Abstract
Here we report a retrospective analysis based on BCR-ABL transcript level at 3 months after the start of imatinib assessing its impact on subsequent response and outcome in children and adolescents with chronic myeloid leukemia (CML) enrolled in the French prospective trial Glivec Phase 4 (Millot F et al, JCO 2011).
44 children were enrolled in the Glivec Phase 4 Study. The median age was 11.5 years (range: 10 months-17 years). The median follow-up was 49 months (range: 16 to 83). We retrospectively analyzed the rates of complete cytogenetic responses (CCR) and major molecular response (MMR) 1 year after the start of imatinib, the progression free survival (PFS) and the overall survival (OS).
At 3 months after the start of imatinib, 40/44 (91%) patients were evaluable for molecular response. BCR-ABL transcripts levels were: BCR-ABL> 10% in 15 (37%) pts and BCR-ABL<10% in 25 (63%) pts. Children and adolescents with BCR-ABL >10% at 3 months had similar Sokal score distribution but a larger spleen size and a higher leukocyte count at diagnosis compared with patients with BCR-ABL <10%. The median dose of imatinib administered within the first 3 months of treatment was similar in patients with BCR-ABL >10% and those with <10% at 3 months. Two patients progressed to blastic phase 25 and 42 months after the start of imatinib and 1 died. Both of them had a BCR-ABL transcript level of more than 10% at 3 months after the start of imatinib. A transcript level <10% correlated with a better PFS (Table 1). Patients with a BCR-ABL transcript level <10% 3 months after the start of imatinib had a higher rate of CCR and MMR 12 months after the start of imatinib compared to those with a BCR-ABL transcript level >10% (Table 1). However the difference is statistically significant only for the molecular response.
| BCR-ABL/ABL at 3 months . | N (%) . | CCyR at 12 months . | MMR at 12 months . | PFS at 36 months . |
|---|---|---|---|---|
| < 10% | 25 (63%) | 18 (72%) | 12 (92%) | 100% |
| > 10% | 15 (37%) | 7 (28%) | 1 (8%) | 92% |
| p=0.177 | p=0.0128 | p=0.034 |
| BCR-ABL/ABL at 3 months . | N (%) . | CCyR at 12 months . | MMR at 12 months . | PFS at 36 months . |
|---|---|---|---|---|
| < 10% | 25 (63%) | 18 (72%) | 12 (92%) | 100% |
| > 10% | 15 (37%) | 7 (28%) | 1 (8%) | 92% |
| p=0.177 | p=0.0128 | p=0.034 |
The children and adolescents with >10% of BCR-ABL at 3 months after the start of imatinib are characterized by a higher propensity to fail the treatment and to progress. The value of a cut-off of 10% of BCR-ABL 3 months after the start of imatinib as a reliable surrogate marker of response at 1 year and outcome remains to be determined in a larger cohort of children and adolescents.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
