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Compression Fracture

Compression = the application of strong pressure
 Fracture = a break in a bone


A compression fracture occurs when part of a vertebra, or bone in the spine, collapses.
A compression fracture is a type of fracture or break in your vertebrae. The vertebrae are the bones in
your back that are stacked on top of each other to make your spine. Your spine supports your weight,
allows you to move, and protects your spinal cord and the nerves that go from it to the rest of your
body.
Compression fractures can cause the vertebrae to collapse, making them shorter in height. This
collapse can also cause pieces of bone to press on the spinal cord and nerves, decreasing the
amount of blood and oxygen that gets to the spinal cord.

a compression fracture is a complete bone break that disrupts the bone tissue and collapses the
affected bone. The spinal vertebral body is the most common site of compression fractures

Lumbar
Low back pain is a very common complaint for a simple reason. Since the lumbar spine is connected
to your pelvis, this is where most of your weight bearing and body movement takes place. Typically,
this is where people tend to place too much pressure, such as: lifting up a heavy box, twisting to move
a heavy load, or carrying a heavy object. Such repetitive injuries can lead to damage to the parts of
the lumbar spine.

Causes
Osteoporosis is a disease in which bones become very weak and more likely to break. It often
develops unnoticed over many years, with no symptoms or discomfort until a bone breaks.
Cause
Osteoporosis is a natural aging phenomenon; as we get older, our bones weaken. When the
vertebrae in the spine weaken, they can narrow and become flatter. This can make elderly patients
shorter and lead to a rounded back, a hump or a "bent forward look" to the spine.
As osteoporosis progresses, the vertebrae weaken and become flatter. This can cause a severely
rounded back ("dowager's hump").
The weakened vertebrae are at a high risk for fracture. A vertebral compression fracture occurs when
too much pressure is placed on a weakened vertebra and the front of it cracks and loses height.
Vertebral compression fractures are often the result of a fall, but people with osteoporosis can suffer a
fracture even when doing everyday things, such as reaching, twisting, coughing, and sneezing.

A vertebral compression fracture (arrow) has a wedged-shaped appearance. The front of the vertebra
has cracked and shortened while the back remains intact.

Your bones are alive and constantly growing -- not static, like you see them drawn in books. Bones
continually change throughout your life, with some bone cells dissolving and new bone cells growing
back in a process called remodeling. With this lifelong turnover of bone cells, you replace most of your
skeleton every 10 years.
But for people with osteoporosis -- a thinning of the bones -- bone loss outpaces the growth of new
bone. Bones become porous, brittle, and prone to fracture. Look at an X-ray of a hip with normal bone
density, and you see a dense matrix of bone cells. But look at a hip with osteoporosis, and you see
mostly air. The bony matrix has all but dissolved, with only a few thin strands left.

Bone density is greatest in your early 20s. But as you age, you can lose bone mass from a variety of
factors. Osteoporosis or its early warning sign, osteopenia, signals an imbalance in the remodeling
process: Too much bone is broken down, and too little new bone is built back up. Brittle bones result,
prone to fracture.

Causes osteoporosis
-low estrogen in women
-low testosteron in man
-hormone imbalance: Several other hormones play a role in regulating your bone density, including
parathyroid hormone and growth hormone. They help orchestrate how well your bones use calcium
-Lack of Calcium, vitamin D
-A Sedentary Lifestyle
-High levels of Thyroid hormones
-smoking
-medications: Most common are corticosteroids, also known as cortisone, hydrocortisone,
glucocortisoids, and prednisone. These drugs are used to treat asthma, rheumatoid arthritis,
psoriasis, colitis,
-medical conditions: genetic diseases like cystic fibrosis to digestive diseases to the tumors called
multiple myeloma, which infiltrate bones with abnormal cells. Abnormal calcium excretion also
contributes to bone loss.
-too much alcohol

Cancer
Bone cancer can begin in any bone in the body, but it most commonly affects the pelvis or the long
bones in the arms and legs. Bone cancer is rare, making up less than 1 percent of all cancers. In fact,
noncancerous bone tumors are much more common than cancerous ones.
The term "bone cancer" doesn't include cancers that begin elsewhere in the body and spread
(metastasize) to the bone. Instead, those cancers are named for where they began, such as breast
cancer that has metastasized to the bone.

Some types of bone cancer occur primarily in children, while others affect mostly adults. Surgical
removal is the most common treatment, but chemotherapy and radiation therapy also may be utilized.
The decision to use surgery, chemotherapy or radiation therapy is based on the type of bone cancer
being treated.

Causes
The cause of most bone cancers is unknown. A small number of bone cancers have been linked to
hereditary factors, while others are related to previous radiation exposure.
Types of bone cancer
Bone cancers are broken down into separate types based on the type of cell where the cancer began.
The most common types of bone cancer include:
Osteosarcoma. Osteosarcoma is the most common form of bone cancer. In this tumor, the cancerous
cells produce bone. This variety of bone cancer occurs most often in children and young adults, in the
bones of the leg or arm. In rare circumstances, osteosarcomas can arise outside of bones
(extraskeletal osteosarcomas).
Chondrosarcoma. Chondrosarcoma is the second most common form of bone cancer. In this tumor,
the cancerous cells produce cartilage. Chondrosarcoma usually occurs in the pelvis, legs or arms in
middle-aged and older adults.
Ewing sarcoma. Ewing sarcoma tumors most commonly arise in the pelvis, legs or arms of children
and young adults.

