Yesterday’s news

“Normal marrow is 50%. Yours is 20%.” And that’s good at this point.

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.long

I 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.

How we got here, Part 1

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.

Vampire Bride … it goes on and on

Beth got a call from Dr. Rossetti’s office again yesterday; her hemoglobin had dropped to 8.2, and so that means another transfusion. There seems to be some rhyme and reason to the way this is going. Cycles of Vidaza are indicated by the arrows above the chart.

  • Hemoglobin: At present, nothing seems to help this except for transfusions. However, these take about 100 days to manufacture, and we are hopeful to see some improvement now, after three cycles of Vidaza.
  • White Blood Cells: Vidaza seems to whack them, but they recover quickly.
  • Platelets: Vidaza seems to have a bit of a harsh effect here, too, although most recently, her platelet count has been falling anyway.
  • Neutrophils: These are very good white blood cells – first responders to bacterial infections – and these are well into the normal range, after having been far off at one time.
  • Monocytes: Again, Beth has “chronic myelomonocitic leukemia” (CMML), and so getting these into the normal range appears to be a good thing.

Please note that none of the above is a genuine medical opinion, just the musings of someone who has an interest in figuring out what these numbers mean.

Click on the chart to view a larger version. The last column is mostly blank because I don’t get all of these numbers right away. But Beth did get a blood sample on Monday and we do know that she needs this transfusion.

Vidaza, Cycle 3

Beth immediately responded to the Vidaza today, in a negative way. After two transfusions in recent weeks, she has been feeling about as well as she has felt in months, over the last few days. However, the Vidaza treatment reminds her that it really is a kind of “chemotherapy,” and the “cytotoxic” effect just knocks her on her butt. Back again are the diarrhea and the body aches and the desire to sleep all the time.

Yet the other thing that Vidaza does is to “change the genes” in the blood cells. Enables the blasts — “baby” undifferentiated blood cells — to differentiate and become normal healthy cells.

There are three major cell lines in your blood: red (hemoglobin), white, and platelets. Beth’s red blood cells are consistently low and they don’t seem to be responding. White counts and platelet counts are low but holding steady. This is one of the good effects of the Vidaza. Neutrophils (white cells) are low but holding steady. Monocytes (another white cell) are high. That’s one of the reasons why this is “chronic myelomonocytic leukemia” (CMML).

The intention is to have her bone marrow in as good a shape as possible in preparation for the transplant. Dr. Jalil said yesterday he wishes her hemoglobin would have shown some signs of recovery by now. But, he says, “after only two treatments, things look good.” If her hemoglobin still was not responding after three, four, five treatments, “we would be a little worried”.

What if it doesn’t respond this time? He says they’ll still go ahead with the transplant. My sense is that it’s the only real option. If she were 75 years old, they’d continue with the Vidaza and blood transfusions so long as they made her comfortable. But the prognosis for this disease is not a good one. They’ll want to do the transplant, to wipe the slate clean anyway.

We’ll find out more about that at the intake meeting today.

What’s coming up

We’ve traveled through a relatively uneventful time in this illness. Beth mostly sleeps a lot, and takes in some blood every once in a while. Now we’ve got a little flurry of activity coming up, and we should learn some important things.

Beth’s hemoglobin level fell below the magical 8.5 level, to 8.4, and so she’ll be going in for another transfusion: type-and-cross-match today, and two units on Wednesday. One of the things that I’ve read on the CMML discussion boards is that there is a kind of deep-down body pain that you get – it’s the pain that prevented her from working back in June – and my thought is that 8.5 + two units will take her to a point at which she won’t have to deal with that for a while.

Then next Monday, August 22, she’ll begin Vidaza Cycle 3, and on the 23rd we’ll have our big Intake Meeting with Dr. James Rossetti from West Penn Hospital. (West Penn is an MDS Center of Excellence ).

We should find out a number of things that day, not least of which will be the status of the donor search, the course of treatment, schedules, and various other odds and ends, I’m sure.

We can still use your help. Please feel free to use the buttons below to like and share these blog posts of mine, and also, be sure to like and share Bethany’s Facebook page and don’t forget we need your help financially as well. Thank you.

