APL, Information and SupportInspired by Anita’s Journey through Acute Promyelocytic Leukemia

Leafy on the LLS discussion board asked me to dig up the FLT3 / APL articles that I mentioned earlier. I will find these articles soon and will post links to them.

Meanwhile, MichaelM who is really a star over on the LLS board because of his very strong overall knowledge on AML, had some very insightful remarks on the FLT3 discussion.

Basically in this post, I am trying to provide some context and discussion to help support APL patients in trying to decide how much they want to learn about their disease. I especially want to express the notion that we all need to be careful about expecting our “lay person” knowledge to be very helpful in improving our treatment outcomes.

I am going to hop out on a limb and paste MichaelM’s remarks below as they provide context for my more lengthy post which appears thereafter,

MichaelM’s post-

This is a little complex in your situation.

APL is still an AML, and the presence of FLT3 _juxtamembrane_ mutations is always a negative indicator to some extent. In considering most APL to be one of the three better prognosis AMLs, though, the presence of such a mutation is not necessarily as bad as you might otherwise expect. (I’m intentionally hedging here, for obvious reasons.) You’ll have trouble finding a consensus on what, exactly, the impact is.

If you are sure testing for an FLT3 mutation was done, then they likely performed testing to determine BCR status (BCR1, BCR2, BCR3). Do you know which she showed? Other considerations would be whether this is an M3v (variant) AML or not.
If you’re just looking at a report that noted FLT3 somewhere, you should understand that there is a prognostic difference between the juxtamembrane (length) mutations (ITD – internal tandem duplications, and insertions, which are the ‘bad’ ones) and the codon mutations in the kinase region, which are generally felt to have less or no real significant prognostic value). There’s also a prognostic difference if there is a low ratio of mutant FLT3 vs wild (normal) FLT3, as well as if wild FLT3 is absent. The size of the mutation probably impacts the prognosis as well.

I know I have read of some protocols under study that involve FLT3 inhibitors front-loaded with traditional chemo or arsenic trioxide.

Chris’s comments:

MichaelM has obviously worked very hard to develop a robust understanding of AML. He is way ahead of me on this stuff.

It is perilous trying to summarize and simplify what he said as he understands much more of this than I. I think there is always a danger of trying to explain things in a way that is simpler than they really are.

If I understand his post, I believe the general idea is that you can’t really say much about interpreting the significance of FLT3 without also considering the subtype of APL along with other factors.

The APL subtypes I am aware of, are: short, long and variant. Also, I believe that the BCR1,2,3 values he mentioned equate (I don’t remember how each matches up) respectively to: short, long and variant types.

Anita has the M3v type and of course she relapsed at 5 yrs post first CR. I have seen a few studies have suggested that the M3v type is more difficult to deal with.

MichaelM’s other comment is that you cannot interpret the significance of FLT3 very well without knowing the concentration at which it was detected. I like how he said “FLT3 written somewhere on the report.”

I think all of this is very very interesting and I want learn all I can about it. Learning the details is interesting, but I still think it is very important to consider if any of this information can impact your treatment or help you in much of any way.

My question is, how can you use this information to help yourself (or others)? I think it can help a little bit but you need to carefully ponder its limitations.

Another point, is that hard data like “FLT3” is important, but is difficult to apply at least in some respects to an individual’s specific treatment needs. For example, if the individual had an odd liver toxicity issue with certain types of drugs, that could trump all kinds of ideas about making incremental adjustments to how APL should be treated.

I think Anita’s Dr carefully consider’s Anita’s overall status along with her APL treatment needs. Of course that sounds like common sense, but us lay people tend to take a narrower view of what we read in scientific articles about APL. I think we can end up missing the “overall approach” that a good Dr takes toward treating their patients.

What I am suggesting here is that it can take a great deal of experience and judgement to relate what you read in this or that article to a patient’s individual needs. Great Dr’s dedicate spend their entire careers developing the judgment and experience to manage tough diseases like APL.

Michael’s post illustrates is that as you dive deeper into the whole subject of APL, you will find that it drives rapidly into other cross connected areas of knowledge. What is a codon? What is a flow cytometry result? What are all these abbreviations? I think you might see what I am saying here. How far do us lay people really want to go with all this learning and can it really help our loved ones?

