9-year-old male. Diagnosed with chronic phase CML in early April 2014. Was asymptomatic and diagnosed incidentally when a hemogram was done for an intercurrent illness. No organomegaly. Weight 33 Kg, Height 143 cms. Body surface area: 1.1.
Started on Imatinib: once a day: 400 mg alternating with 300 mg. Two weeks later had severe knee, thigh and calf pains. Debilitating; had to stop Imatinib for 7 days. Restarted at 200 mg/day - tolerated, however pains reappeared with 300 mg/day. Temporary relief with analgesics (Ibuprofen). It has been 10 weeks since start of Imatinib - not able to hike Imatinib beyond 300/200 mg on alternate days, due to pain in limbs. Serum calcium, Mg, liver and kidney functions normal. Has been supplemented with calcium.
Any solutions? Should we just wait and watch and hope that pains would reduce over a period of time?

It seems to me that these symptoms could be related to muscular cramps, which have been of the imatinib therapy frequently described at the beginning of the imatinib therapy, I would try to keep Imatinib at the maximum tolerated dose, that for the moment seems 200 mg per day and, if possible, I would dosage the plasma concentration of imatinib. Of course I would monitor carefully the response of the patient and I would tune the dosage according to the response and to the symptoms. I think that these initial symptoms will be progressively reduced during this initial phase.

Hi Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase: pediatric dose
340 mg/m2 orally once a day or 170 mg/m2 orally twice a day
Maximum Dose: 600 mg daily
Duration of therapy: Treatment may be continued as long as there is no evidence of progressive disease or unacceptable toxicity.
Dose adjustments for newly diagnosed pediatric chronic phase CML (starting dose 340 mg/m2). Have you checked the cytogenetic and molecular response? All in all is not so under treated. I would be happy to continue IM with a strict qBcr-Abl monitoring.
Best wishes.

Although Prof Saglio may very well be correct in calling these muscle pains, this is not entirely clear to me from the description. I will put a caveat on my discussion as I have very limited (almost no) experience in pediatrics and TKIs. Imatinib therapy can be complicated by 3 basic types of pains, at least in adults. In the acute phase and usually lasting a few weeks at the start of therapy, is fairly severe bone type pain, that usually resolves when blood counts normalize and can usually but not always be controlled with an NSAID. On rare occasions, this pain can go on for several months and on even rarer occasions does not seem to resolve so long as imatinib is continued. More chronically, and I do not think this is the issue here, there are 2 types of pain. The first is the cramping that Prof Saglio discusses. This can be controlled with good hydration, exercise of affected muscle, sometimes calcium or magnesium supplements and most effectively with tonic water (quinine) preferably sugar-free. The second is chronic myalgia/arthralia type pain that usually responds to ibuprofen. It is concerning if suboptimal therapeutic doses of imatinib need to be used as the impact on response and possible disease progression/mutation development become issues. I would go back to 200mg per day and slowly increase the dose if stable using a protocol of increasing one day per week to 300mg waiting a week or two to be sure there is no significant pain and then increasing a second day, etc until you get to a therapeutic dose. As mentioned, monitor response. If sub-optimal, a second TKI with a different side effect profile may be helpful. If milestones are being met and improving at lower doses as sometimes occurs, I would be less concerned that the dose is not "textbook". If symptoms and/or inadequate response persist even with a drug switch, then start thinking BMT before disease progression occurs.

Do not split the dose into two doses daily to avoid developemt of resistance to imatinib. Monitore molecular / cytogenetic response and imatinib drug serum trough level. Administering a single dose of 400 mg to this 9 year old boy (body surface 1.1 sqm) is a slightly higher dose than the recommended dose of 340 mg/sqm but response may be better with higher doses. To administer the dose in the evening together with ibuprofen might reduce the symptoms during the daytime. Check for elevated muscle creatinine kinase (CK) and try tonic water to reduce muscle cramps. If symptoms persist longer than 6 months after diagnosis (under sufficient co-medication) switch to 2. gen. TKI, preferably dasatinib.

Thank you for the useful inputs.
Currently the young boy is unable to tolerate more than 200 mg per day of Imatinib. Scheduled for qPCR in a weeks time, when he will complete 3 months of therapy.