Young patients with chronic-phase chronic myeloid leukemia (CML) with a sustained deep molecular response may be able to safely discontinue tyrosine kinase inhibitor (TKI) therapy. These study findings were reported in the journal Pediatric Blood & Cancer.

Some clinical trials have shown adults with CML who have achieved a deep molecular response may be able to safely discontinue TKI therapy, the study investigators explained in their report. However, research on TKI discontinuation in children with CML has been limited.

This multicenter study (University Hospital Medical Information Network clinical trial registry identifier: UMIN000017644) was conducted by the Japan Pediatric Leukemia and Lymphoma Study Group. It involved prospective discontinuation of TKI therapy in patients younger than 20 years at diagnosis. Among other inclusion criteria were BCR-ABL1-positive CML in either the chronic or accelerated phase, treatment with TKI therapy for 3 or more years, and a sustained molecular response 4.0 (MR4.0) with TKI therapy lasting 2 years or longer. Patients were categorized as having MR4.0 if the detectable BCR-ABL1 transcript level was less than 0.01% on the International Scale (BCR-ABL1IS).

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Following TKI discontinuation, patients were monitored for peripheral blood BCR-ABL1IS levels at varying intervals over time. Patients resumed TKI therapy if molecular relapse occurred. The primary study outcome was the 12-month treatment-free remission (TFR) rate, measured from the date of TKI discontinuation.

All 22 patients in this study had chronic-phase CML. The median age at diagnosis was 9 years (range, 1 to 14), and the median age at TKI discontinuation was 16 years (range, 5 to 26). After TKI discontinuation, patients had a median follow-up duration of 36 months (range, 24 to 41). Patients had a median MR4.0 of 53.5 months (range, 25 to 148) prior to TKI discontinuation.

The 12-month TFR rate was 50% (90% CI, 32%-66%). Loss of major molecular response occurred in 11 patients after discontinuation, occurring at a median of 90 days. These patients reportedly regained MR4.0 upon TKI retreatment. Disease progression reportedly did not occur with any patient.

TKI discontinuation was not associated with withdrawal in any patients, and the incidence of adverse events declined with discontinuation of TKI treatment. The study investigators also reported that some analyses suggested potential positive impacts on growth and school functioning in some patients after cessation of TKI therapy.

The study investigators concluded that TKI discontinuation may be safe for chronic-phase CML in pediatric patients who achieve a deep molecular response. They also highlighted possible impacts on growth and school functioning with TKI discontinuation as issues with particular relevance to children.


Shima H, Kada A, Tanizawa A, et al. Discontinuation of tyrosine kinase inhibitors in pediatric chronic myeloid leukemia. Pediatr Blood Cancer. 2022;69(8):e29699. doi:10.1002/pbc.29699