So much of this is not really in our control and an individual patient in a typical healthcare setting is not a science project. Oncs tend to be pretty conservative and will provide treatment along established lines that have been developed through phased studies.

MichaelM’s comment that there are possibly some trial studies with FLT3 inhibitors out there is of interest. Trial studies are whole new subject though though. See if you have to go across the country to even participate in many of them!

I get frustrated at times, where I look back and see great results from APL treatments that are standard now, like the blended use of AsO3 and ATRA for initial treatment. Those treatments were not standard 5 yrs ago and Anita did not receive them. Relapse seems to be considerably less likely when these blended treatments are used.

Would she have relapsed if she had received the newer treatment that was more experimental in 2002? We will never know. Think of all the thousands of what-if’s in life. If the slow but more sure approach of phased studies had not been carefully used for so many years would APL treatment had ever advanced to where it even was in 2002?

Moving on here, and back to your original FLT3 question, maybe you could somehow thoroughly anonomize your APL friend’s pathology report that mentioned FLT3. After it is carefully anonomized, I could post a scan of it over on www.aplblog.org and perhaps a few APL’rs could try to provide a few comments.

I am not a Dr or an expert on APL but I do think that there is a need for this kind of more technical discussion among lay people. There is such a huge canyon between the non-expert articles that I read regarding APL and stuff that is easier to understand.

Our Dr’s are just too busy to engage in very much this type of more technical discussion with lay people too so maybe we could just talk a bit about it on our own.

I also think it would likely drive most Dr’s crazy trying to talk all my super wide ranging questions through with me so that is probably the case for other caregivers and APL patients as well.

Chris
www.aplblog.org

Someone on the LLS boards asked about the significance of the FLT3 genetic mutation for APL patients. I answered her question as best I could.

When you read my post, think about how my comments could help guide you to asking more relevant questions for your own treatment.

Would you want to know all the negative factors that might surround your specific health situation, even if those negative factors couldn’t be used to help better guide your treatment?

When I think of all this it reminds me that “too much information” – especially information that you cannot use to your advantage, isn’t always a good thing.

Here is my post,

What is the impact of the FLT3 mutation for APL patients?

I asked Anita’s oncologist pretty much the same question a few weeks ago. First question is whether you were even tested for FLT3. He said that Anita had not been tested for it and that FLT3 isn’t usually checked for APL patients.

APL is a rare disease. It comprises only about 10% of AML cases, so when you drop that subset even further by subtyping further there is even less statistical data available to guide any treatment decisions.

There are a few articles out there on FLT3 with APL. I will dig them up if you ask me to. FLT3 is a negative factor but its presence does not alter any standardized treatment protocols that I have heard of.

For example, if you are newly diagnosed, and you have the FLT3 mutation, they would still try to treat you with Atra or Arsenic and chemo – and not send you straight off to a transplant etc. Basically APL, even with FLT3 is still very treatable – usually without a SCT.

All of us APL’rs need to be thankful about all the progress that has been made with APL in the last 20 years. 20 years ago APL was widely regarded as the absolute worst leukemia to get and now it is consider the best by many. The best leukemia – talk about an oxymoron.

If you have FLT3 and it is a negative, are you going to fight harder? I bet you were already fighting APL plenty hard!

So – think about what you would really do with this FLT3 information (if you don’t have it already).

I bet your Dr. would know your FLT3 status already if it had a possible impact on how to best treat you. That was Anita’s Dr’s basic answer to me. He is always many steps ahead of me on this stuff and thank goodness for that.

Chris

I have been trying to post a little more frequently on the Leukemia and Lymphoma Society Website Discussion Groups. The LLS discussion groups are a tremendous resource for anyone that is dealing with a blood based cancer. The LLS website provides an absolute front-line view of what so many are dealing with in fighting leukemia and related diseases.

I just finished a post, where I tried to explain some of the factors that go into choosing an auto or allo stem cell transplant. My very short post just skims the surface of this complex subject but it does touch on why autologous transplants can be a better choice for some people depending on their specific treatment context.

