EARLY DETECTION OF MINIMAL RESIDUAL DISEASE BY REVERSE-TRANSCRIPTASE POLYMERASE CHAIN-REACTION PREDICTS RELAPSE IN ACUTE PROMYELOCYTIC LEUKEMIA

The PML/RAR alpha fusion RNA can be detected in acute promyelocytic le ukemia (APL), cytogenetically characterized by the translocation t(15; 17). Our study included ten newly diagnosed patients with APL who wer e investigated during the course of their diseases using reverse trans cription polymerase chain reaction (RT-PCR). At diagnosis, aberrant fr agments with a size heterogeneity due to alternative spliced products were detected in all patients, we observed breakpoints within bcr3 (sh ort type) in two patients and bcr1 and 2 breakpoints (long type) in ei ght patients. Treatment consisted of all-trans retinoic acid (ATRA) in all patients; six patients received simultaneous cytostatic therapy d uring remission induction. At the time of complete hematological remis sion (CR), only two patients showed a negative RT-PCR result; eight of the ten patients were still PCR positive when nested primers were use d. Subsequently, eight patients received consolidation chemotherapy an d became PCR negative. Seven of eight patients are in continuous compl ete remission (median remission duration: 21 months, range: 11+-26+ mo nths). One patient of the chemotherapy group became PCR positive after 4 months in complete remission and relapsed after 6 months. The remai ning two patients who were treated only with ATRA relapsed, received i nduction chemotherapy, and are in second and third complete remission, respectively. In conclusion, PCR negativity can be achieved only by c hemotherapeutic consolidation; patients treated with ATRA alone remain PCR positive. Relapse is always preceded by a positive PCR result. Su rprisingly, also patients without measurable PML/RAR alpha-mRNA in seq uential analyses after cytostatic treatment became PCR positive and ex perienced relapse.