Near-triploidy and near-tetraploidy in childhood acute lymphoblastic leukemia: association with B-lineage blast cells carrying the ETV6–RUNX1 fusion, T-lineage immunophenotype, and favorable outcome

The prognostic significance of near-triploidy (68–80 chromosomes) and near-tetraploidy (>80 chromosomes) in childhood acute lymphoblastic leukemia (ALL) is unclear. Therefore, we retrospectively evaluated the incidence of and outcome associated with these subtypes of ALL. In 620 children with ALL diagnosed between 1988 and 1999, the leukemic cells were near-triploid (DNA index, 1.50–1.73) in 4 and near-tetraploid (DNA index, 1.79–2.28) in 14. Of 15 patients with B-lineage ALL, 11 (73.3%) had an ETV6–RUNX1 (previously TEL-AML1 and then ETV6–CBFA2) fusion. No differences in age (P = 0.99), leukocyte count (P = 0.99), or immunophenotype (P = 0.99) were observed between patients with near-triploidy and those with near-tetraploidy. Patients with near-triploidy or near-tetraploidy were more likely than those with high-hyperdiploidy (51–67 chromosomes) (n = 159) to be female (P = 0.05) and have T-lineage ALL (P = 0.02), L2 morphology (P < 0.0001), or the ETV6–RUNX1 fusion (P < 0.0001). The median follow-up period was 10.4 years. The 5-year event-free survival estimates (± SE) were 75% ± 19% for patients with near-triploidy, 93% ± 7% for those with near-tetraploidy, and 84% ± 3% for those with high-hyperdiploidy. Although near-triploidy and near-tetraploidy are biologically different from high-hyperdiploidy, the favorable outcomes of patients with any one of these abnormalities suggest that patients with B-lineage ALL and a DNA index ≥ 1.16 can be included in the low-risk arm of treatment protocols. We cannot make similar recommendations for patients with T-lineage ALL because of the small number of cases (n = 3) in this study.