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Leukemia (transcript)
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Major funding for Second Opinion is provided by the Blue Cross and Blue Shield Association, an association of independent, locally operated, and community based Blue Cross and Blue Shield plans supporting solutions that make quality affordable healthcare available to all Americans. 

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(Dr. Salgo)
Welcome to Second Opinion, where each week our healthcare team solves a real medical mystery. When we close this file, in a half an hour from now, you'll not only know the outcome of this week's case but you'll be better able to take charge of your own healthcare and doctors will be able to listen to patients more effectively.  I'm your host, Dr. Peter Salgo, and you've already met our special guests who are joining our primary care physician, Dr. Lou Papa.  Now nobody on this panel knows what's in this case, so it's time to get right to work.  Our story today concerns Henry.  Now Henry is fifty-eight years old.  He drinks alcohol rarely.  He's never smoked.  That should make you happy Lou.

(Dr. Papa)
Yes, very happy.

(Dr. Salgo)   
He exercises regularly.

(Dr. Papa)
Wow.

(Dr. Salgo)
He is reported in the chart as trim.  Again, one of these complex medical phrases that I rarely see.

(Dr. Papa)    
Yes.

(Dr. Salgo)   
In charts.  And by all counts, he's healthy.  So he goes to his primary care physician for a regular check up and he discusses getting a screening colonoscopy.  He did have an uncle who died of colon cancer and another uncle who had prostate cancer.  So at his age what else should Henry's doctor be looking for?

(Dr. Papa)    
Well at his age in addition to just the examination, this blood pressure, he already brought up some of the issues.  He's over fifty. You do want to get a screening colonoscopy.  He's over fifty and has a family history of prostate cancer.  You want to do a digital rectal examination and check the PSA.  And also be interested in seeing what his lipid profile looks like.  Things along those lines.

(Dr. Salgo)   
Well I can tell you what his doctor did.  His physical exam, first of all, which his doctor performed, was reported as normal.  Cardiogram was normal.  His doctor scheduled the colonoscopy and he ordered the following lab work.  A CBC or a blood count, a complete chemistry profile.  A PSA, looking at his prostate levels.  HSCRP, a high sensitive CRP lab test.  Thyroid stimulating hormone, vitamin D level, hemoglobin A one C level. 

(Dr. Papa)    
Okay.

(Dr. Salgo)   
All of these tests for an otherwise healthy asymptomatic guy.

(Dr. Papa)    
That's pretty much overkill.  It really depends on what his risk profile looks like. So some of that stuff you wouldn't do on the average fifty-eight year old person who doesn't have a lot of risk factors.

(Dr. Salgo)   
But come on Lou.  I mean what's the harm, other than to your pocket book.  Maybe you'll pick something up.  Maybe you'll find an abnormal lab value.

(Dr. Papa)    
We're doctors. We don't go fishing.  Your clinical suspicion drives what you do.  There are very few tests that are recommended for screening.  Screening is specifically trying to detect a disease at an early enough stage that you can have an impact on it to reduce morbidity mortality. 

(Dr. Salgo)   
Alright.

(Dr. Rai)
One thing that this is a very telling case that you are talking about.  And is a sad commentary on how we practice medicine today.  A healthy asymptomatic man in his late fifties comes for a routine examination.  You have told what his history is like and examination finds nothing physically abnormal.  To have this battery of tests on a first visit is, in my opinion, unnecessary, outrageously unnecessary. 

(Dr. Burack)
We really try to drive that point home when we teach medical students that one, on every test that we do, one patient out of twenty.  One person out of twenty will be abnormal.  And so if you do twenty tests you are extremely likely to have a "abnormality" and you will cause anxiety. 

(Dr. Papa)    
Something's going to come back as an abnormal.  And you're going to end up chasing it.  Fiscally that's going to be this huge amount of money that's going to be spent chasing that.  You maybe assigning a disease process that doesn't exist to this patient, labeling him with the psychological impact and potential impact it can have on insurance and things like that down the road.  And your goal in this is to detect something that you can treat and have an impact on long term.

