Detection of abnormalities in B-cell differentiation pattern is a useful tool to predict relapse in precursor-B-ALL

Immunophenotypic investigation of minimal residual disease (MRD) has tradit ionally been based on the investigation of phenotypic aberrants at diagnosi s to be used later as a target for MRD detection, This approach has several shortcomings (it is only applicable to patients with aberrant phenotypes, requires a diagnostic sample, and is patient-specific) and therefore a sear ch for simpler alternatives is warranted. The present study is based on the hypothesis that in precursor-B-ALL patients the persistence of residual le ukaemic cells may induce abnormalities in the precursor-B-cell compartment in bone marrow (BM) and these could be used as a criteria to predict relaps e, These abnormalities may include: (1) the presence of an increase in the frequencies of immature B cells (CD34(+)/CD19(+) or CD20(-)/CD19(+)) or (2) the existence of an altered B-cell differentiation pathway due to a blocka de or to the presence of B cells outside the normal pathway. A total of 180 BM samples from 45 consecutive precursor-B-ALL patients who achieved morph ological complete remission (CR) were analysed by multiparametric flow cyto metry. Our results show that a significant increase in immature B-cell subs ets or an altered B-cell differentiation predicts a high relapse rate (P<0. 01) and a shorter disease-free survival (P<0.01). Moreover, abnormalities i n either of these two criteria detected at specific time points during foll ow-up (end of induction, maintenance, or after treatment) were associated w ith a significantly shorter disease-free survival (P<0.01). In summary, the investigation of abnormalities in B-cell differentiation is a relatively s imple and cheap approach for predicting relapse in precursor-B-ALL patients .