TPMT genotype in 814 patients with childhood ALL consecutively enrolled in trial ALL-BFM 2000 (reference cohort) and in 105 patients developing a SMN after treatment on ALL-BFM trials 79 to 2000
| TPMT genotype . | Reference cohort (n = 814) . | All SMN patients (n = 105) . | Hematologic SMN (n = 60) . | Hematologic SMN, AML/MDS only (n = 41) . | Brain tumor SMN (n = 21) . | Solid tumor SMN (n = 24) . | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| n (%) . | n (%) . | Odds ratio (95% CI) . | n (%) . | Odds ratio (95% CI) . | n (%) . | Odds ratio (95% CI) . | n (%) . | Odds ratio (95% CI) . | n (%) . | Odds ratio (95% CI) . | |
| Wild-type | |||||||||||
| *1/*1 | 755 (92.8) | 98 (93.3) | 1.00 | 56 (93.3) | 1.00 | 37 (90.2) | 1.00 | 20 (95.2) | 1.00 | 22 (91.7) | 1.00 |
| Heterozygotes | |||||||||||
| *1/*2 | 3 (0.4) | — | — | — | — | — | |||||
| *1/*3A | 42 (5.2) | 6 (5.7) | 3 (5.0) | 3 (7.3) | 1 (4.8) | 2 (8.3) | |||||
| *1/*3C | 9 (1.1) | 1 (1.0) | 1 (1.7) | 1 (2.4) | — | — | |||||
| *1/*9 | 1 (0.1) | — | — | — | — | — | |||||
| Total heterozygotes* | 55 (6.8) | 7 (6.7) | 0.98 (0.43-2.21),P = .93 | 4 (6.7) | 0.98 (0.34-2.80),P = .97 | 4 (9.8)† | 1.48 (0.51-4.31),P = .47 | 1 (4.8) | 0.69 (0.09-5.21),P = .72 | 2 (8.3) | 1.25 (0.29-5.44),P = .77 |
| Deficients | |||||||||||
| *2/*3A | 1 (0.1) | — | — | — | — | — | |||||
| *3A/*3A | 2 (0.2) | — | — | — | — | — | |||||
| *3A/*1118 | 1 (0.1) | — | — | — | — | — | |||||
| Total deficients | 4 (0.4) | — | n.c. | — | n.c. | — | n.c. | — | n.c. | — | n.c. |
| TPMT genotype . | Reference cohort (n = 814) . | All SMN patients (n = 105) . | Hematologic SMN (n = 60) . | Hematologic SMN, AML/MDS only (n = 41) . | Brain tumor SMN (n = 21) . | Solid tumor SMN (n = 24) . | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| n (%) . | n (%) . | Odds ratio (95% CI) . | n (%) . | Odds ratio (95% CI) . | n (%) . | Odds ratio (95% CI) . | n (%) . | Odds ratio (95% CI) . | n (%) . | Odds ratio (95% CI) . | |
| Wild-type | |||||||||||
| *1/*1 | 755 (92.8) | 98 (93.3) | 1.00 | 56 (93.3) | 1.00 | 37 (90.2) | 1.00 | 20 (95.2) | 1.00 | 22 (91.7) | 1.00 |
| Heterozygotes | |||||||||||
| *1/*2 | 3 (0.4) | — | — | — | — | — | |||||
| *1/*3A | 42 (5.2) | 6 (5.7) | 3 (5.0) | 3 (7.3) | 1 (4.8) | 2 (8.3) | |||||
| *1/*3C | 9 (1.1) | 1 (1.0) | 1 (1.7) | 1 (2.4) | — | — | |||||
| *1/*9 | 1 (0.1) | — | — | — | — | — | |||||
| Total heterozygotes* | 55 (6.8) | 7 (6.7) | 0.98 (0.43-2.21),P = .93 | 4 (6.7) | 0.98 (0.34-2.80),P = .97 | 4 (9.8)† | 1.48 (0.51-4.31),P = .47 | 1 (4.8) | 0.69 (0.09-5.21),P = .72 | 2 (8.3) | 1.25 (0.29-5.44),P = .77 |
| Deficients | |||||||||||
| *2/*3A | 1 (0.1) | — | — | — | — | — | |||||
| *3A/*3A | 2 (0.2) | — | — | — | — | — | |||||
| *3A/*1118 | 1 (0.1) | — | — | — | — | — | |||||
| Total deficients | 4 (0.4) | — | n.c. | — | n.c. | — | n.c. | — | n.c. | — | n.c. |
CI indicates confidence interval; MDS, myelodysplastic syndrome; n.c., not calculated; and —, not observed.
Multivariate odds ratios and 95% CI for TPMT heterozygosity, including immunophenotype, the only variable demonstrating a tendency of being associated with both development of a SMN (P = .09) as well as TPMT genotoype (P = .07) in the model: all patients, odds ratio 0.93, 95% CI 0.41-2.11; hematologic SMN, odds ratio 0.91, 95% CI 0.31-2.62; AML/MDS only, odds ratio 1.42, 95% CI 0.49-4.15; brain tumor SMN, odds ratio 0.59, 95% CI 0.07-4.59; other solid tumor SMN, odds ratio 1.28, 95% CI 0.29-5.65.
Two of the 4 patients presented with AML and 2 with MDS.