Clinical course and mutation analysis of patients treated with imatinib
| Patient . | Age (y)/sex . | Disease status at start of imatinib . | Duration of imatinib treatment (mo) . | Best response to imatinib . | Response at time of mutation analysis . | Time of mutation analysis* . | Mutation result . | Nucleotide substitution (GenBank accession no. M14752) . |
|---|---|---|---|---|---|---|---|---|
| Resistant | ||||||||
| 1 | 61 F | CP (3rd) | 9 | CCR | LBC | Before study | NM | — |
| CP (3rd) | Before study | NM | — | |||||
| CCR | 3 mo | NM | — | |||||
| CCR | 6 mo | NM | — | |||||
| LBC | 9 mo | T315I | 944C>T | |||||
| 2 | 75 F | MBC | 4.5 | PHR | MBC | Before study | NM | — |
| MBC | 4.5 mo1-154 | T315I | 944C>T | |||||
| 3 | 62 M | LBC | 2 | PHR | LBC | Before study | NM | — |
| LBC | 2 mo1-154 | T315I | 944C>T | |||||
| 4† | 59 F | Rel | 3 | CCR | Rel | Before study | NM | — |
| Rel | 5 mo | Y253H | 757T>C | |||||
| Rel | 5.5 mo | Y253H | 757T>C | |||||
| 5 | 40 M | CP | 8 | CHR | CP | Before study | NM | — |
| CHR | 4 mo | F317L | 951C>G | |||||
| PHR | 7 mo | F317L | 951C>G | |||||
| 6 | 66 M | LBC | 81-153 | CHR | LBC | 8 mo | G250E | 749G>A |
| 7 | 54 F | MBC | 10.5 | CHR | MBC | Before study | NM | — |
| CHR | 6 mo | NM | — | |||||
| CHR | 9 mo | NM | — | |||||
| CHR | 10 mo1-154 | G250E | 749G>A | |||||
| PHR | 10.5 mo1-154 | G250E | 749G>A | |||||
| 8 | 41 M | AP | 6 | CHR | AP | 6 mo1-154 | E255K | 763G>A |
| 9 | 60 M | AP | 5 | CHR | CHR | 3 mo | NM | — |
| PHR | 6 mo1-154 | E255K | 763G>A | |||||
| 10 | 44 M | AP | 4.5 | CHR | AP | Before study | NM | — |
| PHR | 3 mo1-154 | E255K | 763G>A | |||||
| 11† | 60 F | Rel | 3 | CHR | Rel | Before study | NM | — |
| Rel | 3 mo1-154 | E255K | 763G>A | |||||
| 12 | 52 F | CP | 9 | CCR | CP | Before study | NM | — |
| CCR | 6 mo | NM | — | |||||
| CCR | 7 mo | NM | — | |||||
| MCR | 8 mo1-154 | M351T | 1052T>C | |||||
| AP1-155 | 9 mo1-154 | M351T | 1052T>C | |||||
| 13 | 64 M | CP | 10.5 | CHR | AP1-155 | 10 mo | NM | — |
| 14 | 78 F | MBC | 8 | CHR | AP1-155,‡ | 8 mo | NM | — |
| 15 | 47 M | AP‡ | 9 | AP‡ | MBC‡ | 7 mo | NM | — |
| 16 | 56 F | CP | 7 | CHR | AP | 6 mo | NM | — |
| 17 | 37 M | MBC | 7 | PHR | MBC | 4.5 mo | NM | — |
| 18 | 63 M | AP | 7 | PHR | AP | 8 mo | NM | — |
| Refractory | ||||||||
| 19 | 55 F | AP‡ | 6 | AP‡ | AP‡ | 3.5 mo | NM | — |
| 20 | 63 M | AP‡ | 11 | AP‡ | AP‡ | Before study | NM | — |
| AP‡ | 3 mo | NM | — | |||||
| AP‡ | 8 mo1-154 | M351T | 1052T>C | |||||
| AP‡ | 9 mo1-154 | M351T | 1052T>C | |||||
| AP‡ | 10 mo1-154 | M351T | 1052T>C | |||||
| AP‡ | 11 mo1-154 | M351T | 1052T>C | |||||
| 21 | 62 F | AP | 10.5 | CHR | PHR | 9 mo | NM | — |
| 22 | 54 M | AP | 8 | CHR | CHR | 6 mo | NM | — |
| 23 | 61 F | CP | 6 | CHR | PHR | 5 mo | NM | — |
| 24 | 61 F | CP | 10.5 | CHR | PHR | 6 mo | NM | — |
| 25 | 47 F | CP | 10 | CHR | CHR | 6 mo | NM | — |
| 26 | 40 F | CP | 6 | CHR | CHR | 3 mo | NM | — |
| 27 | 60 M | CP | 6 | CHR | CHR | 6 mo | NM | — |
| 28 | 42 M | CP | 7 | CHR | CHR | 6 mo | NM | — |
| Patient . | Age (y)/sex . | Disease status at start of imatinib . | Duration of imatinib treatment (mo) . | Best response to imatinib . | Response at time of mutation analysis . | Time of mutation analysis* . | Mutation result . | Nucleotide substitution (GenBank accession no. M14752) . |
|---|---|---|---|---|---|---|---|---|
| Resistant | ||||||||
| 1 | 61 F | CP (3rd) | 9 | CCR | LBC | Before study | NM | — |
| CP (3rd) | Before study | NM | — | |||||
