Recommendations for (Pharmaco)Genetic Sampling in Patients Following Allogeneic Hematopoietic Stem Cell Transplantation

In patients receiving allogenic hematopoietic stem cell transplantation (aHSCT) complete chimerism is desired. However, this brings a challenge when non-invasive assessment of recipient germline DNA is required for genetic testing. Here, we aim to create awareness for (pharmaco)genetic sampling in patients following aHSCT based on a case report of a patient following aHSCT in which pharmacogenetic analysis was performed. Six pharmacogenetic genes were analyzed in DNA extracted from peripheral blood (pre- and post-transplant), buccal swab, and hair follicles. To investigate the presence of donor DNA in post-transplant samples, short tandem repeat and digital droplet PCR analysis were performed. DNA from post-transplantation peripheral blood and the buccal swab showed identical genotypes: CYP2C9*1/*1, CYP2C19*1/*2, CYP2D6*2/*9, CYP3A4*1/*1, VKORC1-1639TT, SLCO1B1*1/*5. Pre-transplant DNA showed different genotypes for CYP2D6 (*1/*2) and SLCO1B1 (*1/*1). Due to the low DNA amount extracted from hair follicles, only CYP2D6 and SLCO1B1 were examined, showing identical genotypes to pre-transplantation DNA. Short tandem repeat analysis showed that the buccal swab contained DNA from both donor and recipient. It was estimated that the buccal swab contained ~63% donor DNA, while DNA from hair follicles showed 0% donor DNA. In conclusion, pharmacogenetic profiling after allogenic HSCT should be done with consideration. Analysis of pre-transplant peripheral blood is preferred over buccal swab due to the presence of donor DNA contamination. DNA extracted from hair is also a reliable source; however, application might be restricted due to limited DNA yield.