D. Levett et al., A demographic study of the clinical significance of minimal residual disease in children with acute lymphoblastic leukemia, MED PED ONC, 36(3), 2001, pp. 365-371
Background. Minimal residual disease (MRD) detected during remission might
predict outcome in children with acute lymphoblastic leukemia. No populatio
n-based studies have been carried out. We studied all children with ALL pre
senting over 5 years within a defined Population to determine its clinical
importance. Procedure. Patients were investigated for the presence of uniqu
e clonal rearrangements of IgH acid T-cell receptor genes. Unique patient s
pecific probes were used to detect, by polymerase chain reaction, the prese
nce of clonal markers indicating MRD in mononuclear cells obtained from mar
row samples at 1, 3, 5, and 24 months. The effect of MRD on event-free surv
ival was determined. Results, Seventy seven of 120 children with ALL had in
formative markers and samples of remission marrow suitable for testing. Pre
sence or absence of MRD did not significantly affect outcome. Gender (P < 0
.04) and white cell count (P < 0.04) were independent prognostic factors. A
nalysis of only those cases with detectable MRD showed that cases with one
blast per 100 mononuclear cells, or more, 28 days after starting treatment
did worse than those with lower levels (hazard ratio 7.77, P < 0.02). Concl
usions. Mere presence or absence of MRD is probably too crude a measure to
be useful and worse than other standard prognostic indicators. A threshold
of 10(-2) blasts at 28 days might be discriminatory, hut should not be over
-interpreted. The number of patients available for this analysis (31) was s
mall, the threshold and sampling points were arbitrary and any effects coul
d be treatment regimen-specific. Large prospective studies are needed. Med.
Pediatr. Oncol. 36:365-371, 2001. (C) 2001 Wiley-Liss, Inc.