Predictive Value of Flow Cytometric MRD Analysis in Childhood Acute Lymphoblastic Leukaemia at the End of Remission Induction Therapy.

Patients with acute lymphoblastic leukaemia (ALL) in morphological remission may still have up to 1010 residual malignant cells. Detection of minimal residual disease (MRD) at the end of induction therapy allows better estimation of the leukaemic burden and can help selection of appropriate therapeutic strategies. Flow cytometric (FC) detection of MRD is based on the identification of immunophenotypic combinations expressed on leukaemic cells but not on normal hematopoietic cells - leukaemia associated immunophenotypes (LAIPs). We prospectively analysed bone marrow samples from 77 patients who presented with ALL to our unit between 1999–2003 and attained morphological remission. These patients were treated on a standard protocol. Multiparameter FC identification of LAIPs was performed at various time points, as dictated by the treatment protocol. Our results show that flow cytometric MRD at the end of induction therapy is an independent and the most significant predictor of relapse, both on univariate and multivariate analysis. The relapse risk was 4% if day 28 MRD was <0.01% and 50% if day 28 MRD was >0.01% (p<0.05). We conclude that flow cytometric based MRD assays can be used to assess early response to treatment and predict relapse in a similar way to molecular MRD analysis at the end of induction therapy. Flow cytometric analysis of MRD offers the advantages of being cheaper, more widely available and has quicker turnaround times.