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Molecularly targeted therapies have transformed the management of PML-RARA+ acute promyelocytic leukaemia (APL), with survival rates now exceeding 80% in clinical trials. This raises questions about the relevance of post-remission monitoring for PML-RARA transcripts, which has been widely used to predict relapse, guiding early intervention to prevent disease progression and the inherent risk of fatal bleeding. Given the treatability of haematological relapse, survival benefits would only be seen if monitoring could identify patients who could be salvaged if treated early but not later on, although it could be argued that early deployment of arsenic trioxide (ATO) can avoid inducing hyperleucocytosis and the associated differentiation syndrome, which frequently complicate treatment of frank relapse. However, given the low rates of relapse now observed in patients presenting with standard risk disease (i.e. presenting WBC<10×10(9)/l) who achieve early molecular remission, subsequent sequential minimal residual disease (MRD) monitoring confers only a marginal benefit, so could be avoided in this group. However, sequential MRD monitoring may still be of value in patients with high risk APL, although evidence tends to come from historically controlled studies. Therefore, there may remain a role for MRD monitoring in the most clinically challenging subsets of APL, but the continuing debate highlights the need for robust evidence in developing a more individualized approach to management of other subtypes of acute leukaemia.

Original publication

DOI

10.1016/j.beha.2014.04.002

Type

Journal article

Journal

Best Pract Res Clin Haematol

Publication Date

03/2014

Volume

27

Pages

53 - 61

Keywords

PML-RARA, acute promyelocytic leukaemia, minimal residual disease, personalized medicine, polymerase chain reaction, real-time quantitative, Anthracyclines, Antineoplastic Combined Chemotherapy Protocols, Arsenic Trioxide, Arsenicals, Biomarkers, Tumor, Cell Differentiation, Clinical Trials as Topic, Disease Management, Drug Monitoring, Drug Resistance, Neoplasm, Historically Controlled Study, Humans, Kaplan-Meier Estimate, Leukemia, Promyelocytic, Acute, Leukocytosis, Neoplasm, Residual, Oncogene Proteins, Fusion, Oxides, Real-Time Polymerase Chain Reaction, Remission Induction, Salvage Therapy, Tretinoin