Intermittent Dosing Of Gleevec Is Efficacious In Cases Of Childhood Chronic Myeloid Leukemia With Poor Compliance
Authors: Moschovi Maria , Adamaki Maria , Athanasiadou Anastasia , Zampogiannis Archontis , Tourkantoni Natalia 
Published: October 2019

Abstract
Chronic myeloid leukemia (CML) is rare in childhood (less than 5% of all childhood leukemias). The main characteristic is the Philadelphia chromosome (BCR-ABL1 positive) and the tyrosine kinase inhibitor imatinib mesylate (Gleevec) is the treatment of choice, with the target oral dose being 440 mg/m2/day asdetermined by the COG-P9973 and COG-ADVL0122 trials, while allogeneic stem cell transplantation is postponed until CML becomes refractory to the drug. We administer a treatment dose of 400mg/m2/day but we have observed high toxicity levels associated with prolonged treatment.
We present a girl with CML, with persistent residual disease (MRD), even two years following diagnosis, and serious side effects (dry skin, significant hair loss, gastrointestinal discomfort and diarrhoea) that affected her quality of life. The patient was tested for polymorphisms in the tyrosine kinase and was found negative. Careful interviewing of the family revealed that the persistent MRD was due to poor compliance of the patient to the therapeutic regimen. The child was unhappy due to the side effects and refused to take her pills (Gleevec), hence the poor compliance. Therefore, taking into consideration the child’s wellbeing and psychological welfare, it was decided that she would receive the drug on alternate months (one on/one off). Gleevec was discontinued when the patient completed two years of being MRD negative. The patient remains in complete molecular remission four years after the discontinuation of Gleevec.
To date, there are few reports on childhood CML so most data come from studies in adults. Even though Gleevec is currently implemented as the primary treatment method in children, there are still doubts as to whether it can result in a permanent cure and of the potential complications of long-term use in the growth and development of these children. No specific guidelines have been set on the dosage and duration of treatment with Gleevec, especially for childhood CML patients facing a potentially lifelong treatment, who might also be faced with a wide range of unknown side effects. Psychological factors should also be taken into account and special attention should be given in avoiding adverse effects that interfere with the quality of life and the psychological welfare of this extremely fragile population.
Overall, in our case, despite the persistent MRD, intermittent dosing of Gleevec proved to be an efficient method both in keeping toxicity levels to a minimum and in achieving complete and continuous remission. Persistent MRD levels in this case were due to the interrupted treatment regime, i.e. due to poor compliance, and not due to additional cytogenetic abnormalities that were resistant to Gleevec. Future clinical trials in children should investigate whether intermittent dosing of the drug produces fewer side effects during the course of treatment and whether it may present a more favourable option when considering the normal growth development of the children treated for CML.

Disclosures:
No relevant conflicts of interest to declare.