Prognostic Relevance of Persisting Minimal Residual Disease in Children with ALL and Slow Early Response to Chemotherapy

Detection of minimal residual disease (MRD) at early treatment time points is widely used to stratify children with acute lymphoblastic leukemia into risk-directed treatments. The role of MRD during the late treatment course is still unclear. Internal laboratory studies in a limited number of cases had indicated that detectable MRD before reinduction therapy (TP3) was highly associated with relapse in children of the medium-risk (MR) group with slow-early-response (SER) to therapy. In this project, it was investigated whether the importance of MRD at TP3 in SER could be confirmed in a larger cohort. RQ-PCR of immunoglobulin/T-cell receptor gene rearrangements was used to determine MRD in cryopreserved bone marrow samples from TP3 of 74 patients with SER of the ALL-BFM 2000 study. The results were classified as positive/quantifiable, positive/not quantifiable and negative. Children with quantifiable MRD positivity at TP3 had significantly poorer 8-year EFS (9 %) compared to positive/not quantifiable (58 %) and negative (63 %) MRD. Persisting MRD at TP3 led to high relapse risk, but negative MRD at TP3 could not prevent relapse in SER patients treated with an MR chemotherapy.