I only met her because I was a Facebook friend of her husband, R.C. Sproul, Jr., whom I know simply through a network of friends. Denise died today from relapsed AML (Acute Myeloid Leukemia). That’s the more aggressive version of what Beth has/had (sort of). Same family of leukemias. She had been hoping to receive a second bone marrow transplant, but that never came about.
Blessed are they that die in the Lord.
My son John asked me this morning, “what’s the greatest danger that Mom is facing?” That’s a pretty good question, and here is my answer.
The first and greatest danger she faces is the leukemia itself. Mom’s bone marrow is damaged. Given that her damaged bone marrow is producing damaged cells, this is the root problem.
In all of us, our bone marrow produces “baby blood cells” called “blasts”, which then differentiate into the other types of blood cells: red cells, white cells (there are various types of white cells), and platelets.
However, Mom’s damaged marrow produces “blasts” that are damaged within their genes. These genetic damages, or defects, then become reproduced, and the primary symptom of this leukemia is to produce an overabundance of “blasts” which build up in the blood and bone marrow. If enough blasts build up, you get what’s called AML, or “acute myeloid leukemia”. This is the disease they first thought Mom had – with 20% “blasts” in the bone marrow, Mom would have been diagnosed with this.
And one of her earlier pathology reports came back saying “acute myeloid leukemia is indicated”. This is sort of a catch-all category of leukemias, with many sub-classes. Mom’s particular subclass is CMML, or “chronic myelomonocytic leukemia” which is characterized by the excess “blasts” in the bone marrow and blood, but it has its own characteristics as well.
AML may be described as “blasts gone wild” – they simply over-run the blood and marrow and overwhelm the person’s system, causing death.
One key danger is that Mom’s CMML will morph into the more aggressive form of AML. But the CMML, as is, is sufficient to kill her within an average of 12-24 months.
And we’re seeing a little bit of that happen right now. While the disease is being “controlled” with the Vidaza, we see that her blood levels continue to fall, generally (though some of them tend to moderate). But in all, her red blood cells have never moderated at all – they simply continue to fall all the time. And without the many transfusions she’s had, she’d drift off into severe anemia, and eventually, it would overwhelm her.
These are the first and biggest dangers that Mom is facing.
The Doctor’s report yesterday was fairly decent. The disease has been “controlled” by the medication she is taking. That’s the biggest thing. The real danger back in June was that she would progress from where she was (“15% blasts in marrow”) to aggressive “acute myelogenous leukemia” (AML, marked by 20% blasts in the marrow). After her biopsy last week, we found out her blasts level was back down to 4% (and all healthy people have 5%).
There are still anomalies in her blood. Overall, her blood levels are very low (though rising), and a certain kind of white blood cells called “monocytes” are doing some crazy things. The marrow report said “in summary, there is an absolute monocytosis consistent with a myeloproliferative disorder.”
The particular brand of leukemia that Beth has, “chronic myelomonocytic leukemia” (CMML) is marked by both “myelodysplastic” and “myeloproliferative” characteristics. And as I’ve written in the recent past, when the disease is marked by a change from “myelodysplastic” to “myeloproliferative”, at least one study I’ve seen has suggested that this is a not-good progression in the disease.
(Our doctor is not one among those who sees this as a progression — he prefers to look at the actual numbers, and to say, “they are still in the good range”. And I am certainly in a position that I need to trust his understanding of things more than my own.)
The bottom line is that, while all of these movements are traceable and discussion-worthy, the only important thing is that Beth be in “the best condition possible” for the bone marrow transplant, which likely will happen in 6-8 weeks. Again, some think the dysplastic–>proliferative switch is a progression that can hurt her chances in the transplant; but our doctor does not.
On that front, we do not yet have a donor, although there are a half-dozen individuals who match on 10 out of 10 specific DNA markers. These folks are going through additional testing. The reason we only have six is because Beth has an unusual combination on a couple of the more important DNA markers. And among these six, none are “ideal” – in the sense that there is an “ideal” profile of a healthy young male, no tattoos or piercings, who has not had any major diseases in his life.
