| 1. |
- Forestier, Erik, et al.
(författare)
-
Cytogenetic features of acute lymphoblastic and myeloid leukemias in pediatric patients with Down syndrome - an iBFM-SG study.
- 2007
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020.
-
Tidskriftsartikel (refereegranskat)abstract
- Children with Down syndrome (DS) have a markedly increased risk of acute lymphoblastic and myeloid leukemias (ALL+AML). To identify chromosomal changes cooperating with +21 that may provide information on the pathogenesis of these leukemias, we analyzed 215 DS-ALL and 189 DS-AML. Unlike previous smaller series, a significant proportion of DS-ALL had the typical B-cell precursor ALL abnormalities high hyperdiploidy (HeH; 11%) and t(12;21)(p13;q22) (10%). The HeH DS-ALL were characterized by gains of the same chromosomes as non-DS-HeH, suggesting the same etiology/pathogenesis. In addition, specific genetic subtypes of DS-ALL were suggested by the significant overrepresentation of cases with +X, t(8;14)(q11;q32), and del(9p). Unlike DS-ALL, the common translocations associated with non-DS-AML were rare in DS-AML, which instead were characterized by the frequent presence of dup(1q), del(6q), del(7p), dup(7q), +8, +11, del(16q), and +21. This series of DS leukemias - the largest to date - reveals that DS-ALL is a heterogeneous disorder that comprises both t(12;21) and HeH as well as DS-related abnormalities. Furthermore, this analysis confirms that DS-AML is a distinct entity, originating through other genetic pathways than do non-DS-AML, and suggests that unbalanced changes such as dup(1q), +8, and +21 are involved in the leukemogenic process.
|
|
| 2. |
|
|
| 3. |
- Blink, Marjolein, et al.
(författare)
-
Normal karyotype is a poor prognostic factor in myeloid leukemia of Down syndrome : a retrospective, international study
- 2014
-
Ingår i: Haematologica. - : Ferrata Storti Foundation. - 0390-6078 .- 1592-8721. ; 99:2, s. 299-307
-
Tidskriftsartikel (refereegranskat)abstract
- Myeloid leukemia of Down syndrome has a better prognosis than sporadic pediatric acute myeloid leukemia. Most cases of myeloid leukemia of Down syndrome are characterized by additional cytogenetic changes besides the constitutional trisomy 21, but their potential prognostic impact is not known. We, therefore, conducted an international retrospective study of clinical characteristics, cytogenetics, treatment, and outcome of 451 children with myeloid leukemia of Down syndrome. All karyotypes were centrally reviewed before assigning patients to subgroups. The overall 7-year event-free survival for the entire cohort was 78% (± 2%), with the overall survival rate being 79% (± 2%), the cumulative incidence of relapse 12% (± 2%), and the cumulative incidence of toxic death 7% (± 1%). Outcome estimates showed large differences across the different cytogenetic subgroups. Based on the cumulative incidence of relapse, we could risk-stratify patients into two groups: cases with a normal karyotype (n=103) with a higher cumulative incidence of relapse (21%± 4%) than cases with an aberrant karyotype (n=255) with a cumulative incidence of relapse of 9% (± 2%) (P=0.004). Multivariate analyses revealed that white blood cell count ≥ 20 × 10(9)/L and age >3 years were independent predictors for poor event-free survival, while normal karyotype independently predicted inferior overall survival, event-free survival, and relapse-free survival. In conclusion, this study showed large differences in outcome within patients with myeloid leukemia of Down syndrome and identified novel prognostic groups that predicted clinical outcome and hence may be used for stratification in future treatment protocols.
|
|
