Hemophagocytic Lymphohistiocytosis (HLH) Treatment

Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder in which the immune system does not work properly.

In healthy people, white blood cells are part of the immune system that help fight infection. Two important kinds of white blood cells are called cytotoxic T cells and natural killer cells. These white blood cells kill cells that have been infected with viruses or other germs. These cells also make chemicals called cytokines. Cytokines are released into the blood. They attract cells to the infection site and help regulate the immune response.

In patients with HLH, cytotoxic T cells and natural killer cells do not kill infected cells as well as they should. That makes it harder for people with HLH to fight infections. They often develop repeated episodes of hyperinflammation. Hyperinflammation is when the immune system is overly activated from cytotoxic T cells and natural killer cells making too many cytokines. These cells damage parts of the body, such as the liver, spleen, bone marrow, and brain.

Without treatment, HLH can lead to severe organ damage and death.

Hemophagocytic lymphohistiocytosis symptoms

Some of the more common symptoms of HLH include:

• Frequent, high fevers
• Enlargement of the spleen, liver, or lymph nodes
• Easy bruising or bleeding
• Feeling very tired
• Headaches, irritability, or other neurological changes
• Red skin rash or tiny, red, pinpoint dots on the skin
• Pale skin

Hemophagocytic lymphohistiocytosis causes

There are 2 main types of HLH:

• Familial or primary HLH: Familial HLH is an inherited condition. It can be passed from parents to children.
• Acquired or secondary HLH: Acquired HLH is thought to be the result of certain infections, cancers, and autoimmune disorders. This type usually occurs in older children and adults.

Genes carry information telling cells within the body how to grow and function. Most cases of familial HLH are caused by a gene change (mutation) in the genes PRF1, UNC13D, STX11, or STXBP2. These genes help white blood cells kill invading viruses and other germs. They also work to calm the immune system once it becomes activated.

Most people have 2 working copies of each of these genes. One copy is inherited from the mother and another from the father. Familial HLH occurs when someone inherits an HLH gene mutation from the mother and another mutation in the same HLH gene from the father. Parents of a child with familial HLH have a 25% or 1 in 4 chance with each pregnancy of having another child with familial HLH.

Hemophagocytic lymphohistiocytosis diagnosis

HLH is diagnosed in fewer than 1 out of every 50,000–100,000 children each year. The condition occurs equally often in boys and girls. The symptoms of HLH look like many other disorders. As a result, doctors think that more children develop HLH than are recognized and reported.

Tests for HLH may include:

• Blood chemistry test: A small sample of blood is taken from a vein. This test can help measure the amount of certain substances in the blood.
• Lumbar puncture: A sample of cerebral spinal fluid is taken from the spine. This test can help doctors see if HLH is affecting the brain.
• Bone marrow aspiration and biopsy: A sample is taken for the bone marrow to help doctors see if a healthy amount of blood cells is being made.
• Imaging tests: These tests may include x-ray, magnetic resonance imaging (MRI), or computed tomography (CT).
• Genetic testing: A small sample of blood is taken from a vein. Certain genes within the sample are checked for possible changes.

Hemophagocytic lymphohistiocytosis treatment

Treatment of HLH depends on the underlying cause and severity of symptoms. HLH is a complex condition. Parents should look for a health care provider who knows this condition well. Only a health care provider who is familiar with the condition should offer treatment for HLH.

Treatment of familial HLH

For children with familial HLH, the first step is to suppress the overactive immune system by reducing the number of activated immune cells and the cytokines. This is often done using a combination of steroids, cytokine inhibitors, and chemotherapy. Cytokine inhibitors such as emapalumab or ruxolitinib reduce the cytokine activity involved in the development of HLH. The goal is to put the condition in remission.

After this treatment, children with familial HLH usually undergo an allogeneic stem cell transplant. This procedure replaces the unhealthy immune system with a healthy one from a different person. This offers the best chance of a cure.

Treatment of acquired HLH

For children with acquired HLH, the goal is to identify and treat the underlying cause (such as an infection, cancer, or autoimmune condition). In many cases, this treatment puts the acquired HLH into remission. But sometimes health care providers will suggest steroids, medicines to inhibit cytokines, chemotherapy, or a combination of therapies.

Health care providers decide to use steroids, cytokine inhibitors, or chemotherapy based on how severe the HLH is. They do not make these decisions based on whether it is familial or acquired.

Living with hemophagocytic lymphohistiocytosis

People of any age with familial HLH should try to limit their exposure to infections of any kind. It is important to seek medical help if anything unusual appears. When a child has familial HLH, parents should talk to a genetic counselor about the chances of future children having the same condition.

Genetic counseling and testing can help patients and families understand familial HLH and the risk of passing it on to children.

Hemophagocytic lymphohistiocytosis care at St. Jude

St. Jude provides the highest quality of care for patients with hemophagocytic lymphohistiocytosis.

• St Jude has a multidisciplinary team called the Histiocytosis and Immune Dysregulation Team (HIT). They take care of patients with HLH. The team has multiple HLH experts, oncologists, infectious disease doctors, rheumatologists, hematologists, genetic counselors, pharmacists, intensive care doctors, and bone marrow transplant doctors. They review every case together as a team to develop an individualized treatment plan to control the HLH and reduce the risk of complications.
• The St. Jude Bone Marrow Transplantation and Cellular Therapy Department is one of the largest pediatric programs of its kind in the world.
• The St. Jude Transplant Program is approved by the Children's Oncology Group, the National Marrow Donor Program, the Pediatric Blood and Marrow Transplant Consortium, and the Center for International Blood and Marrow Transplant Research. The program is certified by the Foundation for Accreditation of Cellular Therapy.
• Doctors in the St. Jude Transplant Program work closely with scientists in the lab to quickly move new discoveries to patient care. This team conducts clinical trials to study new discoveries.
• The Transplant Unit at St. Jude is dedicated to the care of patients receiving bone marrow transplants, stem cell transplants, or cellular therapy. The transplant team includes doctors and nurse practitioners. A pediatric immunologist works closely with the transplant team. They have extensive training and experience in this lifesaving treatment for severe combined immunodeficiency (SCID). The team also includes registered nurses, a pharmacist, clinical dietitian, child life specialist, and social worker.
• Each patient room in the St. Jude Transplant Unit has an attached parent room. That room has a bed, bath, TV, and phone. Parents can stay with their child through the transplant process.

Hemophagocytic lymphohistiocytosis clinical trials