Myelodysplastic syndrome (MDS) represents a heterogeneous group of hematopoietic stem cell disorders. Although the precise pathogenesis of MDS remains to be clarified, cytogenetic abnormalities appear to be involved in the disease mechanism and are considered an important factor in predicting clinical outcome. Here, we report the outcome of conventional cytogenetic analysis performed at diagnosis in 300 children with MDS who were enrolled in the prospective study EWOG-MDS 98. The patients were divided into 3 clinical groups: primary refractory cytopenia (RC) (n=142), primary advanced MDS (aMDS) (n=94), and MDS secondary to chemo- or radiation therapy, bone marrow failure disorders or familial disease (sMDS) (n=64). A full cytogenetic result was obtained in 263 cases (87.7%) including 116 (44.1%) with an abnormal clone. Comparing the 3 diagnostic subgroups, there was a statistically significant difference in the frequency of abnormalities observed. In RC, only 25 of 116 patients with successful analysis had a detectable clone that showed monosomy 7 as sole aberration in the majority of cases (52%). In addition, this subgroup also showed the greatest rate of failure to obtain a karyotypic result. In contrast, 42 (65.6%) of the sMDS cases were cytogenetically abnormal with a broad spectrum of aberrations including 16 patients (25%) with a complex karyotype (≥4 abr.). The presence of karyotypic evolution was also more frequently observed in this group. The overall karyotypic results showed monosomy 7 to be present in 50% of all abnormal cases, a figure that greatly exceeded the prevalence of the other frequent non-random aberrations of −5/del(5q), +8, del(7q), and +21, each of which occurred in 5–10% of abnormal cases. Despite the small numbers of these latter cases, clear trends of karyotypic events occurring in a particular clinical subgroup were demonstrated in the form of +8 with aMDS and −5/del(5q) with sMDS. The clinical and cytogenetic subgroups were further analyzed for correlations with gender and age. Whereas no clinical group showed any correlation between gender and karyotype, in RC and aMDS it was shown that patients with monosomy 7 were significantly younger than those with another karyotypic result (median 3.2 vs. 10.4 yrs and 5.2 vs. 11.0 yrs, respectively). The results demonstrate that while a general karyotypic picture can be defined in childhood MDS, future studies need to clearly differentiate between individual clinical subgroups.

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