Chemotherapy for childhood acute lymphoblastic leukemia (ALL) can cause late-appearing side effects in survivors that affect multiple organs, including the heart and brain. However, the complex ALL treatment regimen makes it difficult to isolate the causes of these side effects and impossible to separate the contributions of individual chemotherapy agents by clinical observation. Using a mouse model, we therefore assessed each of eight representative, systemically-administered ALL chemotherapy agents for their impact on post-natal brain development and heart function.
Mice were treated systemically with a single chemotherapy agent at an infant equivalent age, then allowed to age to early adulthood (nine weeks). Cardiac structure and function were assessed using in vivo high-frequency ultrasound, and brain anatomy was assessed using high-resolution volumetric ex vivo magnetic resonance imaging (MRI). In addition, longitudinal in vivo MRI was used to determine the time course of developmental change after vincristine treatment.
Vincristine, doxorubicin, and methotrexate were observed to produce the greatest deficiencies in brain development as determined by volumes measured on MRI, while doxorubicin, methotrexate and L-asparaginase altered heart structure or function. Longitudinal studies of vincristine revealed widespread volume loss immediately following treatment and impaired growth over time in several brain regions.
Multiple ALL chemotherapy agents can affect postnatal brain development or heart function. This study provides a ranking of agents based on potential toxicity, and thus highlights a subset likely to cause side effects in early adulthood for further study.
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 December 2018.
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#11,884,417
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Outputs from Clinical Cancer Research
#11,355
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#176,939
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Outputs of similar age from Clinical Cancer Research
#153
of 240 outputs
Altmetric has tracked 34,350,842 research outputs across all sources so far. This one has received more attention than most of these and is in the 64th percentile.
So far Altmetric has tracked 17,842 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.3. This one is in the 35th percentile – i.e., 35% of its peers scored the same or lower than it.
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