Here is my post,

Statistics show that autologous or syngeneic transplants are definitely the best choice for some people.

Indeed, relapse rates tend to be higher with auto or syn transplants but the potential complications, and lesser probability of death, with an auto can more than make up for the higher relapse rate with an auto transplant.

Some mild GVH can be a positive sign, but what guarantee does anyone have they will only get a mild case? There are several difficult and sad aGVHD stories that are active right now on this board.

Managing leukemia and picking the right treatment is very complex. The whole subject of choosing an AUTO vs an ALLO is a good example of how thorny and difficult your Dr’s job can be.

Basically the idea with all transplants, including AUTO or SYN transplants, is that your Dr’s can dose you with a very very high dose of chemotherapy. So high, that you would very likely die if they could not re-infuse your own (hopefully cancer free) immune cells back into you, after the chemo.

It’s that ability to blast the patient with incredibly strong chemo that offers the potential cure for an AUTO patient. The whole AUTO thing seems a bit scary and counter intuitive to me but you can’t ignore the statistics that support choosing an AUTO when the context for that decision is correct.

I felt the need to post this because it won’t be too long before we will learn whether an auto or allo is the best choice for her.

Chris

How is Anita?

Anita has been home now since Friday evening. She is doing well and very much enjoys here time home. Her appetite is very good and her body seems to know that this is the time to rebuild after her lengthy (32 day) arsenic treatment regimen.

Now that the arsenic treatment is over for a few weeks, her main lingering side effect has been the tendency to fatigue easily. Basically her entire blood system is depressed to a small degree, enough to limit the amount of energy it can carry. She has plenty of energy in the mornings but tires earlier in the evening than usual.

She has plenty of energy to play with her dogs and perform light chores around our house. Light chores? Just try to stop her from performing any light tasks around the house – I haven’t been able to!

The arsenic treatment was much less harsh for Anita than the traditional chemo she received in 2002. Basically, the arsenic did not make Anita neutropenic, leaving her vulnerable to infections. It just mildly suppressed her immune system and this 3 week break that she has now is the perfect opportunity for her to recover.

Chris

Just a very quick update. I just learned that Anita can finally come home today. She has finished the first phase of her arsenic treatment and she is in remission (CR) now. We received the news that she is in remission early this morning.

She will get a 3 week break from treatment then will return to the hospital for another 5 weeks of arsenic based therapy. The next round of treatment (consolidation round) will be to help further assure that any remaining cancer is destroyed.

We still have a ways to go on all of this. She is still to receive a stem cell transplant after her next round of arsenic therapy. At this stage, it looks like the stem cell transplant might occur sometime in April or May.

We are still waiting for one more test result to arrive. Anita is indeed in remission now, but we are waiting for one more test to come in, which will indicate whether there is any detectable remaining trace of the cancer. This second test result, which may arrive later today, is called a “PCR Test.”

You can have a small amount of residual cancer and be in remission. You might want to check out my earlier post about how many healthy people that will never develop leukemia actually test positive to PCR Tests.

Anita’s spirits are good and she is certainly anxious to come home. She will need to wear a mask when she is outside but that will be temporary, probably for a week or so.

So – off to the hospital I go to get her moved back home. It’s amazing how much stuff has accumulated in her hospital room over the past month. It is going to be fun moving it all!

Chris

Still in the hospital, wasn’t ever able to switch to outpatient treatment

Anita is still in the hospital. Indeed her fever did clear shortly before my prior post but it returned a few days thereafter.

Anyone that fights cancer needs to accept that it can be a real roller coaster. The unfortunate person that is struck by cancer, and his or her loved ones are all brought along for what can be a terrifying ride.

Another fever

The fevers are frustrating and they cause plenty of misery for Anita. I can understand why they take time to resolve though. If they aren’t treated carefully, and mistakes are made, an APL patient can get into serious trouble very quickly.

We were never sure what caused the fever the first time. It could have been an infection, or it could have been from something called “RAS” which is a potentially dangerous complication that can arise during treatment for APL.

