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

The point of this post is this new article – feel free to skip all my discussion and go right to the article.
My post which appears below, tries to provide some context for this (hopefully very helpful) new research.

Let’s start by reciting a basic problem. Here it is: Like many cancer cells, the internal mechanisms (i.e. the things that are broken inside) that make APL cells cancerous are not fully known. Through a series of tests combined by a visual review by experienced eyes, cancer cells can be accurately identified but scientists don’t usually know what made the cell cancerous in the first place.

Here’s the problem. If it’s tough to fully describe and understand your enemy (APL Cells) – you can bet it will tough to fight “them.”

Know your Enemy

It’s a basic tenet of warfare to know who you are fighting. In fact, the most troublesome adversaries are very secretive and difficult to understand. Enemies that hide, don’t reveal their inner nature – etc. Sound familar?

Ask yourself, how can we form an accurate and effective attack without understanding an enemy? Also ask yourself – how effective are generalized attacks against a very specific enemy? What are some of the drawbacks of generalized attacks on a specific enemy? Traditional chemo is a generalized attack in terms of this analogy – compare it to carpet bombing.

The APL Healthies

Let’s return to a subject that highlights the partially unknown nature of APL cells – I call it the problem of the “APL Healthies.” This problem highlights some of ways that the detailed nature of APL cancer calls and many other types of leukemia cells remain poorly understood. The new article I linked in the first sentence of this post might hopefully be a step toward resolving some of these unknowns at least for APL.

We spoke previously about the fact that cells that display the primary genetic markers that are used to identify the presence of Acute Promyelocytic Leukemia (t:15:17) are sometimes detected in apparently healthy individuals that will likely never develop full blown APL. There is a nice outside article located here on the whole subject of detecting leukemia associated cell markings in healthy individuals.

In fact, a few years ago, Quina et al. (2001) tried to create APL cells by exposing healthy human stem cells to radiation. The investigators ran into a little problem though – they found that there were about the same number of cells showing the t15:17 trait in their pre-radiation samples vs the post radiation samples. This sort of observation has actually been made for a variety of leukemias – certainly not just for APL.

I am always watching for APL related articles that will help me better understand the conflict of finding APL cells in so-called “healthies.”

Basically the RXR article discusses an additional genetic trait that must be present in a cell that carries the traditional t15:17 marker before it can become cancerous. Could RXR be missing from the cells that are often found in the healthies?

Another thought is that if RXR really does play a critical role in the development of fulminant APL then it could possibly be used as a specific target for a specially designed highly APL specific drug (think less debilitating chemo and fewer dangerous transplants). Could the RXR marker be an important element of the overall APL enemy (know your enemy)?

How can Dr’s detect something that they can’t fully describe? Experienced eyes and more than one type of test…

** Think of a silly example… even though I don’t know all the details regarding a 1967 Mustang, I do know one when I see one. There are certain visual cues that I look for – like the shape of the front grill for example. A PCR test is kind of like that – it looks for a very specific attribute, but perhaps not all attributes that are required to uniquely distinguish a type of cancer.

Scientists do more than just “look at the front grill” then they look for APL…

Researchers and Dr’s often use an assay called a PCR Test to determine if a specific type of cancer is detectable. PCR Tests can “see” cells that match a specific genetic pattern (i.e. watch for front grill) and they can even report the approximate concentration of those cells, often relative to a healthy cell type that should be present at a known concentration.

Some very important treatment decisions can be heavily influenced by specific PCR results. In Anita’s case, a specific PCR result that failed to find any remaining evidence of APL cells showing the t15:17 transcript helped determine the type of stem cell transplant (autologous) that would be best for her treatment.

Still though – when each of these PCR tests would come in for Anita, I would always ask myself – What does that test result really mean? What is the PCR test really seeing? What does the result mean, especially if that darn PCR test will sometimes be positive for a “healthy”?!!

As I have read more about PCR testing and leukemia in general, I understand better why actually looking at sampled bone marrow cells under a microscope is the gold standard for diagnosing and tracking the progress of any leukemia.

Rather than just looking for a very specific trait, like a PCR test does, an expert pathologist applies his considerable expertise, actually looking at specific cells taken from a bone marrow aspirate sample. The pathologist employs his or her experience to carefully identify any cells that appear to be abnormal – often providing comments that can provide the foundation for an entire treatment regimen.

There are plenty of pictures of what APL cells (scroll down to the M3, acute promyelocytic leukemia (APL) pics) and many other types of leukemia cells actually “look like” under the microscope. Again, this is a manifold subject, with numerous “exceptions to the rule” and some troublesome scenarios where certain types of leukemia cells very very closely resemble other types of leukemia, making it difficult to properly diagnose some types tumor types.

So if you were diagnosed with APL, or any leukemia, you can bet your Dr’s aren’t just relying on a PCR test – they look at many factors that are very carefully aligned and checked before any diagnosis or overall treatment plan is established.

