This weekend we're back home in Selmer for a wedding, and I found a Discover magazine with the 100 top stories of 2011. The potential leukemia cure was #10.
It had some information I didn't see in the newspaper articles.
Doctors David Porter and Carl June treated three leukemia patients for whom standard chemotherapy had not worked. They used a harmless form of the HIV virus to carry a mutation into the patient's T-cells that would cause the T-cells to target the leukemia cells and destroy them.
They chose HIV because the dangerous version attacks T-cells. They "disarmed" it, piggy-backed the mutation they needed onto it, and the virus carried the mutation into the DNA of the T-cells.
Or at least, that's what I got from the articles, and I read about five of them.
What Discover explains is that they actually mutated the patients' T-cells to destroy all B-cells, not just leukemia cells.
Each of the patients had Chronic Lymphocytic Leukemia (CLL), a form of leukemia that affects lymphocytes (hence the name). Lymphocytes are immune system cells that come in the form of T-cells, B-cells, and NK (Natural Killer) cells, and in patients with CLL, at least one type of lymphocyte has become abnormal, useless, and is proliferating, getting in the way of other, useful blood cells. When they crowd out the other white blood cells, you are left prone to infection and disease. When they crowd out the red blood cells, you die of anemia.
CLL is the most common form of leukemia, and B-cells are the most common malignant cell involved in CLL.
Thus, destroying the B-cells will cure most CLL patients. In the trial, it successfully put two patients in remission and lowered the leukemia cells by 70% in the third.
Those are great results, but the treatment does not only destroy the malignant cells. It destroys all B-cells. Forever.
This happens because the T-cells are permanently mutated. As your body produces more B-cells, the T-cells destroy them.
B-cells produce antibodies and develop a memory for germs that attack the body. Losing them weakens the immune system. This is a serious side effect of the new treatment. On the other hand, a weakened immune system is a lot better than dying of leukemia because chemotherapy didn't work on you.
There is a treatment for the loss of B-cells, which involved regular infusions of antibodies pulled from the blood of blood donors.
So how does this apply to other cancers and to me?
Will This Work on Other Forms of Leukemia and Other Cancers?
It is possible this will work on other forms of leukemia and other cancers.
B-cells have a protein on their surface known as CD-19. They are the only cell in the body with that protein marker. So the mutation the doctors put into the T-cell caused them to recognize and destroy cell with the CD-19 protein.
In order to use the same treatment on other leukemias and other forms of cancer, they have to find a similar marker to target, one that is specific to that disease.
In CLL, the doctors can determine which cell in the problem, and usually it's the B cell.
The doctors don't know what my abnormal cells are.
Everyone's bone marrow has stem cells which develop into the various blood cells. First they develop into either a lymphoid stem cell or a myeloid progenitor. If they become a lymphoid stem cells, then they'll eventually be either a T-cell, B-cell, or NK-cell. If they become a myeloid progenitor, they'll eventually become either a neutrophil, eosdinophil, basophil, mast cell, or monocyte.
My leukemic cells are stem cells that began to develop, but then went bad before they ever became lymphoid stem cells or a myeloid progenitors. The doctors also can't figure out which type those cells were intending to become.
My cells do have markers like the CD-19 that is on the B-cells. CD-4 and CD-56 are the ones that usually elicit a diagnosis of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN, see tab above). With that diagnosis, it appears the blasts (the immature cells) intended to become dendritic cells, which are myeloid cells. On the other hand, they used to call that disease NK-cell lymphoma, meaning they were wondering whether the CD-4 and CD-56 markers indicated those blasts were going to become NK-cells, which are lymphoid, not myeloid.
My bad cells have CD-4 and CD-56, but not on the same cells, and the CD-4 is more common. They have other markers (CD-123 and TCL-1), which indicate BPDCN, but they also have CD-10 which is more indicative of a potential lymphocyte.
Acute (fast moving) and chronic (slow moving) leukemias are divided up based on whether the bad cells are descendants of the lymphoid stem cell or the myeloid progenitor. Acute leukemia is usually split into Acute Lymphoid Leukemia or Acute Myeloid Leukemia. ALL has a much better survival rate than AML.
Since they can't determine whether mine is lymphoid or myeloid, they call it Acute Undifferentiated Leukemia, and survival rates for AUL are worst of all, though accurate rates can't be determined because of the rarity of the disease. I'm convinced that survival rates are only worse because doctors have only learned to treat it well in the last five years.
That said, I'm not a blood expert, so I don't know if CD-10 or CD-56 is limited to one certain white blood cells. If so, then perhaps they could use a targeted therapy like they used on those CLL patients, but I would guess that there are not enough cases like mine to find out how to target those markers. Not only would those specific markers be rare, but you would only want to use such a therapy on those that didn't respond to chemotherapy. After chemotherapy, you still have all your white blood cells. Right now, this new therapy destroys one forever.
As for other cancers, the issue will be if they can find a marker that is unique to the cancer cell. That marker will have to be on the surface of the cell because T-cells don't peer down inside of the cells they target.
Anyway, I wrote all that to say that there's a reason that research is progressing slowly on this kind of treatment. They have to see the long term effects even on those who are cured, and they have to find out whether people can handle the treatment. One of the patients developed kidney failure from processing all the dead B-cells.
This was a rather technical blog post. I'll try not to write too many like this, though I love this kind of stuff (especially now).