Tag Archive for: chromosomes

Myelofibrosis Care | The Impact of Test Results

How do test results impact myelofibrosis care? Dr. Naveen Pemmaraju outlines essential tests like bone marrow biopsies and molecular testing and shares how results may guide treatment and prognosis.  

Dr. Naveen Pemmaraju is Director of the Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) Program and Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Pemmaraju.

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What Myelofibrosis Treatment Types Are Available?

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When Should Myelofibrosis Mutational Testing Be Repeated?

When Should Myelofibrosis Mutational Testing Be Repeated?

Transcript:

Katherine Banwell:

Let’s talk about test results. What sort of tests should be done following a myelofibrosis diagnosis?  

Dr. Naveen Pemmaraju:

Well, I think this is something that’s an active area of evolution. I think the good news is I can give you a few standard items. I think most, if not all, of our patients, will require a bone marrow biopsy to be done at baseline and possibly even later on to assess the status of the therapy. Now, in some cases, that may not be available or accessible due to patient preference or comorbidities.  

However, a bone marrow biopsy is a way to look inside and see how the bone marrow tissues are doing. Outside of that, for the blood tests, the two most critical sets are what we call a CBC and a CMP. So, CBC complete blood count. This is where you get your hemoglobin, platelets, and white blood cell count, very important to know at baseline and dynamically.  

Then the complete metabolic profile is very important, Katherine because we need to know how the potassium, kidney function, and liver function are doing. Then finally, I would also say you’ll see your provider add in other blood tests over time, depending on the particular case. Thyroid testing if it’s needed in the case of fatigue, just to name one example. So, I think these are the main categories.  

I think what’s also interesting over time is that this is an issue with us as well in the MPN clinic. You end up seeing your MPN provider and team so much that it’s easy to forget and lose sight of the primary care items too. So, this is a good time to remind folks to stay in touch with their MPN team, the provider, and their caregiver, whether it’s colonoscopies, mammogram, or prostate. I remember over the COVID pandemic time, especially, a lot of that was either sacrificed, forgotten, or on purpose put aside. So, let’s remind people in 2024 to remember to have that partnership as well.  

Katherine Banwell:

How does molecular testing affect treatment options and prognosis? 

Dr. Naveen Pemmaraju:

Right, yeah, I haven’t mentioned that yet because that’s something that we’re trying to layer into. I do find that to be the standard of care now in the treatment of myelofibrosis. What you’re asking about is very important. So, outside of the normal labs in bone marrow morphology, seeing what it looks like under the microscope, we’re starting to add three or four items. One is called cytogenetics, that’s chromosomes. You’re born with 46, so 23 from mother, 23 from father, for example, 46 total.  

Even though most people are not born with an MPN per se, those chromosomes can change and become abnormal over time. So, we want to know that, and that can help us tell low versus high versus intermediate risk. Two is the molecular test you ask about. Most people have heard of JAK2, that’s the most common out of myelofibrosis, maybe 50 percent to 60 percent of cases, JAK2V617F. However, did you know there’s also CALR, which is the second most common molecular mutation, and then MPL. 

Those three are the big three driver mutations. They make up roughly about 90 percent of our cases, 10% being so-called triple-negative. So, you’re negative for all three. When you do deeper sequencing, which is available now clinically, and we check that here, you will find almost always, some other mutation, ASXL1, EZH2, SRSF2, etc. It becomes an alphabet soup very quickly. However, I think basically you should know that there’s JAK2, CALR-MPL, the big three driver mutations, and additional molecular mutations.  

So, therefore we and others believe you should check these as standard. Finally, there’s also flow cytometry. Just want to give a shout-out to that. Most people haven’t heard of that. When you send your bone marrow for testing, in addition to the pathologist looking under the microscope with the human eyes, there’s also a test that does side scatter of light called flow cytometry. That helps to look at a deeper level, maybe the thousandth, maybe even down to the millionth level, what these cancer cells do. 

Katherine Banwell:

What sorts of questions should patients be asking about test results?  

Dr. Naveen Pemmaraju:

I think the number one and number two questions that I advocate for patients or on programs like this, I think the one question that may help a lot is this question of when you hear all the data and ask the question, “Hey, is there any other questions I should be asking that I’m missing?” It’s an interesting question, right? It’s almost a meta, right, kind of a situation. However, when you ask that, every time I’ve been asked in the clinic, it makes me pause and say, “Now that you mentioned it, X, Y, and Z.”  