(Dr.  Salgo)
Well let me tell you.  Henry went back to his doctor for follow up and here's what he learned.  His screening lab tests were all normal.  Urinalysis was normal.  His colonoscopy was normal.  His white blood cell count was normal in terms of its absolute number but he had fifty-two percent lymphocytes.  The absolute lymphocyte count was 5.212, which is just ,by this lab, slightly high.  Now what.  What does all that mean?

(Dr. Papa)    
Exactly.  And his exam was normal. 

(Dr. Salgo)
Yes. 

(Dr. Papa)    
Okay. It's hard to say.  You know, I don't know if he's just getting over a viral illness or if he's just getting over some infection.  That would probably be something I would repeat again down the road. 

(Dr. Salgo)   
Well that's what his doctor thought.  His doctor said, ah it's a slight abnormality probably due to a cold that he had just gotten over.  And I want to repeat your CBC in nine months.  John, when you went to see your doctor did you go routinely before you got ill.  And it's no secret you did get ill, and we will talk about that.  But were you having lab tests routinely?

(John)
No.  No.  But I had a doctor that I had a lot of trust in and when I did see him he got to know me and I think he knew how to deal with me so we could have good conversations. 

(Dr. Salgo)
Okay.  Now Henry had the repeat lab test done in nine months.  He is still completely asymptomatic and is physical exam at that time was totally normal.  There was no significant change in his lab work but here comes the but.  His absolutely lymphocyte count is now outside the reference range at 8.3.  So what's a lymphocyte?  What are lymphocytes doing in your body anyway?

(Dr. Liesveld)
Lymphocytes are part of the immune system, so in general they're involved in a lot of immune response mechanisms such as fighting off infections, responding to inflammatory stimuli, and also part of just the body's general homeostasis in terms of maintaining response to other environmental exposures. 

(Dr. Salgo)   
They come in different flavors, right?

(Dr. Liesveld)
They do.

(Dr. Burack)
All sorts of different flavors.  And we spend a lot of time sorting out the different flavors.  And there's times when you need to sort them out and there are times when you don't. 

(Dr. Salgo)   
His are a little bit high, so what?  Does that worry you?

(Dr. Rai)
Yes.  I think that a person who started off just several months ago at five thousand and now is at eight thousand or whatever, nine thousand.  That, as you pointed out, is certainly out of range.  This kind of situation does require probing to determine what kind of lymphocytes they are and whether a name can put on this. 

(Dr. Salgo)   
Now, John, you went to the doctor.  And at the time that you went to the doctor you weren't feeling well, as opposed to Henry who is pretty much asymptomatic.  What was bothering you?

(John)
I'm kind of a high energy person.  And I didn't have a lot of energy.  I was tired, which was abnormal.  I had lost my appetite and I was not even hungry, so I knew something was going on, so I went to my doctor and told him exactly that.  He gave me a good physical.  He did a blood test.  And based on those two, he had some concerns in that I did have swelling in my lymph nodes and my spleen was enlarged, so he ordered a biopsy. 

 

(Dr. Salgo)   
Okay. So he was going to take a look at some tissue that you had.  Let's hold it there because I want to go back to Henry.  Henry, at this point with his elevated lymphocyte count is referred to a hematologist.  Well I can tell you what they did.  They did a cryptogenic analysis, immunophenotyping, and they did a bone marrow.  What is all this about?

(Dr. Burack)
So essentially there's this process called immunophenotyping, which tries to sort out the flavors by looking at what molecules are present on the surface of these lymphocytes.  And malignancies, when they happen, the cells will all be similar to one another.  In a normal person there are many different flavors of cells in the blood.  In an abnormal person, if there is a cancer of the blood, then all the cells are going to have very similar properties.  And that's really what we do.  Then you mentioned that cytogenetics were done.  Where.  You're.  Probably everybody's used to hearing about cancer being a genetic disease and that means that there's genetic damage that happens to cancer cells.  And to fully diagnose a cancer or a malignancy of the blood, you want to actually look at the genetics of those cells in the purple blood.  And one way to do that is to grow them and actually look at their chromosomes under the microscope. 

(Dr. Salgo)
The buzz word that I hear about all the work that you've just described is what?  Biologic markers?  What are biologic markers?

