Sickle Cell Disease

Sickle cell disease, also known as sickle cell anemia, is an inherited disorder that affects an estimated 100,000 Americans. While sickle cell disease can affect anyone, it is most common in people whose ancestors came from Africa, the Middle East, India and Spanish-speaking regions in the Western Hemisphere (Central and South America except Brazil, Spain and the Caribbean). Currently, the only potentially curative treatment available for sickle cell disease is blood and marrow transplant.

The University of Kansas Cancer Center is uniquely qualified to support patients with sickle cell disease through transplant. As 1 of fewer than 60 National Cancer Institute-designated comprehensive cancer centers in the nation, we offer unparalleled expertise in using blood and marrow transplant to treat both cancerous and noncancerous blood disorders, including sickle cell disease. In our program’s history, our team has performed more than 4,000 transplant procedures, including the first in Kansas to treat adult sickle cell disease.

In healthy red blood cells, hemoglobin carries oxygen, creating a smooth, round cell shape. With sickle cell disease, defective hemoglobin causes red blood cells to become stiff, taking on a sickle or crescent shape that blocks blood flow. While normal blood cells live 90-120 days, sickle cells only last 10-20 days. Making new cells at this rate becomes difficult for the body, resulting in reduced red blood cells and anemia. In addition, sickle cells can stick to blood vessel walls, stopping or slowing the flow of blood. When this occurs, oxygen cannot reach the nearby tissue. This can cause sudden and severe pain.

A defective gene called the sickle cell gene is responsible for the disease. People with sickle cell disease are born with 2 sickle cell genes, 1 from each parent. If you only receive 1 sickle cell gene, you have what is called sickle cell trait. When this occurs, you are generally healthy and do not develop symptoms; however, you can pass the gene on to your children.

In the United States, most cases of sickle cell disease affect people of African American or Hispanic descent. About 1 in 13 African American babies are born with the sickle cell trait while 1 in 365 are born with the disease.

In the United States, most parents learn their child has sickle cell disease long before symptoms occur. Symptoms typically start around 6 months of age and include:

• Jaundice and icterus, or a yellowing of the skin and eyes
• Fatigue and fussiness from the anemia
• Dactylitis, or painful swelling in the hands and feet

As sickle cell disease progresses, symptoms can vary from person to person. Acute and chronic symptoms as well as common complications often occur and may include:

All newborns in the U.S. undergo a blood test to screen for sickle cell disease. This test can also be done before the baby is born through amniotic fluid. As an adult, you can learn with a simple blood test whether you have the sickle cell gene.

Several treatments are available to reduce pain, anemia and other complications of sickle cell disease. Options include hydroxyurea (Hydrea), L-glutamine therapy (Endari), crizanlizumab-tmca (Adakveo), blood exchange transfusion and simple blood transfusion. A blood and marrow transplant or gene therapy are currently the only potential cures for some people. Talk with your doctor about what treatment options are best for you.

Transplants typically occur in children with a matched donor, but only 1 in 10 children has a matched donor who does not have sickle cell disease or trait. Transplants carry more risk for adults.

Gene therapy

Currently, the only gene therapies available for the treatment of sickle cell disease are lovotibeglogene autotemcel (Lyfgenia) and exagamglogene autotemcel (Casgevy). Lyfgenia is a gene insertion therapy created specifically for each patient using the patient’s own blood stem cells (from which red blood cells are produced). It adds working copies of a hemoglobin S gene to your cells. This leads to the production of anti-sickling hemoglobin that may decrease or stop vaso-occlusive events, which happen when sickle-shaped cells stick to blood vessel walls, stopping or slowing the flow of blood. Casgevy is a non-viral CRISPR/Cas9 gene-edited cell therapy in which a patient’s own stem cells are edited through a precise editing technology.

The entire treatment journey for these gene therapies can take 9-12 months and includes 6 steps:

1. Pretreatment – You’ll undergo blood exchange transfusions for at least 2 months (1 per month) so you’ll be able to maintain the hemoglobin levels needed for stem cell collection.
2. Stem cell collection – You will go through a process that moves your blood stem cells from your bone marrow into your blood. Then your blood is withdrawn by apheresis, separating the plasma and blood stem cells needed.
3. Gene therapy creation – Your blood stem cells are sent to a laboratory to have working copies of the hemoglobin S gene inserted for Lyfgenia or to be edited by the CRISPR method for Casgevy. The manufacturing period can take up to 6 months due to rigorous quality testing.
4. Chemotherapy – Before you can receive your modified cells, you’ll undergo a course of high-dose chemotherapy to make room in your bone marrow for the new cells.
5. Infusion – After your conditioning chemotherapy, you’ll be admitted to the hospital so the modified cells can be infused into your body in a process similar to a blood transfusion.
6. Recovery and follow-up – After infusion, you’ll remain in the hospital for 3 to 6 weeks. After you’re released from the hospital, you’ll continue to have regular follow-up appointments.