Growth failure in children with chronic myeloid leukemia receiving imatinib is due to disruption of GH/IGF‐1 axis

Narayanan, Karthik; Bansal, Deepak; Walia, Rama; Sachdeva, Naresh; Bhansali, Anil; Varma, Neelam; Marwaha, Ram Kumar

doi:10.1002/pbc.24397

Cited by 73 publications

(72 citation statements)

References 25 publications

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“…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

155

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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mentioning

confidence: 99%

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

Hijiya

Schultz

Metzler

et al. 2016

Blood

155

176

View full text Add to dashboard Cite

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“…A similar sized pediatric cross-sectional study was conducted for chronic phase CML patients (median age 12.9 years) who had been on imatinib therapy for longer than 6 months. 56 Eighteen children were included in this study. Patients were treated with imatinib for a mean duration of 43.7±32.8 (range 6-89) months.…”

Section: Late Effects Of Imatinib Therapy In Childrenmentioning

confidence: 99%

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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“…A few isolated reports mentioned successful use of TKIs for the treatment of pituitary adenoma. Also, our in vitro study in cultured somatotropinoma and GH3 cells has demonstrated that imatinib inhibits the GH/IGF-1 axis and re-emphasizes the crosstalk [41,42] . In future, TKIs could be the choice of treatment for patients with acromegaly and hematological disorders.…”

Section: Treatment Of CML and Inhibition Of The Gh/igf-1 Systemmentioning

confidence: 99%

Co-Occurrence of Acromegaly and Hematological Disorders: A Myth or Common Pathogenic Mechanism

Gupta¹,

Dutta

2017

Integr Med Int

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Background: Acromegaly is not one disease but an association of clinical, biochemical and radiological features. Altered blood counts are often observed in acromegaly patients. Acromegaly patients presenting with a hematological malignancy are rare. To date, there are several cases that have reported the co-occurrence of these diseases. Summary: The coexistence of the two diseases can be a mere coincidence or may have a common pathogenic mechanism. The rarity of these conditions and the small number of patients makes it difficult to determine the real role of elevated growth hormone and insulin-like growth factor-1 levels in the occurrence of hematological malignancies. Patients with growth hormone (GH) replacement due to GH-deficient acromegaly are at a high risk of developing hematological disorders. Conclusion: In this review, we aim to provide evidence for the correlation between the two disorders.

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Growth failure in children with chronic myeloid leukemia receiving imatinib is due to disruption of GH/IGF‐1 axis

Cited by 73 publications

References 25 publications

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

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

Profile of imatinib in pediatric leukemia

Co-Occurrence of Acromegaly and Hematological Disorders: A Myth or Common Pathogenic Mechanism

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