Prognostic value of morphometry in acute lymphoblastic leukemia of childhood

The prognostic value of morphometric features was studied in a group of 33 children with acute lymphoblastic leukemia (ALL) and compared with clinical and hematologic parameters. Air dried, May-Grunwald-Giemsa-stained specimens were prepared from iliac crest biopsies, and for each patient, 150 blasts and their nuclei were selected according to a stratified selection method and measured on a graphic tablet system. Univariate overall survival analysis showed the French-American-British (FAB) classification to be the strongest clinical parameter (P < .0001). However, the significance was mainly due to the fact that both L3 cases died; the results for L1 and L2 were less satisfactory, with a survival rate (at 10 years) of 69% for the 26 L1 cases and 80% for the five L2 cases. The nuclear/cytoplasmic (N/C) ratio was the best morphometric feature (P < .0001) and provided more satisfactory classification results than did FAB: only 2 of the 21 (10%) cases with N/C ratios > 0.90 died (7 and 9.5 years after the diagnosis, respectively), and 9 of the 12 (75%) cases with N/C ratios ≥ 0.90 died. For recurrence-free survival analysis, essentially the same results were obtained. The N/C ratio retained its significant prognostic value after recurrence: 11 of the 15 patients with eventual recurrences died; 9 of them had an (original) N/C ratio ≤ 0.90. Three of the four recurring cases that survived after recurrence had an N/C ratio > 0.90 (P < .03). Multivariate survival analysis (Cox proportional hazards model) pointed strongly to the N/C ratio. N/C ratio is a strong predictor of overall and recurrence-free survival as well as of survival after recurrence in childhood ALL. It is an objective and reproducible parameter, which is an important advantage considering the subjectivity of the FAB classification.