Two types of cancer that may cause spinal compression fracture are (1) bone metastasis and (2)
multiple myeloma.
Another term for bone metastasis is osseous metastatic disease. “Osseous” means bone. This type of
cancer originates in a primary tumor that spreads to bone. Multiple myeloma is the third most
common type of blood cancer affecting the plasma, the white blood cells.

How Bone Metastasis Weakens Your Bones


Bone metastasis is cancer that spreads to your bones from another site (most commonly from the
breasts, lungs, and prostate). Because the spine is a central structure in the body, the bones of the
spine are the top site for bone metastasis.
Bone metastasis can lead to spinal fractures because it prevents the 2 main types of bone cells—
osteoblasts and osteoclasts—from working properly. Osteoblasts build new bone, while osteoclasts
break down old bone.

This type of cancer produces 2 kinds of lesions, and the type of lesion associated with fractures is
known as an osteolytic lesion. Osteolytic lesions occur when the cancer triggers the osteoclasts to
break down too much bone. This type of lesion causes your bones to weaken and lose density,
making them prone to fractures.
Bone pain is typically the earliest symptom, but some patients may not realize they have bone
metastasis until they develop a fracture.
Multiple Myeloma Makes Spinal Bones Vulnerable to Fracture
Multiple myeloma is a cancer of your plasma cells, which are white blood cells that live in your bone
marrow. White blood cells are part of your body’s immune system. As with bone metastasis, multiple
myeloma wears away at your bones’ mass.
Like bone metastasis, multiple myeloma interferes with the healthy balance of activity between
osteoblasts and osteoclasts. This type of cancer triggers the osteoclasts to work harder—so they
wear away bone quicker than they normally should. Plus, multiple myeloma inhibits the osteoblasts
from rebuilding new bone, so spinal bones become weakened and vulnerable to fracture.
Spinal bone pain is a commonly reported symptom of people who have multiple myeloma.

OSTEOBLAST AND OSTEOCLAST

Osteoblasts are bone-forming cells. They are connective tissue cells found at the surface of bone.
They can be stimulated to proliferate and differentiate as osteocytes. Osteoblasts are derived from the
mesenchymal cell lines.
Osteoblasts are bone forming cells. Of the three types of bone cells, they are the ones that produce the
matrix that makes up bone. The matrix, or organic material, includes molecules such as collagen protein
fibers, which give bone its flexibility, and calcium (Ca2+) and phosphate (PO4-) ions, which give bone
its rigidity. Osteoblasts make and package the matrix molecules for release into the extracellular
environment. Once released, the molecules in the matrix react with each other to form a rigid yet flexible
bone tissue called osteoid that eventually hardens to form bone.
When osteoblasts cease to make new bone they can become trapped within the matrix and differentiate
into osteocytes.
Osteoclasts are bone-resorbing cells ("-clast" means to break; osteoclasts break down bone). They
are large, multinucleate cells that form through the fusion of precursor cells. Osteoclasts are descended
from stem cells in the bone marrow that also give rise to monocytes (macrophages). Osteoclasts are
derived from the Hematopoietic cell lines. Osteoclasts occupy small depressions on the bone’s surface,
called Howship lacunae; the lacunae are thought to be caused by erosion of the bone by the osteoclasts’
enzymes.
Osteoclasts make and secrete digestive enzymes that break up or dissolve the bone tissue. Osteoclasts
then take up or 'absorb' the bone debris and further break it down inside the cell. The collagen is broken
down into amino acids, which are recycled to build other proteins, while the calcium and phosphate are
released to be used elsewhere in the body.

In normal bone, bone formation and bone resorption are closely coupled processes involved in the
normal remodeling of bone. In osteoporosis, the net rate of bone resorption exceeds the rate of bone
formation, resulting in a decrease in bone mass without a defect in bone mineralization. In women,
osteoclast activity is increased because of decreased estrogen after the menopause. (Men with
prematurely decreased testosterone may also have increased osteoclast activity.) These changes
result in further net loss of bone.

Bence Jones Protein

The Bence-Jones protein urine test is used most often to diagnose and check on multiple myeloma, a
type of cancer. Or an abnormal Bence-Jones test result may mean you have a type of malignant
lymphoma. These are cancers of the lymphatic system.Multiple myeloma is a type of blood cancer. It
affects plasma cells. These are immune system cells that make antibodies to help fight infections.
Most plasma cells live in bone marrow, so multiple myeloma tumors are often found in bone.Bone
marrow is where blood cells are made. Multiple myeloma takes up space and leaves less space for
normal bone marrow. This can cause problems such as:

 Anemia. This is not enough red blood cells. It can lead to weakness and tiredness.

 Thrombocytopenia. This is not enough blood platelets called thrombocytes. These are
needed to form blood clots. This causes excess bleeding or bruising.

 Leukopenia. This is not enough white blood cells. It can lead to a weakening of the immune
system.
Healthy plasma cells are just one kind of blood cell affected by multiple myeloma. Myeloma tumors
also make monoclonal antibodies. Monoclonal means they are all of one kind. This makes them
ineffective and even harmful. These cells do not fight infections, and they also can damage the
kidneys. The monoclonal antibodies are made of 2 types of proteins. Bence-Jones proteins are 1 of
the types. These proteins show up in the urine in many people with multiple myeloma.Myeloma cells
also make chemical signals that tell osteoclasts to work a lot. Osteoclasts are cells that break down
bone. Because of this, multiple myeloma can weaken bones and cause breaks. The breakdown of
bone can also lead to higher levels of calcium in the blood. High blood calcium (hypercalcemia) can
cause many problems. These include from thirst and excess urination to dehydration, and kidney
problems. In rare cases, this may cause coma.

