Minimal residual disease in adolescent (older than 14 years) and adult acute lymphoblastic leukemias: early immunophenotypic evaluation has high clinical value

Abstract

[EN]Investigation of minimal residual disease (MRD) in acute leukemias by immunophenotyping and/or molecular techniques is proving to be increasingly valuable for disease monitoring. In acute lymphoblastic leukemia (ALL), most MRD studies have focused on children, whereas in contrast, information on the value of MRD on adult ALL is scanty, and almost exclusively restricted to polymerase chain reaction (PCR) studies. Early response to therapy is one of the most important prognostic factors in acute leukemia, which prompted us to investigate whether or not early immunophenotypic assessment of MRD could also be a valuable tool for predicting relapse in adult patients with ALL. For that purpose we have analyzed the level of MRD during the initial phase of treatment (induction phase) by multiparameter flow cytometry in a series of 102 adolescent (older than 14 years) and adult patients with ALL. Immunophenotypic evaluation of the bone marrow (BM) at day +35 showed that patients with low MRD levels (< 0.05% leukemia-associated phenotype [LAP+] cells) had a significantly longer relapse-free survival (RFS) than patients with high MRD levels, and this prognostic influence was retained when only those patients in morphologic complete remission (mCR) at day +35 were considered (median RFS: 42 months vs 16 months; P =.001). Moreover, immunophenotyping helped to identify a small subset of patients (n = 12) with negative or low MRD levels (< 0.03% LAP+ cells) by day +14, with an excellent prognosis (projected RFS of 90% at 5 years). The contrary is true of patients who achieved late mCR (after day +35), since immunophenotypic investigation of MRD showed that, in spite of the mCR, none of the cases with more than 0.1% LAP+ cells would be relapse-free after 2 years. Multivariate analysis showed that the immunologic evaluation of MRD at day +35 was the most relevant independent prognostic parameter for adult patients with ALL, and together with age, white blood cell (WBC) count at diagnosis, and presence of the Philadelphia (Ph) chromosome, represented the most informative combination of variables for predicting relapse-free survival.