Allogeneic hematopoietic stem cell transplantation creates a persistent interpretive problem for pharmacogenomics: DNA recovered from an accessible post-transplant specimen may belong partly or predominantly to the donor while drug metabolism and response involve distinct recipient and donor-derived tissues. To extend genotype-guided prescribing theory by specifying when a specimen-derived pharmacogene result can be assigned to the biological compartment responsible for a drug-specific effect. This nonempirical analysis integrates verified work on post-transplant sampling, lineage-specific chimerism assays, pharmacogene mechanisms, transplant pharmacokinetics, and genotype-based prescribing. Genotype attribution is treated as a conditional inference linking specimen composition, molecular origin, tissue persistence, the relevant pharmacological process, and time relative to transplantation. The analysis separates evidence that identifies donor or recipient DNA from evidence that establishes enzyme or transporter function and clinical actionability. Recipient-derived nonhematopoietic DNA may be needed to recover inherited metabolic genotypes, whereas donor-derived hematopoietic genotype could matter for selected cellular effects; the latter remains a testable drug-specific proposition, not a general dosing rule. The appropriate genome for prescribing is defined by the drug-relevant functional compartment and a validated sampling-to-phenotype relationship, not by donor chimerism or sampling convenience alone.
IJPRAS
