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Lookup NU author(s): Professor Anthony Moorman
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P>The predictive value of molecular minimal residual disease (MRD) monitoring using polymerase chain reaction amplification of clone-specific immunoglobulin or T-cell Receptor rearrangements was analysed in 161 patients with non T-lineage Philadelphia-negative acute lymphoblastic leukaemia (ALL) participating in the UK arm of the international ALL trial UKALL XII/Eastern Cooperative Oncology Group (ECOG) 2993. MRD positivity (>= 10-4) in patients treated with chemotherapy alone was associated with significantly shorter relapse-free survival (RFS) at several time-points during the first year of therapy. MRD status best discriminated outcome after phase 2 induction, when the relative risk of relapse was 8 center dot 95 (2 center dot 85-28 center dot 09)-fold higher in MRD-positive (>= 10-4) patients and the 5-year RFS 15% [95% confidence interval (CI) 0-40%] compared to 71% (56-85%) in MRD-negative (< 10-4) patients (P = 0 center dot 0002) When MRD was detected prior to autologous stem cell transplantation (SCT), a significantly higher rate of treatment failure was observed [5-year RFS 25% (CI 0-55%) vs. 77% (95% CI 54-100%) in MRD-negative/< 10-4, P = 0 center dot 01] whereas in recipients of allogeneic-SCT in first complete remission, MRD positivity pre-transplant did not adversely affect outcome. These data provide a rationale for introducing MRD-based risk stratification in future studies for the delineation of those at significant risk of treatment failure in whom intensification of therapy should be evaluated.
Author(s): Patel B, Rai L, Buck G, Richards SM, Mortuza Y, Mitchell W, Gerrard G, Moorman AV, Duke V, Hoffbrand AV, Fielding AK, Goldstone AH, Foroni L
Publication type: Article
Publication status: Published
Journal: British Journal of Haematology
ISSN (print): 0007-1048
ISSN (electronic): 1365-2141
Publisher: Wiley-Blackwell Publishing Ltd.
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