Bone marrow transplantation

With a better understanding of immune system of the human being and the advent of better medications and technology, more and more patients are being treated with Bone Marrow Transplantation (BMT). White Blood Cells (WBCs) are the key players in our body's immune system and arise from a population of self-perpetuating bone marrow cells called Stem Cells. As these divide and multiply, some of the daughter cells become new Stem Cells while the others develop into different blood cells - red cells, platelets, neutrophils, monocytes or lymphocytes.
In diseases where the patient is unable to produce blood cells, BMT remains the only option.
Bone marrow is a soft jelly type reddish fluid inside some bones that is involved in the production of blood cells. New white and red blood cells are formed only in the marrow of the flat bones such as the ribs, breast-bone, or pelvis in adults.
WHAT IS BMT?Bone Marrow Transplantation (BMT) is a process in which patients' bone marrow is replaced by donor's bone marrow. It is a complex procedure, but it offers hope to patients suffering from many fatal diseases like Beta Thalassaemia Major, Aplastic Anaemia, Chronic Myeloid Leukaemia, Acute Myeloid Leukaemia, various types of blood cancer, solid organ cancer, Multiple Myeloma, Hodgkin's disease, Non-hodgkin's Lymphoma, Immunodeficiency disorders etc.
There are two BMT techniques - autologous and allogenic. In autologous functional bone marrow from the patient is transplanted in place of the dysfunctional one, whereas in allogenic the bone marrow comes from a donor, most often the patient's matched siblings. The patient and his relatives must however, understand that BMT is a complex, high risk treatment which makes huge demands on the patient and their attendants. The decision to go ahead with a bone marrow transplant must be made with the knowledge that it can fail and even prove fatal. However, given the other option that is death, it remains often the only way.
HOW DOES BMT WORK?Bone marrow cells carry distinct identification tags on their surface, known as tissue types. We inherit half of our tissue types from one parent and half from the other.
However, if bone marrow from a person from one set of tissue types is given to a person with a different set, the two systems recognise each other as foreign and fight! If the recipient's immune system gains the upper hand the donor's bone marrow is rejected; if the donor's system wins, then the patient develops a severe inflammation in the skin, liver and gut, known as Graft versus Host Disease (GvHD), which can be fatal.
Because brothers and sisters each inherit tissue types from the same parents, there is a one-in-four chance that a brother and/or sister will have inherited the same tissue types. When using bone marrow from such a brother/sister, the risks of graft rejection or GvHD are low and such transplants are the most successful.
Although unrelated people carry different tissue types, the number of types is not endless, and by chance, two out of 18,000 people will share more or less the same tissue types. Because of good will, it has been possible to set up registries of several hundred thousand people across the world that are willing to donate bone marrow. In this way patients can be matched with unrelated donors whose tissue types are almost as exactly matched as brothers and sisters who share the same tissue types.
FINDING, A DONOR: The best donor for bone marrow transplantation is a matched sibling (brother or sister). This is because such an individual has inherited an identical tissue type to the patient, which allows the bone marrow to be transplanted with a lower risk of any reaction occurring between the recipient and the donor. In the absence of a matched family member, it is difficult to find an unrelated donor because of the unavailability of bone marrow donor registry in Pakistan.
PROCEDURE OF BONE MARROW DONATION: On identifying a suitable donor, he/she will undergo a medical examination. This is carried out to ensure that the volunteer is fit to donate and also to ensure that their donation causes no harm to the patient. The marrow donor undergoes the same stringent tests as a blood donor, including screening for infectious viruses such as Hepatitis and HIV.
Having identified a suitable donor, the patient must also be carefully assessed. It is important to detect infections that may have already damaged the lungs or liver, as problems here reduce the chances of a successful transplant. The patient is then admitted to a sterile environment and his/her bone marrow is destroyed or burned by drugs, or sometimes radiotherapy is also needed along with the drugs.
By wiping out the patient's immune system the risk of rejection of donor's bone marrow is largely prevented, but infection becomes a risk. After few days of this treatment, marrow is taken from the donor via his blood using a computerised machine called "Cell Separator".
It usually takes 4-5 hours and does not involve any general anaesthesia or surgery. This is a painless procedure. General weakness and tiredness is expected for a few days afterwards. Bone marrow cells are replaced quickly in next few days. There is virtually no risk involved for the donor.
The collected bone marrow is then infused into the patient like blood into a vein and then the donor marrow cells find their way to the patient's bone marrow cavity, start multiplying. It will take two to three weeks. During this time the patient produces no blood cells and needs infusions of the platelets. A very careful watch is kept for signs of infection, which is treated very promptly and thoroughly.
Sometimes there is a degree of GvHD when the new marrow cells start appearing. This may required treatment with immunsuppressant drugs. Occasionally the marrow is rejected and the patient's own marrow reappears, and both rejection and GvHD increase the risk of infection. About six weeks after the graft takes place, the patient's new immune system begins to develop, and a little later he/she can go home.
