Mike's Chemotherapy for Follicular Cancer Experience

For me, this was the most relevant and fascinating presentation. With the research and new technologies that are evolving, they give me hope that soon the lifespan [last noted at 10-12 years from the lecture by Dr. Reeder in a previous post] will be expanded, and possibly a cure is in sight!

These are my notes from it, including additional information that I researched to aid in the understanding of this content.

Presentation 4 (Disease Specific Break Out Session): Dr. Oliver Press, MD, PhD, University of Washington Medical Center, Fred Hutchinson Cancer Research Center, gave a presentation on ‘Follicular Non-Hodgkin Lymphoma’

• This disease in increasing rapidly. It is most common in 50-70 year olds.
• Grading is done by: determining how many cells are little & how many cells are big.  Grade 1=0-5; Grade 2=6-15; Grade 3A >15; 3B= mostly big cells. It behaves aggressively.  In this diagram ‘a’ is follicular lymphoma grade 1/3; ‘b’ is follicular lymphoma grade 3/3.

• 60% of the time Follicular lymphoma involves bone marrow.
• It floats around in the blood stream.
• Definition of Apoptosis: A form of cell death in which a programmed sequence of events leads to the elimination of cells without releasing harmful substances into the surrounding area. Apoptosis plays a crucial role in developing and maintaining health by eliminating old cells, unnecessary cells, and unhealthy cells. The human body replaces perhaps a million cells a second.
• How does a B cell become cancerous? When a mutation is caused there is a break in Chromosomes 14 + 18. Gene 18 is moved to gene 14. BCL2, which is a Proto-oncogene: A normal cellular gene that, when mutated or inappropriately expressed, can cause a cell to become cancerous. In this case it tells the cell not to die. Then the cells don’t die, and proliferate. See diagram:

Regular cells die and are replaced by new ones. But, the high levels of the Bcl-2 protein protect the cells from early death by apoptosis. The Bcl-2 protein suppresses apoptosis by preventing the activation of the caspases [which are enzymes that plays a key role in programmed cell death, or apoptosis] that carry out the process

• Follicular lymphoma cells proliferate and migrate.
• They are usually in the liver.
• It can go from a slow to fast growing lymphoma. It can progress at 3%/year up to 15 years, then after that it won’t happen any more. A second chromosome mutation causes it to become fast growing in 40% of the cases.

There are a lot of treatments and approaches to Follicular Lymphoma, including:

*Observation alone if asymptomatic

*Single agents (Chlorambucil, Fludarabine)

*Rituximab

*Combination Chemotherapy (R-CVP, R-CHOP, R-FND). This is the most common option.

*Radio immunotherapy

*Biologic Agents (Bortezomib, Thalidomide)

* Stem Cell Transplants, (which are only appropriate with 10% of patents)

*Rituximab + Bendamustine therapy has been used in the last 2 years.

• Monocloidal Antibodies are Immunological. They were injected into mice, which created antibodies. Bioengineers then learned how to create these. ADCC killer cells are recruited.
• Apoptosis- inducing cells to kill themselves.
• Retuximab Maintenance- used to keep the disease from coming back. Done for 2-3 years after chemotherapy or other treatment. Retuximab sticks to CD20 molecules. It helps suppress the B cells (which have the lymphoma). It does not suppress the T-cells that much; therefore the immune system is not compromised as much.
• Transplants: the patient first gets a high dose of chemotherapy, and then a peripheral blood stem cell transplant is given. It cures it for 20+ years. Only 10% of follicular lymphoma patients can use this.

Additional information on Transplants:

The following information is excerpted from the American Cancer Society article on ‘Bone Marrow and Stem Cell Transplants’

*Stem cells mostly live in the bone marrow (the spongy center of certain bones), where they divide to make new blood cells. Once blood cells are mature they leave the bone marrow and enter the bloodstream. A small number of stem cells also get into the bloodstream. These are called peripheral blood stem cells.

Stem cell transplants are used to restore the stem cells when the bone marrow has been destroyed by disease, chemotherapy (chemo), or radiation. Depending on the source of the stem cells, this procedure may be called a bone marrow transplant, a peripheral blood stem cell transplant, or a cord blood transplant.

What makes stem cells so important?

