Abnormal chromosomes forecast leukemia relapse

June 16, 2004

COLUMBUS, Ohio - Patients with acute myeloid leukemia (AML) who enter remission with abnormal chromosomes in bone marrow cells are twice as vulnerable to recurrence of their disease as are AML patients with normal bone marrow cells at remission, according to a new study.

The findings by researchers at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute call for routine testing for chromosomal abnormalities in AML patients at diagnosis and again when patients enter remission.

If verified, the findings mean that AML patients showing chromosomal abnormalities early during remission should be considered for more intensive treatment, such as a bone marrow transplant, in an attempt to prevent a return of the disease. Patients with normal-looking chromosomes can receive standard therapy.

The findings are published in the June 15 issue of the Journal of Clinical Oncology.

"For the first time, we have shown in a relatively large group of patients that someone with AML who has abnormal chromosomes early during remission will relapse, even if blood counts and other parameters are favorable," says first author Guido Marcucci, associate professor of internal medicine and a hematologist/oncologist with OSU's James Cancer Hospital.

Since 1990, physicians have said that AML patients were in complete remission following treatment if their blood count was normal, and their bone marrow contained fewer than 5 percent of immature cells known as blasts.

By that definition, 60 percent to 70 percent of AML patients achieve complete remission, but only 30 percent to 40 percent of those patients remain in remission long enough to be considered completely cured of their disease.

"Achieving complete remission is an important step for a successful treatment," Marcucci says, "but it does not predict who will do well in the long run and who will relapse. We need additional diagnostic indicators like the presence of abnormal chromosomes."

The study of abnormal chromosomes is known as cytogenetics. Chromosomal, or cytogenetic, abnormalities are seen at diagnosis in about 55 percent of all AML patients. The remaining 45 percent have normal-looking chromosomes, or normal cytogenetics.

The presence of cytogenetic abnormalities at diagnosis has long proven to be one of the most important prognostic factors for AML. Furthermore, the sensitive technology and methods needed for cytogenetic testing, which were formerly found mainly in research laboratories, are now widely available for use in clinical tests.

This retrospective study examined the outcomes of 118 AML patients who had received cytogenetic testing at the time of diagnosis and at the first day of complete remission.

Of these, 103 patients had abnormal chromosomes at diagnosis and normal chromosomes at complete remission. These patients were compared to 15 others who had abnormal chromosomes at both diagnosis and at complete remission.

The results showed that patients with abnormal chromosomes at remission had a significantly shorter survival. They were twice as likely to relapse and die.

Based on their findings, the researchers concluded that converting from abnormal chromosomes to normal chromosomes at remission is an import predictor of long-term outcome in AML, and supports the use of cytogenetics testing at remission.

"These findings indicate that the old definition of remission isn't good enough," Marcucci says. "We need to include cytogenetic complete remission as a criterion for complete remission in AML."

Funding from the National Cancer Institute supported this research.
-end-


Ohio State University

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