Current HLH Treatment Protocols Potentially Inadequate

Therese Posas-Mendoza, MD

Hemophagocytic lymphohistiocytosis (HLH) patients who were treated with HLH protocol had a high mortality rate, according to new findings presented at the 14th Annual North American Young Rheumatology Investigator Forum (NYRIF 2020).

Additionally, the majority of patients with macrophage activation syndrome (MAS) treated with targeted disease-specific therapy experienced a resolution of symptoms.

A rare life-threatening disease, HLH is often triggered by malignancies, infection—such as Epstein-Barr virus—or an underlying rheumatic condition.

“The approach to the management of secondary HLH can be confusing and problematic due to the rarity of the condition and the heterogeneity of treatment approaches for HLH,” they wrote.

Therese Posas-Mendoza, MD, Fellow at the Department of Rheumatology, Ochsner Medical Center, and colleagues used EPIC slicer dicer to compare predisposing conditions, treatments, and outcomes in patients diagnosed with HLH or MAS between January 2013 and 2019.

Using either the HLH-2004 criteria or H-Score criteria, the investigators included a total of 29 patients in their review.

Of the total assessed, 7 patients had a malignancy, 11 had a rheumatic disease, 6 had an infection along, 2 were transplant patients, and 3 had a combination of malignancy, rheumatic disease, and/or infection.

The investigators also noted that all patients presented with a fever.

In their review, Posas-Mendoza and team reported that 73% (11/15) of patients treated with HLH protocol died. Furthermore, 13% had recurrence of HLH, and 6% developed an invasive fungal infection.

Of the deaths, 45% were secondary to septic shock, 45% were secondary to aggressive HLH and/or advanced malignancy, and 9% were secondary to massive ischemic stroke.

Another 14 of the 29 patients were treated with targeted therapy. Of this cohort, 92% experienced a resolution of symptoms and 7% died from septic shock.

The investigators noted their findings of high mortality rate among patients with HLH were similar to the malignancy-associated mortality rates reported in previous literature (42-88%).

They also indicated that their results showed the importance of treating MAS patients differently from other types of HLH.

Although there is specific recommended protocol to treat MAS-HLH—which is based on concomitant adult onset Still’s disease and MAS-HLH— no such validated management protocols exist for adult secondary HLH.

As they noted, existing protocols are based of case reports and case series.

“Our study highlights that MAS-HLH can be successfully managed in different ways depending on the associated rheumatic disease,” the investigators concluded.

This underscores a potential twofold need to update existing treatment protocols for HLH and employ more targeted treatment.

The study, “Etiologies and Management of Hemophagocytic Lymphohistiocytosis: Is it Time for an Updated Protocol and Targeted Treatments?” was presented at NYRIF 2020.