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

Br J Haematol. 1999 Mar;104(4):755-62. doi: 10.1046/j.1365-2141.1999.01258.x.

Abstract

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 >25x10(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 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.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asparaginase / administration & dosage
  • Bone Marrow Transplantation / methods*
  • Disease-Free Survival
  • Female
  • Humans
  • Idarubicin / administration & dosage
  • Male
  • Middle Aged
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Prednisolone / administration & dosage
  • Remission Induction
  • Risk Factors
  • Transplantation, Homologous
  • Treatment Outcome
  • Vincristine / administration & dosage

Substances

  • Vincristine
  • Prednisolone
  • Asparaginase
  • Idarubicin

Supplementary concepts

  • IVAP protocol