The blood and bone marrow transplantation center at Apollo Hospitals, India has performed over 150 transplantations with an excellent success rate. Apollo Hospitals, India is also a trusted name in BMT for international patients, as the hospital has not just a highly qualified BMT team, but also very stringent infection control norms which are critical for BMT patients.

What is Bone Marrow Transplantation?

Bone Marrow Transplantation is a form of intensive treatment used to treat certain cancers like leukaemias, lymphomas and some non-cancerous diseases like thalassaemia.

Bone marrow is found inside our bones, and is the ‘factory’ that makes blood. It is responsible for producing white blood cells (to protect against infection), red blood cells (to carry oxygen around the body) and platelets (to prevent bleeding). Stem cells are blood cells at their earliest stage of development in the bone marrow, before they have become committed to developing into white cells, red cells or platelets. It is these ‘mother’ cells which are the key factors in transplantation.

What are the different types of bone marrow or stem cell transplantation?

There are two main types of transplants – Autologous and Allogenic.

Autologous Transplants: This means that the bone marrow or stem cells used for the transplant are one’s own. A little bit of the patient’s bone marrow or stem cells is taken and stored before high dose treatment. When the treatment is over, the bone marrow or stem cells are given back through a vein.

Allogeneic Transplants: In this type of transplant, bone marrow donated by someone else is used. It is essential that the donor’s tissue matches. The most suitable donor is usually a close relative, most commonly a brother or sister. It is possible to get a good match from an unrelated donor, but this facility does not exist in India.

What is the basic process?

There are three main steps in the transplantation process -

The first step is the collection of the bone marrow or stem cells (the harvest) from the donor. We now know that the umbilical cord blood is also a rich source of stem cells.

The second step is to completely destroy the existing bone marrow and thereby help the patient receive the new stem cells.

The third step is to infuse the bone marrow or the stem cells through the intravenous route, like a blood transfusion. There may be no signs of a new bone marrow growing for two to three weeks, and occasionally it may be a few months before the new bone marrow produces all the components of the blood adequately.

How does one prepare for transplantation?

Having a transplant can be very demanding, physically and emotionally, and the family and friends too, may find this very stressful. It may help if patients can talk about their fears and concerns.

It is important to understand why one is having the transplant and what the actual processes will be, so that the patient can make practical arrangements and also prepare himself or herself mentally. It is a good idea to discuss the entire process with the doctors and nurses involved, before the patient goes into hospital.

Here are some questions one may like to ask:

• What are the benefits of the treatment?
• What are the risks of the treatment?
• How will the transplant affect the way I live?
• Will I be able to have children after a transplant?
• How long will it be before I can start leading a normal life again?
• What are the other treatments available to me?
• Can one predict how the disease will progress?
• Who can visit me?
• Will my treatment make me feel too unwell to see people?
• Is there a television in the room?
• Is there a telephone link in the room?
• Can I bring in my own clothes?
• What do you suggest that I bring to the hospital to make my stay more comfortable?
• Where can the attenders stay?

Many people find it very helpful to discuss the procedure with someone who has already had a transplantation. The doctor should be able to arrange for this.

Being fully informed and prepared will help to make the transplant process easier for the patient and the family.

Who can be a donor for an Allogenic transplant?

Matching bone marrow is done by blood tests alone. It is not necessary to test the donors bone marrow at this stage.

It is usual to start by testing the brothers and sisters, as they are likely to provide the best match; parents are not usually good matches.

The donor should be in good health. He or she will be given a thorough medical checkup to make sure that there will be no risk to his or her own health from the procedure.

Collecting bone marrow

About a week or two before the bone marrow harvest is done, the patient (or the donor, for an Allogenic transplantation) may have 1 to 2 units of blood withdrawn. This will be given back during the bone marrow harvest.

The harvest itself is carried out under general anaesthesia, so one will feel nothing. It involves the removal of some marrow from inside the bones at the back and front of the pelvis (the hip bones).

The patient or donor will have to stay in hospital overnight to recover fully from the general anaesthesia. Usually it feels sore for a few days and mild painkillers may be required. These will be administered by the nurses or doctors.

How are the stem cells collected?

