Karyotypes and clinical characteristics of dasatinib-treated CML patients with clonal cytogenetic abnormalities in Ph− cells
| Patient no.* . | Previous treatment . | Length of follow up on dasatinib, mo . | Representative karyotype with Ph− clone† . | Time from start of dasatinib to appearance of Ph− clone, m . | Duration of Ph− clone, m‡ . | MDS§ . | Best response on dasatinib, %‖ . | Karyotype of most recent sample . | Outcome . |
|---|---|---|---|---|---|---|---|---|---|
| 1 | HU, IFN, IM | 23 | 47,XY,+8[29]/46,XY,t(9;22) (q34;q11.2)[2] | 6 | 8 | Trilineage dysplasia¶ | 7 | 46,XY,t(9;22)9q34;q11)[30] | A, loss of CyR, AP |
| 2 | HU, IFN, IM | 22 | 47,XY,+Y[36]/46,XY[4] | 7 | 15+ | No | 0 | 46,XY,+Y[3]/46,XY[27] | A, CCyR |
| 3 | HU, IFN, IM | 21 | 46,XX,ins(22;3)(q11;q26q21) [12] | 8.5 | 12 | No | 0 | 46,XX,t(9;22)(q34;q11)[30] | A, loss of CyR |
| Patient no.* . | Previous treatment . | Length of follow up on dasatinib, mo . | Representative karyotype with Ph− clone† . | Time from start of dasatinib to appearance of Ph− clone, m . | Duration of Ph− clone, m‡ . | MDS§ . | Best response on dasatinib, %‖ . | Karyotype of most recent sample . | Outcome . |
|---|---|---|---|---|---|---|---|---|---|
| 1 | HU, IFN, IM | 23 | 47,XY,+8[29]/46,XY,t(9;22) (q34;q11.2)[2] | 6 | 8 | Trilineage dysplasia¶ | 7 | 46,XY,t(9;22)9q34;q11)[30] | A, loss of CyR, AP |
| 2 | HU, IFN, IM | 22 | 47,XY,+Y[36]/46,XY[4] | 7 | 15+ | No | 0 | 46,XY,+Y[3]/46,XY[27] | A, CCyR |
| 3 | HU, IFN, IM | 21 | 46,XX,ins(22;3)(q11;q26q21) [12] | 8.5 | 12 | No | 0 | 46,XX,t(9;22)(q34;q11)[30] | A, loss of CyR |
Ph− indicates Philadelphia chromosome negative; MDS, myelodysplastic syndrome; HU, hydroxyurea; IFN, interferon alpha; IM, imatinib mesylate; A, Alive; CyR, cytogenetic response; AP, accelerated phase; and CCyR, complete cytogenetic response.
Patients were identified from a series of 35 cases of dasatinib-treated CML. Cytogenetic analysis was carried out on 30 metaphases from each of 151 bone marrow samples, with a median of 4 analyses per patient (range, 1-10). Nineteen patients were in chronic phase, 10 in accelerated phase, and 6 in blast crisis. The median follow-up from start of dasatinib was 16 months (range, 4-23 months). Twenty-seven patients (77%) showed at least a 5% reduction in Philadelphia-positive metaphases over the course of dasatinib treatment, of which 8 patients (23%) demonstrated minimal or minor CyR and 19 patients (54%) showed partial or complete CyR.
Karyotype of the sample with the highest level of chromosomally abnormal Ph− clone is presented. Ph− clone is shown in bold.
Calculated as the length of time between the first and last sample with a Ph− clone.
Consistent with the World Health Organization Criteria and corresponding with the emergence of the Ph− clone.
Percentage of Ph-positive cells.
The myelodysplastic features observed in patient 1 disappeared at the same time point as the +8 clone, coinciding with loss of CyR.