(Dr. Burack)
Biologic markers is a vast, you know, it's a term that encompasses many, many different things but it certainly encompasses the molecules which are present on these lymphocytes.  It encompasses the genetic changes that I was describing. At anything that is different between a tumor and the rest of the cells that are normally in the body. 

(Dr. Salgo)
Alright.  I got a list of things they found.  ((Chromolyphmocytosis)), CD5, 1920 and 23 were positive.  CD 20, 11 and 103 were negative.  Dim surface immunoglobulin.  Henry had 13 Q deletion, a mutated heavy chain IGVH gene.  What did I just say?

(Dr. Burack)
All of that is.  Very clearly states Chronic Lymphocytic Leukemia. 

(Dr. Salgo)
Henry has leukemia.  And the lay phrase might be blood cancer of a specific cell type, the lymphocytes.  Yeah.  And you didn't think fishing was a good idea.

 

(Dr. Papa)
No.  I still don't.  I mean part of.  You know what this is.  I'll tell you what this is.  This is like being blindfolded in your car skidding through an intersection while the light is red and not getting hit.  That's not good driving, that's luck.  And that's what this is. 

(Male  Voice)
What we are talking about is, is that we are making a diagnosis of CLL. 

(Dr. Salgo)
Chronic Lymphocytic Leukemia.

(Dr. Rai)
Chronic Lymphocytic Leukemia.  At the point in the person's life when the disease is in its earliest phase and it is a classic example of doing torture to our population by our modern technology advances.  And this person has legitimately been given a diagnosis which in our previous generation would have been missed but no harm was likely to be done.  And this person would then go on for twenty, twenty-five years living a good life and then to find what the symptomatic leukemia is.

(Dr. Salgo)
Let me proceed back to John over here.  You went to the doctor. You said, you had some swollen lymph nodes and a biopsy.  Then what happened?

(John)
My oncologist made the diagnosis that I had lymphoma. 

(Dr. Salgo)
Lymphoma, which is not precisely what Henry has but it's another blood type tumor, this time a solid tumor.  When you were told you had lymphoma what was it like to hear that you had a malignancy?

(John)
Total surprise but my doctor was very positive.  He was up front and said that what you have is very treatable and there's a lot of options out there and we're going to go through those options and we have to find the right treatment for you.

(Dr. Salgo)   
Did you think you were going to die despite all of that?

(John)
No.  I didn't.  I just didn't believe that.  I felt that I would work through this.  I saw it as a bump in the road, not a roadblock.

 

(Dr. Salgo)   
Well I want to go back to Henry.  Let's take some syntax here.  Henry has leukemia.  He has Chronic Lymphocytic Leukemia.  Chronic means its going to last a long time.  Lymphocyte is a kind of blood cell that's growing too much, too fast.  Leukemia meaning it's, for the most part in his blood, not a solid tumor at the moment.  Then he's told he has stage zero disease.  What is stage zero disease?

(Dr. Liesveld)
Stage zero just means that as, in his case, he has an elevation in his lymphocyte count and no other manifestation of the disease.  No lymph node enlargements, no abnormalities in his other blood cells and no other detectible ((hypatos, quenomegalies)), which means an enlargement of his spleen or liver.  And in fact, Conti was the first people to describe a whole classification system that uses these stages to help patients when they are diagnosed at various phases to have a prognostication. 

(Dr. Salgo)
So if he has leukemia now and he had a little tiny bump in his lymphocyte count nine months ago, did he have leukemia then?

(Dr. Rai)
Yes.  Just consider John here.  That if John had had the same test twenty years earlier, for a routine visit to his doctor.  I bet that there would be found five thousand, six thousand, seven thousand lymphocytes whereas the normal upper limit of the normal is about twenty-five hundred to four thousand.  So John was spared and this patient is now being told that he has Chronic Lymphocytic Leukemia.

(Dr. Salgo)   
Are you telling me that his tests are too sensitive?  That we should wait before we use them because you're going to be making the call on people who don't really have much disease and don't need any treatment?

(Dr. Papa)
That's why he called it the torture of technology.

(Dr. Salgo)
I heard that.  I'm trying to.

