Monitoring of BCR-ABL Transcirpt Levels after Discontinuation of Imatinib Therapy in Chronic Myelogenous Leukemia Patients Achieving Complete Cytogenetic Response.

Background Imatinib induces a high complete cytogenetic response (CCR) rate in chronic myelogenous leukemia (CML). None of the studies addressed the important question of how long imatinib treatment should be continued. To answer this question, we tried to assess the minimal residual disease after cessation of imatinib in patients achieving CCR.

Methods A total of 23 patients were enrolled and their disease status at the start of imatinib was chronic phase in 7, accelerated phase in 3, blast crisis in 1, and post-transplant relapse in 12 patients. All the patients were in CCR when imatinib was discontinued and BCR-ABL transcript was undetectable in 9 of them. Minimal residual disease was monitored using nested RT-PCR, real-time quantitative RT-PCR, and conventional cytogenetics.

Findings Duration of imatinb treatment and CCR before cessation of imatnib was a median of 13 months (range, 6–25 months) and 10 months (range, 1–22 months), respectively. After cessation of imatinib treatment, cytogenetic relapse was observed in 12 (53%) of 23 patients and hematological relapse was followed in 8 (67%) of them. Extramedullary relapse was documented in 1 patient. Prior allogenetic transplantation, molecular remission at the time of cessation, and time to CCR were potential variables affecting probability of cytogenetic relapse. Normalized BCR-ABL transcript level progressively increased after cessation of imatinib in all but 3 patients who had been treated with allogeneic transplantation. Restart of imatinib induced down-regulation of normalized BCR-ABL transcript level in 5 patients with available data.

Interpretation Imatnib should be maintained in the most of patients who achieve a short duration of CCR as in the cases with interferon treatment. However, this study suggests that it seems possible to stop imatinib treatment in the minority of CML patients who was treated with allogeneic transplantation.