CHEMOTHERAPY: The patient will have a central venous line, often referred to as a Hickman line, which is inserted into a large vein, under a general anaesthetic. Chemotherapy, blood products, drugs including antibiotics, nutrition, hydration, and even the actual bone marrow are all given through this line which is also used for blood sampling. This means that the patient will no longer have to cope with needles.
The line will not affect patient's mobility nor restrict the types of clothing he/she can wear, bath is also allowed. The line is removed under a general anaesthetic once it is no longer needed. This may be any time from approximately 4-12 months after the transplant depending on the condition of the patient.
Once the patient is in hospital, prior to receiving new bone marrow he/she will be given cytotoxic chemotherapy drugs. Chemotherapy is a necessary part of the process in preparing the body to accept new bone marrow. The function of chemotherapy is to destroy the defective bone marrow, including the stem cells. The patient may receive chemotherapy for up to 12 days before receiving the new bone marrow. Unfortunately there are a number of side effects, which cannot be avoided, and which may cause the patient to become extremely unwell.
Common problems associated with chemotherapy therapy are nausea and vomiting, Stomatitis, Mucositis, in abdominal cramps and diarrhoea, bruising and bleeding, loss of appetite, loss of weight, anaemia, hair loss and infections. Chemotherapy may also cause altered taste but this problem will slowly resolve.
BRUISING AND BLEEDING: When platelets are low, symptoms such as nosebleeding are common and patients will also bruise easily. It will be necessary to give platelet transfusions intravenously until the new bone marrow starts to produce its own platelets.
ANAEMIA: Until the new bone marrow starts to produce its own red blood cells, patient will receive regular blood transfusions, to prevent anaemia.
Hair loss: Hair loss gradually occurs, about 7-10 days after the last dose of chemotherapy. Following the transplant, hair does grow back. Occasionally, it will return with a slightly different texture or colour.
Infection: Once the chemotherapy has destroyed the unhealthy bone marrow, the patient will become extremely susceptible to infection until the stem cells in the new bone marrow produce new white blood cells.
PATIENT MONITORING AFTER BONE MARROW TRANSPLANT:
Monitoring for infection: Specially trained nursing staff on the transplant unit will generally observe the patient, including taking his/her temperature and blood pressure throughout the day and night. Regular collection of blood, urine and stool samples is done in an attempt to identify any infection, which needs treatment.
However, it is a crucial measure as any infection in immunocompromised child can lead to a critical situation if undetected and left untreated.
Isolation room: This is a room within the transplant unit, which have filtered air. When the patient is most susceptible to infection, at the end stage of chemotherapy, he/she will be transferred in this room and will remain there for up to three to five weeks,
The patient is transferred into this room to minimise contact with people other than those crucial to his/her care. Restricting social contact helps to minimise the risk of infection being spread to the patient from other people. This period refer as the 'isolation period' and patient's room as an 'isolation room.'
TRANSPLANT DAY: The patient will receive the new bone marrow after the completion of chemotherapy. The bone marrow is given intravenously, into the central line, over approximately two hours and is similar to receiving a blood transfusion. While receiving the bone marrow, the patient will be monitored for any reactions but normally the procedure is straightforward and uneventful.
BONE MARROW RECOVERY: Following the transplant, blood samples will be taken from the patient daily, to show the number of red blood cells, platelets and neutrophils being produced by the stem cells in the new bone marrow.
During the first 2-3 weeks following the transplant, these cells will remain extremely low. As the new bone marrow begins to grow and function and produce blood cells of its own, the levels of red blood cells, platelets and white blood cells in the blood will increase.
At this stage, a blood test is carried out to confirm that the new blood cells are being produced by the donor bone marrow. This test is referred to as 'engraftment studies' and will indicate that the new bone marrow has begun to function.
PATIENT'S RECOVERY: It may take 1-2 years for full immunity to return. Each patient is different and the transplant centre will continue to monitor patients' immunity once the patient has returned home. Depending on the type of transplant that the patient has received, within 3-4 months after the transplant has taken place, he/she may have adequate immunity to allow infection precautions to relax. At 6-8 months post transplant, the patient may have returned to his/her routine life and the acute stage of treatment for most patients and their carers is over.
AFTER THE TRANSPLANT, RESTORATION AND RECOVERY: Discharge from hospital comes after a period of 6-8 weeks, or longer for some patients. This stage of the BMT process places different demands on the BMT patient and the family, although the critical event is over, the recovery is far from complete. Medication, weekly clinic visits, blood tests are all a continued requirement. Patients may feel tired and unwell, may object to continued restrictions and resist taking medication. Difficulties with eating and persistent nausea and vomiting are common for a while after going home.
The risk of infection is still high and the maximisation of a germ-free environment and continued isolation from children and large public groups remain necessary.
Hospital re-admissions may be necessary and this possibility should be prepared for, both practically and psychologically. In fact, family life rarely gets back to normal immediately but rather undergoes yet another reorganisation and presents a new order to adjust to. For the BMT patients these first few months after returning home can be a frustrating time. But they have to fight to defeat death from whose claws he/she has snatch their life.