Real-time PCR analysis of PML-RAR alpha in newly diagnosed acute promyelocytic leukaemia patients treated with arsenic trioxide as a front-line therapy.

Background: Recently, patients with acute promyelocytic leukaemia (APL) have experienced significant clinical gains after treatment with arsenic trioxide. However, the use of this agent as a front-line therapy for newly diagnosed patients is unclear.

Patients And Methods: Of 95 newly diagnosed APL patients, 85 patients who achieved complete remission (CR) were sequentially evaluated during a 4-60 month period by conventional RT-PCR. A total of 30 patients (six relapsed and 24 in continued CR) were selected and monitored by quantitative real-time PCR (RQ-PCR) assay. The PML-RARalpha fusion transcripts values were normalised to every 10(6) copies of G6PDH transcripts (NQ).

Results: RQ-PCR analyses showed a rapid rate of clearance of NQ levels during the courses of arsenic therapy. In the majority of patients in CR, the NQ levels were below 5 x 10(2) in peripheral blood (PB) samples. In all the relapsed cases with follow-up intervals of 1-6 months (median 3 months) clinical relapse was predictable by increasing NQ level above this threshold.

Conclusions: Our study highlights the usefulness of PB and the definition of threshold level for early prediction of relapse. The threshold level correlates well with risk of relapse; therefore, transcript ratio below the level should be regarded as a goal in the clinical management of this disease.