Early MRD response as a prognostic factor in adult patients with acute lymphoblastic leukemia

Objective To evaluate the prognostic power of minimal residual disease ( MRD ) monitored by polymerase chain reaction at defined time points during early treatment in adult patients with acute lymphoblastic leukemia ( ALL ). Methods Seventy‐one patients were treated according to the GMALL 07/2003 protocol and evaluated for MRD in bone marrow by specific clonal rearrangements of Ig/ TCR in BCR ‐ ABL negative ALL or fusion gene transcript in BCR ‐ ABL positive ALL . Results Three‐year overall survival ( OS ) was 94% in patients with BCR‐ABL negative ALL reaching complete molecular response ( CMR ) after the first course of chemotherapy (vs. 32% if MRD >10 −4 ; P  = 0.001). Patients with CMR prior to the start of consolidation chemotherapy at week 11 had 3‐yr OS 82% (vs. 18% if MRD >10 −4 ; P  = 0.001). Patients with BCR ‐ ABL positive ALL showed slower MRD dynamics. There was a trend to better OS in patients with ≥4 log reduction of BCR ‐ ABL transcript prior to HSCT (92% vs. 50%; P  = 0.065). None of the patients with detectable MRD (both BCR ‐ ABL positive and negative) after HSCT survived 3 yr. Conclusion Early MRD kinetics is an important tool for new prognostication models with direct clinical impact irrespective of standard prognostic factors in patients with BCR ‐ ABL negative ALL .