Role of S-Phase Fraction in Differentiating Aplastic Anemia from Hypoplastic Myelodysplastic Syndrome

Among the patients with bone marrow hypoplasia, differentiating aplastic anemia (AA) from hypoplastic myelodysplastic syndrome (HMDS) can be a difficult and challenging task because of the considerable clinical, cytological and histological similarities between these two disorders. The distinction between AA and HMDS is important because the clinical course and management of these two entities differ. There is a higher risk of progression to acute leukemia in patients with HMDS compared with AA. Various attempts have been made in the past to differentiate these entities. Different patterns of proliferation of bone marrow cells in AA and HMDS have been reported in past using proliferating cell nuclear antigens (PCNA). S-Phase Fraction (SPF) reflects the cellular proliferation and has been proven to be a useful diagnostic and prognostic marker in various hematological malignancies and solid tumors. In the present study, we examined whether flow cytometric analysis of SPF could be used as a tool to differentiate AA from HMDS.

The study group comprised of 25 consecutive patients with AA, 18 patients with HMDS diagnosed on the basis of peripheral blood and bone marrow findings along with 30 age and sex matched healthy controls. The mean age of AA patients and HMDS patients was 27.1 ± 12.7 years (range 13–65 years with median age of 23 years) and 38.8 ± 20.6 years (range 15–75 years with median age of 32.5 years) respectively. The most common clinical presentation in patients with AA and HMDS was anemia. Other manifestations were bleeding and pyrexia. No etiological association could be made in any of these cases. Peripheral blood leucocytes were stained with propidium iodide and analyzed for SPF through flow cytometry using Modfit-LT V 3.0 software.

The mean SPF value in the patients with AA and HMDS was 0.49 ± 0.33% and 0.79 ± 0.28% respectively. The mean SPF value in control subjects was 0.67 ± 0.22%. The SPF value in patients with AA was significantly lower than that of control (p=0.01) whereas there was no significant difference in SPF values in patients with HMDS and control subjects. The SPF value was statistically significant higher in HMDS patients as compared to AA (p=0.003). During follow-up, 3 patients (12%) with AA have revealed the evidence of dysplasia on repeat bone marrow examination. These patients had high SPF values as compared to the median SPF value in AA patients.

We conclude that SPF value may be an important parameter in patients with AA to predict their propensity to evolve into HMDS. SPF value may also be useful in the early diagnosis of HMDS before morphologically evidence of dysplasia is apparent.