Induction‐consolidation with an idarubicin‐containing regimen, unpurged marrow autograft, and post‐graft chemotherapy in adult acute lymphoblastic leukaemia

Between 1991 and 1993 we conducted a collaborative trial in adult acute lymphoblastic leukaemia, introducing an idarubicin (IDA)‐containing regimen for 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 maintenance for 6 months (ABMT patients) or 18 months. 96 patients were evaluable for antileukaemic response after induction with vincristine–prednisone–l‐asparaginase plus cumulative IDA 36 or 20 mg/m2 (IVAP‐1 and IVAP‐2), and for disease‐free survival (DFS) after a minimum follow‐up >3.5 years with an off‐therapy interval >1.5 years. The response rate was 44% (7/16) with IVAP‐1 and 90% (72/80) with IVAP‐2 (P = 0.0001), due to regimen‐related toxicities. Post‐remission therapy was administered as planned to most cases but protocol violation was registered in some patients eligible to ABMT and post‐graft chemotherapy. The 5‐year disease‐free survival (DFS) rate was 31%. Multivariate analysis indicated that DFS was improved in patients receiving a transplant (11 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 × 109/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 response rate and post‐remission treatment including ABMT was feasible and modestly toxic. In spite of the short post‐graft chemotherapy phase, the long‐term DFS rate was good in cases with no high‐risk feature. However, because autografting may be redundant in the standard‐risk category, its role requires further investigation for high‐risk cases.