ABSTRACT
AIM: It is often difficult and challenging task to differentiate aplastic anemia (AA) from hypoplastic myelodysplastic syndrome (HMDS) among the patients with bone marrow aplasia. This is possibly because of the considerable clinical, cytological and histological similarities between these two disorders. As prognostic and therapeutic approach to AA and HMDS are different, it is imperative to differentiate them at the time of initial diagnosis. Various attempts have been made in the past to differentiate AA from HMDS. In the present study, we explored the value of certain new parameters i.e. S-phase fraction (SPF) and aneuploidy that could be used for this purpose. MATERIALS AND METHODS: The study included 46 consecutive patients with aplastic anemia, 15 patients with HMDS along with 32 age and sex-matched control subjects. S-phase fraction and aneuploidy analysis was carried out by flow cytometry using Mod Fit-LT V3.0 software. RESULTS: The mean SPF value was significantly lower (p=0.02) in patients with AA and higher (p=0.01) in HMDS as compared to that of the control. Aneuploidy was present in 15.2% patients with AA and in 33.3% HMDS cases. During follow-up, 4 patients with AA developed MDS, out of these, three patients had aneuploidy as well as high SPF value at the time of diagnosis. Two patients with HMDS who had aneuploidy and high SPF, converted into AML. Eleven patients died during the study, in whom 8 had aneuploidy and high SPF value. CONCLUSION: We conclude that high SPF value and presence of aneuploidy favour the diagnosis of HMDS rather than AA. SPF and aneuploidy may be important parameters in patients with AA to predict their propensity to evolve into myelodysplastic syndrome and acute myeloid leukemia. SPF value may also be useful in the early diagnosis of HMDS before morphologically evidence of dysplasia is apparent.
ABSTRACT
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.
