Immunophenotyping to Detect Minimal Residual Disease in Adult Acute Lymphoblastic Leukemia - Feasibility and Prognostic Significance.

Although well documented for pediatric patients, the prognostic value of minimal residual disease (MRD) detected with the use of immunophenotyping has not been established for adults with acute lymphoblastic leukemia (ALL) so far. With the use of standard “quadrans” analysis based on evaluation of the number of blasts bearing atypicial antigen combinations, the method may be applied to the majority of T-derived and only approximately half of B-lineage ALL. In this study we tested the feasibility and prognostic significance of a new “empty spaces” method taking into account the individual antigen expression pattern for each blast cell tested. The “forbidden” gates were established with the use of triple staining by comparison with the pattern obtained for healthy volunteer bone marrow donors. At least two antigen combinations were tested for each patient. MRD was evaluated after induction and after consolidation therapy. Only patients who achieved complete remission after a single course of induction were analysed with regard to the impact of MRD on long-term outcome.

Thirty adult ALL patients (B-lineage n=24, T-lineage n=6) were included in the study. For all cases it was possible to determine unique antigen expression pattern and to monitor MRD with the use of immunophenotyping at the level of 1/1000 cells. MRD was detected in 8/30 patients after induction and in 7/28 patients after consolidation tharapy (two patients relapsed during consolidation). For 11/30 patients the MRD resulted positive at least once.

At 20 months the relapse rate equaled 53% for patients with MRD detected after induction or consolidation and 28% for those with MRD always negative (p=0.08). The difference was more pronounced for patients with B-lineage ALL (67% vs. 26%, p=0.02). A single MRD evaluation after induction therapy had no significant prognostic value for the risk of relapse whereas there was a trend for higher relapse rate in B-lineage ALL patients with positive MRD after completion of consolidation therapy compared to those MRD-negative at that time-point (75% vs. 32%, p=0.06).

Results of the study prove the feasibility of immunophenotypic MRD evaluation in ALL. “Empty spaces” in addition to the standard “quadrans” analysis allows monitoring of the vast majority of patients regardless the immune subtype. Even with a small number of cases we were able to demonstrate its prognostic value for long-term outcome of adults with ALL.