DNA index and %S‐phase cells determined in acute lymphoblastic leukemia of children: A report from studies ALL V, ALL VI, and ALL VII (1979–1991) of the dutch childhood leukemia study group and the Netherlands workgroup on cancer genetics and cytogenetics

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Abstract
DNA per cell content was routinely recorded by single-parameter flow cytometry in leukemic blasts from 473 children with acute lymphoblastic leukemia (ALL), enrolled in national studies ALL V, VI, and VII (1979–1991) of the Dutch Childhood Leukemia Study Group. The parameters bonemarrow %S-value and DNA Index were compared with clinical features, with chromosome number based on cytogenetic analyses and with treatment results in study ALL VI. %S-values, ranging between 1 and 36%, were unrelated to initial white blood cell count, immunophenotype, and DNA index but were lowest in blasts with L1 morphology. In study ALL VI (non-high risk), the survival of patients with ≦6% S-phase cells was superior to that of patients with %S-values of >6 (P = 0.030). Hyperdiploidy, defined by a DNA index ≧1.16, was compared to the cytogenetic hyperdiploid classification of n > 50. Initially there were 25 discrepancies in 189 samples jointly analysed by flow cytometry and cytogenetics. After review only five discrepancies remained unresolved. Hyperdiploidy, independent of the method used, was found to be unrelated to blast morphology and %S-phase cells but closely associated with c-ALL and was absent in T-ALL. In study ALL VI, event-free survival at 8 years of hyperdiploid patients was 90.6% but was not significantly different from non-hyperdiploid patients (EFS = 82.1%; P = 0.08). Routine DNA flow cytometry appeared a valuable adjunct to cytogenetic analyses and allowed the identification of a large subset of non-high-risk ALL patients in study ALL VI with a DNA index ≥1.16 or %S-value of ≦6.0 with highest survival probability.