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Molecular remission as a therapeutic objective in acute promyelocytic leukemia
- Source :
- Leukemia. 32:1671-1678
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- Acute promyelocytic leukemia (APL) is a subtype of acute leukemia characterized by a unique t(15;17) translocation generating the PML/RARA fusion gene and hybrid oncoprotein. Besides its critical role in leukemogenesis, this genetic aberration serves as a disease-specific biomarker for rapid diagnosis and monitoring of minimal residual disease (MRD). Moreover, PML/RARA is specifically targeted by All-trans retinoic acid (ATRA) and arsenic trioxide (ATO), two agents that synergistically act to induce degradation of the oncoprotein. Large clinical studies including two randomized trials conducted in newly diagnosed APL patients have shown that the ATRA-ATO combination is superior to conventional ATRA and chemotherapy both in terms of efficacy and safety. Preliminary studies using oral formulations of arsenic and ATRA suggest that oral arsenic is as effective and manageable as intravenous ATO. Following early retrospective studies indicating the prognostic relevance of PML/RARA monitoring, several prospective studies were conducted in large cohorts of APL patients enrolled in clinical trials with the aim of better assessing the prognostic value of longitudinal PCR testing. The results consistently showed that molecular remission (defined as negativization of the PCR test for PML/RARA) correlates with a significantly decreased risk of relapse, whereas persistence of PCR positivity for PML/RARA after consolidation or conversion from negative to positive during follow-up is strongly associated with hematologic relapse. Based on these data, various groups started using pre-emptive salvage therapy for patients who persisted PCR-positive after frontline consolidation or converted from negative to positive PCR during follow-up. Finally, several expert panels have recommended that molecular remission should be considered a therapeutic objective in APL, and molecular response has been adopted as a study endpoint in modern clinical trials.
- Subjects :
- 0301 basic medicine
Acute promyelocytic leukemia
Oncology
Cancer Research
medicine.medical_specialty
Salvage therapy
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Leukemia, Promyelocytic, Acute
Internal medicine
medicine
Humans
Arsenic trioxide
Salvage Therapy
Acute leukemia
business.industry
Remission Induction
Hematology
medicine.disease
Combined Modality Therapy
Minimal residual disease
Clinical trial
Leukemia
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
Biomarker (medicine)
business
Settore MED/15 - Malattie del Sangue
Subjects
Details
- ISSN :
- 14765551 and 08876924
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Leukemia
- Accession number :
- edsair.doi.dedup.....0aa340984d1529f659168ee1d8969454