A little more about CMML and Stem Cell Transplants...

 

OK. Last post for a while, and then I'll give it a rest. 

So this is what I've learned about my disease and what I'm going to have to do about it:

What is leukemia?

Leukemia is another combo greek word stemming from leukos,  meaning white, and haima, meaning blood.  There was a German doctor in the 19th century that initially coined the phrase based on a set of illnesses where there was an excess count of white blood cells. 170 years of research has re-defined it in 1,000 different ways. but leukemia is basically a malignant progressive disease where the bone marrow and other blood-forming organs produce increased numbers of immature or abnormal cells, which supress the production of normal blood cells. These cellular imbalances ultimately lead to failure in other critical organs. 

These days, leukemia gets characterized into two kinds: Chronic, which is "slow" moving, and Acute, which is "fast" moving. If you have a choice, go for Chronic. There are four main kinds of leukemia:  Acute Lymphocytic Leukemia (ALL), Acute Myelogenous Leukemia (AML), Chronic Lymphocytic Leukemia (CLL), and Chronic Myelogenous Leukemia (CML). 

So which kind of leukemia do you have?

Within each of those types there are all kinds of subtypes and variations, each with its own set of complexities. My type falls under the CML branch. But it's different. I have CMML which stands for Chronic Myelomonocytic Leukemia. My kind is rare. One hematologist we talked to (who's now retired), said in his 40 years of practice as a blood cancer specialist, he only ever saw one case of CMML. Only 10 people in a million get diagnosed with this. Go figure.

What caused it?

Bad luck. CMML is not hereditary, and to anyone's knowledge is not caused by any prior activity or exposure. My kids won't get it. And nothing about my past would have indicated that I would get this. It's basically a random mutation. 

How bad is it?

Unlike other kinds of cancer, leukemia isn't characterized by tumors or stages. So I don't have stage I or stage IV leukemia. CMML has three levels of progression:, 0, 1, and 2. The levels are determined by the percentage of abnormal cell counts in a given sample. Mine is currently CMML-1. So better than 2 and worse than 0. There are different "prognostic models" used to figure this all out. On a 1-4 scale, my risk of this transforming to acute leukemia is between 2 and 3, depending on which model you use. 

To complicate matters, CMML is marked by certain genetic mutations. I happen to have 5 specific genetic mutations: two mutations of ASXL1, and one each of NRAS, SETBP1 and CBL. These mutations are relevant because they forecast a worse prognosis than for people who don't have them. The ASXL1 mutations are the most worrying part, because they have a tendency to transform the disease from Chronic to Acute. So if there's any urgency to my diagnosis, it's that: we want to head ASXL1 off at the pass and make sure that we kill it before it decides to become acute.

To simplify this, think of the bone marrow as a cell factory. It cranks out 30 billion new cells each and every day. But it's not infallible. Every day, your marrow makes some cells that are just "bad copies"...mutated in some way. Your body is able to deal with those mutations and kill them off without causing any other damage. Happens all day every day in everyone. But in my case, my marrow has developed and decided to accept a few mutated genes that are nasty bad actors that go around screwing up my blood cell balances. The only way to stop this from happening is to kill off my bone marrow and "restart" the factory. Think of it as a "hard reboot", like you might do on your home computer.

Isn't there a medicine for this?

Nope. Because this is such a rare disease, pharmaceutical companies have no incentive to develop new therapies for it. They're focused on curing diseases that are more common and hence more profitable. There are a few targeted therapies that are considered palliative. They've taken drugs that were developed for other illnesses and discovered through trial and error that they are somewhat effective at surpressing the symptoms and slowing the progression of CMML. But it's not curative, and most people that take this approach to treatment die anyway after a few years. There are several clinical trials underway, but each one is really just taking existing meds or combinations of meds to see if they're effective in stopping or slowing the disease. 

Can you be cured? 

Theoretically yes. The only known cure for CMML is to undergo a Stem Cell Transplant (SCT). It's an aggressive treatment, but when it's successful, survivors end up with new bone marrow that shows no signs of disease or malignancy.

Why doesn't everybody with CMML get a SCT? 

