S-phase fraction as a useful marker for prognosis and therapeutic response in patients with aplastic anemia
aDepartments of Medicine, bPathology, and cBiochemistry, CSM Medical University and the dCentral Drug Research Institute, Lucknow, Uttar Pradesh, India
Tripathi AK, Tripathi P, Kumar A, Ahmad R, Singh RK, Balapure AK, Vishwakermad AL. S-phase fraction as a useful marker for prognosis and therapeutic response in patients with aplastic anemia. Hematol Oncol Stem Cel Ther 2008; 1(4): 216-220.
BACKGROUND: The functional definition of aplastic anemia (AA) is the failure of hematopoietic stem cells to proliferate. The aim of the present study was to analyze the S-phase fraction (SPF) (proliferative activity) in patients with AA at diagnosis to explore its relationship with disease characteristics and its value in discriminating among patients with different prognoses. We also investigated whether the SPF value influenced the response to immunosuppressive therapy in AA patients.
PATIENTS AND METHODS: The analysis of SPF at the time of diagnosis was carried out by flow cytometry on peripheral blood samples from 53 consecutive patients with AA and 30 age- and sex-matched controls. All patients were given cyclosporine and followed up periodically to determine response to therapy.
RESULTS: Based on the median SPF, AA patients were divided into two groups: patients with SPF ≤0.59% (n=27) and patients with SPF >0.59% (n=26). An SPF >0.59% was associated with advanced age (P=.02) and elevated serum LDH level (P=.01). Patients with an SPF >0.59% also had a higher incidence of paroxysmal nocturnal hemoglobinuria and cytogenetic abnormalities. During a median follow-up of 18 months, 3.7% of patients with SPF ≤0.59 and 11.5% of patients with SPF >0.59% developed dysplasia and one patient with SPF >0.59% converted into AML. A significantly higher (P=.018) overall response rate of 53.9% was found in patients with SPF >0.59% versus 22.2% of patients with SPF ≤0.59% at 6 months.
CONCLUSIONS: Independently of the peripheral blood count, the SPF at diagnosis may provide information on the expected response to immunosuppressive therapy and the propensity for disease to evolve into MDS/AML. Hence, SPF may serve as an early indicator for the evolution of MDS/AML in patients with AA and thus contribute to therapeutic decisions.