D. Trere et al., PROGNOSTIC RELEVANCE OF PRETREATMENT PROLIFERATIVE RAPIDITY OF MARROWBLAST CELLS IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA, British Journal of Cancer, 70(6), 1994, pp. 1198-1202
Cell proliferation rate is a well-established prognostic factor in can
cer, but it has not been considered to identify the risk group of chil
dhood acute lymphoblastic leukaemia (ALL) at presentation. We carried
out a study to demonstrate the prognostic importance of the rapidity o
f cell proliferation in patients with ALL. To measure the rapidity of
cell. proliferation we used the parameter relative to the area of silv
er-stained nucleolar organiser regions (AgNORs) as evaluated by morpho
metric analysis on smeared marrow blast cells. The mean AgNOR area of
leukaemic marrow cells was measured in 119 children. By using a cut-of
f value of 3 mu m(2), we identified a group of 91 children with low pr
oliferating blast activity (mean AgNOR value 2.11 mu m(2)) and a group
of 28 children with high proliferating activity (mean AgNOR value 3.2
9 mu m(2)). The group of patients with a mean AgNOR value > 3 mu m(2)
was characterised by a higher number of deaths, more frequent relapse
and shorter time interval to relapse than the group of patients with m
ean AgNOR value < 3 mu m(2) (P < 0.01). Multivariate analysis performe
d to include T-cell immunophenotype, FAB morphology, leucocyte count a
nd presence of mediastinal mass showed that the mean AgNOR value was t
he only independent predictor of unfavourable event-free survival prob
ability (P > 0.01). Our results indicate that the rapidity of marrow b
last cell proliferation is an important prognostic parameter in childh
ood ALL and should be routinely introduced in the group risk definitio
n.