1. Human Health and Disease
Lecture 10

3. Functions of stem cells

5. Stem cell/bone marrow transplant
It is a procedure that infuses healthy cells, called stem cells, into the body to replace damaged or diseased bone marrow.
A bone marrow transplant may also be used to treat certain types of cancer and blood related genetic disorders.
A bone marrow transplant may be necessary if your bone marrow stops working and doesn't produce enough healthy stem cells.
Bone marrow transplants may use cells from your patient’s body (autologous transplant) or from a donor (allogeneic transplant).

6. Autologous Transplant

7. Allogeniec transplant

8. Why it is done? A bone marrow transplant may help you by:
Safely allowing treatment of patient’s condition with high doses of chemotherapy or radiation in cancer
Providing new stem cells, which can help kill cancer cells directly
Replacing diseased or damaged marrow with new stem cells in genetic disorders

9. Why it is done? Acute leukemia Immune deficiencies
Stem cell transplants can benefit people with a variety of both malignant (cancerous) and nonmalignant (noncancerous) diseases, including:
Acute leukemia
Adrenoleukodystrophy
Aplastic anemia
Bone marrow failure syndromes
Chronic leukemia
Hemoglobinopathies
Hodgkin's lymphoma
Immune deficiencies
Inborn errors of metabolism
Multiple myeloma
Myelodysplastic syndromes
POEMS syndrome
Primary amyloidosis

11. Risks
Complications that can arise with a stem cell transplant include:
Graft-versus-host disease (allogeneic transplant only)
Stem cell (graft) failure
Organ damage
Infections
Cataracts
Infertility
New cancers
Death

12. Graft-versus-host disease: A potential risk when stem cells come from donors
If you receive a transplant that uses stem cells from a donor (allogeneic stem cell transplant), you may be at risk of graft-versus-host disease (GVHD).
This disease happens when the donor stem cells that make up your new immune system see your body's tissues and organs as something foreign and attack them.
GVHD may happen at any time after your transplant.
However, it's more common after your marrow has started to make healthy cells. Many people who have an allogeneic stem cell transplant get GVHD at some point.
The risk of GVHD is a bit greater with unrelated donors, but it can happen to anyone who gets a stem cell transplant from a donor.

13. Types and Symptoms of GVHD
There are two kinds of GVHD: acute and chronic. Acute GVHD usually happens earlier, during the first months after your transplant. It typically affects your skin, digestive tract or liver. Chronic GVHD typically develops later and can affect many organs.
Mouth sores
Abdominal pain
Diarrhea
Nausea
Vomiting
Joint or muscle pain
Shortness of breath
Persistent cough
Vision changes, such as dry eyes
Skin changes, including scarring under the skin
Rash
Yellow tint to your skin or the whites of your eyes (jaundice)
Dry mouth

14. Pre-transplant tests and procedures
A series of tests and procedures are involved to ensure that the patient is eligible for the transplant.
In addition, a surgeon or radiologist will implant a long thin tube (intravenous catheter) into a large vein in the chest or neck.
The catheter, often called a central line, usually remains in place for the duration of the treatment.
The transplant team will use the central line to infuse the transplanted stem cells and other medications and blood products into your body.

15. Collecting stem cells for transplant
If an autologous stem cell transplant is planned, patient undergoes a procedure called apheresis to collect blood stem cells. Before apheresis, he receives daily injections of growth factor to increase stem cell production and move stem cells into his circulating blood so they can be collected.
During apheresis, blood is drawn from a vein and circulated through a machine. The machine separates the blood into different parts, including stem cells. These stem cells are collected and frozen for future use in the transplant. The remaining blood is returned to your body.
If an allogeneic stem cell transplant is planned, he will need a donor. Stem cells are gathered from that person for the transplant. This process is often called a stem cell harvest or bone marrow harvest. Stem cells can come from the donor's blood or bone marrow. The transplant team decides which is better for the patient based on his situation.

16. The conditioning process
After the completion of pre-transplant tests and procedures, the conditioning process begins.
During conditioning, the patient undergoes chemotherapy and possibly radiation to:
Destroy cancer cells if treated for a malignancy
Suppress the immune system
Prepare the bone marrow for the new stem cells
The type of conditioning process depends on a number of factors, including the disease, overall health and the type of transplant planned. The patient may have both chemotherapy and radiation or just one of these treatments as part of the conditioning treatment.

