MEASUREMENT OF RESIDUAL LEUKEMIA DURING REMISSION IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA

Background Complete remission of B-precursor acute lymphoblastic leuke mia (ALL) has traditionally been defined as the near absence of lympho blasts in a light-microscopical examination of stained bone marrow sme ars, but a patient in remission may still harbor up to 10(10) leukemia cells. We investigated whether there is a relation between the outcom e of treatment and submicroscopic evidence of residual disease. Method s 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 marro w mononuclear cells and a clonogenic blast-colony assay. Bone marrow s pecimens from 24 children were sequentially evaluated during a five-ye ar period, and the results were compared with the clinical outcome. Re sults Seven patients relapsed and 17 remained in remission 2 to 35 mon ths 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-transfo rmed ratio of leukemia-cell DNA to normal bone marrow-cell DNA, 0.38 t o 1.28). Autoregression analyses identified trends for individual pati ents 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 si gns of residual leukemia can persist up to 35 months after the cessati on of chemotherapy in children with ALL in remission. This suggests th at eradication of all leukemia cells may not be a prerequisite for cur e. (C) 1997, Massachusetts Medical Society.