(Dr. Burack)
We.  Our tests are so remarkably sensitive.  They have to be used in a context, in a clinical context, when a patient is ill or has symptoms. The advance of technology is now at the point where should I want to demonstrate the presence of a malignancy in each of you, we can do it.

(Dr. Liesveld)
And I think that in someone, as in Henry's case, for him this is going to be a psychological burden for the years that he carries this diagnosis before he requires any treatment. So his case is different than the patient who does present with symptoms.  Or in a more advanced stage, he will require early intervention.  And so because we don't intervene at the point of these early stages, just this period of need for observation, need for periodic testing is a, not only an economic burden to the medical system but for the individual patient is a significant burden.

(Dr. Salgo)
Why don't we pause just for a minute?  I want to sum up what we've been discussing. The use of biologic markers have greatly increased the ability to diagnose, to stage, and eventually to choose treatments including no treatment and give cancer prognosis. The advances have made cancer treatments more successful and it's made the decision not to treat early on something we can consider as well.  Alright, we got more to do.  Henry now has a diagnosis.  Henry is diagnosed with Chronic Lymphocytic Leukemia.  Now Henry goes back to his PCP's office and he wants to follow up on these lab tests, of course.  And he wants to get some sense of what are his options at this point with stage zero disease.  How do you help a patient decide the best course of treatment when you're dealing with chronic disease like this?

(Dr. Papa)
The best thing to do is to talk about the disease first.  You know, very often you hear cancer and you're terrified and people really don't understand the concept that there are these chronic cancers that can kind of go on for a.  Not everything is like pancreatic cancer.  So you explain to them having stage zero, stumbled upon diagnosis of CLL is not the end of the world.  There is effective treatment and there is a period of time where we do nothing.  We have to be careful about infections.  That's true.  You have to be very cognizant of symptoms.  You need regular follow up with me.  Regular blood work.  And follow up with the hematologist, oncologist.  But there.  It's usually a treatment in evolution.

(Dr. Salgo)   
Jane, what are the others?  Just run me through some bullet points?  What are the other options that Henry has?

(Jane)
I think that stage zero, medically the only option that we would usually consider is a course of observation.  Now many patients are uncomfortable with that and some of them would want you to consider other treatment options, but it's not generally until patients have some symptoms or definite indications for treatments that we would consider immunologic therapies or chemotherapy or other modalities. 

(Dr. Papa)
The treatment has to be something that's going to alter the course of the disease and improve his quality of life.  Right now his quality of life is pretty good.  He doesn't have any symptoms from it. And two, there's toxicity associated with any treatment.  You want to make sure toxicity doesn't outweigh any benefit that you have.

(Dr. Salgo)   
Because right now the toxicity of the disease is pretty much nil, right?

(Dr. Burack)
Nothing.

(Dr. Rai)
There have been studies performed some time ago in India and in France which showed that taking the earliest stage patients, randomly assigning half of those numbers to observation or what we call wait and watch or wait and worry.  And the half with the chemotherapy.  And it was found that the survival rate of the two arms was identical.  But in the early treatment, early chemotherapy patients there were more secondary malignancies and there was a slight reduction in the quality of life.  Since then it has been quite established that early stage disease, symptom free disease should be best left alone.  So one aspect of American Cancer Society admonition is get early diagnosis.  If you get an early diagnosis you can save your life by your curative treatment.  But that applies to what we call solid tumors.  The liquid tumors, the leukemia, the lymphomas, they by definition are spread throughout the bone marrow, which is all over the body, and in the blood.  Whereas early solid tumors such as breast cancer, colon cancer.  There a surgeon can chop it off and the person can be cured. So it is a solid area tumor where the public should now that early diagnosis is critical.

(Dr. Salgo)
Now, John, when you went to the doctor's office you were already symptomatic. 

(John)
Yes.

(Dr. Salgo)   
So at that point did your doctor say watch and wait or did your doctor advise therapy?

(John)
He recommended chemotherapy and I was fortunate it was outpatient basis. So I would go get my treatment and go back to work.  I listened to my body and did what I could do.  I was careful because I knew with the chemotherapy that infections were a concern, so I took some good precautions. 

(Dr. Salgo)
How did your chemo do?  How did you do with it?

(John)
The first one was very successful. 