| CCR | 3 mo | NM | — | |||||
| CCR | 6 mo | NM | — | |||||
| LBC | 9 mo | T315I | 944C>T | |||||
| 2 | 75 F | MBC | 4.5 | PHR | MBC | Before study | NM | — |
| MBC | 4.5 mo1-154 | T315I | 944C>T | |||||
| 3 | 62 M | LBC | 2 | PHR | LBC | Before study | NM | — |
| LBC | 2 mo1-154 | T315I | 944C>T | |||||
| 4† | 59 F | Rel | 3 | CCR | Rel | Before study | NM | — |
| Rel | 5 mo | Y253H | 757T>C | |||||
| Rel | 5.5 mo | Y253H | 757T>C | |||||
| 5 | 40 M | CP | 8 | CHR | CP | Before study | NM | — |
| CHR | 4 mo | F317L | 951C>G | |||||
| PHR | 7 mo | F317L | 951C>G | |||||
| 6 | 66 M | LBC | 81-153 | CHR | LBC | 8 mo | G250E | 749G>A |
| 7 | 54 F | MBC | 10.5 | CHR | MBC | Before study | NM | — |
| CHR | 6 mo | NM | — | |||||
| CHR | 9 mo | NM | — | |||||
| CHR | 10 mo1-154 | G250E | 749G>A | |||||
| PHR | 10.5 mo1-154 | G250E | 749G>A | |||||
| 8 | 41 M | AP | 6 | CHR | AP | 6 mo1-154 | E255K | 763G>A |
| 9 | 60 M | AP | 5 | CHR | CHR | 3 mo | NM | — |
| PHR | 6 mo1-154 | E255K | 763G>A | |||||
| 10 | 44 M | AP | 4.5 | CHR | AP | Before study | NM | — |
| PHR | 3 mo1-154 | E255K | 763G>A | |||||
| 11† | 60 F | Rel | 3 | CHR | Rel | Before study | NM | — |
| Rel | 3 mo1-154 | E255K | 763G>A | |||||
| 12 | 52 F | CP | 9 | CCR | CP | Before study | NM | — |
| CCR | 6 mo | NM | — | |||||
| CCR | 7 mo | NM | — | |||||
| MCR | 8 mo1-154 | M351T | 1052T>C | |||||
| AP1-155 | 9 mo1-154 | M351T | 1052T>C | |||||
| 13 | 64 M | CP | 10.5 | CHR | AP1-155 | 10 mo | NM | — |
| 14 | 78 F | MBC | 8 | CHR | AP1-155,‡ | 8 mo | NM | — |
| 15 | 47 M | AP‡ | 9 | AP‡ | MBC‡ | 7 mo | NM | — |
| 16 | 56 F | CP | 7 | CHR | AP | 6 mo | NM | — |
| 17 | 37 M | MBC | 7 | PHR | MBC | 4.5 mo | NM | — |
| 18 | 63 M | AP | 7 | PHR | AP | 8 mo | NM | — |
| Refractory | ||||||||
| 19 | 55 F | AP‡ | 6 | AP‡ | AP‡ | 3.5 mo | NM | — |
| 20 | 63 M | AP‡ | 11 | AP‡ | AP‡ | Before study | NM | — |
| AP‡ | 3 mo | NM | — | |||||
| AP‡ | 8 mo1-154 | M351T | 1052T>C | |||||
| AP‡ | 9 mo1-154 | M351T | 1052T>C | |||||
| AP‡ | 10 mo1-154 | M351T | 1052T>C | |||||
| AP‡ | 11 mo1-154 | M351T | 1052T>C | |||||
| 21 | 62 F | AP | 10.5 | CHR | PHR | 9 mo | NM | — |
| 22 | 54 M | AP | 8 | CHR | CHR | 6 mo | NM | — |
| 23 | 61 F | CP | 6 | CHR | PHR | 5 mo | NM | — |
| 24 | 61 F | CP | 10.5 | CHR | PHR | 6 mo | NM | — |
| 25 | 47 F | CP | 10 | CHR | CHR | 6 mo | NM | — |
| 26 | 40 F | CP | 6 | CHR | CHR | 3 mo | NM | — |
| 27 | 60 M | CP | 6 | CHR | CHR | 6 mo | NM | — |
| 28 | 42 M | CP | 7 | CHR | CHR | 6 mo | NM | — |
MBC, myeloid blast crisis; LBC, lymphoid blast crisis; Rel, relapsed Ph+ ALL; AP, accelerated phase; CP, chronic phase; PHR, partial hematologic response (blasts in blood + bone marrow < 15%); CHR, complete hematologic response (WBC, < 10.0; platelets, < 450; no blasts, myelocytes, metamyelocytes, < 5%; no promyelocytes, no disease-related symptoms, or extramedullary disease); MCR, major cytogenetic response; CCR, complete cytogenetic response; NM, no mutation detected after sequencing of the kinase region of BCR/ABL in both directions.
Months since treatment initiation.
Patients with Ph+ ALL.
Additional chromosomal abnormalities.
Although the patient was in the study for 8 months, imatinib was alternated monthly with oral arsenic. Therefore, the patient was aministered only 4 months of imatinib during this period.
Double Philadelphia chromosome.
Mixed population of mutant and wild-type BCR/ABL detected by direct sequencing of RT-PCR product.