Hello All,
A number of readers on this list have written to me privately asking me to post something about why I question anyone who says we need to stay on Gleevec or any other therapy for the rest of our lives.
The beginning of this post is a background on what is blood and how does the body make it. I included this because Cindy's post mentioned blood cells. This is a long post, I am sorry, there isn't an easy way of explaining this over the internet.
Blood accounts for 1/16th of our body weight. 1 drop of blood can contain millions of cells. Nearly half of the blood (45%) is made up of RBC (red blood cells – erythrocytes) WBC's (white blood cells – leukocytes) and platelets (thrombocytes). The other 55% is plasma. Interesting fact – the heart pumps about (9-10.5 pints per man) or (7-9 pints per woman) per minute and can pump up to about 50 pints per minute during exercise.
HEMATOPOIETIC SYSTEM
If we consider the marrow to be the blood cell "factory," the "retail store" is the peripheral blood. The circulating cells usually reflect the marrow production. Outside-the-marrow events, however, such as extravascular hemolysis, may change the equation.
- Number of blood cells in the blood stream depends on three factors:
-- Rate of production
-- Rate of release
-- Length of survival
- There are two types of marrow:
-- Yellow marrow (Inactive) composed primarily of fat.
-- Red marrow (active in hematopoiesis)
Distribution of active marrow can be determined by administering radioactive iron:
LOCATION
% of TOTAL MARROW
Pelvis
40
Vertebrae
28
Cranium-mandible
13
Ribs
8
Sternum
2
Ends of long bones
8
Total marrow space in the adult is about 4 liters. About half of this is active. Total marrow space in the child is about 1.6 liters. It is nearly 100% active though.
Remember - The spleen and lymph nodes are also part of this system (this helps us understand why our spleen is usually swollen at diagnosis).
- Development of Marrow
The first hematopoietic stem cells appear in the yolk sac during the 3rd week of embryogenesis. At about the 3rd month of fetal life, some of the cells migrate to the liver which then takes over as the chief site of blood cell formation until just before birth. The spleen, lymph nodes, and the thymus also contribute. This is called extramedullary hematopoiesis. At about the 4th month of gestation the bone marrow spaces begin to become important as the source of cells. If a sufficient stress is placed on the adult, extramedullary hematopoiesis can be a compensatory mechanism.
The terminology employed, based on our knowledge of the pluripotential stem cell, divides the marrow cells into lymphoid and non-lymphoid lines. The term for all non-lymphoid cells is myeloid (this is our area of concern as we have chronic myeloid leukemia). This word includes the erythroid, granulocytic, monocytic/macrophage, and megakaryocytic lines. The normal values for a bone marrow aspirate (at NYH) are as follows:
Normals:
Myeloid:Erythroid ratios
Myeloid cells
60-70%
Normal
2.5 - 4:1
Erythroid cells
20%
Infection
5-6:1
Lymphocytes
10-15%
Anemia
2:1
Plasma cells
2%
Megas, Monos,
fibroblasts, etc1%
HEMOPOIESIS
The Pluripotential (Totipotential) Stem Cell
The pluripotential stem cell is defined as the precursor cell from which all erythrocytes, leukocytes, and megakaryocytes are derived ( i.e. all blood cells have a common cell line of origin).
The above is a lovely diagram of the common cell line. I hope it shows on the list. If not, e-mail me separately, and I will be happy to send it to you.
Interestingly enough the common cell line theory is supported by the Philadelphia Chromosome, which we on this list are all too familiar with.
So, now that we know what blood is and how it is made. We can get to the statement about why patients on Gleevec or any other drug therapy to treat their CML , cannot stop taking their drugs.
The goal of Gleevec therapy and other drugs for CML is to reduce the total load of leukemic cells in the body. What precisely triggers this disease is not completely known, however, ionizing radiation exposure (results of studies conducted in Hiroshima Japan after the atomic bomb) and/ or exposure to benzene. There are probably other factors involved.
Usually within the first three months of starting Gleevec therapy patients will achieve a hematologic response – this means that the amount of WBC's RBC's Basophiles, Eosinophils etc are returning values in the "normal" range. This is encouraging news because it means that the drug is starting to have an effect. However consider this:
At diagnosis you may have approximately (no one knows for sure, obviously) 1,000,000,000,000 leukemic cells in your blood.
At HMR – hematologic response this could mean that you have about 10>11th or 100,000,000,000 leukemic cells
At MCR (Cytogenetic response of 35%) this could mean you might have about 10>10th or 10,000,000,000 leukemic cells
When you reach CCR – Zero FISH, this could mean that you might have about 10>9th
A three log reduction might mean that there are about 10>8th
A four log reduction might mean that there are about 10>7th
PCRU which is the level of detection, still means that there are about 10>5th or 100,000 leukemic cells in your body.
This is not meant to be depressing when you consider that there are many people who have lived for years at even less than zero FISH without having their disease progress. However, there are still many things about this disease that is unknown.
After over 5 years of Gleevec therapy we know that the only people who have stopped Gleevec therapy and not relapsed (a very small number of patients) are patients who had prior therapy with interferon and had a very good response to the interferon therapy. This is the reason why there is so much interest in immunotherapy and vaccines. Some of these findings were presented at ASH last year, which I posted a report on.
This makes sense when we understand how Gleevec works. Gleevec is a very effective inhibitor and stops the pathway that leads to the over proliferation of the leukemic cells. However, the cause of CML seems to be earlier in the blood production phase, where Gleevec does not reach. Interferon on the other hand does seem to stimulate an immune response in a small population of patients. I am not advertising one form of treatment over another. I am not "pro" one treatment over the other. This is interesting to note only because there is research going on that will help scientist understand why and how interferon, vaccines and immunotherapy in general works. There has been two great success stories in this area recently, the vaccine for ovarian cancer and the vaccine at the NCI for melanoma. It is not impossible to think that there will be something for CML.
This is a very long explanation of why some doctors are saying you cannot stop Gleevec therapy. You cannot stop it now. It is very important to continue to keep taking Gleevec.
There is no patient, other than those who were "pre-treated" with interferon that have been able to go off Gleevec without relapsing. The good news is that those patients who did stop Gleevec for whatever reason, and did relapse, have regained their sensitivity to it from what I understand. In some instances some doctors do temporarily interrupt treatment with patients who have had serious un-manageable side effects. Interestingly, when these patients are re-started their side effects are somewhat easier to manage or at least tolerate. However there is a lot of work going on in this area to understand side effects.
The discussions here of the past few days really break down to a case of semantics.
What I have been saying, which may have caused some confusion, is that with all the recent work in vaccines and immunotherapy, it is possible that we can see a future, and not too far away either, where scientist maybe able to work with the immune system to teach the immune system to correct the problem at the stem cell level. That may mean that we may have a vaccine that allows us to be drug free and cancer free, and that is a lovely pleasant thought for me and all of us.
I realize this is a long post, but I hope it has helped. If you have any questions about what I am posting here do not hesitate to contact me. I sincerely hope that no one finds anything here offensive as that is certainly not my objective.
Best,
Cheryl-Anne
Understand that the right to choose your own path is a sacred privilege. Use it. Dwell in possibility. ~Oprah Winfrey
--~--~---------~--~----~------------~-------~--~----~
[CMLHope]
A support group of http://cmlhope.com
-------------------------------------------------
You received this message because you are subscribed to the Google Groups "CMLHope" group.
To post to this group, send email to [email protected]
To unsubscribe from this group, send email to [EMAIL PROTECTED]
For more options, visit this group at http://groups.google.com/group/CMLHope
-~----------~----~----~----~------~----~------~--~---