What do my test results mean?


Test results may vary depending on your age, gender, health history, the method used for the test,
and other things. Your test results may not mean you have a problem. Ask your healthcare provider
what your test results mean for you.

Bence-Jones proteins are not usually in urine. The presence of Bence-Jones proteins in urine can be
a sign of multiple myeloma or another rare condition called Waldenstrom macroglobulinemia. About
50% to 80% of people with multiple myeloma have Bence-Jones proteins in their urine.

This protein can also be in your urine if you have monoclonal gammopathy of undetermined
significance (MGUS). With this condition, your plasma cells make more of one kind of antibody than
they should. But they don't form a tumor or make enough antibodies to do damage. MGUS doesn't
generally need treatment. But if you have MGUS, you are at higher risk of multiple myeloma. You are
also at higher risk for lymphoma, a cancer affecting white blood cells. You are also at higher risk for
amyloidosis, the buildup of certain proteins in tissues. For these reasons, you should be watched by a
healthcare provider.

If you have been diagnosed with multiple myeloma, a Bence-Jones protein urine level can also be
used as one of several ways to find out the stage of the cancer. Stage of cancer means how much it
has grown and spread. The other factors used in staging are your calcium level, hemoglobin level,
and X-ray findings.

The Bence-Jones proteins are also found in some people with lymphoma.

Plasmacytoma

Micrograph of a plasmacytoma. H&E stain.

Plasmacytoma refers to a tumour consisting of abnormal plasma cells that grows within the soft tissue
or bony skeleton. It can be present as a discreet solitary mass of abnormal plasma cells, in which
case it is termed a “solitary” plasmacytoma or it can be present as part of myeloma. The prognosis
and treatment of solitary plasmacytomas is very different to myeloma.

Plasma cells are a type of white blood cell that develops from mature B-lymphocytes in the bone
marrow. They play an important role in protecting the body against infection and disease by producing
proteins called immunoglobulins (Ig), also known as antibodies.

There are two main types of solitary plasmacytomas:

 Solitary bone plasmacytoma (SBP) – where there is localised build-up of abnormal


plasma cells in the bone. Most commonly, these tumours develop in the spinal column
but they may also develop in the pelvis, ribs, arms, face, skull, femur (thigh), and sternum
(breast bone).Some people with SBP may go on to develop multiple myeloma – around
50-70% over 10 years – so you’ll be regularly monitored with blood tests and x-rays
and/or MRI scans.

 Solitary extramedullary plasmacytoma (SEP) – where the clump of abnormal plasma


cells occurs outside the bone in soft tissue. These plasmacytomas most commonly occur
in the head and neck region, particularly in the upper airways (nose, throat and sinuses),
but may also be found in the gastrointestinal tract, lymph nodes, bladder, lung or other
organs. There is less than a 10% chance of this disease progressing to myeloma.

 Solitary plasmacytomas do not have the typical features of myeloma, which include low
red blood cell counts, elevated calcium levels in the blood, or reduced kidney function.
And although 75% of people with SBP and 25% of people with SEP have an M-protein
(abnormal proteins produced by the cancerous plasma cells), they are usually small and
disappear following treatment.
Incidence

A solitary plasmacytoma most commonly occurs in middle-aged or elderly people and is very rare
under the age of 30. The median age at diagnosis is about a decade younger than that of people with
myeloma, 55 to 65 years, compared to a median age of 71 years for patients diagnosed with multiple
myeloma.

Solitary bone plasmacytomas are uncommon and make up approximately 5% of all of the plasma cell
disorders. Solitary extramedullary plasmacytomas are even less common. Solitary plasmacytomas
occur more commonly in men than women.

Causes

It is not known what causes plasmacytomas.

Symptoms

Solitary bone plasmacytomas may cause bone pain or fractures. Symptoms depend on where the
tumour is located.

Diagnosis

A person is diagnosed with a solitary plasmacytoma when: a biopsy reveals a single tumour inside the
bone or tissue comprising abnormal plasma cells; x-rays, positron electron tomography (PET scan) or
magnetic resonance imaging (MRI) scans show no other lesions in the bone or in the soft tissues;
bone marrow biopsy shows no evidence of myeloma; and blood tests show no signs of anaemia, high
calcium or reduced kidney function due to the M-protein.

Treatment

The treatment used most commonly for both types of plasmacytoma is radiotherapy. This is possible
because by definition, “solitary plasmacytomas” are localised. Radiotherapy involves focusing
radiation (similar to x-rays) on the plasmacytoma to kill the abnormal cells. The treatment is generally
given over several days to reduce side-effects.
Although chemotherapy is generally not used in addition to radiotherapy, there are times when the
types of medications used to treat myeloma are considered.

Surgery is rarely necessary but may be required in situations where plasmacytoma involvement of the
bone causes skeletal instability and high risk of fracture. In these cases, radiation therapy may be
delayed until after surgery.

Radiotherapy generally provides excellent local and often durable control of the plasmacytoma.
However, there is a risk that plasmacytomas may recur or progress to myeloma (particularly with
SBP). All people with plasmacytomas require life-long follow-up. This generally involves physical
examination, blood and urine tests, and x-rays, MRI or PET scans at regular intervals for at least the
first five years after treatment has been completed.

Bone Marrow Aspirate


Hematopoietic Stem Cell

The stem cells present in the bone marrow that form blood and immune cells. They are ultimately
responsible for the constant renewal of blood—the production of billions of new blood cells each day.
It can differentiate to a variety of specialized cells, can mobilize out of the bone marrow into circulating
blood, and can undergo programmed cell death, called apoptosis—a process by which cells that are
detrimental or unneeded self-destruct.
Multiple myeloma
Multiple myeloma is a cancer that forms in a type of white blood cell called a plasma cell. Plasma cells
help you fight infections by making antibodies that recognize and attack germs.

