Use of imatinib mesylate in a 15‐month old with Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia

Abstract

To The Editor: We report the safe and effective use of imatinib mesylate (IM) in a 15-month-old female with Philadelphia chromosome positive chronic myelogenous leukemia (Ph+ CML). To our knowledge, this is the youngest patient treated with IM for CML. The patient presented with a total white count of over 400,000/mm3 with all stages of myeloid development present in peripheral blood. Fluorescent in situ hybridization for t(9;22) on a bone marrow aspirate confirmed the diagnosis of Ph+ CML. While awaiting HLA genotypically identical sibling-donor bone marrow transplant, the child was started on IM therapy 200 mg by mouth each day (340 mg/m2/day rounded up to the nearest 100 mg increment 1, administered as a suspension by dissolving 100 mg tablets in water or apple juice). Because of the child's age, IM was used “off label” after obtaining written, informed consent from both parents. On IM therapy, the leukocytosis showed progressive improvement, with total white count stabilizing at 10–20,000/mm3 after 5 weeks of therapy. The patient continued IM until admission for transplant (10 weeks total). The only reported side effect was nausea. There were no significant elevations in liver transaminases or serum bilirubin. CML is uncommon in the pediatric age group, accounting for approximately 2% of all childhood leukemias 2. The majority of cases is Ph+ and diagnosed in patients over 6 years of age 3, 4. The BCR–ABL fusion gene (t(9;22)(q34;q11)) produces a 210-kDa dysregulated tyrosine kinase (P210) which is the specific target of IM. The drug is approved for children as young as 3 years old. Case series have shown efficacy and safety of imatinib mesylate in children with Ph+ CML as young as 20 months 5. One case report described safety and efficacy of the medicine in a child as young as 18 months old, but for a soft tissue sarcoma 6. Pharmacokinetic studies in children show that once-daily doses of 240 and 340 mg/m2 yield plasma concentrations that are similar to those seen in adults at comparable daily doses of 400 and 600 mg respectively. However, there can be marked interpatient variability in the pediatric age group1. Hence, dosage may need to be adjusted depending on individual responses and toxicities. Historically, the only known long-term cure of Ph+ CML in children has been successful hematopoietic stem cell transplantation (HSCT). Although experience with IM has been relatively short, it has provided a high rate of sustained hematological as well as cytogenetic remission, with a much more acceptable safety profile than HSCT. However, while long-term success rates of IM therapy are awaited, most pediatric patients will proceed to HSCT if a suitably matched related or unrelated donor is available. The current literature, and our experience in this child shows that IM may be a safe and effective therapeutic modality, even in very young children, for suppressing the initial frequently severe leukocytosis as well as maintaining an acceptable hematological profile while coordinating HSCT.