Chromosome losses can signal an especially poor response to therapy

May 13 2004

A new international study of children with a severe form of acute lymphoblastic leukemia (ALL) shows that certain chromosome losses can signal an especially poor response to therapy, but that other chromosome abnormalities have no effect on treatment survival.

The finding should enable doctors to identify patients with severe ALL for additional or experimental therapies when such therapies become available. The study was published in the April issue of the journal Leukemia.

“Overall, we found that many chromosome abnormalities in our group of patients made no difference at all, although particular abnormalities could,” says Dr. Nyla A. Heerema, a researcher with The Ohio State University Comprehensive Cancer Center– Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, and first author on the study.

“The results surprised us,” she says. “We expected that additional chromosome abnormalities would mean a worse outcome.”

The retrospective study involved 249 children diagnosed with ALL between 1986 and 1996 by 10 medical centers in the United States and five other countries. The children had received intensive chemotherapy and their disease had gone into complete remission.

All the children had cancers showing the Philadelphia chromosome, an alteration in the genes that indicates a poorer response to treatment. Sixty-one percent of the patients (153), showed secondary chromosome abnormalities; that is, abnormalities present in addition to the Philadelphia chromosome.

Heerema and her colleagues wanted to learn if secondary chromosome abnormalities contributed to a poor prognosis in children with ALL. They found that having most secondary chromosome abnormalities had little affect on a child’s prognosis. It did, however, when they involved the loss of chromosome 7, or the part of it known as 7p, or the loss of a part of chromosome 9 known as 9p.

Among children with cancer cells that were missing one or both of these, only 15 percent were still disease-free five years after entering remission.

On the other hand, 31 to 43 percent of children with intact chromosomes 7 and 9 remained disease-free at five years. That rate held true even when other chromosome abnormalities were present.Surprisingly, cases of this kind of leukemia that showed a second Philadelphia chromosome also did better than all cases combined. ALL is the most common childhood leukemia, and it accounts for about one-fifth of all acute leukemias in adults. About 80 percent of children with ALL have a curable form of the disease, while the others respond less well to therapy, sometimes depending on which chromosome changes are present.

The Philadelphia chromosome, which occurs in 2 to 5 percent of children with ALL, is an abnormal chromosome that sometimes occurs in several types of childhood and adult leukemias. It arises when a piece of chromosome 9 fuses with a chromosome 22. The fusion results in an abnormal protein that plays an important role in the malignancy.

Grants from the National Cancer Institute and from the governments of participating countries supported this research.

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute is a founding member of the National Comprehensive Cancer Network. The James Cancer Hospital is consistently ranked by U.S. News & World Report as one of America’s best cancer hospitals.