Patient characteristics and MP tolerance
| . | NUDT15 novel variant . | ||
|---|---|---|---|
| c.101G>C p.R34T . | c.103A>G p.K35E . | c.37_42delGGAGTC p.G17_V18del . | |
| Position at chr13rsID | 48037847rs766023281 | 48037849NA | 48037783-48037788rs746071566 |
| . | NUDT15 novel variant . | ||
|---|---|---|---|
| c.101G>C p.R34T . | c.103A>G p.K35E . | c.37_42delGGAGTC p.G17_V18del . | |
| Position at chr13rsID | 48037847rs766023281 | 48037849NA | 48037783-48037788rs746071566 |
| . | Subject 1 . | Subject 2 . | Subject 3 . | Subject 4 . | Subject 5 . |
|---|---|---|---|---|---|
| Sex | Male | Male | Male | Female | Male |
| Age, y | 13.8 | 0.3 | 4.4 | 13.7 | 6.3 |
| Race | East Asian | East Asian | East Asian | African | European |
| Diagnosis | B-ALL | B-ALL | B-ALL | T-ALL | B-ALL |
| Protocol | MaSpore 2003 SR | TPOG-2002-infantile ALL | MaSpore 2003 IR | TOT XIIIB HR | TOT XVI LR |
| NUDT15 diplotype* | *1/p.R34T | *1/p.R34T | *2/p.K35E | *1/p.G17_V18del | *1/p.G17_V18del |
| TPMT genotype | WT | WT | WT | WT | WT |
| 4-wk tolerated MP dosage, mg/m2 per day | 17.9 | 16.4† | 8.5 | 82.5 for a 1-wk period‡ | 43.5 |
| Protocol MP dosage, mg/m2 per day | 50 | 25† | 50 | 75 for a 1-wk period‡ | 75 |
| . | Subject 1 . | Subject 2 . | Subject 3 . | Subject 4 . | Subject 5 . |
|---|---|---|---|---|---|
| Sex | Male | Male | Male | Female | Male |
| Age, y | 13.8 | 0.3 | 4.4 | 13.7 | 6.3 |
| Race | East Asian | East Asian | East Asian | African | European |
| Diagnosis | B-ALL | B-ALL | B-ALL | T-ALL | B-ALL |
| Protocol | MaSpore 2003 SR | TPOG-2002-infantile ALL | MaSpore 2003 IR | TOT XIIIB HR | TOT XVI LR |
| NUDT15 diplotype* | *1/p.R34T | *1/p.R34T | *2/p.K35E | *1/p.G17_V18del | *1/p.G17_V18del |
| TPMT genotype | WT | WT | WT | WT | WT |
| 4-wk tolerated MP dosage, mg/m2 per day | 17.9 | 16.4† | 8.5 | 82.5 for a 1-wk period‡ | 43.5 |
| Protocol MP dosage, mg/m2 per day | 50 | 25† | 50 | 75 for a 1-wk period‡ | 75 |
B-ALL, B-cell acute lymphoblastic leukemia; HR, high risk; IR, intermediate risk; LR, low risk; NA, not applicable; rsID, reference SNP ID; SR, standard risk; T-ALL, T-cell acute lymphoblastic leukemia; TPOG, Taiwan Pediatric Oncology Group; WT, wild-type.
The *1 represents the NUDT15 wild-type haplotype, and *2 represents the haplotype with both p.V18_ V19insGV and p.R139C variants.
Patient received MP at 17.9 and 15.2 mg/m2 per day for 17 and 22 days, respectively, during remission, but did not complete the entire treatment regimen due to relapse.
Maintenance therapy (120 weeks) for TOT XIIIB HR consisted of drug pairs administered in weekly rotation. Therefore, the standard MP exposure was 75 mg/m2 per day for only 1 week, followed by other drug pairs for the subsequent 3 weeks. With MP dosed for this short duration, the patient did not experience toxicity. It is likely her actual long-term MP tolerance would be low if MP were given in a continuous fashion similar to other ALL treatment protocols.