Detection of Minimal Residual Disease Using Real-Time Quantitative Polymerase Chain Reaction in Children with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia / 대한소아혈액종양학회지

ABSTRACT

PURPOSE: The aim of this study was to detect the bcr-abl/abl mRNA ratio of the patients with Philadelphia chromosome positive childhood acute lymphoblastic leukemia (ALL) after completing chemotherapy or bone marrow transplantation (BMT), by the real-time quantitative polymerase chain reaction (RQ-PCR). It was also to be proved that these quantitative changes of minimal residual disease (MRD) can be used for early detection of relapse and for treatment response. METHODS: The subjectives of this study were 8 patients diagnosed with Philadelphia chromosome positive childhood acute lymphoblastic leukemia (ALL) from January to November in the year 2001. The change of bcr/abl transcript with chemotherapy were evaluated in 6 patients out of them. RESULTS: All of 6 patients reached in hematologically complete remission state by the induction chemotherapy, but the MRD was cytogenetically detected in 5 out of the 6 patients. While the 5 patients were in the hematologically remission state, only 1 patient had the cytogenetical remission after the serial consolidation chemotherapy at the maximum of 6 times. The increased amount of bcr-abl/abl mRNA ratio (up to 10 3) were correlated with the positive real time polymerase chain reaction (RT-PCR) result, but the results of bcr/abl fluorescent in situ hybridization (FISH) were not correlated with the results of RT-PCR and bcr-abl/abl mRNA ratio. The change of bcr/abl transcript was evaluated in 4 patients after BMT. The RT-PCR in 1 month after BMT showed the negative result in all 4 patients in our study. The bcr-abl/abl mRNA ratio in all patients was constantly decreased. However, bcr-abl/abl mRNA ratio in one patient was increased in 6 months after BMT, and the results of second RT-PCR showed positive value, which made the cyclosporine be discontinued immediately. In the 9th month following BMT, the ratio of bcr-abl/abl mRNA was abruptly decreased and the results of second RT-PCR showed the negative value. CONCLUSION: We suggest that RT-PCR or RQ-PCR rather than FISH is more sensitive and effective for detection of MRD. We also observed that Philadelphia chromosome positive childhood ALL could be cured with the BMT, not with the chemotherapy alone, by monitoring MRD.