Minimal residual disease is a significant predictor of treatment failure in non T-lineage adult acute lymphoblastic leukaemia: final results of the international trial UKALL XII/ECOG2993.
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 (> or =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 8.95 (2.85-28.09)-fold higher in MRD-positive (> or =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 = 0.0002) 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 = 0.01] 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.
Patel
Bella
B
Department of Haematology, University College London Medical School, London.
Rai
Lena
L
Buck
Georgina
G
Richards
Sue M
SM
Mortuza
Yeasmin
Y
Mitchell
Wayne
W
Gerrard
Gareth
G
Moorman
Anthony V
AV
Duke
Veronique
V
Hoffbrand
A Victor
AV
Fielding
Adele K
AK
Goldstone
Anthony H
AH
Foroni
Letizia
L
D000293:Adolescent; D000328:Adult; D002648:Child; D004812:Epidemiologic Methods; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016130:Immunophenotyping; D008875:Middle Aged; D018365:Neoplasm, Residual; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D012008:Recurrence; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult