3 replies to this topic

[Natasha_Austin]

Hello. My son was dx with AML at 9weeks old. He is now 26 monhts in remission. I am writing now about a friend's child. Diagnosed this week with AML with Philadelphia gene. He is eight years old.

I tried to do some research -- it is all so confusing. I posted on AML board, but someone so kindly sent me a private message saying you all may be able to help me and that TREY may be especially helpful in understanding. From what I have read, it seems rare and poor prognosis, esp at his age. But my son had a poor prognosis, too...so who cares about stats, right!   I want to be able to help her. I remember in the begining for us...it was all a blur. If you have any insight, it would be greatly appreciated. Thanks. He starts chemo today...so please keep Justin in your prayers. <3

Thanks, in advance!

[Trey]

All of us send best wishes to your child and your friend's child, Justin.  It is a very difficult disease for the kids.

The bone marrow biopsy (BMB) report enables diagnosis, and shows whether there are multiple chromosome translocations (mutations).  I will assume Justin was diagnosed properly.  Ph+ AML can be tricky to diagnose as separate from CML in some cases, so a second opinion would be a very good idea.  If it were my child, I would contact Dr Brian Druker by email or have his Onc do it himself and ask Dr Druker if he would review the BMB report.   I strongly urge a second opinion on this issue -- the diagnosis of Ph+ AML is not as easy as one might assume.

http://www.ohsu.edu/...earchResult=yes

I will provide some basic information here dealing with the issue in general.

Philadelphia Chromosome positive Acute Myeloid Leukemia (Ph+ AML) is related to CML in that both forms of  leukemia have the Philadelphia Chromosome which creates genetic signals causing uncontrolled growth of leukemic white blood cells.    As  the names imply, CML and AML are predominately diseases of the myeloid  line (neutrophils, etc) of white blood cells (WBCs).  Beyond that, the "chronic" (CML) is generally a less aggressive form than the "acute" (AML) form.  For CML, 3 drugs are available which work for over 90% of all CML cases.

Since Ph+ AML is generally a more aggressive form of leukemia than CML, it often does not respond very well or very long to CML drugs (Gleevec, Tasigna, and Sprycel).  But there are some cases where the drugs have helped, especially in getting the patient into a state where they are in better shape for a bone marrow transplant.  In general, Ph+ AML usually results in the need for a stem cell transplant since it is more likely to become resistant to the drugs than CML.  So Ph+ AML drug response is often short-lived.  Sprycel may have the best chance of working of the 3 drugs, but there is not much data, especially for children.

The Onc will be trying to first put Justin into a stronger state to better withstand a bone marrow transplant.  This will be done using chemotherapy (induction phase).  A CML drug may or may not be used during or after the chemotherapy.  This should be a question to ask the Onc.  If Justin becomes stronger and a suitable donor can be found, it is very likely the Onc would want to proceed with a transplant while Justin is in a stronger state, since that strength can often be lost over time.  The initial chemotherapy will not cure him, so there will need to be a longer term plan.  The only long term solution would be either CML drug therapy (questionable chance of long term success) or transplant (assuming a suitable donor).

Questions for the Onc:

1) Will a "CML drug" be used?  If so, when?  If not, why not?

2) What is the treatment plan and sequence of events?  After the initial chemo, what happens and when?

3) Is a transplant being planned?  If so, when will the donor search process start?

4) Would the Onc contact Dr Druker at Oregon Health & Science University about the case?

Here is some reading (somewhat difficult to understand):

http://www.mdanderso...ital/index.html

http://www.medscape....rticle/554550_3

Let me know if I can help further.  We wish Justin the very best.

[ebliss25]

Trey,

My mom was originally diagnosed with AML M2 and underwent induction chemo at Kaiser Hospital in Clackamas, OR back in April 2009 at age 56. After the induction chemo almost killed her, requiring a 12 inch section of colon to be removed due to damage, her Kaiser docs did not know what else to do and so referred her up to OHSU.

It was the docs at OHSU that diagnosed my mom as Ph+ AML. She started on Gleevec somewhere towards the end of 2009, and then underwent a stem-cell transplant back in June 2010 (her brother was a near perfect match). Initially the transplant was viewed as successful, as her brother's immune system completely replaced hers. She never even developed graft vs host even though they completely took her off of her anti-rejection meds after only a few months. The problem is that his cells never took over her bone-marrow.

Shortly after starting Gleevec, my mom started having trouble with fluid build-up around the heart. This required two separate hospitalizations, the second of which resulted in them cutting a window in her heart sack to allow the fluid to continuously drain. No problems since.

They tried a second induction chemo earlier this year and got her blasts back down to 10%. They were getting ready to do a second transplant when she developed an infection that would not heal, so had to pull her off of Gleevec for a week. In that week her blasts shot back up to 30%... so no transplant.

The doctors are at a loss now... they put her back on the Gleevec for 2 months and it kept the blasts from increasing further, but did nothing to reduce them. They were ready to give up, but we convinced them to try Sprycel. She has been on it for 3 weeks now and sees her oncologist again in 2 days, so hopefully we have good news.

I'm wondering if you know anything about Ponatinib... I've read about the trials and if the Sprycel fails... Anyway, just grasping at straws now and trying to find something that gets her back down to a level where we can try stem-cell transplant again.

Thanks,

Erin

[Trey]

Erin,

Ph+ AML is not very responsive to the TKI drugs, at least not for long.  The best you can hope for is that the Sprycel gets her back into a condition where a second BMT can be performed.  If Sprycel has little or no effect, then I personally doubt that Ponatinib would either, but of course there is always some chance of success.  Also, the Ponatinib trials do not appear to include Ph+ AML patients, only CML and Ph+ ALL.  But you should ask your Onc at OHSU.  Here is the link to the clinical trial info for Ponatinib:

http://clinicaltrial...onatinib&rank=1

There are other clinical trials for Ph+ AML.  Below is the summary of the ones I found (ask your Onc about any others):

http://clinicaltrial...ia positive AML

This one looks like the best option as I see it, if the Sprycel fails and the BMT is not possible:

http://clinicaltrial...tive AML&rank=4

Note that such clinical trials are high risk.  But Your Mother is already in that category.

Here are two others which may be worth looking into, but seem less useful from my perspective:

http://clinicaltrial...ive AML&rank=20

http://clinicaltrial...ive AML&rank=13

I would reiterate that the highest probability of success from my viewpoint (a limited one) is that the Sprycel gets her back into a condition where a second BMT can be performed, probably a "mini transplant" which uses very little chemo and no radiation.