New Attribute of Leukemic APL Cells has been Recognized- RXR
It has been recognized for a long time that APL cells almost always show the translocation of chromosome 15 and 17 PML/RARA, but again let’s return to the fact that cells showing this same t15:17 translocation are sometimes found in healthy individuals (let’s call them “healthies”).

My previous post that discussed Healthies and APL Cells discussed a two major possibilities on this. First, perhaps the natural immune systems in the healthies, have a special way of keeping the APL cells in check, or second, perhaps there are additional heretofore unknown genetic defect exists in fulminant (cancerous) APL cells – maybe even some combination of both of these ideas are true.

I decided to revisit the idea of the APL Healthies when I read the RXR article recently. The article describes the characterization of an additional defect that must be present in t15:17 cells before they can become leukemic (cancerous). Could this be the additional trait that must be present, before active APL can develop?

Generally, as the overall puzzle of how APL develops, becomes active, and potentially relapses, science can better develop more specific drugs to treat it. Indeed, APL is already unique because there are already two highly specific and very effective drugs to treat it (arsenic and retinoic acid). Both of these drugs are highly active against APL but unfortunately, they cannot be regarded as a cure because they don’t fully protect against relapses and resistance can develop to them over time. These drugs also both seem to need support from traditional (difficult to tolerate) chemotherapy to be most effective.

Simply put, there is more work to be done.

I am hopeful that this RXR research will be another “brick in the wall” toward treatments that hold more promise toward a real cure for APL.
One question I am left with after reading the article is whether the RXR structures are found in healthies as a trait in the t15:17 cells that sometimes carry? Is RXR an attribute that is only found in patients that have already or soon will develop full blown APL?

How’s Anita?

Here is a very short update on Anita.

Anita was admitted to the City of Hope about 10 days ago. She is at day zero of her transplant today. In fact, she received her own stem cells back about an hour ago and the process was uneventful. Anita’s nurse and two cell processing technicians stayed with Anita throughout the 90 minute process.

The stem cell transplant turned out to be a quiet event, part of a difficult process that one of Anita’s Dr’s referred to as “rugged” when I spoke with her yesterday. I can and probably will go into more detail on what the transplant preparation chemotherapy was like for Anita but not now. The bottom line is that the transplant has been difficult but is going according to her Dr’s plans.

Overall – when you hear the word “transplant” you can think about the hope that it brings but also realize that the hope comes along with a very tough road that includes alot of suffering, risk and difficulty.

Anita is resting now and as of yet has not developed any serious infections due to her chemotherapy treatment. Day by day her recovery should continue.

A lot has happened since my last post regarding Anita’s progress.

To summarize, Anita reached PCR negative status after her two rounds of arsenic based therapy. The PCR negative status was a great milestone for her as it meant that she qualified for a less intense and less risky type of stem cell transplant called an autologous transplant.   An auto transplant allows Anita to to donate her own stem cells, rather than relying receiving stem cells from a sibling or unrelated donor.

With the good result Anita obtained from Arsenic treatment, this set the stage for her to continue on to the stem cell transplant she needs to help prevent the return of her leukemia.

Anita is to receive an autologous transplant at the City of Hope in Duarte, CA. We are fortunate to have access to the City of Hope, especially since some types of insurance coverage won’t always provide access to a specialized cancer treatment facility like COH.

Our insurance coverage is with Kaiser Permanente and they have provided excellent treatment for Anita since her initial diagnosis in late 2001. Through all of Anita’s treatments, including about 150 days of hospitalization in the last 5 years, I never felt that Kaiser did anything “on the cheap.” We also found the Kaiser staff, including Anita’s primary oncologist and the many nurses that have worked with her for the last 5 years to be very dedicated and focused toward her care.

Back to Anita…

Even though Anita reached PCR Negative status after her Arsenic treatment, there were numerous “pre-transplant” tests she had to clear to make sure she was suitable for her treatment. Some of the tests were performed and San Diego and others at the City of Hope.

Anita has been working through the steps to get ready for her transplant for the past few months and she is finally ready – just a few days to go before it “happens.”   We knew the date for the transplant was getting close but we were waiting for a few test results to come in before it could actually be scheduled. This Thursday, Anita’s transplant coordinator nurse called and said the magic words – “it’s on for Monday.”

Basically COH seems to have made a big push to get Anita’s transplant scheduled quickly – to take advantage of the PCR negative result they obtained from her stem cell collection.
The day after the transplant nurse called we packed up Anita’s things and traveled to the City of Hope. Anita will likely be here for between 45 to 60 days with a lengthy series of recurring follow-ups thereafter.
Anita’s will start 6 days of strong chemotherapy tomorrow morning – Monday July 9th. The chemotherapy will work to destroy her existing immune system. After her immune system is destroyed, the stem cells that were gathered about a month ago will be re-infused into her. The re-infused cells will engraft back into Anita’s bones and will grow a new, hopefully healthy, immune system.

When Anita receives her own cells back (that she donated about a month ago) they will be delivered intervenously – just like you would receive blood after an injury (for example). The stem cells are smart – after being re-infused they return back to the interior of her bones and will get to work toward making a new immune system for her.