HLH Treatment Team: Overcoming Hurdles in Diagnosis and Treatment

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Oncology Update

When a child presents with hemophagocytic lymphohistiocytosis (HLH), taking action quickly is very important to outcomes. However, arriving at a diagnosis and deciding on a treatment plan for HLH is a complex process.

The newly formed HLH treatment team at The Children’s Hospital of Philadelphia helps physicians — including primary care pediatricians, who are often the first to spot symptoms of HLH — order the right tests, interpret the results, and plan treatment. The team includes oncologists, immunologists, pathologists, neurologists, rheumatologists, critical care physicians, clinical pharmacologists, and basic scientists. Within the Division of Oncology, David Teachey, MD, is the lead physician.

“In order to provide the best care for these complex patients, we have developed a unique multi-disciplinary model that provides a rapid, thorough, and highly integrative approach to treatment from multiple specialties,” he says.

Clinical features of HLH may include high and possibly prolonged periods of fever, enlargement of the spleen, rash, irritability, and/or seizures. Laboratory features include lowering of the blood counts and elevated levels of chemicals in the blood such as soluble interleukin 2 receptor (sIL-2r), certain cytokines and ferritin. Patients may exhibit immune cell abnormalities such as reduced expression of perforin, SAP or XIAP, and/or depressed cell functions (reduced cytotoxicity and/or degranulation).

In addition to immune function tests, patients in whom HLH is suspected should undergo mutational analysis of the HLH-associated genes. After these tests determine if the child has HLH and whether is it primary (familial) or secondary (sporadic), the team members at CHOP work together to determine the best course of treatment.

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. CHOP is able to offer options for this group of patients.

CHOP is participating in a multi-site pilot study, led by Cincinnati Children’s Hospital, evaluating hybrid immune therapy (ATG/ dexamethasone/etoposide) for HLH. In addition, CHOP has opened a clinical trial to test another HLH therapy, which adds the IL-6R inhibitor tocilizumab onto a standard HLH backbone (dexamethasone/ etoposide). A major cause of morbidity and mortality in children with HLH is cytokine storm. Recently, investigators at CHOP found that patients with ALL treated with chimeric antigen receptor T cells (CTL019) develop an HLH-like syndrome with cytokine storm that responds to tocilizumab. Based on these results, the HLH team hypothesized the addition of tocilizumab may improve the cytokine storm in children with newly diagnosed HLH.

If you’d like more information about the HLH team at CHOP or would like to discuss a case, please call Mia Benson- Smith, MS, at 267-426-0762 or contact us online.