This case study describes diagnosis and treatment performed in the HLH Center in the Cancer and Blood Diseases Institute at Cincinnati Children’s Hospital Medical Center. A 2-year-old girl was referred from the United Arab Emirates with history of relapsing HLH, a life-threatening genetic condition.  The only curative therapy is hematopoietic cell transplantation (HCT).

Clinical History

At 18 months of age, the patient fell ill with fevers, skin rashes, irritability and loss of appetite. Soon after admission to the local hospital, she developed respiratory distress and severe swelling requiring mechanical ventilation and hemodialysis. She was found to be in liver failure, with very low blood counts and persistently elevated blood markers of inflammation.

A bone marrow biopsy revealed hemophagocytosis (bone marrow cells “eating” normal blood cells), the hallmark of HLH.  Treatment was started with steroids and chemotherapy.  Although some symptoms improved initially, her condition worsened one month later and a recurrence of active HLH followed soon after. The disease had spread to involve the brain.

Our Approach

Soon after, the family came to Cincinnati for additional diagnostic testing and curative treatment with HCT. Although the patient had siblings who appeared to be perfect matches for the transplant, not enough was known about the genetic cause of her disease, and the possibility existed that one of the matching siblings could also be at risk to develop HLH.

This is where the capabilities of the Diagnostic Immunology Laboratory (DIL) and the Molecular Genetics Laboratory at Cincinnati Children’s came into play. These clinical laboratories are the only ones in North America that can test for all known genetic causes of HLH. In short order, the causal gene defect was identified in the sick child and other siblings were found not at risk for the same condition.  The patient’s older brother was identified as the bone marrow donor.

In the meantime, the patient required ongoing chemotherapy and high dose steroids, as well as chemotherapy delivered directly into the spinal fluid (intrathecal chemotherapy) to better control the HLH in the brain. After months of illness and high dose steroid treatment, she gained a great deal of weight, contributing to poor mobility, bed sores, and heightened risk of infections.

The HCT was performed at 2 years of age. Due to the patient’s condition, we used a reduced intensity course of pre-transplant chemotherapy (RIC).  Studies at Cincinnati Children’s comparing outcomes of RIC vs. conventional HCT for HLH had shown that post-transplant survival following RIC was superior to the conventional approaches to pre-transplant chemotherapies (90 percent vs. 50 percent long-term disease-free survival). 

Although the patient still required some intrathecal chemotherapy post HCT, she began to strengthen and achieved a full recovery with normal brain function in a matter of months. She was able to return to the U.A.E. before her third birthday, cured of HLH. At a follow-up visit to Cincinnati Children’s one year later, the patient appeared svelte and energetic – a normal, happy child. 


While this child was fortunate to have a perfect match for HCT, not all patients with HLH will have suitable HCT donors, and other therapeutic approaches are being developed to control the disease.

Current research at Cincinnati Children’s is investigating the feasibility of gene therapy for patients without suitably matched HCT donors, and the use of small molecule therapy for cases of HLH in adults that tend to be milder, but recurrent.

Molecular studies are under way to unravel the complex immunology of active HLH disease in order to identify targeted biologic agents with fewer side effects.

Once universally lethal, HLH is now curable.