RAS – Retinoic Acid Syndrome – some background

RAS occurs in about 35% of patients that are treated with Arsenic Trioxide for APL. It is caused by a complex process that isn’t completely understood. The general idea is that as Arsenic does its job, destroying the APL cancer cells, those cells, as they die, release compounds into the body that can cause a lot of problems.

RAS is serious and it needs to be treated quickly. A lot of APL patients used to die from RAS before the phenomenon was better recognized. Thankfully, Dr’s have learned to manage it pretty well now and it is very seldom fatal.

I can imagine that some APL patients, maybe several years ago (before RAS was so well recognized in the literature), developed RAS related fever that was thought to be infection related such that their treatment for RAS was delayed with possibly catastrophic results.

It also doesn’t help that the main treatment for RAS can be immunosuppressive and can give an active infection a strong boost. I got the distinct impression that Anita’s Dr’s did not want to treat her for RAS until they were sure she didn’t have an infection that was actually causing the fever.

Careful, calculated treatment helps avoid mistakes – navigating through treacherous waters

For Anita, when her fever returned, it took her Dr’s two days to start treating her for RAS with Dexamethasone. They wanted to be as sure as they could that the fever was not being caused by an infection, before they started with the “Dex.”

Anita was miserable for those two days – about the only relief was Tylenol every 4 hours and ice packs. Even with these her fever ran high, at least to 103.5 once when I was there, perhaps higher at other times.

The need to treat RAS quickly creates an interesting problem, because the medicine that is often used to treat it, dexamethasone, can cause problems of its own. It is a powerful, potentially life saving drug, but like lots of these powerful medicines the possible side effects have to be managed carefully.

Dex is a type of steroid and it is an interesting medicine. It is a catabolic steroid, instead of the anabolic steroid that have gotten many athletes into trouble. Basically a catabolic steroid sends a chemical message to the body, telling it to mobilize and use stored reserves of energy or compounds. Anabolic steroids do the opposite – telling the body to save reserves – i.e. to build muscle as one example.

How is Anita doing now?

When Anita received, Dex, her fever quickly dropped and she started feeling much better almost right away.

So here we are, she has been in the hospital for almost 25 days now. She is feeling reasonably well as of today, but she is receiving medicines at various times pretty much throughout an 18 hour today. I don’t think Anita’s prospects for getting out of the hospital are great for now.

Anita makes a new friend, a fellow leukemia patient in the hospital

Anita is doing OK though. She even made a new friend this week – a 66 year old lady that is being treated for leukemia (she’s in the next room over). I have met a lot of 25 yr olds with less energy than Anita’s new friend. I will refer to Anita’s new friend as “M” (to help protect her privacy).

Unless you have experienced it yourself, I think it is very hard for most people to understand what it is like to suffer with a life threatening disease. Even for myself, after spending so much time with Anita trying to help her each day, I still often feel that I just can’t really “get it.”

At least with Anita’s new friend, I could see two people talking and visiting that definitely “get” the whole leukemia thing. Seeing them together, especially seeing the strength they derived from each other was a great experience for me.

“The Hat” – What does it symbolize?

Happily, Anita’s friend checked out the hospital yesterday. She was at a point in her treatment where she was ready for a break. She gave Anita a small gift before leaving – it was a very soft beret type hat. The little hat quickly took on a symbolic meaning to me, representing a link between two people that really understand what it is like to fight leukemia. The hat also symbolizes the strength and wisdom we stand to derive from each other when we take on adversity together.

Why did “M” give Anita a hat? “M” knows that Anita will lose her hair when she receives the chemotherapy that is necessary to prepare for her bone marrow transplant. If someone is going to lose their hair, a soft and warm hat is considerate gift.

Just a quick update…

Anita’s fever continued through Tues evening and finally broke mid-day Weds. She is doing much better now and she was back to taking her lengthy walks today (Thurs).

I believe Anita’s Dr suspected that the fever wasn’t due to an infection from the start and I think he was correct (as usual). It seems more likely that the fever was brought on by changes in Anita’s blood system that are being brought on by the Arsenic treatment.

Hopefully the fever will stay away now and Anita will be able to come home, perhaps early next week. Her treatment will continue as