Minimal/Measurable Residual Disease Monitoring in NPM1-Mutated Acute Myeloid Leukemia: A Clinical Viewpoint and Perspectives

International Journal of Molecular Sciences

Roberto Marasca¹  Mario Luppi¹  Leonardo Potenza¹  Fabio Forghieri¹  Patrizia Comoli² 

[1] Department of Medical and Surgical Sciences, Section of Hematology, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, Via del Pozzo 71, 41124 Modena, Italy;Pediatric Hematology/Oncology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Viale Golgi 19, 27100 Pavia, Italy;

关键词: NPM1-mutated acute myeloid leukemia;    molecular minimal/measurable residual disease monitoring;    prognostic thresholds and timepoints;    intensive chemotherapy;    allogeneic hematopoietic stem cell transplantation;    clinical outcome;   

DOI  :  10.3390/ijms19113492

来源: DOAJ

【 摘 要 】

Acute myeloid leukemia (AML) with NPM1 gene mutations is currently recognized as a distinct entity, due to its unique biological and clinical features. We summarize here the results of published studies investigating the clinical application of minimal/measurable residual disease (MRD) in patients with NPM1-mutated AML, receiving either intensive chemotherapy or hematopoietic stem cell transplantation. Several clinical trials have so far demonstrated a significant independent prognostic impact of molecular MRD monitoring in NPM1-mutated AML and, accordingly, the Consensus Document from the European Leukemia Net MRD Working Party has recently recommended that NPM1-mutated AML patients have MRD assessment at informative clinical timepoints during treatment and follow-up. However, several controversies remain, mainly with regard to the most clinically significant timepoints and the MRD thresholds to be considered, but also with respect to the optimal source to be analyzed, namely bone marrow or peripheral blood samples, and the correlation of MRD with other known prognostic indicators. Moreover, we discuss potential advantages, as well as drawbacks, of newer molecular technologies such as digital droplet PCR and next-generation sequencing in comparison to conventional RQ-PCR to quantify NPM1-mutated MRD. In conclusion, further prospective clinical trials are warranted to standardize MRD monitoring strategies and to optimize MRD-guided therapeutic interventions in NPM1-mutated AML patients.

【 授权许可】

Unknown