Background: Acute non-lymphoblastic leukaemia (ANLL) is characterized by a gradual accumulation of undifferentiated cells, rather than a rapid cell proliferation. Classical kinetic features were inconclusive when used as predictors of prognosis. Aim: We performed the analysis of the nucleolar organizer regions (AgNORs) on blast cells from bone marrow biopsies before therapy, to clarify the role of cell proliferation in predicting complete remission (CR) and survival. Materials and methods: Forty previously untreated patients (22 males and 18 females, mean age: 41.8 years) with adult ANLL were retrospectively studied. According to the FAB classification, there were 1 M0, 11 M1, 9 M2, 16 M4, 2 M5b and 1 M6 leukaemias. Patients were treated for remission induction with standard daunorubicin and cytarabine (1+7) induction regimen. CR patients received intensive consolidation, 2 had autologous and 4 had allogeneic bone marrow transplantation. The mean follow-up was 62 months for censored patients. Jamshidi needle biopsies, taken before therapy, were fixed in formalin, decalcified and embedded in paraffin. Sections were stained with the standardized AgNOR method (Öfner et al. J Pathol 175, 441-8, 1995) and the mean AgNOR count in blast cells was calculated. Chi-square test, ANOVA, Pearson’s correlation coefficient, uni- and multivariate survival analysis were used for statistics. Results: CR was achieved in 26/40 patients. 16 relapsed, and 14 reached a second CR. At the time of survival analysis, 12 patients were alive without evidence of disease and 28 had died. The mean AgNOR count for the whole series was 6.6 (median: 6.43, SD: +1.35, range: 4.44-10.39). It was higher in M5b (8.98) than in M1 (6.3), M2 (6.49) or M4 (6.53) leukaemias (p=0.01), and in CR (7) than in resistant patients (5.94; p=0.02). Patients with AgNOR/cell > 6.43 had 17/20 CR (85%) while those with a lower count had only 9/18 (50%) CR (p=0.04). Disease-free survival was longer for patients with high AgNOR counts than for those having low counts (26 months vs 8 months, respectively; n.s.); the median duration of the second remission was 16 months for patients with high AgNOR counts but 5 months only for those with low counts (p=0.01). The median survival of the whole series was 31 months for patients with high AgNOR counts but 6 months only for those with low counts (p=0.001). In the multivariate analysis, only the achievement of CR retained independent prognostic significance (Chi-square: 13.3; p <0.001). When CR was not considered, AgNOR count became an independent prognostic factor (Chi-square: 6.71; p =0.01). Conclusions: The data indicate that cell kinetic studies have prognostic relevance in patients with adult ANLL and that high proliferative activity of blast cells, as assessed by AgNOR analysis, is a favourable factor for both CR achievement and overall survival.
Clinical significance of AgNOR counts in adult acute non-lymphoblastic leukaemia
PICH, Achille;
1997-01-01
Abstract
Background: Acute non-lymphoblastic leukaemia (ANLL) is characterized by a gradual accumulation of undifferentiated cells, rather than a rapid cell proliferation. Classical kinetic features were inconclusive when used as predictors of prognosis. Aim: We performed the analysis of the nucleolar organizer regions (AgNORs) on blast cells from bone marrow biopsies before therapy, to clarify the role of cell proliferation in predicting complete remission (CR) and survival. Materials and methods: Forty previously untreated patients (22 males and 18 females, mean age: 41.8 years) with adult ANLL were retrospectively studied. According to the FAB classification, there were 1 M0, 11 M1, 9 M2, 16 M4, 2 M5b and 1 M6 leukaemias. Patients were treated for remission induction with standard daunorubicin and cytarabine (1+7) induction regimen. CR patients received intensive consolidation, 2 had autologous and 4 had allogeneic bone marrow transplantation. The mean follow-up was 62 months for censored patients. Jamshidi needle biopsies, taken before therapy, were fixed in formalin, decalcified and embedded in paraffin. Sections were stained with the standardized AgNOR method (Öfner et al. J Pathol 175, 441-8, 1995) and the mean AgNOR count in blast cells was calculated. Chi-square test, ANOVA, Pearson’s correlation coefficient, uni- and multivariate survival analysis were used for statistics. Results: CR was achieved in 26/40 patients. 16 relapsed, and 14 reached a second CR. At the time of survival analysis, 12 patients were alive without evidence of disease and 28 had died. The mean AgNOR count for the whole series was 6.6 (median: 6.43, SD: +1.35, range: 4.44-10.39). It was higher in M5b (8.98) than in M1 (6.3), M2 (6.49) or M4 (6.53) leukaemias (p=0.01), and in CR (7) than in resistant patients (5.94; p=0.02). Patients with AgNOR/cell > 6.43 had 17/20 CR (85%) while those with a lower count had only 9/18 (50%) CR (p=0.04). Disease-free survival was longer for patients with high AgNOR counts than for those having low counts (26 months vs 8 months, respectively; n.s.); the median duration of the second remission was 16 months for patients with high AgNOR counts but 5 months only for those with low counts (p=0.01). The median survival of the whole series was 31 months for patients with high AgNOR counts but 6 months only for those with low counts (p=0.001). In the multivariate analysis, only the achievement of CR retained independent prognostic significance (Chi-square: 13.3; p <0.001). When CR was not considered, AgNOR count became an independent prognostic factor (Chi-square: 6.71; p =0.01). Conclusions: The data indicate that cell kinetic studies have prognostic relevance in patients with adult ANLL and that high proliferative activity of blast cells, as assessed by AgNOR analysis, is a favourable factor for both CR achievement and overall survival.
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