Methods of monitoring immunosuppressive therapies in a transplant recipient

A method of treating transplant rejection in a transplant recipient of an organ transplant from a transplant donor without consideration of genotype information from the transplant recipient or donor, the method comprising:

• (a) providing cell-free DNA from a sample obtained from the transplant recipient;
• (b) amplifying, in a targeted manner from the cell-free DNA, each single nucleotide polymorphism (SNP) in a panel of two or more SNPs, wherein each SNP in the panel is selected to have greater than 0.4 minor allele frequency and low linkage with each other;
• (c) sequencing the amplified SNPs to obtain homozygous or heterozygous allele distribution patterns of the SNPs in the panel;
• (d) assaying, without consideration of genotype information from the transplant donor or recipient, variance in homozygous or heterozygous allele distribution patterns of the SNPs in the panel as compared to expected homozygous or heterozygous allele distribution patterns to determine the level of donor-derived cell-free DNA;
• (e) diagnosing rejection of the transplanted organ in the transplant recipient by discriminating rejection from non-rejection of the transplanted organ, wherein a level of donor-derived cell-free DNA above a suitable threshold is indicative of transplant rejection, and wherein the transplant recipient is diagnosed as exhibiting transplant rejection;
• and
• (f) treating the transplant rejection by administering an immunosuppressive therapy to the transplant recipient diagnosed as exhibiting transplant rejection;
• wherein individual genotyping of the donor and the recipient across the genome as a whole or portions thereof to determine which allele of each SNP in the panel belongs to the donor and the recipient is not performed.