(Dr. Salgo)
But the fact that you say the first means there probably was a second.

(John)
There was a second and there was a third.  The time between the second and third was less than the time between the first treatment and the second.

(Dr. Salgo)
So your doctor became concerned because these episodes of recurrence were getting closer and closer together.  Did he give you another option to consider after chemotherapy?

(John)
Yes, a stem cell transplant.  Basically he explained to me that he would replace my stem cells, and there were options there on where the stem cells would come from.  The perfect situation for me was that I had two brothers and that one of them would be a match for me.  And that's exactly what occurred.  My brother was a perfect match so that met, that was one of the best solutions.  There were other solutions.

(Dr. Salgo)
And the logic here is.  Help me out on this.  That the stems cells are the cells from which other blood cells stem, they come.  I mean there's been a great debate in this country about stem cells but we're talking about adults here and adults stem cells. 

(Dr. Liesveld)
Yes.

(Dr. Salgo)
So if the stem cells you've got are making cancerous cells, get rid of the stem cells.  Get new stem cells that don't make cancerous cells.  I mean it sounds logical anyway.

(Dr. Burack)
It's a little bit different from that.  It's actually that the toxicity of the chemotherapy is going to affect, would affect John's, a normal bone marrow.  And so through the course of that chemotherapy he would lose the function of his normal bone marrow and it would have to be replaced.

(Dr. Rai)
Chronic Lymphocytic Leukemia unfortunately, but most criteria remains an uncurable or incurable disease.  The only cure that can happen is exactly what John received.  And that is with the match sibling who has the same HLA type getting a transplant.  Now we do not call it bone marrow transplant because most of the time the stem cells from the donor are harvested from the blood itself.  And as was pointed out that once the marrow is sort of reasonably emptied out, then putting the donor, his stem cells gives those stem cells to go and home and grow in the patient's bone marrow and body. And the leukemia is completely eradicated. 

(Dr. Salgo)   
Well Henry's heard this.  Henry realizes he doesn't need it today.  He's got stage zero disease.  He also says.  He says I'm young.  I don't have very severe disease.  I bet you could harvest my bone marrow, my stem cells, put them away and save them for a rainy day.  Would you offer that to Henry?

(Dr. Liesveld)
I wouldn't to Henry because in Henry's case, as we talked about, his disease is circulating in the blood and presumably his marrow is filled with his disease and also therefore with abnormal stem cells.  So with Henry's case with a stage zero CLL I wouldn't recommend harvesting his stem cells.  I would only do that if he had been through a treatment that completely eradicated the CLL as best we're able to measure.

(Dr. Salgo)
Let's take a moment and sum up some of what we've been talking about. The best treatment to cure Chronic Lymphocytic Leukemia may not be what the average patient needs.  May not be the best treatment for an individual.  Treatment options need to be weighed based on the patient's overall health and where they are in their life, where they are in their disease.  I could tell you a little bit more about Henry.  Henry talked about having a stem cell harvest.  It just wasn't an appropriate therapy for him.  So Henry elected with his PCP and with his hematologist to be followed periodically to see what happened.  John, how are you doing?

(John)
I'm doing great.  I work forty, fifty hours a week and great energy and you know you're a lucky person but.  And you live one day at a time but that's what everybody else should do anyway.

(Dr. Salgo)
Well I want to thank all of you for being here.  That's all the time that we have for now.  Let me sum up a little bit of what we were discussing.  The use of biologic markers have greatly increased the ability to diagnose stage and choose treatments and give cancer prognosis.  Now while this process takes time the advances have made cancer treatments more successful.  And sometimes the proper treatment is no treatment at all.  The best treatment to cure Chronic Lymphocytic Leukemia may not be the best treatment for most individuals.  Treatment options need to be weighed based on your overall health and where you are in your life.  And our final message is this, taking charge of your health means being informed and having honest communication with your doctors.  I'm Dr. Peter Salgo and I'll see you next time for another second opinion. 

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Major funding for Second Opinion is provided by the Blue Cross and Blue Shield Association, an association of independent, locally operated, and community based Blue Cross and Blue Shield plans supporting solutions that make quality affordable healthcare available to all Americans.  Additional funding provided by...