Monitoring of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia — Preliminary Data from a Prospective Study
Minimal residual disease (MRD) was evaluated in bone marrow samples prospectively obtained from children with acute lymphoblastic leukemia (ALL) during complete remission (CR), using allele-specific markers based on junctional regions generated through the recombination of T-cell receptor δ (TCRδ), TCRγ, immunoglobulin K (IgK) chain or sil-tal genes. Suitable TCRδ, TCRγ, IgK and sil-tal recombinations were identified by Southern blot analysis in 27/29 (93%) T-ALL and 152/174 (87%) precursor-B ALL patients. Two or more independent markers were available in 156/203 (77%) cases. Allele-specific oligonucleotides (ASO) were used either as clonospecific probes or primers and reached a detection level between 10−4 to 10−6 in 192/212 (91%) recombined alleles. Six hundred and forty-one remission samples from 112 cases (20 relapsed, 92 in continuous CR) have been analyzed so far. MRD was demonstrated during a period of 6 months after diagnosis in the vast majority of patients who relapsed during the course of treatment. In contrast, 88% of the patients who remained in continuous CR became PCR-negative within 3 months of treatment. Remarkably, 58% of them achieved PCR-negativity within 1 month. Our data suggest that the MRD status at 3 and 6 months after diagnosis may represent a clinically relevant parameter for a second stratification of childhood ALL.
KeywordsAcute Lymphoblastic Leukemia Minimal Residual Disease Junctional Region Childhood Acute Lymphoblastic Leukemia Continuous Complete Remission
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