Comparison of methods for assessment of minimal residual disease in childhood B-lineage acute lymphoblastic leukemia

Brisco, MJ Sykes, PJ Hughes, E Neoh, SH Snell, LE Dolman, G Peng, LM Toogood, IRG Cheney, K Rice, MS Story, CJ Morley, AA

Mj. Brisco et al., Comparison of methods for assessment of minimal residual disease in childhood B-lineage acute lymphoblastic leukemia, LEUKEMIA, 15(3), 2001, pp. 385-390

22

INGLESE

Article

Onconogenesis & Cancer Research

LEUKEMIA

0887-6924 → ACNP

15

3

2001

385 - 390

ISI

0887-6924(200103)15:3<385:COMFAO>2.0.ZU;2-I

The level of minimal residual disease (MRD) early in treatment of acute lym phoblastic leukemia (ALL) strongly predicts the risk of marrow relapse. As a variety of methods of varying complexity have been separately used for de tecting and quantifying MRD, we compared the prognostic utility of three me thods measurement of blast percentage on day 14 of treatment, detection of monoclonality on day 14 or day 35, and measurement of MRD by PCR-based limi ting dilution analysis on day 14 or day 35, The study group comprised 38 ch ildren aged 1-15 with Philadelphia-negative B-lineage ALL who were uniforml y treated and followed until relapse or for a minimum of 5 years. We also s tudied some of the technical factors which influence the ability to detect MRD, Measurement of blast percentage on day 14 by an expert morphologist, d etection of monoclonality on day 35, and PCR-based measurement of MRD level s on days 14 and 35 all showed significant ability to divide patients into prognostic groups. Measurement of blast percentage on day 14 by routine mor phology or detection of monoclonality on day 14 were not useful. The qualit y of DNA samples varied greatly, as determined by amplifiability in the PCR , However, virtually all amplifiable leukemic targets in a sample were dete ctable which suggests that the level of detection achieved by limiting dilu tion analysis is essentially determined by the amount of DNA which it is pr acticable to study. We conclude that quantification of MRD at the end of in duction provides the full range of prognostic information for marrow relaps e but is complex; detection of monoclonality on day 35 is simple and has go od positive predictive value; and quantification of MRD on day 14 merits fu rther study. PCR-based methods for measurement of MRD levels should incorpo rate a correction for variation in DNA amplifiability.