The Role of Stem Cell Transplantation

In the CML-PAED-II study, 66 of 140 patients permanently stopped imatinib treatment, with imatinib failure reported in 27%; of those who experienced treatment failure, only four patients with an HLA-fully matched sibling donor went on to receive SCT. The remaining patients were switched to a second-generation TKI (31 to dasatinib and 3 to nilotinib); 13 of those patients also experienced treatment failure with the second generation TKI and either underwent SCT or switched to the other second-generation TKI.

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“On the pediatric side, we are often reluctant to move to SCT because the side effects can be so debilitating,” Dr Aplenc said. “There is ongoing discussion in the community right now as to the role of SCT in CML, especially in chronic phase. However, in accelerated and blast phases, SCT is still recommended especially in the setting of TKI failure.” At CHOP, pediatric patients with CML typically receive more than one TKI before SCT, he added. If first-line TKI treatment fails “because [the patient] developed a resistance to medication, then we would want to make sure that CML was sensitive to the second-line TKI.” The cardiovascular toxicities and thyroid dysfunction seen with TKI use in adults has not been reported in children, but monitoring remains necessary.

Most patients treated with imatinib are monitored with a single complete blood test. If, however, dasatinib and nilotinib are used as the first-line therapy, second-line therapy is SCT, Dr Bansal told Cancer Therapy Advisor.

In the United States, the cost of treatment can place a financial burden on families that may inadvertently lead to noncompliance, which may also lead to treatment failure and complicate the potential for SCT, Dr Aplenc explained.

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“Patients who are not compliant with TKI [treatment] likely will not be compliant with SCT supportive care measures, and at CHOP we are hesitant to transplant those patients,” he said.

TKI cost typically is not an issue for noncompliance in Europe, where the government health care system often covers the cost.

“The decision regarding the choice of which TKI to use for a particular patient should take into account not only its effectiveness, but also its impact on quality of life, the drug affordability, accessibility, and ease of compliance,” Dr Bansal said. In India, generic imatinib is available, making it a much more cost-effective option than either second-generation TKIs or SCT.

Trials on TKIs in adults have shown “faster and deeper responses” can be obtained with second-generation TKIs, resulting in fewer transformations to advanced phases of CML.4 In Europe, until the end of 2017 imatinib “was the only TKI licensed for treatment of CML in minors,” but nilotinib was approved by the European Medicines Agency in November 2017.4

Growth Impairment

The authors of the CML-PAED-II study did note “growth is affected irrespective of patients’ gender and results in almost linear growth tempo deceleration, its severity solely depending on the duration of treatment and the pubertal status at diagnosis.”4

Dr Aplenc hopes that with the large cohort in this study the authors will be able to determine more precisely the risk factors for imatinib-associated growth delay.


  1. US Food and Drug Administration. FDA approves dasatinib for pediatric patients with CML. November 9, 2017. Accessed July 9, 2018.
  2. US Food and Drug Administration. FDA approves nilotinib for pediatric patients with newly diagnosed or resistant/intolerant Ph+ CML in chronic phase. March 22, 2018. Accessed July 9, 2018.
  3. Hijiya N, Schultz KR, Metzler M, et al. Pediatric chronic myeloid leukemia is a unique disease that requires a different approach. Blood. 2016;127:392-399. doi: 10.1182/blood-2015-06-648667
  4. Suttorp M, Schulze P, Glauche I, et al. Front-line imatinib treatment in children and adolescents with chronic myeloid leukemia: results from a phase III trial [published online June 20, 2018]. Leukemia. doi: 10.1038/s41375-018-0179-9
  5. Bansal S. Is imatinib still the best choice as first-line oral TKI? South Asian J Cancer. 2014;3(1)83-86. doi: 10.4103/2278-330X.126553