Disappearance of PML/RAR alpha acute promyelocytic leukemia-associated transcript during consolidation chemotherapy

Abstract

BACKGROUND AND OBJECTIVE: Acute promyelocytic leukemia (APL) (M3 according to FAB classification) is a subtype of acute myelogenous leukemia characterized by a specific t(15;17) (q22;q12) chromosomal translocation. The majority of APL patients achieve morphologic remission after induction chemotherapy. They can be followed from this point by cytogenetic and molecular analysis of the persistence of the PML/RAR alpha transcript. In order to determine the influence of successive courses of consolidation chemotherapy on clinical and molecular outcome, APL patients treated with all-trans retinoic acid (ATRA) and chemotherapy (AIDA-GIMEMA-LAP0493 protocol) were investigated. DESIGN AND METHODS: Twenty-four APL patients (pts) (15 males; 9 females) were studied by RT-PCR and cytogenetic analysis at diagnosis, after induction chemotherapy, at each point after any of three consolidation courses, and every 3 months during the first years of maintenance therapy. The median follow-up was 24 months (mths) (range 7-40 mths). RESULTS: All pts achieved hematologic remission after induction chemotherapy. Our results demonstrate that the majority (87%) of APL patients were still molecularly positive for the APL associated transcript after induction chemotherapy, while the majority (80%) of APL patients became PCR-after the second consolidation chemotherapy. INTERPRETATION AND CONCLUSIONS: The role of the third consolidation chemotherapy course in converting patients with persistent molecular evidence of disease from PCR+ to PCR- was minimal. We confirm the validity of molecular follow-up after single courses of chemotherapy in monitoring the role of molecular remission.