Evaluation of MRD after Administration of Imatinib by Measurement of Real-Time Quantitative PCR-Based Major bcr/abl mRNA.

Evaluation of minimal residual disease (MRD) provides prognostic information on various hematological malignancies. We describe here the efficacy of real-time quantitative polymerase chain reaction (RQ-PCR)-based analysis of major bcr/abl mRNA in cases of chronic myeloid leukemia (CML) and Ph-positive acute lymphoblastic leukemia (Ph+ALL), especially in cases administered imatinib mesilate (imatinib) followed by stem cell transplantation (SCT). Twenty-one patients with CML or Ph+ALL were enrolled as subjects to determine the usefulness of RQ-PCR-based measurement of bcr-abl/abl ratios. Seven of the 21 patients were administered imatinib before allogeneic SCT. Hematological relapse or failure of treatment by SCT was observed in 2 out of those patients who showed bcr-abl/abl ratios of more than 0.002%, and 5 of the 7 patients showed both RQ-PCR and RT-PCR negativity immediately after SCT. All of the 5 patients who were not administered imatinib before allogeneic SCT showed RQ-PCR negativity immediately after SCT, but the results of RT-PCR were positive in 3 patients at the same time points, and the results became negative by donor lymphocyte infusion (DLI) or appearance of graft-versus-host disease (GVHD). Administration of imatinib before SCT was thought to result in an earlier remission.

On the other hand, 8 patients who were administered imatinib without SCT showed a remarkable decrease in bcr-abl/abl ratios. However, the ratio gradually rose in one patient with Ph+ALL, enabling prediction of hematological relapse preceding detection by fluorescence in situ hybridization (FISH) analysis. Standardization of RQ-PCR analysis of bcr-abl mRNA will help prediction of early hematological relapse in patients with MRD.

In conclusion, RQ-PCR positivity immediately after SCT in patients pre-treated with imatinib suggests risk of recurrence.