Sickle Cell Disease - Treatment

Bone Marrow or Stem Cell Transplantation

The only true cure for sickle cell disease at this time is bone marrow or stem cell transplantation. The bone marrow nurtures stem cells, early cells that mature into red and white blood cells and platelets. By destroying the sickle cell patient's diseased bone marrow and stem cells and transplanting healthy bone marrow from a genetically matched, or allogeneic, donor, normal hemoglobin may be produced. Trials using a few carefully selected patients have reported very successful results.

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Candidates. Possible candidates for transplantation are patients with the following conditions:

A history of stroke
Sickle pulmonary disease
Recurrent acute chest syndrome or vaso-occlusive crises

Up to 80 - 85% of patients who receive transplants remain disease free. Unfortunately, only about 7% meet the criteria for transplantation, which include:

Age 16 or younger
Severe symptoms but no long-term organ or neurologic damage
Presence of genetically matched brother or sister who will donate their marrow

Complications. Bone marrow transplant carries its own dangers and limitations. About 10% of those treated die from the treatment. Some complications include:

Transplanted cells which come from a donor (called allogeneic grafts) may attack the patient's own tissues, a potentially fatal condition called graft-versus-host disease (GVHD). Drugs that destroy bone marrow and suppress immunity must be administered before the procedure so that the body's immune system does not attack the transplanted tissue. Nonetheless, this does not always prevent the problem.
Other very serious complications include bleeding, pneumonia, and severe infection.
Those who live but are not cured face long-term problems caused by the drugs used in transplantation and by the disease itself.
Even in those who are cured, long-term consequences may include a higher risk for cancer and infertility.

Investigative Approaches. Experts hope that better diagnostic techniques will identify at an early age more patients who are at high risk for developing serious sickle cell disease and in whom the benefits of transplantation would outweigh the risks. Researchers are also investigating regimens that might be suitable for adult patients and less toxic regimens.

The use of umbilical cord blood and cells from placentas is showing promise for providing healthy stem cells to patients who do not have genetically matched donors for bone marrow transplant. Cord blood has certain advantages over stem cell transplantation, including the capacity to produce more cells quickly. Because immune factors in cord blood are immature, the risk and severity of graft-versus-host disease (GVHD) may be reduced.

Early trials are also reporting some success with a process called partial chimerism, in which a mixture of the patient's and a donor's bone marrow is used. The procedure has far fewer side effects because all the bone marrow is not destroyed. Although some sickle blood cells remain, small studies indicate that the patients are still free of the typical infections and pain of the disease.

Transfusion Therapy in Sickle Cell Disease

Transfusions are often critical for treating sickle cell disease. In some cases they may be given on a regular basis to prevent stroke or other life-threatening complications of the disease. Ongoing transfusions can reduce episodes of pain and acute chest syndrome. They can also help improve height and weight in children with sickle cell disease. Regular transfusions, however, can have severe side effects.

Transfusions are may required by sickle cell patients either for specific episodes (used only for specific events) or as chronic transfusions (ongoing transfusions).

Episodic Transfusions. Episodic transfusions are needed in the following situations:

To manage sudden severe events, including acute chest syndrome, stroke, widespread infection (septicemia), and multi-organ failure.
To manage severe anemia, usually caused by splenic sequestration (dangerously enlarged spleen) or aplasia (halting of red blood cell production, most often caused by parvovirus). Transfusions are generally not required for mild or moderate anemia.
Before major surgeries. Some evidence suggests that a conservative transfusion regime is as effective as aggressive transfusions in these cases, but more research is needed. Transfusions are generally not required for minor surgeries.

Chronic Transfusions. Chronic transfusions are used in patients who have:

Pulmonary hypertension and chronic lung disease
Heart failure
Chronic kidney failure and severe anemia
Unusually severe and protracted episodes of pain

Transfusions are also used to prevent first or recurrent strokes. An important study confirmed previous work that shows chronic transfusions reduce the risk for stroke in children by over 90%.

Kinds of Transfusions. Transfusions may be either simple or exchange.

Simple Transfusion. Simple transfusions involve the infusion of one or two units of donor blood to restore blood volume levels and oxygen flow. It is used for moderately severe anemia, severe fatigue, and nonemergency situations when there is a need for increased oxygen. It is also used for acute chest syndrome.
Exchange Transfusion. Exchange transfusion involves drawing out the patient's blood while exchanging it for donor red blood cells. It can be done as manual procedure or as automatic one called erythrocytapheresis. Exchange transfusions should be used promptly if there is any evidence that the patient's condition is deteriorating. It prevents stroke and also may be used in patients with severe acute chest syndrome and to reduce the risk of iron overload in patients who require chronic transfusion therapy. Other indications are not fully defined. Studies suggest that it may improve oxygenation and reduce hemoglobin S levels. Exchange transfusion may also reduce the risk of heart failure and help prevent fat embolism, a life-threatening condition in which fatty tissue from the bone marrow travels to blood vessels in the lungs and cuts off oxygen.

Iron Overload and Chelation Therapy. Iron overload increases risk for complications including liver cancer and heart failure. A liver biopsy accurately determines whether excess iron levels are present. A non-invasive test called a superconducting quantum interference device (SQUID) should be used if available.

Chelation therapy is used to remove excess iron stores in the body that can harm the liver, heart, and other organs. The drug deferoxamine (Desferal) is commonly used during such therapy. Unfortunately, deferoxamine has some severe side effects and must be used with a pump for about 12 hours each day. Many patients do not continue treatment. In 2005, the drug deferasirox (Exjade) was approved for the treatment of transfusion-related iron overload in patients ages 2 and older. It is taken once a day by mouth. Patients mix the pills in liquid and drink the mixture. This new treatment may make chelation therapy much easier and less painful for patients.

Other Complications of Transfusion Therapy.

Immune reactions. An immune reaction may occur in response to donor blood. In such cases, the patient develops antibodies that target and destroy the transfused cells. This reaction, which can occur five to 20 days after transfusion, can result in severe anemia and may be life threatening in some cases. It can be generally prevented with careful screening and matching of donor blood groups before the transfusion.
Hyperviscosity. With this condition, a mixture of hemoglobin S and normal hemoglobin caused the blood to become sticky. The patient is at risk for high blood pressure, altered mental status, and seizures. Careful monitoring can prevent this condition.
Transmission of viral illness. Before widespread screening, transfusions were highly associated with a risk for hepatitis and HIV. This complication has decreased considerably.