Stem cells make the 3 main types of blood cells: red blood cells, white blood cells, and platelets

We need all of these types of blood cells to keep us alive. And in order for these blood cells to do their jobs, you need to have enough of each type in your blood. In some diseases, like leukemia, aplastic anemia, certain inherited blood diseases, and diseases of the immune system, the stem cells in the bone marrow don’t work the way they should. They either make too few blood cells, too few immune cells, or too many abnormal cells. Any of these problems can cause the body to not have enough normal red blood cells, white blood cells, or platelets. A stem cell transplant may help correct these problems.

In some cancers, such as certain leukemia’s, multiple myeloma, and some lymphomas, a stem cell transplant can be an important part of treatment. It works like this: high doses of chemotherapy or radiation work better than standard doses to kill cancer cells. But high doses can also cause the bone marrow to completely stop making blood cells, which we need to live. This is where stem cell transplants come in. They can be used to replace the body’s source of blood cells after the bone marrow and its stem cells have been destroyed by the treatment. The rescue transplant allows doctors to use much higher doses of chemo or radiation to try and kill all of the cancer cells.

Types of Stem Cell Transplants:

Autologous stem cell transplant:

In this type of transplant, your own stem cells are taken before you get cancer treatment that destroys them. Your stem cells are removed, or harvested, from either your bone marrow or your blood and then frozen. After you get high doses of chemo and/or radiation the stem cells are thawed and given back to you.

One advantage of autologous stem cell transplant is that you are getting your own cells back. This means there is no risk that your immune system will reject the transplant or that the transplanted cells will attack or reject your body.

A possible disadvantage is that cancer cells may be harvested along with the stem cells and then put back into your body. To prevent this, doctors may give you anti-cancer drugs or use other methods to treat your stem cells and reduce the number of cancer cells that may be present.

This kind of transplant is mainly used to treat some leukemia’s and lymphomas, and multiple myeloma. It is sometimes used for other cancers, especially in children.

Allogeneic stem cell transplant

Here, the stem cells do not come from the patient, but from a donor whose tissue type closely matches the patient. The donor is most often a family member, usually a brother or sister. If you do not have a good match in the family, a donor may be found from the general public through a national registry. This may be called a MUD (matched unrelated donor) transplant.

Blood taken from the placenta and umbilical cord of newborns is a newer source of stem cells for allogeneic transplant. Called cord blood, this small unit of blood has a high number of stem cells. But the number of stem cells in a unit of cord blood is often too low for large adults, so this source of stem cells has so far been used more in small adults and children. Doctors are now studying different ways to use cord blood for transplant.

An advantage of allogeneic stem cell transplant is that the donor stem cells make their own immune cells, which may help destroy any cancer cells that may remain after high-dose treatment. Another possible advantage is that the donor can often be asked to donate more stem cells or even white blood cells if needed. Stem cells from healthy donors are also free of cancer cells.

Still, there are many possible drawbacks to allogeneic stem cell transplants. The transplant, also known as the graft, may not “take” — that is, the donor cells may be more likely to die or be destroyed by the patient’s body before settling in the bone marrow. Another risk is that the immune cells from the donor can attack the patient’s body — a condition known as graft-versus-host disease. There is also a very small risk of certain infections from the donor cells, even though donors are tested before they donate. The higher risk comes from infections you have had, and which your immune system has under control. These infections often surface after allogeneic transplant because your immune system is held in check (suppressed) by medicines called immunosuppressive drugs. These infections can cause serious problems and even death.

Allogeneic transplant is most often used to treat certain types of leukemia, lymphomas, and other bone marrow disorders such as myelodysplasia.

Non-myeloablative or mini-transplants (allogeneic)

Another type of allogeneic transplant is sometimes called a “mini-transplant.” Compared with a standard allogeneic transplant, this one uses less chemo and/or radiation to get the patient ready for the transplant. Your doctor may refer to it as a non-myeloablative transplant or mention reduced-intensity conditioning (RIC). The idea here is to kill some of the cancer cells, some of the bone marrow, and suppress the immune system just enough to allow donor stem cells to settle in the bone marrow. The new immune cells then begin to destroy the remaining cancer cells, in what is known as a “graft-versus-cancer” effect.

Unlike the standard allogeneic transplant, cells from both the donor and the patient may exist together in the patient’s body for some time after a mini-transplant. But slowly, over the course of months, the donor cells take over the bone marrow and replace the patient’s own bone marrow cells. These new cells can then develop an immune response to the cancer and help kill off the patient’s cancer cells.

