Stem cell transplantation commonly known to people as Bone marrow transplantation is an important modality of therapy to cure incurable cancers and other blood related diseases.
I would use the term BMT to represent either Stem cell transplant or bone marrow transplant further in write up.
BMT came to light in early 1960s though it did not materialize well till late 1980s. By then two important events happened in science; firstly, identification of HLA antigens which are like blood groups present on every cell in body which needs to be matched between recipient and donor; and effective strategies to prevent donor cells becoming too much strong and kill the weak and diseased recipient.
Both the discoveries won Nobel prize, Dr. Jean Dausset for HLA typing and Dr. Donald Thomas for pioneering BMT for saving mankind from incurable diseases.
How is the procedure done?
Normally the blood is formed in bone marrow, that is the juicy part of the bone. Majority of blood cancers begin in this space. It is the home for blood cancer (Leukemia) cells to reside and cause trouble if left to stay there. These are resistant to conventional chemotherapies which are given for leukemia.
Majority of other diseases like Aplastic anemia, Thalassemia, Myeloma, Immuno Deficiency disorders do start in bone marrow. All these diseases can be cured with a bone marrow transplant.
The procedure in simple words follow like this,
1. We match between patient and potential donors using DNA PCR based HLA typing.
2. Once a match is identified, we evaluate the donor for fitness to donate and also evaluate for diseases donor can transmit to patient.
3. We evaluate patient for fitness to choose the right therapeutic strategies.
4. Once we have both evaluations in hand, we start with giving high dose chemotherapy or radiation to patients which will kill 99.9% of blood forming cells in bone marrow (which will have cancer cells or diseased cells), which typically lasts for 4-5 days. We choose doses carefully to make sure that we do not damage the other organs of body.
5. In the mean time we collect normal stem cells (blood forming cells) from donor using a special technique called apheresis using a specialized equipment called Therapeutic apheresis machine.
6. Once we have donor cells in hand we administer the donor cells through the large venous access (Central line or Hickman line) to patient.
7. These stem cells reach bone marrow which is their home and sit there and prepare towards forming new blood cells.
8. In about 10-20 days depending on different types of transplant these stem cells produce normal hemoglobin, white cells and platelets.
Major complications that can arise,
Though the procedure looks pretty simple, it is not so in reality.
One of the most beautiful part of transplant is the same blood forming cells also are the ones which form immune related cells.
The strong immunity from donor cells compared to recipient; though is very helpful in fighting infections, cancer also can cause trouble.
Main problem which happens with strong donor cells include Graft Versus Host Disease (GVHD), in which donor cells will start to fight against recipient cells. It often affects intestines, skin and liver. This can be life threatening if not prevented or treated early.
Other important adverse event is infection. Patients will have no immune system for nearly 10-20 days till donor cells start becoming active and also immune system will not mature completely till 3 -12 months after transplant depending on drugs patient is on. It is vital for patients to be cared closely during this episode. They need clean air, water and food. Cross infection between patient and health care staff, neighboring patients need to prevented with utmost precision. Infections are the commonest cause of mortality in patients undergoing transplantation. They need prophylaxis for preventing infection with antibiotics, antifungals and antivirals etc.
Other side effects include problems in Liver, kidney, brain can happen though are not frequent.
Coming to different type of transplantations include,
1. Autologous: where once own stem cells are used.
2. Allogeneic: Stem cells from a donor is used
a. Related
Siblings: Matched
Siblings or other family: partially matched
b. Unrelated
3. Cord: Stem cells from cord blood bank is used.
Understanding some of the diseases that can be cured (managed) only with transplantation
Autologous transplantation : Relapse Hodgkin's Lymphoma, Multiple Myeloma, Neuroblastoma
Relapse Non-Hodgkin's Lymphoma, Plasma cell disorders, POEMS syndrome, Primary amyloidosis
Allogeneic: Cancers - Acute leukemia, Acute Myeloid Leukemia, Chronic Leukemia
Myelodysplastic Syndromes
Allogeneic: Non Cancers - Aplastic Anemia, Hemoglobinopathies (Thalassemia etc), Bone Marrow Failure Syndromes, Immune Deficiencies, Inborn errors of metabolism, Adrenoleukodystrophy, Platelet function disorders
Few examples on how transplant can change patient’s life,
Thalassemia: It is a type of Hemoglobinopathy disorder which prevents normal hemoglobin from being produced. Child from the age of 6 months after birth will need repeated transfusions monthly once to twice to live. The child develops complications because of repeated transfusions, hardly only 10-20% would see second decade of their life. If we transplant these children at right time (usually < 3 years of age) almost 85-90% would become disease free and live normal life as others which is like a black and white difference in one’s life.
Acute myeloid leukemia: It is one of the commonest life threatening blood cancers affecting adults and old people. Without transplant only a handful of patients can be cured. If we do transplant almost 60% of patients can be cured.
Aplastic Anemia: It is a type of disease in which bone marrow stops producing any blood cells. They will have very low hemoglobin WBC and platelets leading them to die either with infections of bleeding. Medical treatment is hardly effective in children. If we transplant them almost 75-80% of children and 60% of adult patients can be cured.
Overall to conclude BMT is a complex procedure which requires,
1. Complex infrastructure: To support patients during their most vulnerable defense less phase of no immunity.
2. Complex lab support: To assess donor and patients sample and search for infections and cancers when they try to initiate trouble.
3. Competent team: Team not only includes a competent transplant physician but competent nurses, housekeeping, engineers, pharmacists and auxiliary staff.
4. Supportive management: Unrestricted support to compensate the people and support the infrastructure which require constant efforts to improve patient outcome.
5. Supportive departments: Nephrology, ICU, Gastroenterology, Neurology etc when patients develop complications.