Measurement of residual leukemia during remission in childhood acute lymphoblastic leukemia.
BACKGROUND
Complete remission of B-precursor acute lymphoblastic leukemia (ALL) has traditionally been defined as the near absence of lymphoblasts in a light-microscopical examination of stained bone marrow smears, but a patient in remission may still harbor up to 10(10) leukemia cells. We investigated whether there is a relation between the outcome of treatment and submicroscopic evidence of residual disease.


METHODS
We conducted a prospective study of patients during a first clinical remission using a quantitative polymerase-chain-reaction (PCR) assay capable of detecting 1 viable leukemia cell among 200,000 normal marrow mononuclear cells and a clonogenic blast-colony assay. Bone marrow specimens from 24 children were sequentially evaluated during a five-year period, and the results were compared with the clinical outcome.


RESULTS
Seven patients relapsed and 17 remained in remission 2 to 35 months after the completion of treatment. The levels of residual leukemia-cell DNA in the two groups were significantly different (P<0.001; 95 percent confidence interval for the difference in the mean log-transformed ratio of leukemia-cell DNA to normal bone marrow-cell DNA, 0.38 to 1.28). Autoregression analyses identified trends for individual patients that were associated with relapse. Despite continued remission in 17 patients, evidence of residual leukemia was detected by PCR in 15 and by both PCR and blast-colony assays in 7.


CONCLUSIONS
Molecular signs of residual leukemia can persist up to 35 months after the cessation of chemotherapy in children with ALL in remission. This suggests that eradication of all leukemia cells may not be a prerequisite for cure.
Roberts
W M
WM
Division of Pediatrics, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Estrov
Z
Z
Ouspenskaia
M V
MV
Johnston
D A
DA
McClain
K L
KL
Zipf
T F
TF
D001853:Bone Marrow / Q000473:pathology*; D002648:Child; D002999:Clone Cells; D004273:DNA, Neoplasm / Q000032:analysis; D018572:Disease-Free Survival; D006801:Humans; D018365:Neoplasm, Residual; D014411:Neoplastic Stem Cells / Q000473:pathology*; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000473:pathology*; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D014410:Tumor Stem Cell Assay
D004273:DNA, Neoplasm