Beth was crying last night when I got home

She woke up yesterday with a new pain in her spleen. An enlarged spleen is one of the symptoms of CMML (chronic myelomonocytic leukemia). This Detailed Guide to CMML by the American Cancer Society is one of the best that I’ve found, and it gives a fairly complete overview of this disease. I’ve also found this 2005 summary from the National Institutes of Health (NIH) : “Intensive chemotherapy alone is of little benefit, and stem cell transplantation is the only curative modality in the small number of eligible patients, although outcome remains suboptimal.”

That doesn’t strike me as too hopeful, though it is easy simply to be bewildered by this disease. As medical science has learned more and more about it through DNA, it has been found to be more rare than at first thought. Originally, Beth was diagnosed with MDS (a pre-leukemia with certain tell-tale signs), but after a second biopsy, her diagnosis was changed to CMML (more specifically dysplastic CMML-2).

One thing that you don’t see much of is the prognosis for CMML patients who undergo a Bone Marrow Transplant (BMT). That’s because the population of these patients is so small. There are only about 1,100 cases diagnosed each year — and 90% of them in people over 60 who can’t have the BMT.

I’ve also found this overview in the France-based Atlas of Genetics and Cytogenetics in Oncology and Haematology :

The median survival for patients with CMML is about 24 months. … Of adult patients who underwent allogeneic bone marrow transplantation the disease-free survival was 39% at 3 years.

But this disease is so rare, the population upon which this study was based is very very small. I believe it is only in the 10s of patients. (They didn’t even study “hundreds” of CMML patients with CMML).

An oncology textbook notes that:

Median survival in CMML is approximately 12 months, with a range from approximately 1 to more than 60 months. …Unfortunately, at this time, unless the patient is a candidate for imatinib therapy or stem cell transplantation, long-term salutary therapeutic effects are uncommon.

But even for those who receive a stem cell or bone marrow transplant, the NIH says:

Allogeneic hematopoietic SCT (HST) offers the only curative potential for patients with chronic myelomonocytic leukemia (CMML). However, there is a paucity of data addressing this approach in CMML. The disease is a relatively under-represented myelodysplastic (MDS)/myeloproliferative subtype among transplant eligible patients. Non-randomized studies suggest that long-term remissions are achievable when using myeloablative or reduced intensity conditioning transplantation. Allogeneic SCT for CMML is often reported as part of MDS registry data. The largest series in adult patients reported a disappointing long-term relapse-free survival (RFS) of 18%. The Fred Hutchinson Cancer and Research Center group reported a 40% long-term RFS for a mixed group of adults and children with CMML who were transplanted over two decades. In this study, we performed a literature search and reviewed available data for adult CMML patients undergoing HST. The dearth of data that span two decades with changing transplant practices prohibited us from performing a formal meta-analysis. However, we elected to present the current status of HST in adult CMML patients. Carefully selected CMML patients may have the most benefit from this curative approach.

Really, this seems to be all that’s available out there.

Vidaza vs CMML, and the graft-vs-tumor effect

We met with Dr. James Rossetti yesterday, who is going to be my wife’s doctor overseeing her treatment.

He gave us an overview of the complete diagnosis, and we finally got a complete overview of the treatment plan:

1. Two or three courses of Vidaza to try to slow or mitigate the effects of the disease (which is the CMML version of the various Myelodysplastic syndromes).

2. Then she will undergo a “conditioning” period of intense chemo and full-body radiation.

3. The bone marrow transplant which will really be an infusion of adult stem-cells from an anonymous donor (“www.bethematch.org”).

4. Follow-up to check on the effects of the transplant.

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. (The “risk level” is the risk that the disease will further progress and turn into leukemia). The “transplant” will then do two things: put new stem cells into her body to repopulate her bone marrow, and rely on the “the graft-vs-tumor effect” to suppress and kill any latent cancer function within her body.

At the beginning of this process, there is a 50% chance now that she can see a complete cure. As we move forward, and as things don’t go wrong, the hope is that those odds will rise. The main challenges in this process would be the dangers from the Vidaza (which she seems to be tolerating very well right now), infection down the road, the “conditioning” process, and of course, the big one would involve complications arising from the host-vs-donor or donor-vs-host process. If she is in good shape six months from now, we can be very hopeful, and at the two-year mark, there is something like a 98% chance that she will be completely cured of this.

Thanks for your ongoing prayers.