So, I think it’s a good one to ask either your physician or whoever healthcare provider is in the room, again, nurse, or PA. It’s an interesting one, right? It kind of makes someone maybe even put themselves in your shoes. So, I like it as a device to make people pause in a busy clinic. Yeah, the second question that I think is a good one is to say, “While things are going well right now, I wanted to ask you, doc, what are some things that could happen in the next six months, one year, or two years, adverse events or abnormal things, and is there something I can do to plan for it?” 

Again, it may be somewhat of a theoretical question. The doctor may say, “Okay, right now things are going well,” but it kind of makes people think about contingency plans, and alternative things. Well, now that you mention it, there is this one side effect of this drug. I don’t know, I think those are two kinds of go-to questions that I want people to be equipped with. 

AML Treatment Decisions | Understanding Factors That Impact Your Options

AML Treatment Decisions | Understanding Factors That Impact Your Options from Patient Empowerment Network on Vimeo.

An acute myeloid leukemia (AML) diagnosis can be different for each individual patient, so how is a treatment approach determined? AML specialist Dr. Jacqueline Garcia provides an overview of factors taken into consideration when choosing therapy, including age, overall health, and the patient’s preference. 

Dr. Jacqueline Garcia is an oncologist and AML researcher at the Dana-Farber Cancer Institute. Learn more about Dr. Garcia.

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Transcript:

Katherine Banwell:

With all the treatment options available, how do you decide who gets what? Tell us what is considered when choosing treatment for a patient. 

Dr. Jacqueline Garcia:

When I – this is a complicated question, because it’s not like you follow any particular algorithm. But when I meet a patient, I make a decision on what’s important to the patient and what’s  their goal. If I know – I need to understand their overall health to get a sense of are there ongoing competing risk factors that are active and more likely to impede with response, ability to deliver chemo, ability to get to transplant, something that tells me that’s not a possibility, or is their age too advanced – meaning greater than 75 – where we know that some of the treatments are not safe to deliver in that setting?   

So, I take a look at a patient’s overall health and age to make a decision. I take a look at bone marrow biopsy and lab findings to understand the flavor of their leukemia, from chromosomes to mutations. And because I am familiar with the data to give me a sense of what’s safe, what’s tolerable, and importantly what types of diseases, or subtypes of AML, would respond to one therapy over another, that’s how I formulate a recommendation.  

And based on all of that, all together, I’ll talk to them about treating the AML in steps. The first step is getting them into a remission, which can be done regardless of therapy type. That means to get their bone marrow under control, blood counts to recover. The second step, which is a more involved conversation that I often give a little bit of a hint of, but I go into greater detail over time, because we will see each other quite a lot, whether in the hospital or in clinic, is how to keep them in remission.  

And that’s where details about things like transplant come into play. I do my best to not overwhelm them, because when a patient hears the word transplant – and that’s often what they hear from family and friends because that’s what you can Google – they don’t know that there are many things, or many weeks of therapy, that have to happen in advance of transplant even being considered or happening. And transplant can’t even happen until someone’s in remission.  

But that is always on the forefront of a leukemia doctor’s mind, “Can I bring this patient to a transplantation? How successful will I be and what else do I need to give them to get them there sooner, safer, with a deeper response?” So, that way transplant could be successful. Transplant, by the way, is when we give a patient someone else’s stem cells that match their HLA typing, or their white blood cell signature.  

And it helps us to use someone else’s immune system to completely irradicate any microscopic leftover leukemia in a patient. But that is only successful when patients have good disease control or remissions. And that is only also successful if we have a donor for the patient, both of which  require at least several weeks to a couple of months of therapy. But that process is always initiated and ongoing in the background. And so, we often do this in piecemeal, because getting a diagnosis is already overwhelming. Learning about treatment is overwhelming.  

Learning about the frequency of labs, transfusions, being hospitalized, and then details about what a transplant would entail can be also overwhelming. But a lot of family and friends like to ask, because they feel like that is one way they might be able to help a patient. So, I know that they often eagerly ask the patient, “Well, what about this? How can I help?”  

Katherine Banwell:

Right. I can imagine that patient preference is also considered. But what kind of questions should patients ask about their treatment regimen?  

Dr. Jacqueline Garcia:

I always tell patients that I care very much about things like travel, hotels, all that jazz. But I always tell them let’s first talk about their health, what treatment I would recommend based on the available options and what their disease would mostly respond to, because I want it to be successful. And I always tell them let’s reserve questions on how it’s going to be done for last. I call that the logistics. I will never bring up or recommend something that could never be possible. But that being said, I try not to let the commute determine the decision.  