These folks are older, some of them are older females who have had multiple pregnancies (and the related antigens that can cause some issues).
Our doctor says that we will move ahead with the transplant just as soon as one of these donors is selected. And I’m hoping to place a call today to the “transplant coordinator” at the hospital who is actively working on this to find out what’s happening.
We have an appointment at 1:45 today with Dr. Rossetti, our usual monthly appointment with him. My hope is that we’ll hear some good news about a donor, and possibly a schedule for the transplant. So today I’ll go in and work from about 6 am till 10 am, and then take Beth to her Vidaza treatment at 11:30, and then out to West Penn.
One of the women I work with has a mother-in-law who has had a mild, chronic version of leukemia since 1988. Over the years, she had no treatment at all for it; now she is in her 70’s and it has increased a bit and so now they’re bringing her in for chemo.
The danger always is that these “pre-leukemias” (MDS, CMML, etc.) will progress to AML (“acute myeloid leukemia”). That’s when it’s really aggressive.
Beth has gone the other way. They’ve beaten down her leukemia function, but in the process they’ve seemingly hollowed her out as well. She had some difficulty walking up the three steps to our bridge last night. She has 20% bone marrow, instead of the usual 50%. And all her other blood levels are just bumping along at a very low rate.
When I first started reading about Vidaza, I was under the impression that “The expectation is that the Vidaza will reduce her overall ‘risk level’ and strengthen her body for ‘conditioning’, which will kill most if not all of the cancer-causing function”, as I wrote at the time.
In a randomized controlled trial comparing azacitidine to supportive treatment of MDS, around 16% of people receiving the drug had a complete or partial response—blood cell counts and bone marrow morphology returning to normal—and 2/3 patients who required blood transfusions before the study no longer needed them after receiving azacitidine (emphasis added).
So Beth is not among those who has not needed the transfusions. She’s needed them. The Vidaza is killing the cancer-causing function, but on the other hand, it doesn’t seem to be strengthening her at all.
This will be something to ask Dr. Rossetti today.
We learned a few things in our appointment with Dr. Jalil yesterday, though I’m not certain I understand it all. Dr. Jalil’s is where Bethany has been getting her Vidaza treatments. He had received a copy of Bethany’s bone marrow biopsy results, but he hadn’t had a chance to read them closely yet.
We did learn a few things. Large, trendy things, I guess you could say.
First is that the treatment seems to be working effectively. “As expected”. That is, while we have been watching Bethany’s blood levels go up and down, the general trend is that almost everything is going down.
Early bone marrow biopsies showed her being “hypercellular” – that is, her bone marrow was marked by extra tissue, and even some scar tissue. Now she is at about a 20% level of bone marrow. That is, yes, very low. Explanation: “the medication is controlling the disease”. (Blasts and monocytes, in aggressive leukemia, would tend to build up. That Bethany’s is so well cleared out is seen to be a good thing.)
For example, in an early biopsy, her blast counts were 10-15%; now they are 4%. Normal folks are at 5% blasts in their bone marrow (blasts are “baby blood cells” that grow up and differentiate. In aggressive leukemia, the blast number tends to exceed 20% to 30%, and they really “gum up the works”. So this level is good).
Beth’s monocytes are still hovering around the 10% level. That they have not gone higher is a positive thing. (They could have moved from 10% to 20%, but they didn’t.)
In short, the treatment kills both bad cells and good cells. And we have seen some good cell production in this.
Finally, I saw something I had noted in all of my poking around to learn things about CMML. I emailed Dr. Rossetti about it:
I believe I saw that Beth’s condition, once “dysplastic”, now more exhibited the “myeloproliferative” characteristics. Without knowing exactly what that means, I want to point you to this recent study (again, with the low number of patients from CMML), in a school of thought that may or may not be well accepted, that the shift from myelodysplastic to myeloproliferative properties is really a progression of the disease.
http://www.ncbi.nlm.nih.gov/pubmed/20371679
http://clincancerres.aacrjournals.org/content/16/8/2246.longI realize that we are dealing with some pretty nasty stuff — it’s not quite AML, and the low numbers of blasts and other numbers are good. But I hope you can put this into context for us.