17. Side effects of conditioning process
Nausea and vomiting
Diarrhea
Hair loss
Mouth sores or ulcers
Infection
Bleeding
Infertility or sterility
Anemia
Fatigue
Cataracts
Organ complications, such as heart, liver or lung failure

18. Stem cell transplant procedure
On the day of transplant, called day zero, the patient is given the stem cells through his central line using a process known as infusion.
The transplant infusion is painless and a patient is awake during the procedure.
The transplanted stem cells make their way to the bone marrow, where they begin creating new blood cells.
It can take a few weeks for new blood cells to be produced and for the blood counts to begin recovering.

19. Side effects of DMSO
Bone marrow or blood stem cells that have been frozen and thawed contain a preservative called dimethyl sulfoxide (DMSO) that protects the cells. Just before the transplant, the patient may receive medications to reduce the side effects the preservative may cause. He'll also likely be given IV fluids (hydration) before and after the transplant to help rid the body of the preservative. Side effects of DMSO may include:
Nausea
Fever
Diarrhea
Chills
Hives
Red urine

20. After Stem Cell Transplant
When the new stem cells enter the body, they begin to travel to the bone marrow.
In time, they multiply and begin to make new, healthy blood cells. This is called engraftment. It usually takes several weeks before the number of blood cells in the body starts to return to normal. In some people, it may take longer.
In the days and weeks after the stem cell transplant, the patient will have blood tests and other tests to monitor his condition. He may need medicine to manage complications, such as nausea and diarrhea.
After the stem cell transplant, the patient will remain under close medical care. If he is experiencing infections or other complications, he may need to stay in the hospital for several days or sometimes longer.
Depending on the type of transplant and the risk of complications, he'll need to remain nearby for several weeks to months to allow close monitoring.
He may also need periodic transfusions of red blood cells and platelets until his bone marrow begins producing enough of those cells on its own.
He may be at greater risk of infections or other complications for months to years after your transplant.

21. ALD, x-linked disorder

22. ALD
Adrenoleukodystrophy, or ALD, is a genetic disease that affects 1 in people.
It most severely affects boys and men.
This brain disorder destroys myelin, the protective sheath that surrounds the brain's neurons -- the nerve cells that allow us to think and to control our muscles.
It knows no racial, ethnic or geographic barriers.
The most devastating form of ALD appears in childhood, generally between the ages of four and ten years old.
Normal, healthy boys suddenly begin to regress. At first, they simply show behavioral problems, such as withdrawal or difficulty concentrating.
Gradually, as the disease ravages their brain, their symptoms grow worse, including blindness and deafness, seizures, loss of muscle control, and progressive dementia.
This relentless downward spiral leads to either death or permanent disability, usually within 2 to 5 years from diagnosis.

24. Brain after gene therapy

25. Types of ALD CHILDHOOD CEREBRAL DEMYELINATING ALD
This is the most common form of ALD, representing about 45% of all ALD cases. It is characterized by an inflammatory process that destroys the myelin, causing relentless progressive deterioration to a vegetative state or death, usually within five years.
ADRENOMYELONEUROPATHY (AMN)
The majority of other cases of the disease occur as the adult form, known as AMN. In about half of the sons who inherit the mutated ALD gene, symptoms of the disease do not develop until young adulthood, and in general, they progress more slowly. Beginning in their 20s and 30s, these young men exhibit neurological based motor lesions in their extremities. These lesions progress over many years and are inevitably accompanied by moderate to severe handicap. In approximately one third of these patients the central nervous system also becomes involved. These young men undergo the same mental and physical deterioration as the previously described boys. The progress of the disease is slower, usually declining to a vegetative state and/or death in 5 years or longer. There is no effective treatment for the adult onset of ALD, which is commonly referred to as adrenomyeloneuropathy (AMN); rather, medication and therapies are employed in a palliative manner.

26. Types of ALD ADDISON’S DISEASE (HYPOADRENOCORTICISM)
Most boys and men with ALD/AMN have Addison’s disease, a disorder of the adrenal gland; in about 10% of ALD cases, this is the only clinical sign of the disorder. The adrenal glands produce a variety of hormones that control levels of sugar, sodium, and potassium in the body, and help it respond to stress. In Addison’s disease, the body produces insufficient levels of the adrenal hormone, which can be life-threatening. Fortunately, this aspect of ALD is easily treated, simply by taking a steroid pill daily (and adjusting the dose in times of stress or illness)
FEMALE ALD
Although women who carry the ALD gene mutation do not generally develop the brain disease itself, some display mild symptoms of the disorder. These symptoms usually develop after age 35, and primarily include progressive stiffness, weakness, or paralysis of the lower limbs, numbness, pain in the joints, and urinary problems.

27. ALD treatment with Gene Therapy
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