Tuesday, April 25, 2006

Glomerular amyloid deposition, AL type, positive for monoclonal lambda immunoglobin light chain

My dad is sick. He is going to be ok, but before he is well, he has to be made more sick. This is how healing works. I haven't mentioned it before, because I wanted his permission to talk about it in this forum, and it is rather complicated. Because it is complicated, I want to take a bit of space here to explain it to as great a degree as I am able. This is the result of a hodgepodge of research and talking with him and his doctors. I don't pretend to understand it all, I am confident that my explanation will contain errors, and I'll update this post as I gain clarification. Also, I won't be hyperlinking in the post. Instead, I'll footnote the links at the end.
Abstract: The plasma cells in dad's bone marrow are producing too much AL Amyloid proteins. Normally, these are used to create immunoglobulins. The excessive numbers are clogging up his kidneys. To fix this, doctors will harvest stem cells, administer chemotherapy to kill the defective plasma, and transplant the harvested stem cells to rebuild his blood. His kidneys will be ok. He will have a normal life after treatment.
What dad is officially diagnosed with is Glomerular amyloid deposition, AL type, positive for monoclonal lambda immunoglobin light chain. Lets break that down, shall we?

Glomerular: pertaining to the Glomerulus, a tiny ball-shaped structure in the kidney that is composed of capillary blood vessels actively involved in the filtration of the blood to form urine. The glomerulus is one of the key structures that make up the functional unit of the kidney.

Amyloid: Any of a number of complex proteins that are deposited in tissues.

Deposition: for molecules to settle out of a solution and be deposited. The amyloid proteins are not able to be dissolved in liquid and flushed out by the kidney--they are simply collecting. Amyloid may be deposited widely in the body, or the deposition may be organ-specific and limited, for instance, to the pancreas, as in type 2 diabetes, or the central nervous system, as in Alzheimer's disease, Parkinson's disease, Huntington disease, Creutzfeldt-Jakob disease and bovine spongiform encephalopathy (mad cow disease). In this case, it is specific only to the kidneys. I think this is because it is normal for there to be some extra amyloids of this type in the body and the kidney normally filters them without a problem.

AL type, positive for monoclonal lambda immunoglobin light chain: all of this simply refers to the specific type of amyloid proteins that we are dealing with. These are "light chain" molecules that are combined with "heavy chain" molecules to build immunoglobulins--components of our immune system.

So that describes what dad has--a whole gob of proteins are building up in his kidney. If something is not done about it, then they can destroy the kidneys, the liver, the pancreas (leading to diabetes), even the heart and the brain.

However, not to fear, we can stop this from happening. He showed symptoms early, and he has a particularly treatable form of the condition. Chances are very slim that there will be severe or chronic problems. Even his kidney will be ok.

So, where the heck are all the proteins coming from and why are they clogging up his kidney? It is really complicated. There are tissues in our bone marrow called Myeloid Tissues, which produce the stem cells that eventually become all of the different kinds of blood cells. One of these cells is the plasma cell (also called plasma B cells or plasmocytes). Plasma cells secrete antibodies, which are proteins that the immune system uses to identify and neutralize foreign objects like bacteria and viruses. Specifically, they produce AL-type Amyloid, which combine with other proteins to create immunoglobulins. There is a common form of cancer of these plasma cells call Multiple Myeloma. Dad does not have that. What he has is called AL Amyloidosis, which is similar. Instead of the cells reproducing out of control and forming cancerous tumors, they are out-of-control producing AL Amyloids. These are clogging up his kidneys.

AL Amyloidosis is a rare disease; only 1200 to 3200 new cases are reported each year in the United States. There are a variety of symptoms. I believe that dad's initial symptom was edema--swelling of the his ankles and legs with retained fluid that his impaired kidney could not properly process.

So, what to do? It is very simple, actually--destroy the cells that are creating these defective plasma cells. But then, where is he going to get new Plasma cells--plasmocytes-R-us? No. All cells begin with stem cells. The tissues in our bone marrow produce the type of stem cell which eventually differentiates into all of the different kinds of blood cells--including the defective Plasma cells. So dad is going to Wichita, where doctors will harvest some stem cells. Dad is given a drug which will stimulate the production of an excess number of stem cells, which will move out into the blood stream. His blood will be pumped through a machine that can separate out these stem cells, which will then be frozen.

Then dad will be given a high dose of chemotherapy, which will destroy his myeloid tissue, killing the cells that create the excess Amyloids. After a few days, the harvested stem cell will be put back in his body, where they will immediately get back to work producing new blood cells. The process of being frozen for storage is stressful to the stem cells, which are fragile. Only the strongest and healthiest cells will actually survive. This means that the defective cells which caused the problem in the first place will be destroyed.

The schedule is like this: On the first of May, they will harvest the stem cells and insert a catheter in his shoulder. This will act like a spigot for the insertion and removal of all of the fluids that they'll be putting in and taking out. On May 8th, they will administer the chemotherapy drugs through the spigot. His immune system will be destroyed. Three days later, the stems cells will be put back in. Then he just waits around. He will get daily infusions of drugs and hydrating fluids while his stem cells rebuild his immune system. For up to three weeks after the Chemo on May 8th, he will be under constant supervision because of potential side-effects of the compromised immune system. He has to have someone around to get him to the emergency room. The nurse promised that he would probably have to be in the hospital with a fever at some point during those three weeks. However, the chances of serious damage or death are less than three percent. It is considered very safe.

Then, three months later, he will do it again. After these treatments, about half of the patients are completely cured, and the rest are able to manage the disease with medication. There is a strong possibility of relapse within ten years, which would mean a repeat of the treatment--again, with very good success rates.

We, the family, went to his treatment facility last week for "Family Day," which was simply a discussion of the treatment process with his doctor. Part-way through the discussion, I observed a radically different perspective between him and us. Have you ever seen those "maps" of the world as a New Yorker sees it? New York is great big in the center and everything else is just negligible slivers around the fringes. Well in the doctor's vision of the process, the giant, huge thing in the middle was the stem cell harvesting and transplant. That is breakthrough technology he is actively researching, is primarily focussed on, and discussed the most. For the rest of us the stem cell stuff was, like "yeah yeah yeah, you are taking some cells out and putting them back in, don't tell the president." For us, the elephant in the room was CHEMOTHERAPY. Oh my, isn't that what they give to cancer patients? Isn't that horrible--almost as horrible as the cancer itself? But his doctor didn't seem too concerned about the chemo. Not a big deal. They have been doing it for decades, they know how to manage it, he'll be fine, let's get back to the stem cells, aren't they cool. The conversation was a bit like watching engineers talk when they don't realize that one is using inches and the other is using centimeters--a little frustrating and bewildering.

In the end, all indications are that everything will be fine. But, before dad gets to fine, he has to go through some suffering. It is going to be hard, and we all wish he didn't have to do it but we all thank God that it is not something worse. Months ago, when he told us that he was getting a bone marrow biopsy, I think all of our hearts skipped a beat. So, in the end, we are relieved and thankful.

I'll update as I am able.


Amyloidosis Support Network. Take this with a grain of salt. While it is my primary source of information, I think that it was developed before new and more successfull treatments of this disease. It is one the most uninspiring "Support Networks" I have encountered.

Definition of Amyloid

Wikipedia on: Bone Marrow, Plasma Cells, pluripotential hemopoietic stem cells

Definition of the Glomerulus

Light Chain-Associated Renal Disorders: Article by Malvinder S Parmar

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