And he responded:
The two variants remain largely distinguished by the height of the white count. Beth’s white count is well controlled and her marrow is actually exhibiting lower cellularity than before. Thus, on a clinical basis, I do not think she is transforming.
While there are emerging data suggesting a continuum, this does not seem to be universal. At her young age, I would be inclined to the same treatment either way: first an MTI [methyltransferase inhibitor – Vidaza], then transplant. If at anytime we see evidence of progression, we may consider chemo. At present, I like where we are headed.
The good thing, then: there is no “progression”. Dr. Jalil summed it up: “We want to see the least number of bad cells.” That, he suggested, was the definition of healthy marrow. Even if it’s only at a 20% level.
Now that summer has come and gone, I’d like to recount what kind of what summer it’s been for us. It’s been almost exactly three months since all of this started, and we’ve not yet begun to fight. Literally. For all that Beth has been through, the hard part still lies ahead of us.
Of course, hearing that you have cancer, in itself, is an incredible shock. And it was unexpected.
It started Sunday, June 5. For a little over a year, I’d been working days at Black Box, and Beth working full-time nights, so that we could share our one car, try to pay off some bills, and at least one of us could be home to get our youngest daughter, Dani (6) on the school bus in the morning. Typically, I’d start getting her ready; Beth would get home at 8:00, and I’d leave for work. Then she’d finish getting Dani ready for the bus at 8:30.
We had been doing this for months. But we’ve needed to do it; I had been laid off in the recession in 2009, and had spent about eight months unemployed. I took my job at Black Box at about 2/3 of my old salary, just to have a job, and one with the hopes of moving up. And Beth had been working nights, first at Sheetz, and later at Overlook Green. Over the past several months, they’d made her a shift supervisor, and she liked the work.
“Critically low”
But over the previous several months, Beth had been coming home more tired than usual, and having more headaches. On this Sunday morning, she came home and went right to bed. That afternoon, she was complaining that she couldn’t go to work. Headache, body aches, swelling of the legs. She called off, which was almost unheard of for her. Her boss said, “why don’t you go to MedExpress and get yourself checked?” So we did.
The Nurse Practitioner on duty that night checked her over, and came back in and said, “you need to have some tests tonight that I can’t give you. I’m going to send you up to the Emergency Room”. So we went up there and waited among the kids crying and broken arms and old people. When they brought her in, and took some tests, they came back and said, “your hemoglobin level is dangerously low. We need to give you some blood transfusions, and admit you for some further tests.”
Her hemoglobin level was 5.7, critically low; the normal range is 12-15. One of the nurses told us that if she had cut herself and bled out to that level, she’d be unconscious. But because she dropped slowly to that level, her body gradually adapted to it.
The Bone Marrow Biopsy
She got three units of whole blood over the next couple of days, and among the tests was a bone marrow biopsy. We could tell that this wasn’t a typical test, because Dr. Jalil, the blood doctor who came in to do the biopsy, had to wait around for some 20 minutes in our room, chit-chatting about little things, because the hospital did not have the right kind of needle on hand.
A bone marrow biopsy is not the kind of thing you want to go through. A long, thick needle is inserted into the buttocks at the hip bone to deliver a local anesthesia; once removed, a longer, thicker tool is inserted and screwed into the bone; a syringe is then attached to this longer tool, and marrow and fluid are suctioned out. It’s quite painful, in spite of the local anesthetic, and like any broken bone, it takes a good bit of time to heal.
After all the tests that had been done, and once the bone marrow biopsy was headed for the lab, Dr. Jalil said he thought that it was most likely a viral infection causing her severe anemia.
