Imatinib mesylate causes growth deceleration in pediatric patients with chronic myelogenous leukemia

Rastogi, Maynika V.; Stork, Linda C.; Druker, Brian J.; Blasdel, Carolyn; Nguyen, Thuan; Boston, Bruce A.

doi:10.1002/pbc.24121

Cited by 53 publications

(66 citation statements)

References 27 publications

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“…There was an inverse correlation between duration of imatinib therapy and the proportionate decrease in height-for-age z-scores. This study, along with other reports regarding the detrimental effect of imatinib on growth and bone metabolism, [57][58][59][60] provides further evidence that the off-target effects of imatinib must continue to be collected over longer periods of time so we can better understand how long-term continuous inhibition of c-ABL1 may impact our patients. This is particularly true for younger children treated with imatinib who may be exposed to these effects prior to puberty when they are skeletally most vulnerable.…”

Section: Late Effects Of Imatinib Therapy In Childrensupporting

confidence: 52%

Profile of imatinib in pediatric leukemia

Burke

2014

PHMT

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Using targeted therapy for treatment of cancer has become the paradigm to which clinical trials aspire. Imatinib, the BCR-ABL1 tyrosine kinase inhibitor (TKI), was the first of its kind to specifically target and inhibit the underlying Philadelphia chromosome (Ph+) oncogene found to be driving chronic myeloid leukemia in adults, and has since become standard of care for the treatment of chronic myeloid leukemia in children. Imatinib, with its ability to target Ph+ leukemia, has been successfully incorporated into the treatment of not only pediatric chronic myeloid leukemia but also Ph+ acute lymphoblastic leukemia. With the incorporation of imatinib into combination chemotherapy for pediatric Ph+ acute lymphoblastic leukemia, current survival rates are far higher than at any other time for this once dreadful disease. With more children today receiving treatment with imatinib for either chronic myeloid leukemia or Ph+ acute lymphoblastic leukemia, knowledge is accumulating surrounding the short-term and long-term toxicities observed in children, adolescents, and young adults treated with this TKI. In summary, the TKI imatinib has made a historic impact in the treatment of pediatric Ph+ leukemias, transforming what were once very high-risk diseases with considerable morbidity and mortality into ones that are now very treatable but with a new awareness surrounding the long-term toxicities that may come with this price for cure.

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Section: Late Effects Of Imatinib Therapy In Childrensupporting

confidence: 52%

Profile of imatinib in pediatric leukemia

Burke

2014

PHMT

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“…Patients with HP exposure to radiotherapy for other reasons than CNS tumors, such as acute lymphoblastic leukemia (ALL) with CNS involvement requiring CRT or historic cases where this was done prophylactically (18,19,20), diseases requiring hematopoietic stem-cell transplant (HSCT) after conditioning with total body www.eje-online.org GHD has been described in a small number of patients treated with conventional chemotherapy alone (5, 6, 7) and may also occur following treatment with targeted chemotherapy agents. Children treated for chronic myelogenous leukemia with imatinib mesylate, a TKI, may experience linear growth deceleration or arrest, but whether this side effect is related to GHD, resistance to GH or direct skeletal toxicity remains unclear (9,33,34). Ipilimumab, an anti-CTLA4 monoclonal antibody that is increasingly used to treat unresectable melanoma has been associated with hypophysitis and GHD, possibly persisting after the discontinuation of therapy (10).…”

Section: Prevalence and Risk Factorsmentioning

confidence: 99%

DIAGNOSIS OF ENDOCRINE DISEASE: Endocrine late-effects of childhood cancer and its treatments

Chemaitilly

Cohen

2017

European Journal of Endocrinology

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Endocrine complications are frequently observed in childhood cancer survivors (CCS). One of two CCS will experience at least one endocrine complication during the course of his/her lifespan, most commonly as a late-effect of cancer treatments, especially radiotherapy and alkylating agent chemotherapy. Endocrine late-effects include impairments of the hypothalamus/pituitary, thyroid and gonads, as well as decreased bone mineral density and metabolic derangements leading to obesity and/or diabetes mellitus. A systematic approach where CCS are screened for endocrine late-effects based on their cancer history and treatment exposures may improve health outcomes by allowing the early diagnosis and treatment of these complications.

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“…45,46 In children, various groups have reported substantial growth abnormalities associated with imatinib in children with CML. [47][48][49][50][51][52][53][54][55] There is less experience with second-and third-generation TKIs in children, but dasatinib also seems to have a similar effect on growth. 48 It appears that prepubertal children are affected more significantly, 29 and though they may experience "catch-up" growth in puberty, their final height is lower than the predicted midparental height.…”

mentioning

confidence: 99%

“…48 It appears that prepubertal children are affected more significantly, 29 and though they may experience "catch-up" growth in puberty, their final height is lower than the predicted midparental height. 47 Some reports suggest that the growth hormone/IGF-1 axis is affected by TKIs, 45,48,56,57 and cotreatment with growth hormone or recombinant IGF-1 may improve the final adult height in children receiving TKIs; however, no study has demonstrated the safety or efficacy of this strategy.…”

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confidence: 99%

Pediatric chronic myeloid leukemia is a unique disease that requires a different approach

Hijiya

Schultz

Metzler

et al. 2016

Blood

167

176

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Chronic myelogenous leukemia (CML) in children is relatively rare. Because of a lack of robust clinical study evidence, management of CML in children is not standardized and often follows guidelines developed for adults. Children and young adults tend to have a more aggressive clinical presentation than older adults, and prognostic scores for adult CML do not apply to children. CML in children has been considered to have the same biology as in adults, but recent data indicate that some genetic differences exist in pediatric and adult CML. Because children with CML may receive tyrosine kinase inhibitor (TKI) therapy for many decades, and are exposed to TKIs during a period of active growth, morbidities in children with CML may be distinct from those in adults and require careful monitoring. Aggressive strategies, such as eradication of CML stem cells with limited duration and intensive regimens of chemotherapy and TKIs, may be more advantageous in children as a way to avoid lifelong exposure to TKIs and their associated adverse effects. Blood and marrow transplantation in pediatric CML is currently indicated only for recurrent progressive disease, and the acute and long-term toxicities of this option should be carefully evaluated against the complications associated with lifelong use of TKIs.

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Imatinib mesylate causes growth deceleration in pediatric patients with chronic myelogenous leukemia

Abstract: Growth in children with CML appears to be adversely impacted by imatinib therapy. BMI and IGF-1/IGFBP-3 are maintained during treatment, suggesting a direct effect of imatinib on the growth plate.

Cited by 53 publications

References 27 publications

Profile of imatinib in pediatric leukemia

Profile of imatinib in pediatric leukemia

DIAGNOSIS OF ENDOCRINE DISEASE: Endocrine late-effects of childhood cancer and its treatments

Pediatric chronic myeloid leukemia is a unique disease that requires a different approach

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