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

ObjectiveTo 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). MethodsSeventy-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. ResultsThree-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 3yr. ConclusionEarly 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.