As we left it, we thought we were going to hear the results of this test from Dr. Jalil; we had also scheduled an appointment with our GP. Since we heard nothing from Dr. Jalil, and thinking “no news is good news,” we were almost in a giddy mood seeing our GP. On the other hand, he was under the impression that we’d have heard the diagnosis from Dr. Jalil, and so when he said “blood cancer,” it was awkward for him and an incredible shock to us.
He gave us a copy of the lab results, which said that “Acute Myeloid Leukemia (AML) is indicated.”
Learning About Leukemia
There are four types of these “blood cancers”: chronic and acute myeloid leukemia, and chronic and acute lymphoma. Of course, these are just terms that set the four types in contrast with each other, for the purpose of categorization; there are really a bunch of different types of these, with a broad range of things that can go wrong.
In the particular “group” of leukemias that Beth has, AML, is a very nasty one. The preliminary diagnosis was for a “pre-” version of this, one of the “myelodysplastic syndromes” (MDS), and we were scheduled to see yet another specialist, Dr. James Rossetti from West Penn hospital.
He told us that the diagnosis pretty clear about “what” it was but somewhat inconclusive on the severity continuum. There is a “risk factor” chart called the IPSS chart, and Beth was either at a “high” risk level (the highest of the four) for developing AML, or she actually had gotten it. Dr. Rossetti did another bone marrow biopsy, and admitted her to the hospital for yet further testing.
A Diagnosis of CMML
What came back was something called CMML, or chronic myelomonocytic leukemia. Briefly:
In CMML, the body tells too many bone marrow stem cells to develop into two types of white blood cells called myelocytes and monocytes. Some of these bone marrow stem cells never become mature white blood cells. These immature white blood cells, called blasts, are unable to do their usual work. Over time, the myelocytes, monocytes, and blasts crowd out the red blood cells and platelets in the bone marrow. When this happens, infection, anemia, or easy bleeding may occur.
More specifically, Beth has “dysplastic CMML-2”, which is not as bad as having the “myeloproliferative” version of CMML, but it is not a good thing; I’ve published the prognoses both from the medical journals that I could find online, and also from Dr. Rossetti.
Much of what I’ve written over the last several months is a chronicle of what I’ve learned, and how I’ve learned it. As I said, all of this is just the beginning. The hard part is yet to come.
We talked with the bone marrow transplant folks at West Penn yesterday. MDS has four separate risk levels; the chart nearby outlines them. Please keep in mind that the “median survival” is for untreated cases (yes, those numbers scared me very much); with treatment, they can be extended somewhat, and following a course of chemotherapy and bone marrow transplantation, an outright cure (or at least, what they call “complete remission”) is possible. And this is the treatment method they will follow.
It seems to the doctor at West Penn as if Beth is either at risk level 4 (which is the last before being on full blown acute myeloid leukemia – AML), or she has a kind of emerging AML. Both are kind of nasty. The treatment will vary, to some degree, based on which is the actual diagnosis. I’ll explain momentarily.
They took a second bone marrow biopsy yesterday to confirm which form of the disease she has. Meanwhile, she has been admitted to West Penn’s hematology/oncology unit (“hem/onc”).
There may be two possible courses of treatments. If she has the emerging AML (which at this point seems less likely), she will remain in the hospital for 30 days and undergo a pretty intensive chemotherapy. At the end of that time, she is a candidate for a bone marrow transplant. (There is a “national registry,” they will have to find a donor, etc. More about that at some future point).
If she has the MDS, there will be a lighter-weight kind of chemo and drug therapy, which may enable her to proceed on an outpatient basis. This will obviously be easier on all of us, but I believe it will take longer. And following this, they are also looking to do the bone marrow transplant.
This is a very weird disease, or set of diseases. It is a potent one; at Beth’s level, there is not a lot of life expectancy, unless the bone marrow transplant is successful. And if it is successful, there is a chance that it will result in a complete cure.
All of this is made possible by various research efforts over just the last 5-10 years.
More later, as I learn things.
