Primary and Familial Myelodysplastic Syndromes in the Greek Pediatric Registry. Clinical Course and Correlation with Congenital Disorders, Other Than Marrow Failure.

De novo myelodysplastic syndromes (MDS) arise in previously healthy children, however congenital physical abnormalities often accompanying the disease, strengthen the assumption that predisposing genetic lesions may contribute to the disturbance of hematopoiesis. In our series of Greek Pediatric patients, emphasis is given to the possible clinical correlation of classifiable and unclassifiable coexisting congenital disorders to the pathogenesis of MDS.

Thirty children with primary MDS (mean age 7.5 y) and 10 familial cases (mean age 8.1 y) were consecutively diagnosed and treated during a period of 21 y (1988–2009). Diagnosis was based on clinical manifestations, morphology of peripheral blood, marrow aspirate and bone marrow trephine and conventional and molecular cytogenetic analysis of bone marrow cells. Patients with secondary MDS on a background of inherited, well characterized, bone marrow failure syndrome were excluded.

Thirty two children had refractory cytopenia (RC), 2 refractory anemia with excess of blasts (RAEB) and 6 refractory anemia with excess blasts in transformation (RAEB-T). Dysplastic features of the erythroid, myeloid and megakaryocytic lineage were detected at marrow aspirates in 77.5%, 42.5% and 72.5% of the patients, respectively, while decreased cellularity was found at bone trephine in 25/40 patients (65%). Several chromosomal aberrations were revealed in 18/40 patients: monosomy 7 in 6 children (2 RC, 1 RAEB, 3 RAEB-T), 5q- in 1 (RC), del(20)(q13) in 1 (RC), hypodiploidy in 1 (RAEB-T), inv(8)(p32q12) in 1 (RC), inv(9)(p12q13) in 1 (RC), 1qh+ in 4 (RC), trisomy 8 in 1 (RC) and complex abnormalities in 2 (RAEB-T). Treatment modalities included: Allo HCST in 13 children (9 RC, 1 RAEB, 3 RAEB-T), immunosuppression in 2 (RC), chemotherapy in 2 (RAEB-T), supportive care in 12 (10 RC, 1 RAEB, 1 RAEB-T 1) and “watch and wait” strategy in 11 (all RC). The 5-year survival for primary MDS and familial cases was 78 % and 67% respectively, while for RC cases was 90% and for RAEB/RAEB/T 15%. Physical abnormalities were identified in 16/40 patients (40%) (13/32 RC, 3/8 RAEB/RAEB-T), among whom 14 patients were characterized as having: Naxos disease 2; Velocardiofacial-like syndrome 2; Löwe syndrome 1; Congenital lymphoedema 1; Hemifacial microsomia 1; Immunodeficiency, centromeric region instability, and facial anomalies-like syndrome (ICF-like) 1; Cornelia De Lange's syndrome 1; Dandy Walker syndrome 1 and complex, unclassifiable abnormalities 6. The genes of these disorders are known to be located close to genes implicated in normal or malignant hematopoiesis or involved in chromosomal aberrations often seen in hematological malignancies (Table).

Low grade MDS prevailed among the primary or familial MDS, in our series. Physical abnormalities were common and classifiable or unclassifiable genetic disorders were identified in both low grade and advanced MDS. We hypothesize that the genes of some of these disorders could be directly or indirectly involved in hemopoiesis/oncogenesis either by being located close to genes implicated in normal or malignant hemopoiesis, or involved in chromosomal aberrations often seen in hematological malignancies. However, to clarify whether these or other underlying genetic abnormalities may be regarded as initiating or contributing events/mechanisms for MDS in childhood, requires further specific and well-planned basic and clinical studies.

No relevant conflicts of interest to declare.