Stem cell transplants

 

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Stem Cell Transplants

Stem cell transplants have been used increasingly over the past decades as novel new drugs are discovered, and researchers learn better ways to prevent or manage toxicity and side effects. Once, the last treatment of choice they are now frequently used in first relapse or even up front for patients with high risk disease. This begs the question, "Who should be transplanted and at what point in their NHL journey?" Here are some links to experts opinions and research on this topic.

Additional SCT topics

Please check out the various SCT topics of importance on the left menu. Below are some additional topics of interest. If you can't find what you are looking for please click on the Questions link at the top to ask us a question.

On this page we will attempt to bring to you the most important information that you want to know about when contemplating your own SCT. If you are looking for a very detailed look at transplants then you should check out the BMT-Info on-line book on the subject.

Many of you will be familiar with the term "Bone Marrow Transplant" and essentially that is the same thing as a Stem Cell Transplant. The difference is the source of the stem cells.

In a traditional Bone Marrow Transplant, the stem cells are collected by placing the donor under a general anaesthetic, then using a surgical procedure to extract bone marrow directly from the bones. This consists of a number of needle insertions to extract the marrow. The patient feels no pain since they are asleep, but after waking up they will in all likelihood be very sore for a number of days. This method of collecting the stem cells is rarely used anymore unless they cannot collect them from the blood as described below.

In a Stem Cell Transplant, the stem cells are collected from the circulating blood. This procedure is called aphaeresis. It is accomplished by inserting an IV into both arms of the donor. Blood is drawn out of an IV in one arm and pumped through a machine which separates out the stem cells, then the remaining blood is pumped back into the donor through an IV in the other arm. In many cases instead of using an IV in both arms they will use a central line similar to a Hickman catheter. Under normal circumstances there are usually very few stem cells circulating in the blood, therefore it is necessary to "mobilize" the stem cells out of the marrow and into the blood. This is done by giving the patient chemotherapy. Giving the patient chemotherapy kills many of the normal red and white blood cells. When this happens your bone marrow must go into overdrive to replace them which means the stem cells go to work. Stem cells are the cells which can become any type of blood cell, and which normally reside in the bone marrow. This sudden drop in red and white counts causes many of them to be pushed out into the circulating blood at this time. Then they can be collected by aphaeresis. 

 

Allogeneic (al-o-gen-ay-ic)

In this transplant someone else is the donor. Most often it will be a sibling who has HLA matched blood. When a sibling match is not available another relative may be a candidate or the bone marrow registry may be searched.  Allogeneic transplants have the highest chance of curing the patient, and in fact even those who have indolent varieties which are generally not curable, may be cured with an allogeneic transplant. Unfortunately along with this excellent chance of cure, also comes a corresponding risk of death. Although the risk of death has been dropping over the past decade it is still quite high and is in the range of 20-35%. The risks can be even higher for patients already in poor health. 

This risk comes primarily from the Graft Versus Host Disease (GVHD). This is caused by the donors immune cells mounting a response against the patient. This is quite opposite to what you may be used to thinking. Most of us are familiar with a typical transplant rejection where the patients body tries to reject the donated organ. However since an SCT involves transplanting a new donor immune system into the patient it is the donated immune system that is trying to reject the patient. This can be fatal if it gets out of hand. There is a great deal of research being done to find better ways to deal with GVHD. Check out the ASH abstracts for lots of medical abstracts about GVHD.

Here is an excellent (though technical) discussion of the state of the art of GVHD from Blood Journal (2009)

Acute graft-versus-host disease: from the bench to the bedside

GVHD is not all bad. In fact GVHD is part of what can cure the patient and a limited amount of it is a good thing for patients undergoing an allogeneic transplant. When the donors immune system mounts its attack on the patient, it also mounts an attack on the patients cancer because this healthy new immune system works properly and recognizes cancer as more foreign than the patient. If controlled properly the new immune system will kill the cancer and not the patient. The good aspect of Graft Versus Host Disease is often called Graft Versus Lymphoma (or Leukaemia ) in recognition of the beneficial effect that it has.

 

Haploidentical transplants

Finding a perfect HLA match for an allogeneic transplant can be challenging. This is especially true for racial minorities. When a sibling donor is not a perfect match, finding an unrelated donor can take months, or can be entirely unsuccessful. A haploidentical match is a family member is who only a 50% match. This makes parents, and other siblings possible candidates as donors.  Below are some studies about this new technique.

Long-term outcome after haploidentical stem cell transplant and infusion of T cells expressing the inducible caspase 9 safety transgene

A Peer review of the above study: A GVHD kill switch helps immune reconstitution

Here is a look at who is the best candidate for a mismatched transplant.

Who is the best donor for a related HLA haplotype-mismatched transplant?

 

Mini-Allogeneic

A mini-allogeneic transplant is called by several names and it is important to distinguish what they really mean. Allogeneic transplant conditioning regimens fall into 3 categories.

