Serial monitoring of 2 patients with detectable PRα/LBD mutations at diagnosis by high-sensitivity mutation-specific primer assay
| . | PRα/LBD mutation level . | PML-RARα transcript level* . | ||
|---|---|---|---|---|
| Marrow . | Blood . | Marrow . | Blood . | |
| Patient 27 (R276Q)† | ||||
| Diagnosis | < 1/1000 | ∼ 1/800‡ | 400 | 40 |
| Postinduction | < 1/1000 | ∼ 1/300‡ | 1 | NA |
| Postconsolidation | < 1/1000 | < 1/1000 | 0.003 | 0.007 |
| Maintenance 4 months | < 1/70 | < 1/70 | < 0.001 | < 0.001 |
| Maintenance 9 months | < 1/10 | NA | 0.01 | NA |
| Relapse/postmaintenance 1 month | > 90/100‡ | > 90/100‡ | 1000 | 10 |
| Patient 31 (K238E)† | ||||
| Diagnosis | ∼ 1/900‡ | ∼ 1/300‡ | 900 | 600 |
| Postinduction | ∼ 1/900‡ | < 1/1000 | 3 | 1 |
| Postconsolidation | < 1/1000 | < 1/800 | 0.007 | NA |
| Postmaintenance | < 1/1000 | < 1/1000 | < 0.001 | < 0.001 |
| Postmaintenance 8 months | < 1/1000 | < 1/1000 | 0.008 | < 0.001 |
| Postmaintenance 20 months | < 1/1000 | ∼ 1/1000‡ | 0.9 | < 0.001 |
| Relapse/postmaintenance 28 months | ∼ 1/700‡ | > 90/100‡ | 200 | 4 |
| . | PRα/LBD mutation level . | PML-RARα transcript level* . | ||
|---|---|---|---|---|
| Marrow . | Blood . | Marrow . | Blood . | |
| Patient 27 (R276Q)† | ||||
| Diagnosis | < 1/1000 | ∼ 1/800‡ | 400 | 40 |
| Postinduction | < 1/1000 | ∼ 1/300‡ | 1 | NA |
| Postconsolidation | < 1/1000 | < 1/1000 | 0.003 | 0.007 |
| Maintenance 4 months | < 1/70 | < 1/70 | < 0.001 | < 0.001 |
| Maintenance 9 months | < 1/10 | NA | 0.01 | NA |
| Relapse/postmaintenance 1 month | > 90/100‡ | > 90/100‡ | 1000 | 10 |
| Patient 31 (K238E)† | ||||
| Diagnosis | ∼ 1/900‡ | ∼ 1/300‡ | 900 | 600 |
| Postinduction | ∼ 1/900‡ | < 1/1000 | 3 | 1 |
| Postconsolidation | < 1/1000 | < 1/800 | 0.007 | NA |
| Postmaintenance | < 1/1000 | < 1/1000 | < 0.001 | < 0.001 |
| Postmaintenance 8 months | < 1/1000 | < 1/1000 | 0.008 | < 0.001 |
| Postmaintenance 20 months | < 1/1000 | ∼ 1/1000‡ | 0.9 | < 0.001 |
| Relapse/postmaintenance 28 months | ∼ 1/700‡ | > 90/100‡ | 200 | 4 |
See supplemental Methods and supplemental Figure 3 for serially plotted data. The “<” symbol indicates mutation not detected at indicated assay sensitivity limit.
NA indicates not available.
Numbers indicate the number of PML-RARα transcript copies per 105 copies of GAPDH.
Maintenance therapy for 1 year was single-agent ATRA in patient 27 and ATRA plus 6-mercaptopurine and methotrexate in patient 31.
Detectable at the indicated level (eg, 1 mutant copy detected per 800 total PML-RARα copies).