The advantage of a mini-transplant is the lower doses of chemo and/or radiation. This makes it especially useful in older patients and those with other health problems who aren’t strong enough for a regular stem cell transplant. It may rarely be used in patients who have already had a transplant. And, because the your stem cells aren’t all killed, your blood cell counts don’t drop as low while you wait for the new stem cells to start making blood.

Mini-transplants have been found to treat some diseases better than others. They may not work well for patients with a lot of cancer in their body at the time of transplant or those with fast-growing cancer. Also, the lowered immune response can still lead to graft-versus-host disease.

This procedure is actively being studied, but it has only been in use since the late 1990s and long-term patient outcomes are not yet available. There are lower risks of complications, but the cancer may be more likely to return (relapse). Ways to improve the outcomes are still being studied.

Another future possibility is autologous transplant followed by an allogeneic mini-transplant. This is being tested in certain types of cancer, such as multiple myeloma. The autologous transplant can help decrease the amount of cancer present so that the lower doses of chemo given before the mini-transplant can work better. And the recipient gets the benefit of the graft-versus-cancer effect of the allogeneic transplant.

Syngeneic stem cell transplant

This is a special kind of allogeneic transplant because the donor is an identical twin with identical tissue types. Since few people are identical twins, this type of transplant is very rare. An advantage of syngeneic stem cell transplant is that graft-versus-host disease will not be a problem. There are no cancer cells in the transplant, either, as there would be from an autologous transplant. A disadvantage is that this type of transplant won’t help destroy any remaining cancer cells because your twin’s immune system is so much like yours. Every effort must be made to destroy all the cancer cells before the transplant is done to help keep the cancer from coming back (relapse).

Sources of stem cells for transplant

There are 3 possible sources of stem cells to use for transplants: bone marrow, the bloodstream (peripheral blood), and umbilical cord blood from newborns. Although bone marrow was the first source used in stem cell transplant, peripheral blood is used most often today.

Bone marrow is the spongy tissue in the center of bones. Its main job is to make blood cells that circulate in your body and immune cells that fight infection.

Bone marrow was the first source used for stem cell transplants because it has a rich supply of stem cells. The bones of the pelvis (hip) contain the most marrow and have large numbers of stem cells in them. For this reason, cells from the pelvic bone are used most often for a bone marrow transplant. Enough marrow must be removed to collect a large number of healthy stem cells. For a bone marrow transplant, the donor gets general anesthesia (drugs are used to put the patient into a deep sleep). Several large needle sticks are made through the skin into the back of the pelvic bone to remove marrow. The thick, liquid marrow is pulled out through the needle. The harvested marrow is filtered, stored in a special solution in bags, and then frozen in liquid nitrogen. When the marrow is to be used, it is thawed and then given just like a blood transfusion. The stem cells travel to the recipient’s bone marrow. They engraft or “take” there over time and begin to make blood cells. Signs of the new blood cells usually can be measured in the patient’s blood tests in about 2 to 4 weeks.

Normally, very few stem cells are found in the blood. But giving hormone-like substances called growth factors to stem cell donors a few days before the harvest causes their stem cells to grow faster and move from the bone marrow into the blood.

For a peripheral blood stem cell transplant, the stem cells are taken from the blood. A very thin flexible tube (called a catheter) is put into one of the donor’s veins and attached to tubing that goes to a special machine. The donor’s blood is run through the machine, which separates and keeps only the stem cells. The rest of the blood goes back to the donor. This takes several hours, and may need to be repeated for a few days to get enough stem cells. The stem cells are filtered, stored in bags, and frozen until the patient is ready for them. After the patient is treated with chemo and/or radiation, the stem cells are given in an infusion much like a blood transfusion. The stem cells travel to the bone marrow, engraft, and then grow and make new, normal blood cells. The new cells are usually found in the patient’s blood a few days sooner than when bone marrow stem cells are used, usually in about 10 to 20 days.

