Clinical significance of peripheral blood minimal residual disease detection at the eighth day of induction therapy in children with B-cell acute lymphoblastic leukemia

Objective To analyze clinical significance of peripheral blood minimal residual disease (MRD) detection at the eighth day of induction therapy in evaluating prognosis of children with B-cell acute lymphoblastic leukemia (B-ALL) based on the TARGET database.

Methods Data of 359 B-ALL children with peripheral blood MRD at the eighth day of induction therapy and bone marrow MRD at 29th day of induction therapy from year 2000 to 2010 were downloaded from TARGET database. Spearman correlation analysis was used to explore the association between peripheral blood MRD at the eighth day and morphology of bone marrow cells in the same period. Kaplan-Meier curve was used to analyze the relationship between peripheral blood MRD at the eighth day and event free survival (EFS), and further analyze the relationship of combined detection of peripheral blood MRD at the eighth day and bone marrow MRD at 29th day with EFS. Cox regression model was used to analyze the risk factors for prognosis in B-ALL children.

Results Spearman correlation analysis showed that the level of peripheral blood MRD at the eighth day was positively correlated with the proportion of bone marrow blasts at day 8 (r=0.620, P < 0.001). Survival analysis showed that there were significant differences in 5-year EFS rates of MRD < 0.01%, 0.01% to 0.10%, 0.10% to 1.00% and ≥ 1.00% in peripheral blood at the eighth day(P < 0.001). Double-negative patients with peripheral blood MRD at the 8th day and bone marrow MRD at the 29th day had the best prognosis, followed by single-positive patients, and double-positive patients had the worst prognosis, the differences were statistically significant (P < 0.001). The combined MRD at both time points showed that the prognosis was best in the double-negative group, followed by the single-positive group and worst in the double-positive group (P < 0.001). In children with negative bone marrow MRD at day 29, the 5-year EFS rate of children negative for MRD in peripheral blood at the eighth day was significantly higher than those positive for MRD in peripheral blood at the eighth day(P=0.009). Cox regression analysis showed that MRD ≥ 0.10% in peripheral blood on day 8(HR=1.967; 95%CI, 1.234 to 3.134; P=0.004), MRD ≥ 0.01% in bone marrow on day 29 (HR=2.076; 95%CI, 1.423 to 3.027; P < 0.001) were independent risk factors for EFS in B-ALL children.

Conclusion Peripheral blood MRD at day 8 of induction therapy has important clinical significance in prognosis assessment in children with B-ALL, and can be used as a strong supplement for the prognosis assessment of B-ALL children with bone marrow MRD at day 29.