Medline ® Abstracts for References 60-62

We describe the clinical, cytological and cytogenetic features of 49 cases of myelodysplastic syndromes (MDS) in childhood. Three children had received prior cytotoxic treatment (group 1); all of these had cytogenetic abnormalities and died shortly after diagnosis. 22 children had constitutional anomalies (group 2). The remaining 24 MDS were considered as 'primary' (group 3). Hypoplastic marrow was found in nine cases, and only 53% of the MDS fitted the adult FAB classification. Transformation to AML occurred in 11 cases, development of aplastic anaemia in three cases, and spontaneous remission in one case each of RA and RAEB. Differences were observed between groups 2 and 3 in terms of mean age at diagnosis (11.1 months v 5 years), rate of cytogenetic anomalies (15% v 38%) and rate of progression towards acute leukaemia (13% v 29%). In group 2, all the fur girls studied exhibited a polyclonal pattern of X-inactivation, which suggests that MDS may be only the haematological expression of an embryological defect with different target tissues. This study suggests that some MDS in childhood can exhibit particular features such as congenital anomalies associated with MDS, bone marrow hypoplasia, polyclonality, and spontaneous remission. It emphasizes that the FAB classification is not adequate for children and addresses the question of whether these MDS are always malignant diseases.

Clinical, morphologic, and cytogenetic features were examined in a group of 68 children with myelodysplasia (MDS) referred to a single institution between 1971-1991. The morphologic French-American-British (FAB) system of classification proved of limited value in this group of patients because 50% of the cases were categorized as chronic myelomonocytic leukemia and three patients with eosinophilia and MDS were unclassifiable. Cytogenetic analysis was performed in 63 cases and clonal abnormalities were detected in 55%; the most common chromosome involved was number 7. Modification of the FAB system to incorporate additional diagnostic features such as pretreatment fetal hemoglobin (Hb F) and cytogenetics allowed incorporation of the categories of juvenile chronic myeloid leukemia (JCML) and infantile monosomy 7 syndrome (IMo7). The resulting groups of patients had highly significant differences in survival (P = .00009). The overall 5-year survival for the patients was 31.9% (95% CI 21.7 to 44.1) and factors influencing prognosis included: modified FAB type, platelet count, Hb F level, and cytogenetic complexity. We developed a scoring system ("FPC") where each of the following findings at diagnosis scored one point: HbF greater than 10%, platelets<or = 40 x 10(9)/L, and complex karyotypic changes (two or more clonal structural/numerical abnormalities), which produced groups with highly significant differences, patients witha score of 0 having a 5-year survival of 61.6% (CI 33% to 84%), whereas those with a score of two or three all died within 4 years of diagnosis. The revised classification and scoring system may prove helpful in making treatment choices in pediatric MDS and now needs to be tested prospectively in large scale population-based studies.

Much of the applied terminology of myelodysplastic syndromes (MDS) in childhood is confusing and not mutually exclusive. It is therefore proposed that the FAB classification of MDS is used in children in order to improve diagnostic precision and to facilitate epidemiologic, clinical, and therapeutic comparisons. The true incidence of childhood MDS is unknown but the rate may approximate the incidence of acute myelogenous leukemia. A pooled analysis of eight larger series representing 110 children less than 15 years old at diagnosis with de novo MDS classified according to the FAB recommendations showed that the more aggressive subtypes dominated, which partly may reflect that the less advanced cases are underdiagnosed. The median age at presentation was 6.0 years. The male/female ratio was 1.6. Monosomy 7 was the most frequent cytogenetic abnormality. The median survival was 13 months and the probability of survival three years from diagnosis was 16%. Spontaneous remission may be observed very infrequently. Allogeneic bone marrow transplantation (BMT) represents the only potentially curative treatment. The survival rate three years after BMT is about 50%. Major differences between childhood and adult MDS exist with respect to the distribution of FAB subgroups, the rate of progression, and the cytogenetic findings. The literature on MDS in children is still sparse and there is an obvious need for more studies designed to determine the incidence, clinical and laboratory characteristics, the natural course, and the efficacy of contemporary treatment options.