Molecular Responses At 3 Months Are Associated With a Better Subsequent Molecular response and Outcome In Children and Adolescents With CML In Chronic Phase: Results Of a Retrospective Analysis From The French Glivec Phase 4 Study

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.

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.