Diagnosis and follow-up of acute promyelocytic leukemia by detection of PML-RAR alpha gene rearrangement.

BACKGROUND

Rapid and accurate diagnosis of acute promyelocytic leukemia (APL) is essential for management of the disease, as all-trans retinoic acid (ATRA) therapy only induces complete remission in patients whose leukemic cells harbor a t(15;17) translocation, resulting in promyelocytic-retinoic acid receptor alpha (PML-RAR alpha) fusion transcripts. Moreover, a positive reverse transcriptase-polymerase chain reaction (RT-PCR) of PML-RAR alpha is reported to be a sensitive predictor of relapse in APL. This prompted us to use RT-PCR for rapid diagnosis and monitoring of minimal residual disease in APL patients.

METHODS

A nested RT-PCR technique was applied to detect the unique PML-RAR alpha fusion transcript in 13 APL patients. The test was applied to help clarify the diagnosis and monitor minimal residual disease after treatment.

RESULTS

All 13 APL patients had a positive test result: five patients with the S-form, seven patients with the L-form and one patient with the V-form of mRNA fusion transcripts. Minimal residual disease was prospectively monitored using this technique in six patients. Although in clinical remission, all four patients treated with ATRA alone were persistently PCR positive. Of the six patients receiving various forms of consolidation chemotherapy, one was persistently PCR positive while in remission and relapsed four months after the positive PCR test. Five patients were PCR negative. One of the five negative patients relapsed six months after a negative PCR test. The other four patients remained in remission, with a follow-up period of 25 to 46 months after the negative test. PCR was performed in two patients who had been in continuous remission for 3.5 and seven years, respectively. They both had negative PCR tests.

CONCLUSIONS

Nested RT-PCR is valuable for confirming the diagnosis of APL and in monitoring minimal residual disease. However, we found that negative test cannot absolutely exclude the possibility of future relapse.