Multiple myeloma causes cancer cells to accumulate in the bone marrow, where they crowd out
healthy blood cells. Rather than produce helpful antibodies, the cancer cells produce abnormal
proteins that can cause complications.

Treatment for multiple myeloma isn't always necessary for people who aren't experiencing any signs
or symptoms. For people with multiple myeloma who require treatment, a number of treatments are
available to help control the disease

Definition
Multiple myeloma is a malignant plasma cell dyscrasia, a group of conditions characterized by the
abnormal proliferation of the same type (=monoclonal) of a plasma cell that may also secrete a
monoclonal immunoglobulin and/or immunoglobulin fragment (e.g., light chain)
 Multiple myeloma: diffuse infiltration of the bone marrow
Symptoms

Signs and symptoms of multiple myeloma can vary and, early in the disease, there may be none.

When signs and symptoms do occur, they can include:

· Bone pain, especially in your spine or chest

· Nausea

· Constipation

· Loss of appetite

· Mental fogginess or confusion

· Fatigue

· Frequent infections

· Weight loss

· Weakness or numbness in your legs

· Excessive thirst

Causes

It's not clear what causes myeloma.

Doctors know that myeloma begins with one abnormal plasma cell in your bone marrow — the soft,
blood-producing tissue that fills in the center of most of your bones. The abnormal cell multiplies
rapidly.

Because cancer cells don't mature and then die as normal cells do, they accumulate, eventually
overwhelming the production of healthy cells. In the bone marrow, myeloma cells crowd out healthy
white blood cells and red blood cells, leading to fatigue and an inability to fight infections.

The myeloma cells continue trying to produce antibodies, as healthy plasma cells do, but the
myeloma cells produce abnormal antibodies that the body can't use. Instead, the abnormal antibodies
(monoclonal proteins, or M proteins) build up in the body and cause problems such as damage to the
kidneys. Cancer cells can also cause damage to the bones that increases the risk of broken bones.

Risk factors

Factors that may increase your risk of multiple myeloma include:

· Increasing age. Your risk of multiple myeloma increases as you age, with most people
diagnosed in their mid-60s.

· Male sex. Men are more likely to develop the disease than are women.
· Black race. Black people are about twice as likely to develop multiple myeloma as are white
people.

· Family history of multiple myeloma. If a brother, sister or parent has multiple myeloma, you
have an increased risk of the disease.

· Personal history of a monoclonal gammopathy of undetermined significance (MGUS).


Every year 1 percent of the people with MGUS in the United States develop multiple myeloma.

Complications

Complications of multiple myeloma include:

· Frequent infections. Myeloma cells inhibit your body's ability to fight infections.

· Bone problems. Multiple myeloma can also affect your bones, leading to bone pain, thinning
bones and broken bones.

· Reduced kidney function. Multiple myeloma may cause problems with kidney function,
including kidney failure. Higher calcium levels in the blood related to eroding bones can
interfere with your kidneys' ability to filter your blood's waste. The proteins produced by the
myeloma cells can cause similar problems.

· Low red blood cell count (anemia). As myeloma cells crowd out normal blood cells, multiple
myeloma can also cause anemia and other blood problems.

Pathophysiology
 Neoplastic proliferation of plasma cells
o Bone marrow infiltration → suppression of hematopoiesis → leukopenia,
thrombocytopenia, anemia
o Cell proliferation → osteolysis → hypercalcemia
 Overproduction of monoclonal immunoglobulin and/or light chains
o Non-functioning antibodies → functional antibody deficiency
o ↑ Serum viscosity → hyperviscosity syndrome

Stages
There are two staging systems. The international staging system is preferred because it is less
subjective than the Durie-Salmon staging system (can be accessed under extra information).
International Staging System (ISS)

Classification
 Based on immunoglobulin type
o IgG: 50% of multiple myelomas
o IgA: 25% of multiple myelomas
o Bence Jones myeloma (free light chains excreted in urine): 20% of multiple
myelomas
Treatment
The choice of therapy depends on the outcome of the patient's category, general condition, and
eligibility for hematopoietic stem cell transplantation (HCT).
 Asymptomatic patients: watch and wait, unless patients have ≥ 60% clonal cells, excessive
free light chainsor ≥ 1 bone lesion
 Symptomatic patients
o Standard and intermediate risk
 HCT eligible : induction therapy followed by autologous HCT
 HCT ineligible: chemotherapy alone (e.g., dexamethasone and lenalidomide)
o High-risk patients should be enrolled in clinical trials
 Supportive therapy
o Osteolysis and bone pain
 Bisphosphonates
 Radiation therapy of osteolytic regions
o Pancytopenia with anemia and increased risk of infection
 Blood transfusions
 Granulocyte-colony stimulating factor (G-CSF) and erythropoietin (EPO)

Imaging

Pathological protein electrophoresis in multiple myeloma: the monoclonal antibodies cause a peak in
gamma globulin zone of the electrophoresis.
Red blood cells are aggregated in chains and appear like stacked coins (green overlay)

Bone marrow biopsy shows plasma cells, which typically have an eccentric nucleus (marked in green)
with dense heterochromatin (light area). The nuclear cytoplasmic ratio is increased. The cytoplasm is
characteristically basophilic (blue) because of the increase in RER for the synthesis of antibodies.

