Aplastic anemia bone marrow transplant

Aplastic anaemia is a rare disorder in which the bone marrow fails to produce enough blood cells. This happens because the normal blood forming cells (stem cells) are replaced by abnormal fat cells.

Although aplastic anaemia is not a malignant disease (cancer) it can be very serious, especially if the bone marrow is severely affected and there are very few blood cells left in circulation. Without adequate numbers of blood cells people with aplastic anaemia can become anaemic (low red blood cells) and more susceptible to infections (low white blood cells), and to bleeding and bruising more easily (low platelets).

The term aplastic anaemia is usually understood to refer to the acquired disorder which is a non-malignant bone marrow disease. There are other conditions that are congenital (present at birth), inherited (e.g. Fanconi Anaemia) or a form of aplastic anaemia that may develop over a person’s life as a result of treatment (like chemotherapy) for malignant diseases. These conditions need to be ruled out before a diagnosis of acquired aplastic anaemia can be made.

Fanconi anaemia can be diagnosed and distinguished from acquired aplastic anaemia by a blood test. Fanconi anaemia affects brothers and sisters within a family. Children with Fanconi anaemia are short and have abnormalities of the forearms or hands and a gradual but progressive failure of the bone marrow. The anaemia usually develops in childhood but may present later in life as adolescent or adult.

There is common thought that acquired aplastic anaemia results when the bone marrow stem cells are damaged by an auto-immune reaction in the body. An auto-immune reaction can result from no specific trigger or underlying cause. The body’s own immune system attacks its own cells in an auto-immune reaction. Some types of aplastic anaemia may have an identifiable trigger that caused the auto-immune response.

Aplastic anemia symptoms vary from person to person. Specific symptoms depend on which of your blood cell types are affected and how low your blood counts have fallen.

Low Red Blood Cell Counts

A low red blood cell count is called anemia. If you have a low red blood cell count, you may:

1. Feel a little tired or very tired
2. Feel less alert or have trouble concentrating
3. Have a loss of appetite or lose weight
4. Have paler-than-normal skin
5. Have trouble breathing
6. Have rapid heartbeat
7. Have difficulty exercising or climbing stairs

Low White Blood Cell Counts

A low white blood cell count is called neutropenia. In general, a low white cell count lowers an aplastic anemia patient’s ability to fight bacterial infections. If you have a low white blood cell count, you may:

1. Have repeated fevers and infections
2. Get bladder infections that make it painful to urinate or make you urinate more often
3. Get lung infections that cause coughing and difficulty breathing
4. Get mouth sores
5. Get sinus infections and a stuffy nose
6. Get skin infections
7. A fever in an aplastic anemia patient is potentially serious. A doctor should be notified if a fever occurs.

Low Platelet Counts

A low platelet count is called thrombocytopenia. If you have a low platelet count, you may.

1. Bruise or bleed more easily, even from minor scrapes and bumps
2. Get heavier than normal menstrual periods
3. Get nose bleeds
4. Get tiny, flat red spots under your skin (petechiae) caused by bleeding
5. Have bleeding gums, especially after dental work or from brushing your teeth.

If platelet counts are not too low, there may be no obvious symptoms. In rare cases, the number of platelets can get so low that dangerous internal bleeding occurs.

Bleeding that will not stop is a medical emergency. An aplastic anemia patient needs to seek immediate medical help if they have bleeding that can’t be stopped by usual methods, such as applying pressure to the area.

Aplastic anemia develops when damage occurs to your bone marrow, slowing or shutting down the production of new blood cells. Bone marrow is a red, spongy material inside your bones that produces stem cells, which give rise to other cells. Stem cells in the bone marrow produce blood cells – red cells, white cells and platelets. In aplastic anemia, the bone marrow is described in medical terms as aplastic or hypoplastic – meaning that it's empty (aplastic) or contains very few blood cells (hypoplastic).

Factors that can temporarily or permanently injure bone marrow and affect blood cell production include:

Radiation and chemotherapy treatments: While these cancer-fighting therapies kill cancer cells, they can also damage healthy cells, including stem cells in bone marrow. Aplastic anemia can be a temporary side effect of these treatments.

Autoimmune disorders: An autoimmune disorder, in which your immune system begins attacking healthy cells, may involve stem cells in your bone marrow.

Use of certain drugs: Some medications, such as those used to treat rheumatoid arthritis and some antibiotics, can cause aplastic anemia.

Pregnancy: Aplastic anemia that occurs in pregnancy may be related to an autoimmune problem – your immune system may attack your bone marrow during pregnancy.

Exposure to toxic chemicals: Exposure to toxic chemicals, such as some used in pesticides and insecticides, may cause aplastic anemia. Exposure to benzene- an ingredient in gasoline – also has been linked to aplastic anemia. This type of anemia may get better on its own if you avoid repeated exposure to the chemicals that caused your initial illness.

A viral infection: Viral infections that affect bone marrow may play a role in the development of aplastic anemia in some people. Viruses that have been linked to the development of aplastic anemia include hepatitis, Epstein-Barr, cytomegalovirus, parvovirus B19 and HIV.

Unknown factors: In many cases, doctors aren't able to identify the cause of aplastic anemia. This is called idiopathic aplastic anemia.

Confusion with myelodysplastic syndrome

Aplastic anemia can be mistaken for a condition called myelodysplastic syndrome. In this group of disorders, the bone marrow produces new blood cells, but they're deformed and underdeveloped. The bone marrow in myelodysplastic syndrome is sometimes called hyperplastic – meaning that it's packed with blood cells. But some people with myelodysplastic syndrome have empty marrow that's difficult to distinguish from aplastic anemia.