Stem cell harvesting is done following a course of daily injections of a growth factor. This procedure takes about 3 hours. The patient will be made to lie down on a couch and a transfusion will be put into the vein of each arm. Blood will be collected from one arm, into a machine called a centrifuge, which spins it to separate out the stem cells. These are collected, and the remaining blood is returned through the IV in the other arm. The stem cells can even be frozen.

What is Umbilical Cord Blood Transplantation?

Many children and young adults with serious blood diseases, such as leukaemia, need a bone marrow transplantation to give them a chance to live. Unfortunately a marrow donor cannot always be found. Sometimes searching for a donor takes so long that the patient dies before a compatible donor is available.

However, now a new source of blood forming stem cells has been found – Umbilical Cord Blood.

This is the blood that is left behind in the placenta and the umbilical cord after the delivery of a baby. Cord blood is rich in stem cells and can be used instead of bone marrow for transplantation.

The stem cell in the cord blood is of high quality and very potent in producing blood cells. Cord blood transplants appear to cause less serious immunological side effects. The ‘matching’ between donor and recipient appears to be less critical. This means that the chance of finding suitable cord blood for transplantation is much greater than that of bone marrow.

What is Conditioning Treatment?

The patient will normally be admitted into a single room for protection against the risk of infection. This is especially important when the blood count is at its lowest – about two to four weeks after the transplantation.

While the patient is in hospital, regular doses of drugs and many blood tests will be required, over several weeks. To save the patient having numerous individual injections, a tube known as a central line is inserted. This may be done under local or general anaesthesia.

The treatment lasts 4 to 5 days in total and consists of high doses of chemotherapy or sometimes radiotherapy.

Transplanting the bone marrow or stem cells or cord blood

A day or more after the intensive chemotherapy is finished the patient will start to feel slightly better. The patient’s own, or the donated bone marrow or stem cells or cord blood will then be given through the central line into a vein. They will find their way back via the bloodstream to the bones, where they will start to grow and develop into mature blood cells. It will be at least two or tree weeks before some of the ‘new’ blood cells are released into the blood stream, and it may be up to six weeks before one can leave the hospital. The patient will be very vulnerable to infection until the body once again starts producing sufficient numbers of blood cells to defend the individual.

What are the risks of bone marrow and stem cell transplantation?

The main risk occurs during the period when the marrow is recovering and is not yet able to produce normal blood cells. During this time there is a risk of potentially life-threatening infection and bleeding.

Allogenic transplantation carries a higher risk, because of the possibility of graft versus host reactions. Very occasionally too, the graft (donated marrow) is not accepted (graft failure), and it may be necessary to have more bone marrow donated by the same donor, or resort to ‘autologous rescue’, which is using some of one’s own bone marrow which has been stored as a precaution.

Autologous Transplants using one’s own marrow have a much lower risk, since graft versus host disease does not occur. With a stem cell transplant, the risks are still lower, a the time the marrow takes to recover (during which one is at most risk of infection) is reduced. However, the conditioning procedures for all forms of transplant are equally intensive. The age and state of health are also factors that need to be taken into account as the procedure is lengthy and may make the patient very ill. If the patient is nearer the upper age limit, and if the general health is not good, the patient is more likely to experience complications.

What are the side effects of transplantation?

a) Infection - The number of white blood cells in the body will decrease during treatment, making the patient very susceptible to infection caused by the bacteria that normally live in the body. These bacteria are present on the skin and in the stomach and intestine. In healthy people they are beneficial. However, when the immune system is impaired, as will be the case following high-dose treatment and a transplant, these bacteria may become harmful and cause infection. To prevent this, the patient will be given regular antibiotics and mouthwashes. Great care will also be taken to ensure that the food does not contain harmful bacteria.

Particular attention will be paid to make the room infection-free. The room and its contents will be thoroughly cleaned daily. Only one attender will be allowed in with the patient.

b) Anaemia and low platelet count will need to be treated. About 10-15 donors would be needed for the whole procedure.

c) Eating problems - The patient will probably see a dietician regularly during the transplant, who will prescribe an adequate diet. It is very important that the patient does not lose too much weight, and the nurses in charge will encourage intake of small meals and snacks. If there are eating problems, because of lack of appetite, nausea or a sore mouth, one may need to have nutritional drinks. If even these are difficult due to diarrhea, it may be necessary to give the patient special fluids and central line, which will ensure the necessary nutrition.

d) Graft Versus Host Disease - With an Allogeneic transplantation (a transplant from a donor) there is a possibility that the new cells (the graft) will react against the recipient’s tissue (the host), even when the donor is one’s own brother or sister. This is called Graft Versus Host Disease (sometimes referred to as GVHD). It is usually mild, since one will be prescribed drugs to prevent it occurring. However in some cases, it can become very severe and even life threatening. It can cause diarrhoea, skin rashes and acute or chronic liver damage. The disease can occur up to six months after the transplant.

