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Chromosomal Abnormalities Predict Poor Outcome in Multiple Myeloma

Chromosomal Abnormalities Predict Poor Outcome in Multiple Myeloma

LITTLE ROCK—Deletion of chromosome 13 and hypodiploidy are major
independent predictors of poor prognosis in multiple myeloma, according to a
study involving close to 1,500 multiple myeloma patients (ASCO abstract
1054). "Chromosomal studies are the most important prognostic factor in
the treatment of myeloma," said lead investigator Guido J. Tricot, MD,
PhD, head of the Academic Division of Myeloma Transplant, Myeloma Institute
for Research and Therapy, at the University of Arkansas for Medical Sciences
in Little Rock. "Chromosome 13 deletion and hypodiploidy are associated
with poor prognosis, but too many institutes are failing to do these studies
which can predict outcome and help customize treatment."

Although Dr. Tricot’s team has previously shown the adverse effect of
chromosome 13 abnormalities, other researchers have suggested that
hypodiploidy is the major prognostic factor in multiple myeloma. To confirm
the relative effects of these markers, this study examined the outcome of
1,475 multiple myeloma patients who received their first transplant before
July 1, 2000.

In this patient population, median age was 54 years, median
beta-2-microglobulin was 2.3 mg/L, median C-reactive protein was 5.0 mg/L,
and 40% had received more than 12 months of standard dose chemotherapy.
Cytogenetic analysis revealed: hypodiploidy in 131 patients, including those
with hypodiploid or hypotetraploid karyotype; pseudodiploidy in 82 patients;
hyperdiploidy in 278 patients; and normal karyotypes in the remainder.

Risk-Adjusted Strategy

"Cytogenetic analysis is clinically important as a prognostic
factor, and it is the most important single factor to predict the outcome of
multiple myeloma," Elias J. Anaissie, MD, told ONI. He is coauthor of
the study and professor of medicine and director of supportive care at the
Myeloma Institute for Research and Therapy, University of Arkansas for
Medical Sciences. "Our group uses a risk-adjusted strategy to optimize
treatment. For patients with unfavorable genetics, we use a different
approach."

Since event-free and overall survival were similar in pseudodiploid and
hyperdiploid patients, these subgroups were combined into a nonhypodiploid
group. Outcome was significantly worse in patients with hypodiploid than
with nonhypodiploid or normal karyotypes. Median event-free survival was 10
months in hypodiploid patients, 19 months in nonhypodiploid patients, and 28
months in those with normal karyotypes (P < .001). Median overall
survival was 19 months in hypodiploid patients, 36 months in nonhypodiploid
patients, and 56 months in those with normal karyotypes (P < .001).

Regardless of ploidy status, patients with chromosome 13 deletion had
similarly poor outcomes. Among patients with chromosome 13 deletion, median
event-free survival was 12 months for those with hypodiploidy and 12 months
in those with nonhypodiploidy, and median overall survival was 17 months and
22 months, respectively. Five-year event-free survival was 9% in those with
hypodiploidy and 7% in those with nonhypodiploidy, and 5-year overall
survival was 17% and 22%, respectively.

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