Few facts about Bone Marrow (or stem cell)Transplantation.

  • What is a bone marrow and what does it do?

The bone marrow is a small space inside most of the bones, where all the blood cells are produced. There are three types of blood cells namely red cells, white cells and platelets. The bone marrow is a factory which produces these cells. Millions of cells are produced every day to replace the cells lost in the circulation. All these cells are produced from a single ancestor cell called “stem cells”. In other words, the so called ‘stem cell’ when activated, can produce millions of red cells, white cells and platelets. The function of red cell is to carry oxygen. Blood is red in color as these red cells are abundantly seen than any other cells. White cells fight against infections and platelets are necessary to arrest bleeding wherever, there is an injury to blood vessel.

  • How are the stem cells collected?

These stem cells can be collected in two ways. Since they are present in large numbers in the marrow, they can be collected by ‘tapping’ the marrow. This is done by making repeated punctures in the marrow space usually in the hip bones and collecting the sample. This is done under anaesthesia. However, now- days, there is no need to ‘tap’ the marrow. Instead, there are special machines which can recognize these cells. Since these cells also circulate in the blood, the blood can be concentrated and these cells can be separated. So, a donor is connected to this machine which draws blood from the donor, separates only the stem cells and returns the blood back to the donor. By this method, a donor is just connected with one or two needles with the machine and the procedure is just like blood donation. It takes only 2-3 hours and the donor loses nothing as the blood is sent back to him at the end of the procedure. The stem cells separated from the donor by the machine are very small cells, not visible to the naked eye and it is mixed with small amounts of plasma.

So, if the stem cells are collected from the bone marrow directly, it is called bone marrow transplantation. If they are collected from the blood while they are circulating and then used it is called as stem cell transplantation. More of stem cell transplantations are only done now-a-days, as it is easy to collect stem cells from the peripheral blood.

  • How are these cells preserved?

So, unlike other transplantation, this doesn’t involve any surgery and the donor does not lose anything as the stem cells can regenerate fast in the marrow. These cells collected from the donor along with the plasma will be stored in a deep freezer in a special plastic bag. The temperature is maintained at very low levels, so that these cells live for many years. A chemical substance called DMSO is added to preserve these cells in frozen temperature. The process of storing is called cryopreservation.

  • How are the cells transferred to the patient?

Again, giving these cells to the patient (recipient) is also a very simple procedure.  High dose chemotherapy and/or immunosuppression is given to the patient. This is to kill all the cells in the bone marrow and also make the residual lymphocytes to a non-fuctional state so that they won’t fight against the donor stem cells later on.This is called as ‘conditioning’, which takes place over 5-10 days. After that, just like blood transfusion, these cells are infused into the patient within few minutes. These stem cells go and lodge in the marrow space and start producing new cells which comes out from 2- 5 weeks time. The white cells come out first, red cells later and then the platelets.

  • What is the basic principle of stem cell transplantation?

            The basic principle is to wipe out the patient’s own marrow cells and allow the marrow to form new cells with different type of stem cells infused from the donor. This can be achieved by two ways and they are called as myeloablative and non-myeloablative transplants. In myeloablative, using high dose chemotherapy, the marrow cells are killed and so a vancant space is created for the new stem cells to lodge there and grow. In addition to that immunosuppressive therapy is also given to prevent any residual cells in the patient from rejecting the donor cells. The very high dose chemotherapy also kills residual leukemic cells, which was not possible with prior therapies.

            In non-myeloablative transplants, instead of high dose chemotherapy, patient is given high dose immunosuppression only. So all the patients cells do not die. But they cannot perform proper function. This will allow donor cells to take over slowly and completely over a period of time, say 1-2 months. The major advantage of this form of transplant is that since the chemotherapy  load is low, this can be given easily in older patients as well and the toxicity due to chemotherapy is very less. The only disadvantage is since it takes few months for the new cells to take over completely, this is useful only in  low grade malignancies and also in patients who do not need immediate control of the disease. This is also an excellent option for patients with non-malignant conditions like immune deficiency or aplastic anemia (bone marrow failure) wherein there is no need to completely eliminate the patient’s cells immediately.

  • What are the diseases in which this transplantation is useful?

There are various diseases where this ‘bone marrow transplantation’ is indicated. In cancers such as blood cancers and lymphoma, the treatment is directed towards eradicating the disease with chemotherapy. There is a limit to the dose which can be administered as they are toxic to normal cells in the bone marrow. So, in refractory blood cancers and lymphoma one has to give very high doses of chemotherapy. The high doses are given to entirely eradicate the blood cancer cells, which will eradicate the normal stem cells also. After that, the stem cells from the donor are infused into the patient, which will find its home (bone marrow) and will start producing normal cells. In addition to these cancers, which need high dose chemotherapy, there are lots of other conditions which will require this stem cell transplantation. As the bone marrow can malfunction due to various reasons, the transplantation can be used in those conditions to correct the marrow function. This is done by eliminating the abnormal marrow cells by giving chemotherapy and then replacing them normal stem cells taken from some other donors. To quote a few examples, a red cell disorder called thalassemia requires blood transfusion every month throughout life time as the marrow cannot produce normal red cells. And if the white cells malfunction, they are called as immune deficiency disorders, wherein the individual suffers from severe infections, throughout life, and in severe forms usually dies early in life unless the bone marrow cells are replaced by doing transplantation. In general, stem cell transplantation is useful in many marrow diseases, but only if the preliminary therapy is not working or feasible.

