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Clinical significance of low levels of minimal residual disease at the end of remission induction therapy in childhood acute lymphoblastic leukemia

2010; Elsevier BV; Volume: 115; Issue: 23 Linguagem: Inglês

10.1182/blood-2009-11-253435

1528-0020

Patricia Stow, Laura Key, Xiaohua Chen, Qiulu Pan, Geoffrey Neale, Elaine Coustan‐Smith, Charles G. Mullighan, Yinmei Zhou, Ching‐Hon Pui, Dario Campana,

Acute Myeloid Leukemia Research

Abstract Minimal residual disease (MRD) at the end of remission-induction therapy predicts relapse in acute lymphoblastic leukemia (ALL). We examined the clinical significance of levels below the usual threshold value for MRD positivity (0.01%) in 455 children with B-lineage ALL, using polymerase chain reaction amplification of antigen-receptor genes capable of detecting at least 1 leukemic cell per 100 000 normal mononucleated cells (0.001%). Of the 455 clinical samples studied on day 46 of therapy, 139 (30.5%) had MRD 0.001% or more with 63 of these (45.3%) showing levels of 0.001% to less than 0.01%, whereas 316 (69.5%) had levels that were either less than 0.001% or undetectable. MRD measurements of 0.001% to less than 0.01% were not significantly related to presenting characteristics but were associated with a poorer leukemia cell clearance on day 19 of remission induction therapy. Patients with this low level of MRD had a 12.7% (± 5.1%; SE) cumulative risk of relapse at 5 years, compared with 5.0% (± 1.5%) for those with lower or undetectable MRD (P < .047). Thus, low levels of MRD (0.001%-< 0.01%) at the end of remission induction therapy have prognostic significance in childhood ALL, suggesting that patients with this finding should be monitored closely for adverse events.