Hemophagocytic lymphohistiocytosis is a rare disorder usually affecting infants and young children, but it can occur at any age. While the exact cause of HLH is unknown, it is felt to be caused by a disorder of immune system regulation, which leads to the activation of infection fighting cells called histiocytes and lymphocytes. Their normal function is to travel throughout the body and destroy foreign material and fight infections. Patients with HLH have too many of these activated histiocytes and they begin to accumulate in normal tissue and cause inflammation and damage to a variety of organs. Common sites of involvement include the bone marrow, lymph nodes, liver, spleen, and brain.
There are two main types of HLH, the familial form and the secondary form. The familial form of HLH (FHL) is genetic, and families who have more than one child with HLH will be diagnosed with this form. In these families, there will be a 25% risk that each subsequent sibling will develop FHL usually within the first 2 years of life.
The secondary form of HLH develops secondary to abnormal activation of the immune system, which can occur after certain infections or after the use of drugs which suppress the immune system. It is very difficult to tell these two forms apart without a previously affected sibling. However, early age of onset is suggestive of the familial form and onset in older children is more common in the secondary form and there may be an association with a recently detected infection. It is important to note though, that children with FHL may also have the disease triggered by an infection.
Most children with HLH will develop fevers, enlargement of the liver, spleen and sometimes lymph nodes. They will have low blood counts (anemia and low white blood cell and platelet counts). Some may also develop bleeding and seizures. The first step in the treatment of the disease is to get it controlled and into remission. This is usually accomplished with chemotherapy and immunosuppressive medications. In the primary form of HLH disease control is temporary and the disease will eventually return if treatment is discontinued. In secondary HLH, if the underlying cause of the disease can be treated the HLH may be cured, however, even in some of those children remission may only be temporary.
The only know cure for HLH is blood or marrow transplantation. For this procedure high doses of chemotherapy are given to destroy the patients bone marrow, which is where the abnormal immune system cells come from. Ideally, the transplant should be performed when the disease is in complete remission (no signs of any active disease). Blood or marrow transplant is most successful when a normal sibling who has the same tissue (or HLA) type is used for the donor. Unfortunately, only about 10-15% of children with HLH will have a sibling donor available. However, the University of Minnesota has been a leader in research that has led to the successful use of bone marrow from unrelated donors, peripheral blood stem cells, or umbilical cord blood, for the source of normal bone marrow and immune system cells. Because of this, a donor can be identified for the majority of children with HLH.