Bone Marrow Transplant

Bone marrow transplant is mostly done in the case of bone marrow destruction or depletion due to some chronic diseases. Some of these diseases are:

• Leukaemia: A type of blood cancer.
• Lymphoma: Cancer of infection-fighting cells in the body.
• Acute lymphocytic leukaemia (ALL): A type of cancer of the blood and bone marrow. ALL is the most common type of cancer in children. 
• Chronic lymphocytic leukaemia: Cancer that affects white blood cells called lymphocytes. 
• Multiple myeloma: Cancer of the white blood cells. It is a condition in which cancerous cells displace healthy blood cells in the bone marrow.
• Aplastic anaemia: A condition in which the bone marrow can’t make enough new blood cells.
• Primary immunodeficiency: A birth disorder that affects the immune system and makes the person more prone to getting infections.
• Hemoglobinopathies: A group of genetic disorders that affect red blood cells, including sickle cell disease, where the red blood cells are unable to carry oxygen to every part of the body.
• Myelodysplastic syndrome: A set of disorders in which the body produces abnormal blood cells that die prematurely in the bone marrow rather than developing normally.
• POEMS syndrome: POEMS stands for Polyneuropathy - pain in different parts of the body; Organomegaly - enlargement of organs; Endocrinopathy - a disease of endocrine glands like the thyroid gland; Monoclonal protein - abnormal protein formed in the bone marrow; and Skin changes.
• Amyloidosis: A rare disease in which an abnormal protein is made in your bone marrow and builds up in your organs and tissues.

Bone marrow transplant can be done in two ways. One, the bone marrow is taken from the patient herself, which is medically known as autologous bone marrow transplant. Two, the bone marrow is donated by a healthy individual, which is medically known as allogeneic bone marrow transplant.

Autologous stem cell transplant involves using the remaining good stem cells in the patient’s body to generate new cells. This type of transplant is often used to treat blood cancers such as Hodgkin lymphoma, non-Hodgkin lymphoma and myeloma.

The procedure involves:

• Administration of certain drugs, like mozobil, into the body which increase the production of stem cells and also allow their movement from the bone marrow into the bloodstream.
• Healthy stem cells are collected - typically from the blood and sometimes from the bone marrow. The blood is drawn through the veins of the patient’s arm whereas the bone marrow is removed either from the spine or from the pelvic bone.
• The patient’s blood is passed through a machine that processes the stem cells. Those stem cells are then frozen and the rest of the blood is put back into the patient’s veins. The stem cells that are removed are kept frozen until they can be transplanted again.
• Chemotherapy: after the doctors have taken out healthy stem cells, and put the blood back in the patient’s body, they give the patient high doses of chemotherapy (either with or without radiation therapy), to kill the remaining cancer cells in the body.
• After the chemotherapy, the frozen stem cells are re-infused into the patient’s body. If everything goes well, the stem cells then move to the bone marrow and start producing new blood cells.

The benefits of this type of transplant are:

• The chances of failure or rejection of the graft (received stem cells) are very slim, as the procedure uses the patient’s own stem cells.
• There is no chance of getting graft-versus-host disease (GVHD). GVHD is a disease where the donated bone marrow views the recipient’s body as foreign, and the donated bone marrow starts attacking the body.

Tandem Autologous Transplant

There is one other kind of autologous transplant, medically known as a tandem autologous transplant. It involves stem cell infusion into the body in two parts. 

• All the stem cells are collected from the patient before the chemotherapy. After the first-high dose chemotherapy, half of these stem cells are infused into the patient’s body.
• The second course of high-dose chemotherapy is given after several weeks or months. After the second course, the other half of the healthy stem cells are infused into the body.

The allogeneic stem cell transplant involves taking stem cells or bone marrow from a healthy individual and infusing it into the patient’s body to generate new blood cells.

The procedure involves:

• Collection of stem cells, mostly from the blood and sometimes from the bone marrow of the donor. The blood is drawn through the veins of the donor’s arm whereas the bone marrow is removed either from the spine or from the pelvic bone. 
• The patient is given high-dose chemotherapy, either with or without radiation therapy, to kill the remaining cancer cells in the body and also to weaken the patient’s immune system (to reduce the chances of the patient’s body rejecting the graft containing donor stem cells).
• Once chemotherapy is completed, the donated stem cells are infused in the patient’s body through the veins. These donated stem cells then rush to the bone marrow to start the production of new blood cells.

The benefit of this type of transplant is that after the donated cells start working in the patient’s body, they create a new immune system. The donated cells produce white blood cells that attack any remaining cancer cells in the patient’s body. This is called the graft-versus-tumour effect.