 

  • How is the donor selected?

Like all other transplantation, a tissue matching should be necessary before proceeding with transplantation. This is called as ‘HLA typing’. And the matching should be perfect in at least in 6 major subtypes. But unlike other transplantation, a blood group matching is not necessary.  Since a complete match is necessary, normally only brothers and sisters are suitable candidates, as they share common tissue types from the parents. But still, the chances of getting a perfect match are only 1 in 4. So, it is often difficult to get a perfect match and it is especially difficult in case of small families. This difficulty is overcome by finding the same tissue type from out side the family members. It is possible in two ways. In Western countries, just like the blood bank maintain the list of donors, the bone marrow registry maintains the list of thousands of tissue types of various people. And if one of the tissue type matches with the patient, the donor is called on, his stem cells are separated in a few hours and transported to where the patient lives and is used for stem cell transplantation. This is called unrelated transplant. The other method is searching suitable matches from the ‘cord blood banks’. The cord blood obtained from the new born babies is a rich source of stem cells and these cells can be tissue typed and stored for many years for future use. This is now available in India for people who do not have tissue matching from brothers or sisters.

Since the stem cells are collected from the blood without any operation, this can be done in even in a child or older persons without much problems. In very young patients, the machine has to be initially primed with matched blood to avoid any circulatory compromise.

 

  • Does the patient have to take immunosuppressive drugs life long?

            No, unlike other transplant, the immunosuppression can be stopped after few months, if there is no evidence of graft vs. host disease. They can lead a normal life provided everything goes well. But patients with acute or chronic graft vs. host disease may have to continue immunosuppression for many years.

  • Can a patient’s own marrow cells be used?

            Yes, but only in certain conditions. In diseases such as lymphoma, where this is commonly used, the patients own stem cells are collected either from the bone marrow or from the blood by connecting to the machine. And this is usually done, when the disease under maximum control. The stem cells thus collected are stored. The patient then receives high dose chemotherapy which kills all the normal cells and also the residual lymphoma cells after which his own marrow is infused. This type of transplantation is called autologous stem cell transplantation, whereas the conventional method of infusing cells from some other donors is called allogenic stem cell transplantation. This type of autologous transplantation may not work properly in aggressive blood cancers like leukemia. But there are limited indications.

  • What are the complications of stem cell transplantation?

            Stem cell transplantation (allogenic) involves transfusion of cells taken from the donor who has a perfect tissue match. However, in practice what is being observed is, in spite of the perfect match, there are numerous minor antigen mismatches which can cause the donor stem cells to recognize the patients’ body cells as foreign. So after infusion, they cause damaging the patients’ body cells which are rapidly proliferating such as intestinal, liver and skin cells. This can cause serious problems and called as graft versus host disease or GvHD.  This is one of the dreaded complications of allogenic transplants, accounting for majority of the post transplant morbidity and mortality. (morbidity –Defective performance status of a patient due to malfunction of organs. Mortality-death) The other serious problems are infections. They can be in any form, but the most dreaded one is the cytomegalovirus (CMV) infection which is normally dormant in most of us, but can get activated after transplants due to heavy immunosuppression. So, since allogenic transplants pose a serious threat to life, these are performed only when the disease itself poses a serious risk of death and it is not curable by other means.

            In the long term, chronic form of graft vs. host disease can affect any organ, mimicking an auto-immune disease. Depending on the organ affected, this can also cause serious morbidity.

            In addition various drugs given for treatment of these complications may also reduce immunity and may cause damage to any organs.

            In autologous transplants (which means transfusing stem cells from the patient’s own)most of these complications are not seen except the toxicity associated with the drugs used in conditioning. However autologous transplants can be of use only in limited situations.

  • What are the advantages of transplantation?

            Even though the allogenic transplants pose serious threat to life due to GvHD and infections, they are potentially powerful tools to cure serious blood disorders. They act by two ways. The high dose chemotherapy given prior to the transplants help in eradicating the disease. And these stem cells when infused recognize the residual cancer cells if any as foreign cells, and eliminate them just like any white cells remove foreign bacteria. And this is called graft vs. leukemia effect and this is the major reason for the effective cure rates obtained with these types of transplants where chemotherapy or radiotherapy alone is not helpful.

  • Can I store my own  (future) baby’s cord blood?

            Yes, of course. It will be useful if one of the other siblings (like brothers or sisters) need them in immediate future, for conditions mentioned above. Also, it can be useful to any third party patient living elsewhere, if the tissue typing matches with those of yours baby. This cord blood collected at the time of birth can be stored for many years, but needs special processing and storage conditions. But remember, that these cells are may not be useful for the same baby, in case of leukemia or high grade lymphoma as the indications for autologous transplants in leukemia and high grade lymphomas are limited. And of course, you can’t use the same baby’s cord blood, if the baby is later known to have immune deficiency or other metabolic disorders requiring transplantation. So when you decide to store your baby’s cord blood, you have to bear in mind that it will be useful for some third party patients more often, rather than for your own children.

 

Department of Hemato oncology,

Amended on Dec 14th, 2014 @VNCC, GKNM by Dr Suthanthira kannan,

Amended on 2nd Nov, 2016 @ Coimbatore Kidney centre by Dr Suthanthira Kannan

 

 
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