Classification of Childhood Bone Marrow Failure Syndrome Based On Revised WHO Classification.

Abstract 4212

The WHO classification revised in 2008 proposes the term, “refractory cytopenia of childhood (RCC)” for children with myelodysplastic syndrome (MDS) and a low blast count. This condition is characterized by persistent cytopenia with < 5% blasts in the bone marrow and < 2% blasts in the peripheral blood. Dysplastic changes must be recognized in more than two cell lineages, or exceed 10% in a single cell line on bone marrow aspirate smears. To differentiate between RCC and aplastic anemia (AA) is challenging, especially when the bone marrow is hypoplastic and chromosomal abnormalities are undetectable. Aplastic anemia can progress to MDS and some patients with RCC respond to immunosuppressive therapy, suggesting that the two conditions have an overlapping pathophysiology. The spectrum of RCC ranges from mild cytopenia to cytogenetic abnormalities of monosomy 7, which carries an increased risk for disease progression. However, few studies have attempted to differentiate the two diseases. To compare the clinical and biological features of AA and RCC, we retrospectively reviewed bone marrow smears from 140 patients registered for the childhood AA-97 study. The smears were classified as AA (no morphologically dysplastic changes in any hematopoietic cell lineages), AA-RCC borderline (< 10% dysplastic changes only in erythroid lineage) and RCC groups. Disease severity was classified as non-severe (n = 32), severe (n = 43) and very severe (n = 65). Aplastic anemia was idiopathic in 116 patients and associated with hepatitis in 24. Two patients had chromosomal abnormalities at presentation. The AA, AA-RCC borderline and RCC groups comprised 96 (67%), 20 (16%) and 24 (17%) patients, respectively. Bone marrow smears in the RCC group frequently presented megaloblastoid changes in cells of erythroid lineage and the pseudo-Pelger-Huet anomaly in those of myeloid lineage. Dysplastic changes in the megakaryocytic lineage were rare. The median ages were 9, 9 and 11 years in the AA, AA-RCC borderline and RCC groups, respectively. The AA group included most of the patients with hepatitis-associated AA and those with very severe AA. On the other hand, 6 (9%), 7 (16%) and 11 (35%) patients in the RCC group had very severe, severe and with non-severe disease, respectively. Four patients in the AA group developed new chromosomal abnormalities: trisomy 8 (n = 2) and monosomy 7 (n = 2). Two patients with monosomy 7 progressed to acute myeloid leukemia (AML). Three patients in the RCC group developed new chromosome abnormalities; 2 had trisomy 8 and 1 had ? X. None of the patients in the RCC group developed MDS or AML. The response rates for immunosuppressive therapy with cyclosporine and antithymocyte globulin were 55%, 50% and 67% in the AA, AA-RCC borderline and RCC groups, respectively. To determine whether the two diseases are truly different entities, response rates to immunosuppressive therapy, the frequency of clonal evolution and the genetic background should be prospectively compared between AA and RCC in a larger patient cohort.