STEM CELL
Definisi : undifferentiated cells that can turn into specific cells, as the body needs them.
a cell with the unique ability to develop into specialised cell types in the body. In the future they may
be used to replace cells and tissues that have been damaged or lost due to disease.

Types of stem cells

There are several types of stem cells that can be used for different purposes.

Embryonic stem cells

Embryonic stem cells come from human embryos that are three to five days old. They are harvested
during a process called in-vitro fertilization. This involves fertilizing an embryo in a laboratory instead
of inside the female body. Embryonic stem cells are known as pluripotent stem cells. These cells can
give rise to virtually any other type of cell in the body.

Non-embryonic (adult) stem cells


Adult stem cells have a misleading name, because they are also found in infants and children. These
stem cells come from developed organs and tissues in the body. They’re used by the body to repair
and replace damaged tissue in the same area in which they are found.

For example, hematopoietic stem cells are a type of adult stem cell found in bone marrow. They make
new red blood cells, white blood cells, and other types of blood cells. Doctors have been performing
stem cell transplants, also known as bone marrow transplants, for decades using hematopoietic stem
cells in order to treat certain types of cancer.

Adult stem cells can’t differentiate into as many other types of cells as embryonic stem cells can.

Induced pluripotent stem cells (iPSCs)

Scientists have recently discovered how to turn adult stem cells into pluripotent stem cells. These new
types of cells are called induced pluripotent stem cells (iPSCs). They can differentiate into all types of
specialized cells in the body. This means they can potentially produce new cells for any organ or
tissue. To create iPSCs, scientists genetically reprogram the adult stem cells so they behave like
embryonic stem cells.

The breakthrough has created a way to “de-differentiate” the stem cells. This may make them more
useful in understanding how diseases develop. Scientists are hoping that the cells can be made from
someone’s own skin to treat a disease. This will help prevent the immune system from rejecting an
organ transplant. Research is underway to find ways to produce iPSCs safely.

Cord blood stem cells and amniotic fluid stem cells

Cord blood stem cells are harvested from the umbilical cord after childbirth. They can be frozen in cell
banks for use in the future. These cells have been successfully used to treat children with blood
cancers, such as leukemia, and certain genetic blood disorders.

Stem cells have also been found in amniotic fluid. This is the fluid that surrounds a developing baby
inside the mother’s womb. However, more research is needed to help understand the potential uses
of amniotic fluid stem cells.

5 Types of Stem Cells by Differentiation Potential

1. Totipotent (or Omnipotent) Stem Cells

They can differentiate into embryonic, as well as extra-embryonic tissues, such as chorion, yolk sac,
amnion, and the allantois. In humans and other placental animals, these tissues form the placenta.

The most important characteristic of a totipotent cell is that it can generate a fully-functional, living
organism.

The best-known example of a totipotent cell is a fertilized egg (formed when a sperm and egg unite to
form a zygote). 0-4 days

2. Pluripotent Stem Cells

The importance of this cell type is that it can self-renew and differentiate into any of the three germ
layers, which are: ectoderm, endoderm, and mesoderm. These three germ layers further differentiate
to form all tissues and organs within a human being.

Mampu berdiferensiasi menjadi segala jenis sel (hampir semua) tetapi tidak bisa membentuk jaringan
penunjang - gabisa bikin placenta. 5-14 days.

3. Multipotent Stem Cells


Multipotent stem cells are a middle-range type of stem cell, in that they can self-renew and
differentiate into a specific range of cell types.

An excellent example of this cell type is the mesenchymal stem cell (MSC).

Mesenchymal Stem Cells

Mesenchymal stem cells can differentiate into osteoblasts (a type of bone cell), myocytes (muscle
cells), adipocytes (fat cells), and chondrocytes (cartilage cells).

4. Oligopotent Cells

The next type of stem cells, oligopotent cells, are similar to the prior category (multipotent stem cells),
but they become further restricted in their capacity to differentiate.

While these cells can self-renew and differentiate, they can only do so to a limited extent. They can
only do so into closely related cell types.

An excellent example of this cell type is the hematopoietic stem cell (HSC).

Hematopoietic Stem Cells

HSCs are cells derived from mesoderm that can differentiate into other blood cells. Specifically, HSCs
are oligopotent stem cells that can differentiate into both myeloid and lymphoid cells.

Myeloid cells include basophils, dendritic cells, eosinophils, erythrocytes, macrophages,


megakaryocytes, monocytes, neutrophils, and platelets, while lymphoid cells include B cells, T cells,
and natural kills cells.

5. Unipotent Stem Cells

least potent and most limited type of stem cell.

An example of this stem cell type would be muscle stem cells.

Muscle Stem Cells

While muscle stem cells can self-renew and differentiate, they can only do so into a single cell type.
They are unidirectional in their differentiation capacity.

Stem Cell Transplant


Stem cell transplant
A stem cell transplant replaces stem cells. It is used when stem cells or bone marrow have been
damaged or destroyed by disease, including some types of cancer, or by high doses of chemotherapy
or radiation therapy used to treat cancer.

Bone marrow is the soft, spongy tissue inside your large bones. The bone marrow’s main job is to
make blood cells that flow through the body. Stem cells are the most basic cells in the bone marrow,
and they develop into different types of blood cells. There are 2 major types of stem cell transplant –
allogeneic and autologous. In an allogeneic stem cell transplant, stem cells are removed from another
person (a donor) and given to you (the recipient). In an autologous stem cell transplant, you provide
your own stem cells. If you receive stem cells from your identical twin, this is called a syngeneic
transplant.

