Minimal residual disease is a significant predictor of treatment failure in non T-lineage adult acute lymphoblastic leukaemia: final results of the international trial UKALL XII/ECOG2993

The predictive value of molecular minimal residual disease (MRD) monitoring using polymerase chain reaction amplification of clone-specific immunoglobulin or T-cell Receptor rearrangements was analysed in 161 patients with non T-lineage Philadelphia-negative acute lymphoblastic leukaemia (ALL) participating in the UK arm of the international ALL trial UKALL XII/Eastern Cooperative Oncology Group (ECOG) 2993. MRD positivity (≥10⁻⁴) in patients treated with chemotherapy alone was associated with significantly shorter relapse-free survival (RFS) at several time-points during the first year of therapy. MRD status best discriminated outcome after phase 2 induction, when the relative risk of relapse was 8·95 (2·85–28·09)-fold higher in MRD-positive (≥10⁻⁴) patients and the 5-year RFS 15% [95% confidence interval (CI) 0–40%] compared to 71% (56–85%) in MRD-negative (<10⁻⁴) patients (P = 0·0002) When MRD was detected prior to autologous stem cell transplantation (SCT), a significantly higher rate of treatment failure was observed [5-year RFS 25% (CI 0–55%) vs. 77% (95% CI 54–100%) in MRD-negative/<10⁻⁴, P = 0·01] whereas in recipients of allogeneic-SCT in first complete remission, MRD positivity pre-transplant did not adversely affect outcome. These data provide a rationale for introducing MRD-based risk stratification in future studies for the delineation of those at significant risk of treatment failure in whom intensification of therapy should be evaluated.