Different organisations have different criteria for bone marrow donation. As per the Marrow Donor Registry India, the basic criteria for registering as a bone marrow donor are:

• The person must be 18-50 years old.
• He/she should be free from major heart, liver and kidney diseases.
• The donor must not be overweight.
• The donor should not have cancer, diabetes or a chronic incurable ailment like HIV/AIDS.

After a person registers as a bone marrow donor, several tests are done to make sure that he/she is eligible for donation. Tests done for bone marrow donor eligibility include:

• Marrow Donor Registry India (MDRI) explains that prior to bone marrow donation, HLA Typing of the patient and the donor is done. HLA stands for Human leukocyte antigen, which is a protein found on the surface of a cell - it helps the body’s immune system recognise which cells belong to it and which do not. HLA typing of donor and recipient should match for a transplant to happen.
• A person must have at least six types of HLA, two HLA-A, two HLA-B and two HLA-DR, for registering with MDRI as a donor.
• It takes one to two weeks for the typing results to come.
• Once a person is registered as a donor, he/she is contacted if a preliminary match is found and further tests are arranged.
• If a compatible match is found, special counsellors talk to the donor about the stem cell donation process in detail. The donor also receives a thorough medical examination.
• The donor still has a choice, if he/she wants to be a stem cell donor or not.

After all the medical and legal documentation, stem cells are collected from the donor by peripheral blood stem cell collection (PBSC) using an apheresis machine. This involves taking stem cells from the blood circulating in the body only. Around 90% of the donations are done by this method.

Stem cells collected through the blood

• A medical practitioner will draw blood from the donor’s arm using an IV (intravenous) line. Next, this blood will flow to a machine that spins at high speed and separates the different components of the blood into layers based on the weight of the different cells.
• A professional will collect the stem cell layer, before pumping the remaining blood back into the donor’s body via the other arm by setting up another IV tubing.
• The whole procedure takes four to six hours for each collection.

Stem cells collected from the hip

In the remaining 10% of cases, marrow cells are collected from the backside of the pelvic bone. Donors are given general anaesthesia to numb the pain during marrow extraction. This is a one to two hour procedure.

There are many reports of donors experiencing little or no pain and discomfort and going back to work the following day.

Within a week of donating, most donors are able to return to work and resume their usual activities.

Usually, a person who has undergone bone marrow transplant has to stay in the hospital for at least four weeks after the transplant, as the new stem cells typically take 14-28 days to start working in the patient’s body. During this time, the patient might need a blood transfusion or antibiotics through the veins.

This is also a crucial time as a patient who has received an allogeneic stem cell transplant (donor stem cells) may develop graft-versus-host disease. So, to administer the medications and prevent such complications, the patient needs to stay in a hospital for 40-50 days at least.

Even after discharge from the hospital, the patient should keep these things in mind:

• Since the patient's immune system is immature for the first year following bone marrow transplant, the patient must follow the guidelines given by the doctor for preventing infections. 
• Patients must keep their follow-up appointments with their doctor for at least one year after the transplant.
• Patients must tell the doctor about any physical difficulties they might be facing after the transplant.
• For the first three months after the transplant, patients are usually advised to eat small frequent meals and avoid spicy, oily and raw food items.
• The food items that a patient should include in their diet are high-nutrient liquids like juices or milk, nutrient-dense, high-calorie foods like pasteurized cheese, ice-creams, avocados, eggs, peanut butter, and fruits.
• Patients must not indulge in any vigorous activity or exercises, as the body may not have much endurance.
• Patients who feel weak or dizzy, have shortness of breath, have a bad case of nausea or have a platelet count equal to or less than 10,000 microlitre (a millionth of a litre) should not exercise at all.
• All patients must check with their doctor before they start any form of exercise.

The side-effects of bone marrow infusion are similar to those seen in a blood transfusion, which includes allergic responses such as fever, chills, urticaria (skin rashes) and shortness of breath.

The most common complications associated with the chemotherapy done before bone marrow transplant are:

• Infections
• Bleeding
• Anaemia 
• Fatigue
• Mucositis (infection and bleeding in the oral cavity)
• Esophagitis (infection and bleeding in the oesophagus)
• Nausea and vomiting 
• Diarrhoea 
• Hemorrhagic cystitis (inflammation of the bladder)
• Renal dysfunction
• Veno-occlusive disease (blood clots and obstructed blood flow in the liver)
• Fluid and electrolyte imbalances
• Neurotoxicities (damage to the nervous system of the body)
• Cardiac toxicities (damage to the heart due to drugs of chemotherapy) 
• Interstitial pneumonia (deadly inflammation of the alveoli of the lungs)

When the donated stem cells start to grow, usually after 14-28 days of the transplant, and make healthy blood cells in the patient’s body, that stage is called engraftment.

The complications related to engraftment could be:

• Graft-versus-host disease (GVHD)
• Graft rejection
• Graft failure
• Disease relapse