Minimal residual disease quantification predicts relapse in children with ALL

Zhou J et al. (2007) Quantitative analysis of minimal residual disease predicts relapse in children with B-lineage acute lymphoblastic leukemia in DFCI ALL Consortium Protocol 95–01. Blood 110: 1607–1611

Minimal residual disease (MRD) is a significant prognostic factor in childhood acute lymphoblastic leukemia (ALL). Previous studies have shown the utility of real-time quantitative polymerase chain reaction (RQ-PCR) in the detection of MRD but were limited by the small number of participants. Zhou et al. have reported the clinical utility of RQ-PCR analysis of MRD in a large cohort of children with ALL.

The study included 284 children with B-lineage ALL in whom MRD was quantified by RQ-PCR to assess immunoglobulin heavy chain and T-cell receptor rearrangements. MRD was undetectable in 176 (62.0%) children; the 5-year risk of relapse in this group was 5%. The 5-year risk of relapse was much higher at 44% in the 108 (38.0%) children with detectable MRD. Moreover, there was a significant linear association of MRD with risk of relapse (P <0.001). On the basis of recursive partitioning analyses and clinical characteristics, the optimum cutoff level of MRD to predict relapse was identified as 1 leukemic cell per 10³ normal cells. For children with 'low' MRD (<1 leukemic cell per 10³ normal cells), the 5-year risk of relapse was 12%. Children with 'high' MRD (>1 leukemic cell perT10³ normal cells) had a 10.5-fold higher risk of relapse (72%, P<0.001), and a shorter time to relapse, than those with low MRD. MRD was the only significant independent predictive factor for risk of relapse (P <0.001), and there was no difference in the effect of MRD on risk of relapse between groups with different white blood cell counts.

This study shows that the quantification of MRD is the most important predictive factor in childhood ALL.