The significance of peripheral blood minimal residual disease to predict early disease response in patients with B-cell acute lymphoblastic leukemia.

INTRODUCTION

Minimal residual disease (MRD) assessment in the bone marrow (BM) postinduction therapy is now standard of care in patients with B-cell acute lymphoblastic leukemia (B-ALL). We examined the use of peripheral blood as a less invasive means of MRD assessment at days 8 and 15 of induction therapy and established the cutoff level that would allow the most accurate prediction of BM MRD postinduction therapy.

METHODS

MRD analysis was performed using 5-color flow cytometry on BM and PB samples from 77 B-ALL patients. BM MRD at diagnosis and day 29 of induction therapy was analyzed using the following antibody combinations: CD45-PC5/CD19-PC7/CD20-PE/CD10-ECD/CD38-FITC/CD13 + CD33-PE/CD10-ECD/CD34-FITC. PB MRD at days 8 and 15 was determined using CD45-PC5/CD19-PC7/CD20-ECD/CD10-PE/CD34-FITC.

RESULTS

Day 8 and day 15 PB MRD levels were significantly higher in patients who had persistent BM MRD at day 29. PB MRD <0.01% at day 8 and/or day 15 predicted negative day 29 BM MRD status with 100% sensitivity but poor specificity. ROC curve analysis showed that day 15 PB MRD level of 0.1% yielded the highest sensitivity (78%) and specificity (82%).

CONCLUSIONS

PB MRD cutoff level of 0.1% at day 15 has the best predictive value in determining positive day 29 BM MRD.