Table 3.
Comparison of Thiopurine Treatment and AEs According to NUDT15 Genotypes
| NUDT15 genotype | C/C (n = 158) | C/T (n = 46) | T/T (n = 6) | P-value (C/C vs. C/T) | |||
|---|---|---|---|---|---|---|---|
| Sex (male/female) | 106/52 | 27/19 | 2/4 | 0.293 | |||
| Age (yr) | 40 (27–51) | 41 (31–49) | 42 (28–53) | 0.860 | |||
| Thiopurine use | 108 (68.4) | 30 (65.2) | 4 (66.7) | 0.689 | |||
| 6-MP | 42 (38.9) | 20 (66.7) | 2 (50.0) | 0.016 | |||
| AZA | 66 (61.6) | 10 (33.3) | 2 (50.0) | 0.011 | |||
| Discontinuation | 11 (10.2) | 3 (10.0) | 4 (100) | 0.976 | |||
| Switching | 7 (4.4) | 2 (4.3) | - | 0.919 | |||
| Duration of treatment (mo) | 27.0 (10.0–63.0) | 26.0 (11.0–57.0) | 0.5 (0.4–0.9) | 0.691 | |||
| Initial dose of 6-MP (mg/kg/day)a | 0.28 (0.10–0.74) | 0.26 (0.14–0.42) | 0.33 (0.26–0.38) | 0.555 | |||
| Maintenance dose of 6-MP (mg/kg/day)a | 0.48 (0.37–0.65) | 0.25 (0.19–0.36) | - | < 0.001 | |||
| 6-TGN levels (pmol/8 × 108 RBCs) | 328 (224–528) | 230 (104–298) | - | 0.014 | |||
| Total AEs | 19 (17.6) | 11 (36.7) | 4 (100) | 0.025 | |||
| Leukopenia (WBC < 3,000) | 5 (4.6) | 9 (30.0) | 4 (100) | < 0.001 | |||
| Early leukopenia (within 8 wk) | 1 (0.9) | 2 (6.7) | 3 (75.0) | 0.056 | |||
| Grade 2 (WBC < 3,000) | 1 | 2 | 2 | ||||
| Grade 3 (WBC < 2,000) | 0 | 0 | 1 | ||||
| Grade 4 (WBC < 1,000) | 0 | 0 | 0 | ||||
| Late leukopenia (after 8 wk) | 4 (3.7) | 7 (23.3) | 1 (25.0) | < 0.001 | |||
| Grade 2 (WBC < 3,000) | 2 | 2 | 1 | ||||
| Grade 3 (WBC < 2,000) | 2 | 5 | 0 | ||||
| Grade 4 (WBC < 1,000) | 0 | 0 | 0 | ||||
| Alopecia | 0 | 0 | 3 (75.0) | ||||
| Liver dysfunction | 4 (3.7) | 0 | 0 | ||||
| Elevation of serum amylase | 2 (1.9) | 0 | 0 | ||||
| Nausea and vomiting | 5 (4.6) | 1 (3.3) | 1 (25.0) | 0.924 | |||
| Fever | 4 (3.7) | 1 (3.3) | 0 | 0.924 | |||
Values are presented as median (interquartile range) or number (%).
a
AZA doses were adjusted to 6-MP equivalents using a conversion factor of 2.08.
AEs, adverse events; 6-MP, 6-mercaptopurine; AZA, azathioprine; 6-TGN, 6-thioguanine nucleotides; RBCs, red blood cells; WBC, white blood cell.