Korean J Pediatr Hematol Oncol.  2002 Oct;9(2):177-185.

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

Affiliations
  • 1Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea. hakkikim@cmc.cuk.ac.kr

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.

Keyword

Philadelphia chromosome positive childhood acute lymphoblastic leukemia; Real-Time quantitative polymerase chain reaction; Minimal residual leukemic disease; Fluorescent in situ hybridization; Bone marrow transplantation; bcr/abl

MeSH Terms

Bone Marrow Transplantation
Child*
Consolidation Chemotherapy
Cyclosporine
Drug Therapy
Humans
In Situ Hybridization, Fluorescence
Induction Chemotherapy
Neoplasm, Residual*
Philadelphia Chromosome*
Polymerase Chain Reaction*
Precursor Cell Lymphoblastic Leukemia-Lymphoma*
Real-Time Polymerase Chain Reaction
Recurrence
RNA, Messenger
Cyclosporine
RNA, Messenger
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