A stem cell transplant is also called:

 a bone marrow transplant – when the stem cells are taken from the bone marrow
 a peripheral blood stem cell transplant (PBSCT) – when the stem cells are taken from the
blood
 a blood cell transplant (BCT)
 a hematopoietic stem cell transplant (HSCT)
 a high-dose therapy with stem cell rescue
How a stem cell transplant works
Most stem cells are found in the bone marrow. The stem cells in the bone marrow turn into red blood
cells, white blood cells and platelets. When these blood cells mature they move into the peripheral
blood (the blood that flows through the body). If the bone marrow is damaged or destroyed, it can’t
make normal blood cells. In a stem cell transplant, healthy stem cells are placed in your body to help
your bone marrow start to work properly. The new stem cells make healthy blood cells.

Why a stem cell transplant is used


A stem cell transplant may be used to treat some cancers such as leukemia, lymphoma, multiple
myeloma and neuroblastoma. It may also be used after high-dose radiation and chemotherapy to
treat the cancer.

When to choose a stem cell transplant


Doctors consider some important factors before deciding to treat cancer with a stem cell transplant,
including:

 your age – younger people often cope better with stem cell transplants and have fewer
complications. Some transplant centres set upper age limits, but this may depend on your
general health and other factors
 your overall health and other medical conditions
 the characteristics of your cancer – such as the type and stage of the cancer, whether you
are in remission or have had a relapse, the chance of relapse after transplant and how
sensitive the cancer is to chemotherapy
Types of stem cell transplant
The type of transplant is based on who gives the stem cells.

Autologous transplants use stem cells from your own bone marrow or blood.

A double autologous (tandem) transplant means that you receive 2 autologous transplants. Before
each one, you are given high-dose chemotherapy. Your stem cells for both transplants are usually
collected before the first course of chemotherapy. The second transplant is usually done between
several weeks and 6 months after the first.

Allogeneic transplants use stem cells from someone else. The donor may be a relative or someone
who is not related to you.

A mini-transplant means that lower doses of chemotherapy and radiation are given before an
allogeneic transplant. This may be useful for older people and those with other health problems who
may not be able to handle a standard transplant and the side effects. A mini-transplant is also called a
reduced intensity transplant or non-myeloablative transplant.

Syngeneic transplants use stem cells from an identical twin.

Collecting stem cells


The process of collecting or removing stem cells is called harvesting. The stem cells can come from
the bone marrow, the peripheral blood or the umbilical cord (from a newborn baby).

For autologous transplants, the stem cells are usually collected when the person is in remission and
has recovered from other treatments.

Stem cells from the bone marrow


Bone marrow is most often taken from the pelvic bones because they have the most bone marrow
and a large supply of stem cells.

Removing stem cells from the bone marrow is usually done using a general anesthetic (you will be
asleep) in the operating room. A large needle is put into the back of the hip bone. Bone marrow is
pulled out through the needle. This is repeated until enough marrow has been collected for the
transplant. It usually takes 1 to 2 hours.

A dressing is put on where the needle went in, and you will recover from the anesthetic in the
recovery room. The hip area may be sore for a few days. Medicines can be taken to relieve pain. The
body usually replaces the collected stem cells within a few weeks.

The cells are filtered to remove bone fragments and fat particles, stored in special solution bags and
frozen until they are needed for the transplant.

Stem cells from the peripheral blood


Blood does not normally have many stem cells. Growth factors, such as G-CSF or plerixafor, may be
given for a few days to stimulate stem cells to grow faster and move into the blood from the bone
marrow.

Removing stem cells from the blood is done through an IV (intravenous) line. An IV is placed in a
large vein in the donor’s arm. The IV tubing is attached to a machine that separates and collects stem
cells from the blood. After the stem cells are removed, the blood is returned to the donor. The process
takes several hours and may need to be repeated once a day for a few days to collect enough stem
cells for a transplant. The collected stem cells are filtered, stored in bags and frozen until they are
needed for a transplant.

Stem cells from the umbilical cord


The blood of newborn babies normally has a large number of stem cells. After birth, the blood that’s
left behind in the placenta and umbilical cord can be collected. Blood is collected from the umbilical
cord shortly after a baby is born. A machine separates and collects stem cells from the cord blood.

The number of stem cells that needs to be collected from an umbilical cord is less than what needs to
be taken from adult bone marrow. This is because more blood cells can be formed from each cord
blood stem cell than from each adult bone marrow stem cell. The stem cells are filtered, put in bags
and frozen.

Some cord blood banks store the stem cells until the family needs them (private use). Other places
store cord blood to be used in people who are unrelated (public use).

Donating cord blood


Healthy parents who are expecting a baby can donate their child’s cord blood. To be eligible to
donate, parents usually have to register with the cord blood bank when they are pregnant. Blood
screening tests may be done on the mother before collection.

A cord blood donation may not be accepted if there are certain illnesses that run in the family or that
have happened during or before the pregnancy that could be transmitted by a cord blood transplant.

Some private cord blood banks may charge collection and storage fees.

Having a stem cell transplant


There are a few steps to get a stem cell transplant. Before the transplant, you will talk with the
healthcare team about each of the steps and the effects of the transplant. A transplant is both
physically and emotionally hard on you.

Preparing for a stem cell transplant


If a stem cell transplant is a treatment option, the doctor will examine you and do some tests to find
out if a transplant will work for you.