Not everyone who needs an allogeneic stem cell transplant can find a well-matched donor among the people who have signed up to donate. For these patients, umbilical cord blood may be a potential source of stem cells. A large number of stem cells are normally found in the blood of newborn babies. After birth, the blood that is left behind in the placenta and umbilical cord (known as cord blood) can be taken and stored for later use in a stem cell transplant. The cord blood is frozen until needed. Cord blood transplant uses blood that is normally thrown out. The first cord blood transplant was done in 1988, and its use has been growing ever since. A possible drawback of cord blood is the smaller number of stem cells present. But this is partly balanced by the fact that each cord blood stem cell can form more blood cells than a stem cell from adult bone marrow. To be safe, most cord blood transplants done so far have been in children and smaller adults. Researchers are now looking for ways to use cord blood for transplants in larger adults. One approach that is being taken is to find ways to increase the numbers of these cells in the lab before the transplant. Another approach is the use of the cord blood from 2 infants at the same time for one adult transplant, called a double-unit cord blood transplant. A third way cord blood is being used is in the setting of a “mini-transplant.” In this case, the bone marrow is not completely destroyed so there are some stem cells left in the host before and during the time that the cord blood stem cells engraft.

Which stem cell source is best?

All 3 sources of stem cells can be used for the same goal: to give the patient healthy stem cells that will mature into healthy blood cells. There may be some pros and cons to each source, but all are usually able to provide the needed number of stem cells (with the exception noted above in umbilical cord blood).

At first, all stem cell transplants done were bone marrow transplants. But today peripheral blood stem cell transplants are far more common. Often, doctors are able to harvest more stem cells from peripheral blood than from bone marrow. It’s also easier to donate peripheral blood stem cells than bone marrow. Another plus for peripheral blood stem cell transplant is that the recipient’s blood count often recovers faster than with a bone marrow transplant. But the risk of graft-versus-host disease is somewhat higher with peripheral blood stem cell transplants than with bone marrow transplants.

Cord blood transplant may be an option if a good match can’t be found among volunteer stem cell donors. Even though well-matched cord blood is best, studies suggest that cord blood may not have to be as closely matched as bone marrow or peripheral blood. This may be an advantage for patients with rare tissue types. This type of transplant also does not require a separate donation procedure and may reduce the severity of graft-versus-host disease (Cord blood cells usually take longer to engraft.) This leaves the patient at a high risk for infection longer than is seen with transplanted marrow or peripheral blood stem cells. Another drawback is that, unlike bone marrow transplant or peripheral blood stem cell transplant, the donor cannot be called back to give more if needed after the cord blood stem cells are used.

For additional information on this topic and a description of the transplant process please see: http://www.cancer.org/Treatment/TreatmentsandSideEffects/TreatmentTypes/BoneMarrowandPeripheralBloodStemCellTransplant/bone-marrow-and-peripheral-blood-stem-cell-transplant-toc

Treatments that could prevent a stem cell transplant:

• In terms of toxicity Fludarabine is the worst. It knocks out the T-cells.
• Retuximab has no impact on the stem cells.
• RCHOP & CVP are very mild on the stem cells
• Bendamustine- it is not known yet what effect it has on the stem cells.

Doing a lot of PET Scans for monitoring is not recommended because the follicular activity is lower. CT Scans to monitor lymph node/tumor cells is very adequate and recommended.

Many oncologists will not use stem cells harvested 5 or more years previous. Most oncologists will not harvest stem cells after the first remission.

Note that Medicare will not cover allogeneic stem cell transplants.

Novel therapies are evolving in clinical research that may prove vital in curing Follicular Lymphoma. They include:

• RIT
• Bendamustine
• Multiple Antibodies
• Non-myeloablative allogeneic transplants
• Adoptive T-Cell Immunotherapy
• siRNA

Explore posts in the same categories: Recovery from the Chemotherapy Treatments, the journey continues

This entry was posted on March 9, 2011 at 11:50 am and is filed under Recovery from the Chemotherapy Treatments, the journey continues. You can subscribe via RSS 2.0 feed to this post's comments.

Tags: allogeneic stem cell transplant, apoptosis, autologous stem cell transplant, BCL2, bendamustine, bone marrow, dr. Oliver Press, follicular lymphoma, genetic mutation, lymphoma grading, monocloidal antibodies, non-myeloablative transplants, peripheral blood, radio immunotherapy, syngeneic stem cell transplant, treatments for follicular lymphoma, treatments preventing a stem cell transplant, types of stem cell transplants, umbilical cord blood

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