© F e r r a t a S t o r t i F o u n d a t i o ndren who present over 4 years of age are in fact suffering from sporadic AML occurring in a child with DS, rather than from 'true' ML-DS. 18 In addition, ML-DS patients with a history of transient myeloproliferative disease have a significantly better outcome than children with ML-DS without documented transient myeloproliferative disease. 19 Until now, no other prognostic factors have been identified in ML-DS.The leukemic blasts from the majority of patients with ML-DS (72%) show additional cytogenetic changes apart from the constitutional trisomy 21. 20 A previous international-BFM study, performed by Forestier et al., showed that the most frequent gains involved chromosomes 8 (27%), 21 (23%), 11 (8.1%), and 19 (7.4%), whereas chromosomes X (3.2%; only females), 5 (1.5%), and 7 (2.2%) were commonly monosomic. The most frequent partial imbalances were duplication 1q (16%), deletion 7p (10%), and deletion 16q (7.4%). 20 However, the potential clinical impact of these cytogenetic abnormalities is not known and has not been well studied, mainly due to the small numbers of patients in individual series. 9,10,[20][21][22] In current treatment protocols of non-DS pediatric AML patients, stratification is based on cytogenetics and response to therapy. 23 In ML-DS, no prognostic cytogenetic groups have yet been identified, nor any other prognostic factors allowing a risk-stratified approach.We, therefore, conducted a large international study of clinical and outcome data including cytogenetic records from children with ML-DS collected from 13 collaborative study groups. Our aim was to identify differences in outcome related to cytogenetics and clinical characteristics in ML-DS. This was approached by analyzing differences in the cumulative incidence of relapse (CIR), reflecting leukemia resistance, and hence avoiding the influence of toxic (non-leukemic) events on survival estimates. This may result in risk-group stratification and risk-group directed therapy for these patients in the future. In addition, we compared the outcome of ML-DS patients in the different cytogenetic groups with that of non-DS AML patients from the same era treated on AML-BFM regimens as a reference cohort.
Methods
PatientsData on 451 patients with ML-DS were collected from 13 collaborative study groups participating in the International AML-BFM Study Group. For comparison, a reference cohort of non-DS AML patients (n=543) from the same treatment era, kindly provided by the AML-BFM Study Group, was used. This study was approved by the Institutional Review Boards in accordance with local legislation and guidelines.Patients were eligible if diagnosed between January 1, 1995 and January 1, 2005. Patients who were not treated with curative intent from diagnosis were excluded. The data collected at diagnosis comprised karyotype, sex, age, white blood cell (WBC) count, hemoglobin level, platelet count, immunophenotypic data and FAB morphology. In addition, we collected data on treatment, such a...
