Induction-consolidation with an idarubicin-containing regimen, unpurged marrow autograft, and post-graft chemotherapy in adult acute lymphoblastic leukaemia
R. Bassan et al., Induction-consolidation with an idarubicin-containing regimen, unpurged marrow autograft, and post-graft chemotherapy in adult acute lymphoblastic leukaemia, BR J HAEM, 104(4), 1999, pp. 755-762
Between 1991 and 1993 we conducted a collaborative trial in adult acute lym
phoblastic leukaemia, introducing an idarubicin (IDA)-containing regimen fo
r induction and early consolidation, and increasing consolidation intensity
with an autologous bone marrow transplantation phase (ABMT, patients aged
<51 years) followed by further chemotherapy for 12 weeks and low-dose maint
enance for 6 months (ABMT patients) or 18 months. 96 patients were evaluabl
e for antileukaemic response after induction with vincristine-prednisone-L-
asparaginase plus cumulative IDA 36 or 20 mg/m(2) (IVAP-1 and IVAP-2), and
for disease-free survival (DFS) after a minimum follow-up >3.5 years with a
n off-therapy interval >1.5 years. The response rate was 44% (7/16) with IV
AP-1 and 90% (72/80) with IVAP-2 (P = 0.0001), due to regimen-related toxic
ities. Post-remission therapy was administered as planned to most cases but
protocol violation was registered in some patients eligible to ABMT and po
st-graft chemotherapy. The 5-year disease-free survival (DFS) rate was 31%.
Multivariate analysis indicated that DFS was improved in patients receivin
g a transplant (II allogeneic, DFS 70%: 32 ABMT. 36%; 37 neither, 17%: P <
0.001) and was negatively affected by high-risk features such as blast cell
count > 25 x 10(9)/l, T-cell or mature B-cell immunophenotype, and t(9;22)
/t(4;11) (all P values < 0.05). The 5-year DFS rate was 54% for 26 patients
with no high-risk factor, 26% for 35 patients with any one, and 6% for 18
patients with any two (P < 0.005), IVAP-2 brought about a high complete res
ponse rate and post-remission treatment including ABMT was feasible and mod
estly toxic. In spite of the short postgraft chemotherapy phase, the long-t
erm DFS rate was good in cases with no high-risk feature. However, because
autografting may be redundant in the standard-risk category, its role requi
res further investigation for high-risk cases.