Connections with other rare disorders

Some people with aplastic anemia also have a rare disorder known as paroxysmal nocturnal hemoglobinuria. This disorder causes red blood cells to break down too soon. Paroxysmal nocturnal hemoglobinuria can lead to aplastic anemia, or aplastic anemia can evolve into paroxysmal nocturnal hemoglobinuria.

Fanconi's anemia is a rare, inherited disease that leads to aplastic anemia. Children born with it tend to be smaller than average and have birth defects, such as underdeveloped limbs. The disease is diagnosed with the help of blood tests.

Aplastic anemia affects men and women of all ages. In most cases it has no clear cause.

Some risk factors include the following:

1. Having received radiation or chemotherapy for cancer treatment
2. Being exposed to certain toxins, such as pesticides or benzene (a chemical used to make a variety of materials that is also present in cigarette smoke)
3. Having an infectious disease, such as hepatitis, or an autoimmune disorder, such as lupus or rheumatoid arthritis
4. Being pregnant, though the condition usually goes away when the baby is born.

Aplastic anaemia is diagnosed by examining samples of your blood and bone marrow.

Blood tests: Normally, red blood cell, white blood cell and platelet levels stay within a certain range. Your doctor may suspect aplastic anemia when all three of these blood cell levels are very low.

Bone marrow biopsy: To confirm a diagnosis, you'll need to undergo a bone marrow biopsy. In this procedure, a doctor uses a needle to remove a small sample of bone marrow from a large bone in your body, such as your hipbone. The bone marrow sample is examined under a microscope to rule out other blood-related diseases. In aplastic anemia, bone marrow contains fewer blood cells than normal.

Once you've received a diagnosis of aplastic anemia, you may need additional tests to determine an underlying cause.

Aplastic anemia treatments focus on increasing the number of healthy cells in your blood (blood count). When your blood counts go up, you will experience fewer symptoms and require less treatment.

People who have mild or moderate aplastic anemia may not need treatment as long as the condition doesn't get worse. People who have severe aplastic anemia need medical treatment right away to prevent complications.

Treatments for aplastic anemia may include observation for mild cases, blood transfusions and medications for more-serious cases, and in severe cases, bone marrow transplantation. Severe aplastic anemia, in which your blood cell counts are extremely low, is life-threatening and requires immediate hospitalization for treatment.

Blood transfusions

Treatment for aplastic anemia usually involves blood transfusions to control bleeding and relieve anemia symptoms. Blood transfusions aren't a cure for aplastic anemia. But they do relieve signs and symptoms by providing blood cells that your bone marrow isn't producing.A transfusion may include:

1. Red blood cells: Transfusions of red blood cells raise red blood cell counts. This helps relieve anemia and fatigue.
2. Platelets: Transfusions of platelets help prevent excessive bleeding.

While there's generally no limit to the number of blood cell transfusions you can have, complications can sometimes arise with multiple transfusions. Transfused red blood cells contain iron that can accumulate in your body and can damage vital organs if an iron overload isn't treated. Medications can help your body get rid of excess iron.

Over time, your body may develop antibodies to transfused blood cells, making them less effective at relieving symptoms. The use of immunosuppressant medication makes this complication less likely.

Stem cell transplant

A stem cell transplant to rebuild the bone marrow with stem cells from a donor may offer the only successful treatment option for people with severe aplastic anemia. A stem cell transplant, which is also called a bone marrow transplant, is generally the treatment of choice for people who are younger and have a matching donor – most often a sibling.

If a donor is found, your diseased bone marrow is first depleted with radiation or chemotherapy. Healthy stem cells from the donor are filtered from the blood. The healthy stem cells are injected intravenously into your bloodstream, where they migrate to the bone marrow cavities and begin generating new blood cells. The procedure requires a lengthy hospital stay. After the transplant, you'll receive drugs to help prevent rejection of the donated stem cells.

A stem cell transplant carries risks. There's a chance that your body may reject the transplant, leading to life-threatening complications. In addition, not everyone is a candidate for transplantation or can find a suitable donor.

Immunosuppressants

For people who can't undergo a bone marrow transplant or for those whose aplastic anemia may be due to an autoimmune disorder, treatment may involve drugs that alter or suppress the immune system (immunosuppressants).

Drugs such as cyclosporine (Gengraf, Neoral, Sandimmune) and anti-thymocyte globulin are examples. These drugs suppress the activity of immune cells that are damaging your bone marrow. This helps your bone marrow recover and generate new blood cells. Cyclosporine and anti-thymocyte globulin are often used in combination.

Corticosteroids, such as methylprednisolone (Medrol, Solu-Medrol), are often given at the same time as these drugs.

Immune-suppressing drugs can be very effective at treating aplastic anemia. The downside is that these drugs further weaken your immune system. It's also possible that after you stop taking these drugs, aplastic anemia may return.

Bone marrow stimulants

Certain drugs – including colony-stimulating factors, such as sargramostim (Leukine), filgrastim (Neupogen) and pegfilgrastim (Neulasta), and epoetin alfa (Epogen, Procrit) — may help stimulate the bone marrow to produce new blood cells. Growth factors are often used in combination with immune-suppressing drugs.

Antibiotics, antivirals

Having aplastic anemia weakens your immune system. You have fewer white blood cells in circulation to fight off germs. This leaves you susceptible to infections.

At the first sign of infection, such as a fever, see your doctor. You don't want the infection to get worse, because it could prove life-threatening. If you have severe aplastic anemia, your doctor may give you antibiotics or antiviral medications to help prevent infections.

Other treatments

Aplastic anemia caused by radiation and chemotherapy treatments for cancer usually improves once you complete those treatments. The same is true for most other drugs that induce aplastic anemia.

Pregnant women with aplastic anemia are treated with blood transfusions. For many women, pregnancy-related aplastic anemia improves once the pregnancy ends. If that doesn't happen, treatment is still necessary.