A promising method indicates success

Dresden, 23.02.2016 - Allogeneic stem cell transplantation (HSCT) is an effective therapy for hematopoietic disorders such as Acute Myeloid Leukemia (AML) or the Myelodysplastic Syndrome (MDS). However, imminent relapse remains a serious problem. Routinely, monitoring of minimal residual disease (MRD) by diseases-specific markers such as FLT3, NPM1, BCR-ABL, AML-ETO and others is performed to signify threatening relapse as early as possible. However, a high number of patients lack specific disease-markers. For such patients quantitative chimerism monitoring in the posttransplantation period is widely discussed to serve as surrogate MRD-marker, representing a prognostic factor that predicts the clinical outcome. 

Biotype Diagnostic developed a quantitative diagnostics for chimerism monitoring after Allo-HSCT. By the combination of two established methods, Biotype has engineered a product that allows engraftment control along with quantitative chimerism monitoring. Detecting only 1 - 5 diseased blood cells in 10.000 healthy cells this new product increases the sensitivity by a factor of 20 compared to standard methods.

Biotype’s DIPscreen/DIPquant strategy for chimerism analysis deploys Insertion/Deletion DNA-polymorphisms (INDELs) that allow an allele-specific quantification by qPCR. More than 50 assays are available that were shown to accomplish a detection limit lowered to 0.05 % sensitivity. The DIP-marker assortment was strictly led by scientific data and bioinformatics and can be predicted to be sufficiently informative to analyse > 90 % of donor/recipient pairs.

Together, this analysis reflects a new and promising strategy to reliably and quantitatively monitor the post-transplant progress. Based on highly accurate information it supports decision making and provides a quantitative monitoring opportunity for leukaemia patients lacking common disease-specific markers. This method may therefore help to elucidate the overall question whether quantitative chimerism analysis can serve as a surrogate MRD-marker in the posttransplant period.

Abbildung: Quantitative Strategy for Chimerism Monitoring – new method provides significant increase in sensitivity by factor 20 which translates into massive time advantage.