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Clonal evolution predicts myelodysplastic syndrome progression
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Cytogenic clonal evolution had an adverse effect on disease progression and OS in patients with myelodysplastic syndrome, according to a retrospective analysis published in Cancer.
“The unfavorable prognostic impact of cytogenetic clonal evolution suggests that serial karyotype analysis should be performed, especially in patients with lower-risk or intermediate-risk myelodysplastic syndrome (MDS), to identify those individuals with an unfavorable prognosis who may benefit from earlier or more intensified treatment,” Judith Neukirchen, MD, professor of hematology, oncology and clinical immunology at Heinrich-Heine University in Germany, and colleagues wrote.
Previously, the prognostic impact of chromosomal aberrations had been evaluated only based on their presence at the time of diagnosis. Studies by Bernasconi and colleagues and Jabbour and colleagues demonstrated that clonal evolution occurs more frequently in patients with higher-risk MDS and is significantly associated with inferior prognosis.
Neukirchen and colleagues used the Dusseldorf MDS Registry to retrospectively evaluate the impact of cytogenetic clonal evolution in a group of 549 patients (median age, 63 years; 62.4% men) with at least two karyotype analyses (median, 3 per patient).
The median time between the first and second karyotype analyses was 8.4 months, and median observation time was about 142 months.
Median OS for the entire cohort was 45 months.
Researchers reported clonal evolution in 24% (n = 131) of the study group, which included 19% of patients undergoing allogenic hematopoietic stem cell transplantation, 39% of patients receiving cytotoxic chemotherapy, 40% treated with epigenetic drugs, 33% treated with immunomodulatory treatment, and 18% of patients receiving best supportive care.
To exclude the impact of disease-modifying treatment, researchers restricted the OS analyses to patients receiving best supportive care.
Seventy-nine of the 294 patients (27%) assigned best supportive care progressed to acute myeloid leukemia.
Clonal evolution increased risk for leukemic transformation (HR = 2.23; 95% CI, 1.05-4.73) and poor OS (HR = 3.67; 95% CI, 2.65-5.08).
Patients with subclones detectable at the time of diagnosis demonstrated shorter OS and a higher 5-year probability of AML progression (30% vs. 22%).
“The study demonstrates that clonal evolution and, to a lesser degree, the presence of subclones at the time of diagnosis, have an unfavorable influence on survival and progression to AML,” Neukirchen and colleagues wrote. “Cytogenetic clonal evolution is a frequent event in patients with MDS, as well as those with other myeloid malignancies and, similar to the development of point mutations, reflects the heterogeneous and dynamic nature of the disease.” – by Chuck Gormley
Additional references:
Bernasconi O, et al. Ann Hematol. 2010;doi:10.1007/s00277-010-0927-z.
Jabbour E, et al. Am J Hematol. 2013;doi:10.1002/ajh.23513.
Disclosures: Neukirchen reports travel expenses from Bristol-Myers Squibb and Celgene and honoraria from Janssen. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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