HLH Treatment Team: Overcoming Hurdles in Diagnosis and Treatment

Hemophagocytic lymphohistiocytosis (HLH) is a disorder in which too many infection-fighting cells are produced and activated, causing organ inflammation and damage. If HLH is diagnosed quickly and accurately at a center equipped to manage this complicated disease, a cure is possible. The Children’s Hospital of Philadelphia (CHOP) has a team of experts dedicated to treating HLH.

Our approach to HLH

HLH is not a cancer, but it is treated with some of the same medications as leukemia and lymphoma. To provide the best outcomes for children, CHOP has formed an HLH Treatment Team consisting of oncologists, immunologists, pathologists, neurologists, rheumatologists, clinical pharmacologists and basic scientists. These experts work together to coordinate the care required for a child with HLH.

The HLH treatment team helps CHOP pediatricians, and other local physicians, with the diagnosis and treatment of HLH. Because taking action quickly is important to getting the best outcome for children with HLH, the team helps guide physicians through the complex process of ordering the right tests, interpreting their results, diagnosing the disease and deciding on the treatment plan. Together, these services ensure that the patient gets the care he or she needs as quickly as possible.

Diagnosis of HLH

A suspicion of HLH is raised when children exhibit specific clinical and laboratory manifestations.

The clinical features include high and often prolonged periods of fever, enlargement of the spleen, and at times rash, irritability and/or seizures.

Laboratory features include lowering of the blood counts, elevated levels of chemicals in the blood such as soluble interleukin 2 receptor (sIL-2r), certain cytokines and ferritin. Patients with HLH also often exhibit abnormalities in their immune cells, such as reduced expression of proteins such as perforin, SAP or XIAP, and/or depressed cell functions (reduced cytotoxicity and/or degranulation).

Testing for HLH

In addition to routine blood work, children suspected to have HLH will undergo specialized diagnostic tests. These include:

• A panel of immune function tests
• Genetic testing; mutational analysis of the HLH associated genes

These tests will help determine whether your child has HLH, and if so, whether it is primary (familial) or secondary (sporadic) HLH.

• Primary HLH is genetic, and often requires stem cell transplantation as a part of the treatment.
• Secondary HLH is an acquired form of the disease that is triggered by an infection, malignancy, auto-immune disease or other immune challenge. It does not require that patients undergo stem cell transplantation.

How we treat HLH

For children with primary HLH, the first step is to suppress the overactive immune system, commonly by treatment with a combination of steroids and chemotherapy; the goal is to put the disease in remission.

After this initial treatment, children with familial HLH generally undergo allogeneic stem cell transplantation (replacing their defective immune system with a healthy one from a different person), which offers the best chance of a cure.

For children with secondary HLH, the medical team will try to identify and treat the underlying cause of the HLH (the trigger). Generally, this is sufficient to put the HLH into remission. However, it is sometimes necessary to use steroids and/or chemotherapy, as in the case of primary HLH.

Finding more options to treat HLH

The biggest hurdle in HLH treatment is identifying alternatives for children who don’t respond to currently available combinations of chemotherapy, steroids and stem cell transplantation. HLH experts at CHOP are hard at work in the lab studying the functions of immune cells in HLH patients, trying to identify new genetic causes for familial HLH and testing new drugs that might be effective for patients who experience a relapse or whose HLH does not respond to current treatments.

CHOP is also participating in a multi-site pilot study led by Cincinnati Children’s Hospital, which is evaluating the safety and effectiveness of a novel treatment regimen for patients with HLH. CHOP will open its own in-house clinical trial to test another type of HLH therapy in the spring of 2014. Check back for more information.

CHOP would like to acknowledge the family of Sean Fischel, a young boy who died of HLH. The Fischels have raised nearly $50,000 for HLH research at CHOP. Their support is invaluable in our search to find new, more effective treatment options for children with this disease.

Other services provided by HLH treatment team

For HLH patient families

For those children with HLH, our experts offer a variety of services in addition to the many treatment-related recommendations. The team:

• Educates families about the different causes of HLH
• Explains and coordinates HLH genetic testing
• Offers genetic counseling about the risk of occurrence of HLH in future offspring
• Provides access to and enrollment in ongoing research on HLH biology, genetics and treatment
• Offers psychosocial support services for patients and their families
• Connects your family to other families facing a diagnosis of HLH

For referring physicians

The HLH treatment team works closely with primary care physicians, who are often the first to spot signs of HLH. For these physicians, the team:

• Provides a comprehensive, detailed written review of a patient's consultation
• Collaborates in the medical management of patients
• Recommends patient referrals to additional specialists, as needed
• Explains and interprets the results of HLH genetic and immunologic tests
• Provides educational materials on HLH genetics and genetic testing