If graft versus host disease occurs, it does not mean that the transplant has failed. It may even be of benefit, as some of the cells involved in the reaction may also attack any cancer cell that has survived the intensive treatment.

e) Fertility Issues - Unfortunately, for both men and women, infertility is almost always a side effect of the intensive treatment. It may be possible for men to store sperm before they have the treatment, so that it can be used later if they want to have a family. Parents of teenage boys should also be aware of this so that, where possible, sperm can be stored for later years.

Follow-up

For the first two to three months after leaving hospital will need to undergo frequent blood tests to monitor the blood counts. Regular doses of several different drugs to reduce the risk of infection and/or graft versus host disease will be necessary and these will be monitored regularly.

It is essential that the patient takes good care of his/her health during this time. There are a number of possible problems that might occur due to the reduced immunity.

The patient should get in touch with the hospital immediately if he or she experiences any of the following symptoms:

• Feels unwell
• Persistent temperature of over 37.5ºC for more than 2 hours
• Infections e.g. in the skin, teeth, bottom
• Skin rash
• Several diarrhea
• Shortness of breath or breathing difficulties

It is vital that these symptoms are dealt with quickly.

BY the end of the first year, the immune system will probably have returned to normal, and the bone marrow will be manufacturing blood normally. Sometimes this may take a little longer.

How will life be after a transplant?

Diet
For the first few months after a transplant, while the immune system is in the process of returning to normal, it is important to eat a healthy and balanced diet and take care to avoid all possible risk of infection from blood.

This means eating freshly cooked food and avoiding reheated food. Fast foods are best avoided, as are cream cakes and any product that is not entirely fresh. Patients should avoid soft cheeses containing uncooked or, lightly cooked egg.

Socialising
One should avoid crowded places such as cinemas and public transport, until the white blood cells are well within the normal range, in order to avoid infection. 3 to 6 months after the transplant, a patient should be able to resume a full social life. Patients must avoid contact with children who have an infectious disease such as chickenpox or measles.

Going back to work/school/college
When the blood count has returned to normal, a patient should discuss with the doctor whether it is advisable to return to work, school or college. If possible, it would be better to start gradually, by going only part-time to begin with. It would be a good idea to discuss this with the employer, head teacher or tutor and work out a satisfactory way of getting back to a normal routine slowly.

Exercise
Regular gentle walking is a good exercise to keep the muscles reasonably toned until the platelet count has returned to normal. After this, one can start doing regular exercise. It would however be advisable to build up the quantum of exercise gradually.

Holidays and Travel
For the first three to six months following bone marrow transplantation, while a patient still has to visit then hospital regularly and may require blood transfusions, it is inadvisable to travel too far from the transplant centre.

After the first year, when the immune system is usually working well, it should be possible to travel. However, certain types of vaccinations should be avoided, and again it is advisable to discuss travel plans with the transplant doctors.

It is usually helpful to carry a short letter from the doctor outlining the treatment the patient has received and giving a contact telephone number.

Sex
The physical ability to have sex will not be affected by the bone marrow transplantation, and there is no medical reason why one cannot go back to his or her normal sex life after leaving hospital.

Women whose treatment has caused them to have an early menopause may find themselves troubled by menopausal symptoms such as hot flushes, dry skin, dryness of the vagina and loss if libido. Most women can be helped by Hormone Replacement Therapy (HRT) which quickly reverses these symptoms. If the doctor has not already talked to you about HRT, it might be worthwhile raising the subject, to see whether it would be suitable.

Bone marrow transplantation in children

The procedure for transplanting bone marrow in children is the same as those for adults, described earlier in this booklet.

In planning the transplants, doctors will consider very carefully the effects of the intensive preparatory regime to minimize the long-term effects, for example on the child’s growth, development and future fertility.