotherapy. The researchers presented their data at the annual meeting of the American Society of Hematology in Philadelphia on Dec. 9.

It was previously known that only slightly over half of the patients with this disease could be cured with chemotherapy. Adult ALL patients often undergo transplants in an effort to beat back the stubborn disease. Until now there was no way to identify those who have a more favorable outlook and shouldn’t undergo risky bone marrow transplantation.

Earlier this year, these scientists, led by Look, reported in the journal Cancer Cell a detailed analysis of the genes involved in the pathogenesis of T-cell ALL measured using high-tech “gene chips” or microarrays.

“The microarray analysis shows that cases of T-cell ALL with expression of HOX11 behave in a very particular way,” says Ferrando. “They have their own genetic program that creates a type of leukemia cell that’s easier to kill with chemotherapy.”

What distinguished the good-prognosis patients was having high activity of a gene called HOX11 in their leukemia cells; those with low HOX11 expression were much less likely to do as well.

The discovery of a gene test could be a major advance for the treatment of the adult T-cell ALL. According to Ferrando, it could ease the dilemma of which patients to treat with transplants and at what point in their disease. “Some say you should wait until a patient relapses [following a first remission achieved with drugs] to transplant, while others say you should transplant them early after achieving the first remission.” And some patients don’t need a transplant at all.

In the study, researchers obtained bone marrow samples from two groups of adult T-cell ALL patients ? one group of 24 patients and another of 30. Of these 54 patients, 16 were found to have the HOX11 genotype. Forty-three of the patients received only chemotherapy and 11 had bone marrow transplants when they were in their first remission.

Four of the HOX11 patients died, three of them from transplant complications. All of the HOX11 patients treated with chemotherapy alone survived for three years, and were most likely cured, while only 53 percent of the patients lacking that gene activity survived for three years.

“Our results demonstrate that these patients with high HOX11 gene activity have an excellent prognosis when treated with intensive chemotherapy and should be spared the toxic effects and early death that can accompany the use of bone marrow transplantation in first remission,” say the researchers.