Kotrova M, Muzikova K, Mejstrikova E, Novakova M, Bakardjieva-Mihaylova V, Fiser K, Stuchly J, Giraud M, Salson M, Pott C, Brüggemann M, Füllgrabe M, Stary J, Trka J, Fronkova E. Blood. 2015 Aug 20;126(8):1045–7. doi: 10.1182/blood-2015-07-655159. IF: 10.45
MUDr. Michaela Kotrová, Department of Paediatric Haematology and Oncology
To the editor:
Minimal residual disease (MRD) monitoring via antigen receptor quantitative polymerase chain reaction (qPCR) is an important predictor of outcome in childhood acute lymphoblastic leukemia (ALL), is rigorously standardized within the EuroMRD consortium and has a greater sensitivity than flow cytometry (FC), which has been used in other trials. However, qPCR is laborious, expensive, and time consuming because of the development of patient-specific assays. MRD detection based on next-generation sequencing (NGS) of antigen receptor gene rearrangements is a promising tool that permits sequencing of large numbers of rearranged V-(D)-J segments and thus provides the picture of not only residual leukemia but also the normal immune repertoire of respective cells.
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In conclusion, the NGS risk group assignment is partly different from current approaches. This is mostly because of discrepancies in low-positive samples in SR/IR groups, but with no negative impact on final outcome. The NGS even provided a more precise prediction of relapse than qPCR at day 33 in our limited cohort. However, a prospective validation study comparing both methods will be needed to definitely accept NGS as the replacement for qPCR. A redefinition of stratification criteria for childhood ALL will be only the final step of a complex process that has just started. The main challenge in NGS-MRD methodology is standardization aiming at highly reproducible results between different centers, as it was achieved previously within the Euro-MRD group for qPCR. A European network, the EuroClonality-NGS Consortium, has been formed to standardize the workflow of analytics, preanalytics, and bioinformatics. Before this is accomplished, the methodology described in our study can serve as a broadly accessible and relatively inexpensive noncommercial solution for centers that do not perform antigen receptor qPCR but want to start using benefits of MRD monitoring in their clinical setting.
