Adverse effects of imatinib in children with chronic myelogenous leukemia

Choeyprasert, Worawut; Yansomdet, Thitinun; Natesirinilkul, Rungrote; Wejaphikul, Karn; Charoenkwan, Pimlak

doi:10.1111/ped.13136

Cited by 21 publications

(31 citation statements)

References 45 publications

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“…Children diagnosed with CML who are treated with TKI, specifically imatinib, demonstrate varying degrees of growth restriction. The decrease in Ht-SD appears to be more significant when treatment is initiated prior to the onset of puberty [56, 57] and may result in declines to heights less than 2 SD below the mean [56, 58]. At the onset of puberty, an increased growth velocity is often noted in children treated with TKI.…”

Section: Growth Impairment and Short Adult Height In Ccs Treated Withmentioning

confidence: 99%

“…At the onset of puberty, an increased growth velocity is often noted in children treated with TKI. However, there is limited and conflicting data on the net loss in growth potential at the final adult height in these survivors, as final adult heights are unavailable in most studies [56, 58, 59]. The precise mechanism for the growth impairment in children treated with TKI is unclear but it may be due to disrupted GH signaling [60], inadequate signal transduction through the IGF1-receptor (a tyrosine kinase receptor), or inhibition of PDGF-R signaling and disrupted chondrocyte recruitment at the growth plates [61].…”

Section: Growth Impairment and Short Adult Height In Ccs Treated Withmentioning

confidence: 99%

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Growth Disturbances in Childhood Cancer Survivors

Antal

Balachandar

2019

Horm Res Paediatr

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Survival from childhood cancer has improved dramatically over the last few decades, resulting in an increased need to address the long-term follow-up and care of childhood cancer survivors. Appropriate linear growth is an important measure of health, with alterations of growth in children and short adult height in those who have completed growth serving as potential indicators of the sequelae of the underlying diagnosis or the cancer treatments. It is therefore critical that clinicians, particularly endocrinologists, be familiar with the patterns of altered growth which may be seen following diagnosis and treatment for childhood cancer. In this article, we will review the growth alterations seen in childhood cancer survivors, focusing on risk factors and considerations in evaluation and care.

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Section: Growth Impairment and Short Adult Height In Ccs Treated Withmentioning

confidence: 99%

Section: Growth Impairment and Short Adult Height In Ccs Treated Withmentioning

confidence: 99%

Growth Disturbances in Childhood Cancer Survivors

Antal

Balachandar

2019

Horm Res Paediatr

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“…Prolonged imatinib treatment is associated with significantly diminished vitamin D 3 synthesis (13) leading to low bone mineral density, which may effectively mask other relevant bone parameters. For this reason, there is an urgent need for monitoring vitamin D3 levels in paediatric patients under continuous imatinib treatment (14). All our patients were carefully monitored for vitamin D3 deficiency.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Imatinib in Paediatric CML – A Single Centre Study

Smeding

Szydło

Pieluszczak

et al. 2019

In Vivo

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Background/Aim: Chronic myeloid leukaemia (CML) rarely affects the paediatric population and has an incidence of 0.06-0.12/100,000 children per year. The dire clinical course of paediatric CML is further exacerbated by the adverse effects of long-term imatinib therapy. Patients and Methods: Our cohort comprised 14 CML patients who were treated with imatinib between July 2010 and September 2018. The European Leukaemia Net (ELN) standard milestones of response criteria were used to evaluate its therapeutic effectiveness. Results: Complete haematological remission and partial cytogenetic response were achieved in all patients. Complete cytogenetic response was achieved in seven patients. Major molecular response was achieved in six patients. Two patients underwent haematopoietic stem cell transplantation due to unsatisfactory response to imatinib. Conclusion: Imatinib is effective in treating paediatric CML and limits the progression to advanced stages, however, the quality of life still needs to be optimised. Chronic myeloid leukaemia (CML) rarely affects the paediatric population and has an estimated incidence of 0.06-0.12 per 100,000 children per year (1). The tyrosine kinase inhibitor (TKI) therapy improves the overall and event-free survival (EFS) rates in paediatric CML (2). Imatinib, a firstgeneration TKI, is proposed as the first-line therapy for improved effectiveness (3). CML presents, within paediatric patients, with a clinically more aggressive course compared to that of adults, and is further exacerbated by several longterm side effects of imatinib (4). A potential resistance to the drug due to mutations in the BCR-ABL1 gene may significantly limit its effectiveness, rendering the evaluation of severity and management of the disease exceedingly challenging (5). Knowledge on the definite efficacy and safety of imatinib treatment within the paediatric population is scarce. The aim of this retrospective observational study was to assess the safety of long-term administration in terms of adverse effects from the use of imatinib in paediatric CML patients, as well as to estimate the probability of progression to advanced stages of the disease. Patients and Methods Patients. Our cohort included 14 patients (males, n=12; females, n=2) who were diagnosed with BCR-ABL1 positive CML and were treated with imatinib between

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“…Imatinib is a tyrosine kinase inhibitor (TKI) approved for the treatment of chronic myelogenous leukaemia (CML), gastrointestinal stromal tumours and other uncommon haematologic malignancies. In a small study of children with CML, imatinib treatment appeared to reduce linear growth . Consistent with these results, a pre‐clinical young rodent model showed that continuous imatinib exposure was associated with dose‐dependent reductions in long‐bone length and BMD, as well as decreased resistance to fracture and lower circulating levels of the bone formation marker osteocalcin .…”

Section: Haematologic Malignanciesmentioning

confidence: 99%

The skeletal impact of cancer therapies

Bedatsova

Drake

2019

Brit J Clinical Pharma

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Both cancer and therapies used in the treatment of cancer can have significant deleterious effects on the skeleton, increasing the risks for both bone loss and fracture development. While advancements in cancer therapies have resulted in enhanced cancer survivorship for patients with many types of malignancies, it is increasingly recognized that efforts to reduce bone loss and limit fractures must be considered for nearly all patients undergoing cancer therapy in order to diminish the anticipated future skeletal consequences. To date, most studies examining the impact of cancer therapies on skeletal outcomes have focused on endocrine-associated cancers of the breast and prostate, with more recent advances in our understanding of bone loss and fracture risk in other malignancies. Pharmacologic efforts to limit the adverse effects of cancer therapies on bone have nearly universally employed anti-resorptive approaches, although studies have frequently relied on surrogate outcomes such as changes in bone mineral density or bone turnover markers, rather than on fractures or other skeletal-related events, as primary study endpoints. Compounding current deficiencies for the provision of optimal care is the recognition that despite clearly written and straightforward society-based guidelines, vulnerable eligible patients are very often neither identified nor provided with appropriate treatments to limit the skeletal impact of their cancer therapies. KEYWORDS androgen deprivation therapy, aromatase inhibitor, bone loss, breast cancer, myeloma, prostate cancer

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Adverse effects of imatinib in children with chronic myelogenous leukemia

Cited by 21 publications

References 45 publications

Growth Disturbances in Childhood Cancer Survivors

Growth Disturbances in Childhood Cancer Survivors

Efficacy and Safety of Imatinib in Paediatric CML – A Single Centre Study

The skeletal impact of cancer therapies

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