Whether or not there needs to be a hospitalization versus a hotel stay. I always consider then the background, but that financial decision should not drive the best treatment choice for a patient. Very fortunately, we’re in a country where patients have the ability – often, not always – to seek second opinions or to travel to academic centers.  

And because AML is an emergent or life-threatening disease, many insurance providers allow patients to come up to a big center to be treated, which I think is more than appropriate. So, we get into details of logistics last, because that’s the one thing that we can often overcome by providing additional resources and support. In terms of patient preference, if that’s what you mean with that, I would say I leave logistics to last, but we always consider and we do our best to accommodate.  

And that might be where we inform them we will look into getting a local partner to help us with additional therapies after the first month or upon discharge. So, it totally depends on the scenario for a patient, whether or not they have a local provider and a local hospital that could accommodate acute leukemia. I always tell patients ideally you don’t want to go to a place that only sees this once per year. You want to go to a place where everyone has seen it multiple times, including the nurses on the floors.  

So, that way, when there’s a complication, everyone knows what to do. We don’t want any “surprises” when it’s really just run-of-the-mill standard stuff for us every day. In terms of what patients desire, we always keep that in the conversation of their level of support. Can they swallow pills? Are they able to cope with being in and out of the hospital? All that stuff gets considered, but I think if they hear about the plan, about what’s required, when my expectation would be for a response, when the frequency of trips to a big city would decrease, how I could get a local partner to help with some of the lab or transfusion burden.  

Many of those preferences that they thought they had diminished, because they recognize that we found a way to make it work.  

Katherine Banwell:

Dr. Garcia, you mentioned earlier the fact that some therapies can cause a lot of side effects, like nausea. And certainly, speaking up and telling your healthcare team how you’re feeling and what some of the symptoms and side effects are, that’s really essential. What is the impetus for someone to consider changing treatment if something is just absolutely not agreeing with them?  

Dr. Jacqueline Garcia:

So, there are many reasons to change a treatment. One is a patient doesn’t tolerate it. It depends on what the issue is. Is it something that’s serious, like a liver or enzyme abnormality that is very abnormal, or a new cardiac problem where it would warrant a change or a dose reduction? That makes sense. There is definitely – often, there’s a lot of guidance in the package inserts or within a clinical trial and how to manage that. But if patient has some intolerabilities that could be overcome with standard supportive care methods, I would make sure we’ve done that.   

So, I would make sure you give you medical team the chance to fix any nausea. We have so many great antinausea drugs. I would want to make sure – or if constipation or diarrhea. It’s often a GI issue that patients get really bothered by.  

I would try to delineate whether or not the side effect was really from the chemo or is from the leukemia that is not yet under control. Or is it another medical condition or a drug-drug interaction that was missed. So, I would do my best to make sure there wasn’t something that was fixable or something else that should be addressed. We otherwise would recommend changing therapy for an extreme intolerability if there was another equivalent better option. And if someone’s disease does not respond to treatment, then we would consider another therapy, too.  

What Is the Purpose of AML Genetic Testing?

What Is the Purpose of AML Genetic Testing? from Patient Empowerment Network on Vimeo.

How is genetic testing for AML administered, and what is the purpose? Dr. Sanam Loghavi explains the methods of genetic testing and the function of each method.

Dr. Sanam Loghavi is a hematopathologist and molecular pathologist at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Loghavi.

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Transcript:

Katherine Banwell:

Dr. Loghavi, let’s start by defining molecular or genetic testing for AML. How is the test administered, and what is the purpose? 

Dr. Sanam Loghavi:

Sure. So, genetic testing at diagnosis of acute myeloid leukemia is now considered standard of care, and it must be performed for every patient with acute myeloid leukemia.  

We have different methodologies of doing genetic testing, and we can use – so the best sample to perform genetic testing on is really bone marrow. But if there are circulating leukemic cells, then we can also use peripheral blood instead of bone marrow. 

And the genetic tests really three main methodologies are used. One is called routine karyotyping, where we look at and characterize the chromosomes of the cancer cells for the leukemic cells. The other one is fluorescence in situ hybridization, which is another method for visualization of chromosomes, and we can look for deletions, addition of chromosomal material or certain translocations or rearrangements.  

And then next-generation sequencing allows us to look for smaller changes at the DNA level. So, these are single nucleotide variations at the DNA level or smaller insertions or deletions of genetic material.