Tests and procedures


The exams and tests may include:

 a complete health history and physical exam


 HLA testing
 a bone marrow biopsy
 a CT scan or an MRI
 an electrocardiogram (ECG) or echocardiogram (echo) or a wall motion study to check your
heart
 a chest x-ray and pulmonary function tests to check your lungs
 blood tests such as complete blood count, blood chemistry tests and tests to check for
viruses such as hepatitis, cytomegalovirus (CMV) and HIV
Consulting with the healthcare team
You may see other members of the healthcare team for:

 a dental exam and dental care


 a nutritional assessment
 a social work assessment
 a psychological and emotional evaluation
 fertility counselling
Once you have been told about all of the tests and procedures and agree to have a stem cell
transplant, you will sign an informed consent form.

Conditioning therapy
You will receive conditioning therapy, or intensive therapy, and the stem cell transplant either as an
in-patient (you will stay overnight in the hospital) or an outpatient. The name of the therapy is based
on the type of transplant. For an allogeneic or syngeneic transplant, it is usually called conditioning
therapy or a conditioning regimen. For an autologous transplant, it is usually called intensive therapy.

Conditioning or intensive therapy is used to:

 make room in the bone marrow for the donor stem cells
 destroy any cancer cells still in the body
 suppress your immune system to lower the chance of rejecting the transplanted stem cells
Conditioning or intensive therapy usually includes giving high doses of chemotherapy through a
central venous catheter (tube). It is sometimes followed by radiation therapy. These treatments vary
depending on the disease being treated and the methods used at the transplant centre. The treatment
is usually given over a few days.

Usually a combination of chemotherapy drugs is given. Radiation therapy is given to the entire body.
This is called total body irradiation (TBI). TBI may be given in divided doses over a few days or in a
single treatment.

Receiving the stem cells


The stem cells are given to you through a central venous catheter. They settle in the bone marrow
and begin to multiply and mature. The day the stem cells are given is usually referred to as day 0.

The transplant is usually done 1 to 3 days after the end of conditioning or intensive therapy.
Medicines are given before the transplant to help lessen your risk of side effects and reaction to the
preservatives that are used when freezing the stem cells (in autologous transplants only).

If the stem cells were frozen, they are thawed in warm water and given to you. If the stem cells were
not frozen, they may be removed in the operating room and processed in the lab then given to you
right away.

The transplant can take about 1 to 2 hours. The length of time varies with the number of stem cells
being given. The amount is calculated based on your weight.

When you are receiving the stem cells, the healthcare team will watch you closely for side effects.
These effects may include chills, fever, chest pain, headache, nausea, shortness of breath and hives.

If the stem cells were frozen, you might get a garlic taste in your mouth from the preservative used.
Your body will also have this odor. The taste and the odor will slowly fade over a few days.

Stem Cell Transplant for Multiple Myeloma


In a stem cell transplant, the patient gets high-dose chemotherapy to kill the cells in the bone marrow.
Then the patient receives new, healthy blood-forming stem cells. When stem cell transplants were
first developed, the new stem cells came from bone marrow, and so this was known as a bone
marrow transplant. Now, stem cells are more often collected from blood (a peripheral blood stem cell
transplant).

Stem cell transplant is commonly used to treat multiple myeloma. Before the transplant, drug
treatment is used to reduce the number of myeloma cells in the patient’s body. (See Drug Therapy for
Multiple Myeloma).)

Stem cell transplants (SCT) can be autologous or allogeneic.

Interpretasi hasil Lab

Laju Endap Darah (LED)


