Our Treatment Approach

Cincinnati Children’s Approach to LCH and Histiocytic Disorder Treatment

At Cincinnati Children’s Histiocytosis Center, we take a comprehensive approach to every patient case. That means getting a full view into a patient’s condition, including clinical information, radiology and pathology.

Our team also has some of the country’s leading experts in Langerhans cell histiocytosis (LCH) and histiocytic disorders. We have the expertise in conducting concise but broad immunophenotypic panels, allowing us to make more accurate and complete diagnoses.

We also believe in finding new treatment options for these diseases, as the standard therapy fails close to 50% of patients. With the knowledge that many histiocytic disorders are tied to BRAF and MEK gene mutations, our team has explored a novel treatment regimen that uses the gene inhibitors dabrafenib and trametinib — including use in frontline treatment. These treatments have proven to be successful in every one of our patients, and we are actively exploring new clinical trials in hopes of finding an improved standard of care.

Overview of Histiocytic Disorders

Histiocytic disorders include conditions that result in the over-production of histiocytes (dendritic cells and macrophage cells). We classify these disorders based on the type of histiocyte involved. The classifications include:

  • Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD) and juvenile xanthogranuloma (JXG), Rosai-Dorfman disease (RDD) and ALK histiocytosis
  • Malignant histiocytic conditions, which include histiocytic sarcomas, blood cancers and other malignant tumors
  • Post-leukemic / lymphoma histiocytic disorders

Symptoms of histiocytic disorders vary depending on the type of disease, but can include rash lesions, lymph node swelling, and/or mass lesions of the bones or organs. In some cases, histiocytic disorders can cause diabetes insipidus, which can cause increased thirst and excessive urination.

Treatment for histiocytic disorders depends on the level of system involvement and can range from observation to systemic therapy.

At the Histiocytosis Center, we treat all forms of histiocytic disorders. Cincinnati Children’s also has a comprehensive treatment program for hemophagocytic lymphohistiocytosis (HLH).

How We Treat Histiocytic Disorders 

We treat most histiocytic disorders similarly. If the lesion is confined to just one area, we may decide not to pursue treatment right away. Histiocytic disorders that are confined to just the skin or a single bone often go away on their own. 

Combination Chemotherapy

If the histiocytic disorder involves multiple organ systems or multiple bony lesions, systemic therapy is recommended. The current standard of care is one year of combination chemotherapy treatment using prednisone and vinblastine. In some instances, 6-MP may be added to the prednisone-vinblastine combination. 

Another, single-drug chemotherapy regimen using cytarabine is currently being tested as an alternative to prednisone-vinblastine. However, early results show it has marginally better results. 

Gene Inhibitor Therapy

The standard chemotherapy regimen fails many patients, even those who initially respond to treatment. In patients with Langerhans cell histiocytosis who undergo chemotherapy, the relapse rate at the one-year mark is as high as 40%, and the treatment doesn’t work for 15% to 20% of patients. 

In an effort to find a more effective treatment option for patients, the Histiocytosis Center has explored novel gene inhibitor therapies. These oral therapies included the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib. Since starting to explore these treatments in 2016, we have seen a positive response in all patients while on therapy. 

MEK Inhibitors 

Recent findings have shown that MEK inhibitor treatment is therapeutically effective against most genetic mutations that cause histiocytic disorders, including those with BRAF-V600E mutation. With that knowledge, we have been using MEK inhibitors as a universal frontline treatment for patients with any genetic mutations that need systemic therapy.

Because of the positive patient response we’ve seen with the MEK inhibitors, Cincinnati Children’s is actively pursuing a clinical trial that would study a new MEK inhibitor. 

We are also actively studying the ideal length of treatment for gene inhibitors. While we see positive effects in some patients within a few weeks, many patients need to be on the treatment for at least one or two years. Our laboratory studies are focusing on finding the best way to monitor the clinical course of disease and better predict when the mutant cells have completely disappeared from the body.


One of the challenges in treating histiocytic diseases has been the lack of reliable tools to assess the presence of minimal residual disease (MRD) cells that can cause recurrence. Historically, clinicians have relied on imaging studies to determine the response to treatment and for the presence of active disease. However, imaging studies (MRI, PET-CT) cannot detect MRD. In recent years, we have relied on a blood test to detect the most commonly found mutation in histiocytic diseases, namely BRAF-V600E. This test uses a methodology called real-time PCR which can detect minute amounts of mutant DNA in blood. However, we and other researchers found that even this test was not sensitive enough to detect residual disease cells (Lee et al, Blood Advances 2020). A more sensitive technique called droplet-digital PCR (ddPCR) has recently been devised. In recent research studies, we were able to detect BRAF-V600E mutant cells in the blood of patients who did not have detectable disease either by imaging or even by real-time PCR. In collaboration with our colleagues Dr. Somak Roy and Dr. Jennifer Picarsic, we have now developed ddPCR for BRAF-V600E as a clinically available test called HistioTrak. This test has already helped us make treatment decisions in several patients – identifying the presence of mutant cells in patients in whom imaging and real-time PCR were negative. Most importantly, HistioTrak helped us confirm the diagnosis of histiocytosis in patients in whom a tissue diagnosis was not feasible.

HistioTrak Test Information

How to Order HistioTrak