Disease outcome of the 14 patients in late-CP with mutations
Patient no. . | Age, y/sex . | Y from diagnosis . | Mutation . | Mo mutation first detected . | Best response by 6 mo . | Status when mutation first detected . | Disease status (mo after imatinib start) . |
|---|---|---|---|---|---|---|---|
| 1 | 48/M | 3.4 | Met244Val | 7 | PHR | PHR | Primary imatinib resistance at 400 mg, dose increased to 600 mg at 6 mo because of lack of response, MCR achieved, 25% Ph (18) |
| 2 | 51/F | 6.9 | Leu248Val | 11 (all mutations) | CHR | PHR | Died in AP (14), acquired imatinib resistance |
| Gly250Glu | |||||||
| Ser417Tyr | |||||||
| Glu459Lys | |||||||
| 3 | 65/F | 5.3 | Gln252His (G>C) | 6 | PHR | MBC | Died in MBC (6.5), acquired imatinib resistance |
| 4 | 71/M | 2.4 | Gln252His (G>T) | 3 | PHR | PHR(3) | WCC decreased to 4.9 but was not sustained; WCC increased (3), MBC (11); died in MBC (15); the mutations were not detected when tested at 13 mo in MBC when double Ph-chromosome was present; acquired imatinib resistance |
| Gln252His (G>C) | 3 | ||||||
| Met351Thr | 8 | PHR (8) | |||||
| 5 | 65/M | 4.2 | Gln252His (G>C) | 18 | CHR | CHR | Autograft (16); recommenced imatinib 1 mo after autograft (17); mutation detected at 18 mo but not subsequently in MBC (19) when double Ph-chromosome was present; died in MBC (23); acquired imatinib resistance |
| 6 | 52/M | 4.3 | Tyr253Phe | 7 | CHR | PHR | Dose increased to 600 mg at 7 mo because of increased WCC, died in AP (12), acquired imatinib resistance |
| 7 | 27/M | 1.7 | Glu255Lys | 7 | CHR | PHR | Died from disease progression (11), acquired imatinib resistance |
| 8 | 60/M | 9.3 | Thr315lle | 8.5 | MCR | MCR | Ph percentage increased (12), dose increased to 600 mg because of 100% Ph positive (19), acquired imatinib resistance |
| 9 | 61/M | 1.1 | Phe317Leu | 4 | CHR | CHR | MBC 3 mo after mutation detected, acquired imatinib resistance, imatinib withdrawn (11), in remission after chemotherapy (19) |
| 10 | 59/F | 2.3 | Phe317Leu | 18 | CCR | CCR | Remains in CCR (20) |
| 11 | 53/F | 5.8 | Met351Thr | 8 | CCR | CCR | AP* at 9 mo, acquired imatinib resistance, dose increased to 600 mg (9), MCR maintained (21) |
| 12 | 67/M | 3.6 | Met351Thr | 6 | MCR | MCR | PHR (11), CP (15), dose increased to 500 mg, acquired imatinib resistance |
| 13 | 51/F | 6.3 | Glu355Gly | 16 | CCR | AP* | Acquired imatinib resistance, dose increased to 600 mg (17), MCR (22) |
| 14 | 51/M | 11.0 | Glu355Gly | 15 | MCR | MCR | MCR (17) |
Patient no. . | Age, y/sex . | Y from diagnosis . | Mutation . | Mo mutation first detected . | Best response by 6 mo . | Status when mutation first detected . | Disease status (mo after imatinib start) . |
|---|---|---|---|---|---|---|---|
| 1 | 48/M | 3.4 | Met244Val | 7 | PHR | PHR | Primary imatinib resistance at 400 mg, dose increased to 600 mg at 6 mo because of lack of response, MCR achieved, 25% Ph (18) |
| 2 | 51/F | 6.9 | Leu248Val | 11 (all mutations) | CHR | PHR | Died in AP (14), acquired imatinib resistance |
| Gly250Glu | |||||||
| Ser417Tyr | |||||||
| Glu459Lys | |||||||
| 3 | 65/F | 5.3 | Gln252His (G>C) | 6 | PHR | MBC | Died in MBC (6.5), acquired imatinib resistance |
| 4 | 71/M | 2.4 | Gln252His (G>T) | 3 | PHR | PHR(3) | WCC decreased to 4.9 but was not sustained; WCC increased (3), MBC (11); died in MBC (15); the mutations were not detected when tested at 13 mo in MBC when double Ph-chromosome was present; acquired imatinib resistance |
| Gln252His (G>C) | 3 | ||||||
| Met351Thr | 8 | PHR (8) | |||||
| 5 | 65/M | 4.2 | Gln252His (G>C) | 18 | CHR | CHR | Autograft (16); recommenced imatinib 1 mo after autograft (17); mutation detected at 18 mo but not subsequently in MBC (19) when double Ph-chromosome was present; died in MBC (23); acquired imatinib resistance |
| 6 | 52/M | 4.3 | Tyr253Phe | 7 | CHR | PHR | Dose increased to 600 mg at 7 mo because of increased WCC, died in AP (12), acquired imatinib resistance |
| 7 | 27/M | 1.7 | Glu255Lys | 7 | CHR | PHR | Died from disease progression (11), acquired imatinib resistance |
| 8 | 60/M | 9.3 | Thr315lle | 8.5 | MCR | MCR | Ph percentage increased (12), dose increased to 600 mg because of 100% Ph positive (19), acquired imatinib resistance |
| 9 | 61/M | 1.1 | Phe317Leu | 4 | CHR | CHR | MBC 3 mo after mutation detected, acquired imatinib resistance, imatinib withdrawn (11), in remission after chemotherapy (19) |
| 10 | 59/F | 2.3 | Phe317Leu | 18 | CCR | CCR | Remains in CCR (20) |
| 11 | 53/F | 5.8 | Met351Thr | 8 | CCR | CCR | AP* at 9 mo, acquired imatinib resistance, dose increased to 600 mg (9), MCR maintained (21) |
| 12 | 67/M | 3.6 | Met351Thr | 6 | MCR | MCR | PHR (11), CP (15), dose increased to 500 mg, acquired imatinib resistance |
| 13 | 51/F | 6.3 | Glu355Gly | 16 | CCR | AP* | Acquired imatinib resistance, dose increased to 600 mg (17), MCR (22) |
| 14 | 51/M | 11.0 | Glu355Gly | 15 | MCR | MCR | MCR (17) |
MBC indicates myeloid blast crisis; LBC, lymphoid blast crisis; PHR, partial hematologic response (blasts in blood + bone marrow < 15%); CHR, complete hematologic response.
Double Philadelphia chromosome.