Myeloablative
Myeloablative means it destroys all bone marrow function. This type causes irreversible cytopenia (low blood cell counts) and requires stem cell support for the patient to survive.

Reduced intensity
This type is very myeloablative  but not necessarily completely. It should be used with stem cell support but it is not always required.

Non-myeloablative
This type does not require stem cell support, though it may still be used.

Here is a research paper that discusses these types of conditioning regimens in detail.

Defining the intensity of conditioning regimens: Working defintions

 

The basic procedure is the same as for all three. The primary difference is the type of drugs used and the doses.  More and more studies are showing that you don't need to give a myeloablative dose of chemotherapy because the donors immune system does a lot of the work killing the lymphoma. This is the Graft versus Lymphoma effect which is part of the GVHD discussed above. It is the "good" part of the GVHD. Therefore lower (safer) doses of chemotherapy is all that is needed, which drastically lowers the mortality rate, down to about 5-10% and still provides the potential for a cure.

 

Autologous 

In this transplant the patient donates their own stem cells/marrow. You might think this sounds strange since the patient already has cancer. However there are two characteristics of NHL that are important to understand. First the patient who has NHL has cancer of the white blood cells that circulate in the lymphatic system. Therefore very few if any cancer cells are in the blood. Second, the aphaeresis procedure collects only stem cells not white blood cells. In theory there should not be any risk of collecting any cancer cells, but unfortunately theory and fact don't quite match. 

The fact is that we have not perfected the art of separating the stem cells from the blood during the aphaeresis procedure so some other blood products will be collected. And although NHL does not normally circulate in the blood there are always a few roaming cancer cells in the blood. This means that there is a pretty good risk of getting some cancer cells in the stem cell harvest. Many cancer centres are experimenting with various techniques to eliminate this problem. There are some mechanical filtering systems in use in which the harvest is run through a machine which is able to detect and eliminate the cancer cells. However one of the more promising techniques for "purging" the harvest is to use monoclonal antibodies such as Rituxan to purge the patient before the harvest is collected.

There is no risk of Graft vs Host Disease (GVHD) with this type of transplant since the patient is only getting their own stem cells. For this reason the risk of death is far lower (only 2%-5%).

 

Syngeneic

There is also a third type of transplant which you might think of a a combination of the two mentioned above. The syngeneic transplant is a transplant where the donor and patient are identical twins. Obviously this type of transplant is not very common because NHL alone is uncommon enough, but someone who has an identical twin to get it would be even less common. The advantage to this type of transplant is that the identical twin is 100% guaranteed to match so there is no chance of Graft Versus Host Disease. The disadvantage is that since there is no GVHD there is also no GVLE (graft versus lymphoma effect). GVHD and GVLE are actually the same thing, it is just a matter of degree. You must keep in mind that in a typical allogeneic transplant, the donated stem cells recognized the patient as being "different" and they attempt to attack the patient. This is GVHD and it can kill the patient if it gets out of hand. While it is risky for the patient it is necessary because those same stem cells will recognize any remaining cancer cells as VERY different and attack them even more than normal cells. Graft versus Lymphoma Effect (GVLE) is referring to this phenomenon where the donated cells attack any remaining cancer cells and with some luck all the cancer cells, without attacking too many normal cells and killing the patient.

With an identical twin as the donor neither phenomenon can happen. The donated stem cells are identical to the original ones the patient had, and both of them will fail to recognize the cancer cells as bad bad cells that should be killed. Luckily the donor cells also will not try to kill the patient so the risk of GVHD is eliminated. The reason for doing this type of transplant is that it means you can still give the patient extremely high doses of chemotherapy to kill all the cancer, and then rescue them with brand new stem cells that are guaranteed to match their blood type and also guaranteed not to be contaminated with any residual cancer cells.

 

Trivia

Just in case you are interested in trivia, SCT is a really shortened form of what the procedure's proper name is. The proper name is "Peripheral Blood Stem Cell Transplant" or PBSCT. This name reflects the fact that the stem cell transplant came from the peripheral blood and not the bone marrow.

But even that is a short form. A really really formal long name is:
High Dose Therapy with Peripheral Blood Stem Cell Rescue (HDT PBSCR). You will almost never come across that name since it is so formal that no one would use it. But it is far more accurate in describing the procedure than SCT is. The first part HDT is pretty easy to understand. You get a really really big dose of Chemotherapy. The second part PBSCR describes the fact that you are getting Peripheral Blood Stem Cells. The final letter R is, from a medical point of view more accurate. In the situation of an Autologous transplant you are not getting a transplant at all. After all those are your own stem cells. What you are really getting is a "rescue" from death by getting an infusion of your own healthy stem cells.  If the procedure is an allogeneic one then the word "transplant" would be appropriate

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