Not everybody is eligible for it. You may be too old. Or you may have other "co-morbidities" (diabetes, obesity, heart disease, etc) that would make surviving the process unlikely. So, if you're not a candidate for SCT, then you'd probably choose a targeted therapy approach like hydroxyurea. You'd never be cured, but you might live longer than the median expectation. 

So...what's involved in the Stem Cell Transplant?

1. They determine if I'm a good candidate. So far, the answer is yes. But I will undergo a series of tests to ensure that I'm healthy enough, and that my critical organs are strong enough to withstand the chemo and possible radiation treatments.

2. CMML requires a donor from another body (allogeneic) as opposed to using my own stem cells (autogenous). We'll search for a stem cell donor. We need to find someone whose genetic makeup is sufficiently close to mine, but not identical to mine, who's willing to give up some of their stem cells for me to use. The most likely candidate is one of my siblings – about a 30% chance one of them could be a donor. Failing that, they'll search an international registry of 15 million donors. The most likely candidate will be a young caucasian male from someplace in northern or western Europe. Failing to find a good match in the registry, they'll turn to one of my children, who are both guaranteed to be at least a 50% suitable match. 

3. After a match is found, they schedule the transplant. Two things happen: first, the donor goes to a clinic for about 1 week prior to the transplant. For five or six days they will get injections of a medicine that will boost their body's production of stem cells. At peak stem cell production, they'll siphon off some of their blood from an IV, centrifuge it to separate the stem cells and collect them all in a baggy (picture right).

If that person is indeed in Europe, then someone will hand carry that bag of cells and deliver it to the hospital where I will be waiting to receive them.

Second, while the donor is getting ready to give me their stems, simultaneously here in Milwaukee I'll be admitted into the hospital and will undergo preparations to receive the donation. First, they'll put a "port" into my chest. It's a catheter that simplifies all the subsequent infusions and withdrawals that I will need to have over the subsequent months. Once that's in place, we'll begin an aggressive chemo treatment. In order for the donated stem cells to be able to live in me, they need to kill my bone marrow. So it will be about 5-6 days of chemo sessions. Hopefully that does the job, but if my marrow's not entirely dead, then they'll follow the chemo up with TBI...total body irradiation. Once my marrow is well and dead, then they transplant the donated stem cells into my body. That's called the graft. Functionally it's just another intravenous infusion. 

Call that Week 1. From that point, I'll stay at the hospital in a special antiseptic wing where we'll watch and wait to see what happens. Because the chemo that kills the marrow also kills my immune system, I'll be subject to infection. Even the slightest little infection at this point could kill me. The chemo/radiation combo will also eliminate my platelets, so bumping up against anything will cause extensive bruising, and cuts won't stop bleeding. So my room will be baby-proofed. Rounded soft corners on everything, no sharp objects, nothing that I could possibly cut myself on. My stay at the hospital under close observation and daily testing will last for for 4-6 weeks or until my bone marrow starts producing normalized blood and my immune system begins to redevelop. I'll be able to have visitors, but they'll have to "scrub in" and wear gloves, masks and gowns to come into my room. 

4. Discharge and recovering. After the hospital stay, I get to go home to begin the recuperation process. I'll spend the next 100 days going back to the hospital 2-3x per week for progress and monitoring. I'll be as weak as a newborn baby for probably 2-3 months after the transplant, and then the real fun begins: managing the graft so that my body doesn't reject the cells or vice versa. 

As you can imagine, we're not thrilled with the prospect of having to do this. There are many risks along the way. It will be difficult for me, but perhaps just as difficult for Karla as she'll be needing to care for me as well as her aging parents. Curing the leukemia will not mean that I will absolutely return to a normal pre-leukemia life. The complications and long-term effects of the treatment will likely be with us for the rest of my life. It makes us alternately angry and sad. But short of denying treatment and letting the disease run its course, it's really the only option available to us. As my dad always reminded us, quoting from Mexican President Luis Echeverría, "Arriba y adelante! Seguiremos trabajando!" I think my best translation would be, "Heads up and eyes front! We shall continue the effort!"