Nilai normal:
Pria <15mm/1 jam Wanita <20mm/1 jam
Deskripsi:
LED atau juga biasa disebut Erithrocyte Sedimentation Rate (ESR) adalah ukuran kecepatan endap
eritrosit, menggambarkan komposisi plasma serta perbandingan eritrosit dan plasma. LED
dipengaruhi oleh berat sel darah dan luas permukaan sel serta gravitasi bumi.
Implikasi klinik
· nilai meningkat terjadi pada: kondisi infeksi akut dan kronis, misalnya tuberkulosis, arthritis
reumatoid, infark miokard akut, kanker, penyakit Hodkin’s, gout, Systemic Lupus
Erythematosus (SLE), penyakit tiroid, luka bakar, kehamilan trimester II dan III. Peningkatan
nilai LED > 50mm/ jam harus diinvestigasi lebih lanjut dengan melakukan pemeriksaan terkait
infeksi akut maupun kronis, yaitu: kadar protein dalam serum dan protein, immunoglobulin,
Anti Nuclear Antibody (ANA) Tes, reumatoid factor. Sedangkan peningkatan nilai LED
>100mm/jam selalu dihubungkan dengan kondisi serius, misalnya: infeksi, malignansi,
paraproteinemia, primary macroglobulinaemia, hiperfibrinogenaemia, necrotizing vaskulitis,
polymyalgia rheumatic.
· nilai menurun terjadi pada: polisitemia, gagal jantung kongesti, anemia sel sabit,
Hipofibrinogenemia, serum protein rendah Interaksi obat dengan hasil laboratorium:
etambutol, kuinin, aspirin, dan kortison.
Kreatinin
Nilai normal : 0,6 – 1,3 mg/dL SI : 62-115 μmol/L
Deskripsi :
Tes ini untuk mengukur jumlah kreatinin dalam darah. Kreatinin dihasilkan selama kontraksi otot
skeletal melalui pemecahan kreatinin fosfat. Kreatinin diekskresi oleh ginjal dan konsentrasinya dalam
darah sebagai indikator fungsi ginjal. Pada kondisi fungsi ginjal normal, kreatinin dalam darah ada
dalam jumlah konstan. Nilainya akan meningkat pada penurunan fungsi ginjal.
Serum kreatinin berasal dari masa otot, tidak dipengaruhi oleh diet, atau aktivitas dan diekskresi
seluruhnya melalui glomerulus. Tes kreatinin berguna untuk mendiagnosa fungsi ginjal karena
nilainya mendekati glomerular filtration rate (GFR).
Kreatinin adalah produk antara hasil peruraian kreatinin otot dan fosfokreatinin yang diekskresikan
melalui ginjal. Produksi kreatinin konstan selama masa otot konstan. Penurunan fungsi ginjal akan
menurunkan ekskresi kreatinin.
Implikasi klinik :
· Konsentrasi kreatinin serum meningkat pada gangguan fungsi ginjal baik karena gangguan
fungsi ginjal disebabkan oleh nefritis, penyumbatan saluran urin, penyakit otot atau dehidrasi
akut.
· Konsentrasi kreatinin serum menurun akibat distropi otot, atropi, malnutrisi atau penurunan
masa otot akibat penuaan.
· Obat-obat seperti asam askorbat, simetidin, levodopa dan metildopa dapat mempengaruhi
nilai kreatinin pada pengukuran laboratorium walaupun tidak berarti ada gangguan fungsi
ginjal.
· Nilai kreatinin boleh jadi normal meskipun terjadi gangguan fungsi ginjal pada pasien lanjut
usia (lansia) dan pasien malnutrisi akibat penurunan masa otot.
· Kreatinin mempunyai waktu paruh sekitar satu hari. Oleh karena itu diperlukan waktu
beberapa hari hingga kadar kreatinin mencapai kadar normal untuk mendeteksi perbaikan
fungsi ginjal yang signifikan.
CRP
Pengukuran kadar CRP sering digunakan untuk memantau keadaan pasien setelah operasi. Pada
umumnya, konsentrasi CRP akan mulai meningkat pada 4-6 jam setelah operasi dan mencapai kadar
tertinggi pada 48-72 jam setelah operasi. Kadar CRP akan kembali normal setelah 7 hari pasca-
operasi. Namun, bila setelah operasi terjadi inflamasi atau sepsis maka kadar CRP di dalam darah
akan terus menerus meningkat.
Pada kondisi terinfeksi aktif, kadar CRP di dalam tubuh dapat meningkat hingga 100x kadar CRP
pada orang normal sehingga pengukuran CRP sering digunakan untuk mengetahui apakah pasien
dalam kondisi terinfeksi atau mengalami inflamasi tertentu. Pada saat terjadi infeksi bakteri atau
inflamasi, leukosit akan teraktivasi kemudian melepaskan sitokin ke aliran darah. Sitokin akan
merangsang sel-sel hati (hepatosit) untuk memproduksi CRP.
Pada tahun 2003, Centers for Disease Control and Prevention (CDC) dan the American Heart
Association (AHA) merekomendasi penggunaan hsCRP untuk memprediksi risiko penyakit
kardiovaskular terutama untuk pasien penderita sindrom koroner akut dan penyakit koroner stabil.
Nilai yang dijadikan acuan untuk penilaian risiko penyakit kardiovaskular tersebut adalah :
· < 1 mg/L : risiko rendah
· 1-3 mg/L : risiko menengah (intermediate)
· > 3 mg/L : risiko tinggi
· > 10 mg/L mengindikasikan adanya inflamasi atau infeksi aktif.
Beta - 2 Microglobulin
In patients on long-term hemodialysis, it can aggregate into amyloid fibers that deposit in joint spaces,
a disease, known as dialysis-related amyloidosis.
Low levels of β microglobulin can indicate non-progression of HIV.
2

Levels of β microglobulin can be elevated in multiple myeloma and lymphoma, though in these cases
2

primary amyloidosis (amyloid light chain) and secondary amyloidosis (amyloid associated protein) are
more common. The normal value of β microglobulin is <2 mg/L. However, with respect to multiple
2

myeloma, the levels of β microglobulin may also be at the other end of the spectrum. Diagnostic
2

testing for multiple myeloma includes obtaining the β microglobulin level, for this level is an important
2

prognostic indicator. As of 2011 A patient with a level <4 mg/L is expected to have a median survival
of 43 months, while one with a level >4 mg/L has a median survival of only 12 months. β 2

microglobulin levels cannot, however, distinguish between monoclonal gammopathy of undetermined


significance (MGUS), which has a better prognosis, and smouldering (low grade) myeloma.
Loss-of-function mutations in this gene have been reported in cancer patients unresponsive to
immunotherapies.
Fibrinogen

Fibrinogen Level Interpretation


Fibrinogen levels DIC due the the consumption of clotting factors
are reduced in: Liver disease due to decreased synthesis.
An abnormal fibrinogen may be also be found in patients with liver
disease due to an abnormal (increased) sialic acid content
Massive transfusion leading to a dilutional coagulopathy
Inherited deficiencies e.g. Hypofibrinogenaemia, afibrinogenaemia and
dysfibrinogenaemia [the latter is often associated with reduced
fibrinogen levels as well as activity]
Following thrombolytic therapy
In some patients following treatment with asparaginase

Fibrinogen levels Increasing age


are increased in: Female sex, pregnancy, oral contraception
In post-menopausal women
Acute phase reaction
Disseminated malignancy [but may also be decreased if this is
associated with DIC]

Alfa – 2 Globulin

Increased in :
· Acute Phase Reaction
· Nephrotic syndrome
· Hyperthyroidism
· Pregnancy
· Oral contraceptive or steroid use
Decreased in :
· Hemolysis
· Liver disease
· Malnutrition