Table 2. Pharmacogenomic (PGx) discoveries relevant to HCT patient management.
| Gene | Specific drug implicated | Clinical correlates of polymorphism | Method of identification | Patient cohort studied | Reference (PMID) |
|---|---|---|---|---|---|
| TPMT | Thiopurines (azathioprine, 6-MP) | (homo) toxicity (het) lower risk of detectable MRD | Candidate | ALL | 10580024 |
| CNTNAP2, LEPR, CRHR1, NTAN1, SLC12A3, ALPL, BGLAP, APOB | Glucocorticoids | Hypertension | Candidate | ALL | 18496130 |
| CYP2C8 | Bisphosphonate | Jaw osteonecrosis | GWAS | Multiple myeloma | 18594024 |
| IL15 | RIC | Likelihood of sustained MRD | GWAS | ALL | 19176441 |
| CYP3A5 | Tacrolimus | Toxicity, EFS | Candidate | ALL | 22215203 |
| ABCB1 | Cyclosporine | Nephrotoxicity | Candidate | Renal transplant | 15772250 |
| DPYD, TYMS. GSTP1. ABCC2 | Fluoropirimidine and oxaliplatin | Mucositis, neutropenia, GI toxicity | Candidate | Multiple cancers | 23047504 |
| VDR, CYP3A5 | Induction therapy | GI toxicity/infection | Candidate | ALL | 17264302 |
| CYP2C9 | Cyclophosphamide | Toxicity | Candidate | Thalasemia major | 22231460 |
| TYMS, VDR, PAI-1 | Glucocorticoids | Osteonecrosis | Microarray | Pediatric ALL | 15459215 |
| ABCC2 | Methotrexate | Plasma concentration | Candidate | ALL | 17112803 |
| SLCO1B1 | Methotrexate | Disposition | GWAS | ALL | 22147369 |
| ACP1 | GC | Osteonecrosis | GWAS | Pediatric ALL | 21148812 |
| CYP2B6 | Cyclophosphamide | Toxicity | Candidate | Leukemia | 19005482 |
| MTHFR | Busulfan Cyclophosphamide | Hyperbilirubinemia | Candidate | Adult HSCT | 18214047 |
| ITPA | Mecaptopurine | Reduced drug metabolism, febrile neutropenia | Candidate | Pediatric ALL | 20021291 |
| DHFR | EFS | Candidate | Pediatric ALL | 19861437 | |
| VDR | TRM | Candidate | Leukemia | 19005482 | |
| MTHFR | Mucositis | Candidate | Pediatric ALL and malignant lymphoma | 21509569 | |
| TYMS | TRM | Candidate | ALL | 11937185 | |
| MTHFR, TYMS | Increased risk of relapse | Candidate | Pediatric ALL | 15781665 |
Abbreviations: ALL, acute lymphoblastic leukemia; EFS, event-free survival; GC, glucocorticoids; GI, gastrointestinal; HCT, hematopoietic stem cell transplant; MRD, minimal residual disease; TRM, transplant-related mortality.
Method of identification refers to the original technology/approach used to discover the association. Patient cohort refers to the original patient population in which this variant was first shown to be linked to variation in drug response. Where blank, no specific drug was reported in the study.