The differential diagnosis between aplastic anemia and hypocellular myelodysplasia in patients with pancytopenia.

Sir, The differential diagnosis between hypocellular myelodysplasia (h-MDS) and aplastic anemia (AA) may be diffucult.1-5 In the present study we looked for new parameters that could be used for this purpose. Adult patients with pancytopenia and hypocellular bone marrow were studied. The criteria for h-MDS were: >5% of blasts in BM smears, ALIPs in BM sections, clonal cytogenetic abnormality or at least two of the following parameters: 1. blasts in the peripheral blood; 2. ring sideroblasts; 3. atypical granulocytic precursors or megakaryocytes. BM sections were analyzed for number of factor VIII positive cells. Cellularity was classified as: 1. pronounced hypocellularity; 2. highly variable cellularity ranging from normocellular areas to markedly hypocellular ones; 3. moderately decreased hemopoiesis. Significant (p<0.05) parameters were included in a stepwise linear discriminant analysis (LDA) (criterium: minimization of Wilk’s l) followed by a jackknife procedure.6,7 An index was created by summing the mean standardized coefficients divided by the means of the variables (categorical variables: 0/+1). The cutoff-range was defined as the 99%-CI of the cut-points, obtained by LDA of 150 bootstrap samples (with replacement). In h-MDS atypical neutrophils and blasts were not observed in peripheral blood. In BM, megakaryocytes were atypical in 71% (Table 1). ALIPs were found in 11/29. An irregular distribution of hemopoiesis was seen in 51.7%, accompanied by clustering of megakaryocytes (Figure 1). Cytogenetic analysis gave mitoses in 20% of the samples (one trisomy 8, 7 normal karyotypes). In AA, cell atypias was found only in erythroblasts. Megakaryocytes were seen in only one case. In 24/30 cases hemopoiesis was markedly decreased in BM sections. Discriminant analysis was performed with the peripheral blood and BM histologic parameters which were available for all cases. The final model (Wilk’s l = 0.367; p<0.0001) contained age, percentage of circulating neutrophils; marked BM hypocellularity and presence of megakaryocytes and correctly classified in 89.8% (before and after the jackknife procedure) The diagnostic index was defined as I = 0.01 x age + 0.01 x percentage of neutrophils + 0.85 x presence of megakaryocytes – 1.58 x marked BM cellularity; (cut-off between 0.40 and 0.80). Values < 0.40 favored the diagnosis of AA and those > 0.80 that of h-MDS. Applied to our initial data 86% of cases were correctly classified. A significant proportion of patients with MDS have a hypocellular marrow, and this proportion increasTable 1. Clinical and hematologic data of the patients. (95% confidence intervals in brackets).