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Molecular remission as a therapeutic objective in acute promyelocytic leukemia.

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.

journal_name

Leukemia

journal_title

Leukemia

authors

Cicconi L,Fenaux P,Kantarjian H,Tallman M,Sanz MA,Lo-Coco F

doi

10.1038/s41375-018-0219-5

subject

Has Abstract

pub_date

2018-08-01 00:00:00

pages

1671-1678

issue

8

eissn

0887-6924

issn

1476-5551

pii

10.1038/s41375-018-0219-5

journal_volume

32

pub_type

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