LONG-TERM FOLLOW-UP OF MINIMAL RESIDUAL DISEASE IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA PATIENTS BY POLYMERASE CHAIN-REACTION ANALYSIS OFMULTIPLE CLONE-SPECIFIC OR MALIGNANCY-SPECIFIC GENE MARKERS

Two types of markers, namely the clone-specific markers including T-ce ll receptor (TCR) gamma, TCR delta, and Ig heavy-chain (IgH) gene rear rangements, and malignancy-specific fusion gene mRNA such as SIL-TAL-1 , BCR-ABL, and HRX-partner genes, were investigated by molecular biolo gy techniques in 65 Chinese patients with acute lymphoblastic leukemia (ALL). In combination, these markers were informative among 96% of pa tients. Minimal residual disease (MRD) was followed up in 23 of these patients with available materials over a period varying from 8 to 54 m onths with at least one leukemia-specific probe. In most children, MRD was decreased continuously to an ultimately undetectable level within 6 to 12 months after remission induction therapy. One patient exhibit ed low-level residual leukemic cells for 4 years before the MRD turned negative. Another patient remained in complete remission for 45 month s, although a positive signal tvas detected at 34 months using TCA del ta probe, but was negative with a TCR gamma marker which was positive at presentation. In three patients who relapsed, MRD either persisted through the clinical course or became positive and eventually increase d 3-11 months before clinical relapse. These data suggested that the c ombined use of multiple gene markers is a valuable tool for the PCR-ba sed MRD detection, since it con cover most ALL patients. Furthermore, longterm follow-up of MRD is helpful for determining the dosage as wel l as the period of maintenance chemotherapy and for predicting impendi ng relapse.