DNA aneuploidy study for early detection of chromosomal abnormality in patients with aplastic anemia: prognostic and therapeutic implications.

Background: Undetected aneuploidy exists in a large percentage of patients with aplastic anemia at the time of diagnosis, which may not be identified by conventional cytogenetics. The presence of aneuploidy at any time in the clinical course implies poor prognosis in such patients. This warrants a need for the early detection of chromosomal abnormalities for prognosis and delineation of therapeutic modalities.

Patients And Methods: Fifty patients with aplastic anemia and 30 controls were studied with an aim to determine the role of aneuploidy as an indicator of chromosomal abnormalities. DNA aneuploidy analysis was carried out by flow cytometry using Mod Fit-LT V3.0 software, whereas chromosomal analysis was performed by conventional cytogenetics.

Results: DNA aneuploidy was present in 14% of cases and chromosomal abnormalities were found in 4% of cases of aplastic anemia at the time of diagnosis before therapy. Overall, DNA aneuploidy was detected in 36% of cases by flow cytometry, whereas the cytogenetic method revealed chromosomal abnormalities in 14% of cases of aplastic anemia. Flow cytometric analysis showed hypodiploidy in one patient at the time of diagnosis who developed monosomy 7 during follow-up. All patients with hypodiploidy had short survival and they did not respond to therapy.

Conclusion: The present study demonstrates the role of flow cytometry in the early detection of chromosomal abnormalities in patients at a time when they remain undetected by conventional cytogenetics. The presence of DNA aneuploidy in patients with aplastic anemia may be an early indicator of subsequent overt cytogenetic abnormality, associated with poor response to immunosuppressive therapy and a lower survival.