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Disappearance of PML/RAR alpha acute promyelocytic leukemia-associated transcript during consolidation chemotherapy
G Martinelli1, E Ottaviani, N Testoni
1Institute of Hematology and Medical Oncology Seràgnoli, University of Bologna, Italy. seragnol@kaiser.alma.unibo.it
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.
Insights
Consolidation chemotherapy effectively clears the acute promyelocytic leukemia (APL) transcript, with most patients achieving molecular remission after the second course. The third consolidation course showed minimal additional benefit in molecular clearance for APL patients.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Acute promyelocytic leukemia (APL) is a distinct subtype of acute myelogenous leukemia characterized by the t(15;17) translocation.
- Most APL patients achieve remission after induction chemotherapy but require monitoring for the PML/RAR alpha transcript.
- The AIDA-GIMEMA-LAP0493 protocol investigates the impact of consolidation chemotherapy on molecular outcomes in APL.
Purpose of the Study:
- To assess the influence of sequential consolidation chemotherapy courses on clinical and molecular outcomes in APL patients.
- To evaluate the effectiveness of all-trans retinoic acid (ATRA) and chemotherapy in achieving molecular remission.
- To determine the role of molecular follow-up in monitoring treatment response.
Main Methods:
- Twenty-four APL patients were analyzed using RT-PCR and cytogenetics.
- Samples were collected at diagnosis, post-induction, post-consolidation courses, and during maintenance therapy.
- Median follow-up was 24 months.
Main Results:
- All patients achieved hematologic remission post-induction chemotherapy.
- 87% of APL patients remained molecularly positive for the APL transcript after induction.
- 80% of patients became PCR-negative after the second consolidation chemotherapy course.
Conclusions:
- The third consolidation chemotherapy course had a minimal impact on converting PCR-positive to PCR-negative status.
- Molecular follow-up is a valid method for monitoring the achievement of molecular remission in APL.
- Sequential consolidation chemotherapy is effective in achieving molecular clearance of the APL transcript.