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Extent of decreased growth in children from TKI therapy?


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#1 MichelleH

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Posted 03 October 2011 - 09:36 AM

I have come into contact with a small number of parents whose children have CML.  Most comment that their children's height has been affected since CML treatment.  Obviously response to TKI's is the most important thing but I think many of us are wondering what extent the growth impairment will be, is their height the only thing affected or would this have other implications and is there anything we can do?

My own Son's age/height ratio was in the Aus/NZ 95percentile when he was 2 years old.  At nearly 6 years old (we had his 3 year CML anniversary in September) he is now lower than the 1 percentile.

Kayne is on Dasatinib and I found this article but so much of it is beyond my understanding and I'm not sure which articles to give the most attention to.

http://www.nature.co.../bcj20111a.html

Another mum posted yesterday (in a different section of this site) questioning the growth issue for her son on Imatinib. Here is one poster article for CML children on Imatinib  http://www.posterses...P_670_16eha.pdf

When the kids reach a  stable response, would platelet derived growth factors (or alternatives) be something we should look at?  If so, are there known side effects?

Would appreciate anyones thoughts or further knowledge in this area.

Michelle



#2 Trey

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Posted 03 October 2011 - 06:43 PM

Michelle,

Decreased growth in children on TKI drugs has been observed in some, but not all.  It appears that the younger they are, the more susceptible they may be to decreased growth.  That would make some sense given the bone growth profile for children.  You have posted a couple useful articles, but they may imply that more is understood about the root cause than is really known.  It may have something to do with PDGF inhibition, but maybe not.  The secondary effects ("off-target" inhibitions) of the TKI drugs is complex and generally hard to figure out which is doing what.

Just as the articles you posted discussed decreased bone growth, others suggest increased bone "formation" (although that may not be the same as actual growth):

http://www.biomedcen...471-2407/10/298

I do not think that there is enough information to suggest a specific approach, whether PDGF enhancers or something else.  And there are various PDGF Receptors (PDGF-R) in the body, including A, B, C, D.

If you wanted to discuss PDGF/PDGF-R with someone, I would suggest the researchers in Sydney who wrote this article (not about CML or TKI drugs -- the article just provides their names for you):

http://www.jbc.org/c...254200.full.pdf

You could have Kayne tested for a number of deficiencies.  Many are shown by a Complete Metabolic Panel.  But those will not likely help much.  Maybe testing serum immunoglobilin to see if it is low, since it is related to PDGF activity.  The TKI drugs can lower serum immunoglobulin levels.  In some ways I am just fishing for possible answers.

We all wish Kayne very well.  The children with CML are very special to all of us here.






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