LCH is a rare disease of the myeloid cells that may affect any age group. It can affect many different organs, including the skeleton, skin, lymph nodes, liver, lungs, spleen, hematopoiesis, or central nervous system (CNS). Accordingly, the range of clinical symptoms is wide. There are two widely recognized disease extent categories: 1) single-system LCH (involvement of a single organ or system), and 2) multisystem LCH (involvement of two or more organ systems). Patients with SS-LCH of the skeleton, skin, or the lymph nodes have an excellent prognosis and are felt to need a minimum or sometimes even no treatment at all.
The course of multisystem LCH (MS-LCH) is unpredictable upon diagnosis, ranging from spontaneous resolution to fulminant progression and fatal outcome. Involvement of crucial organs like the hematopoietic system, liver, or spleen has been found to herald a poor prognosis in different studies. Recent large clinical trials have shown that the response to initial treatment is a highly important prognostic factor. Patients with MS-LCH without involvement of “risk organs” have very high (>95%) probability of survival when treated with a standard regimen consisting of vinblastine and steroids. In contrast, involvement of risk organs carries the risk of unfavorable outcome.
Patients with reactivations or chronic disease may experience severe permanent consequences (PC) reducing the patient’s quality of life, in particular when they affect the CNS or lungs and lead to hormone deficiencies, a neurodegenerative syndrome, lung fibrosis, etc.
The international efforts of the past 20 years have shown that combination therapy with vinblastine and prednisone is an effective therapy for MS-LCH. The previous prospective trial LCH-III confirmed this regimen as a standard regimen for MS-LCH in patients with and without risk organ involvement. It also showed that prolonged treatment in the latter group (treatment duration of 12 vs. 6 months) is superior in preventing disease reactivations. The results of this trial are encouraging and serve as a basis for the LCH-IV study design.
Due to the complexity of the disease presentations and outcomes, the LCH-IV study seeks to tailor treatment based on features at presentation and on response to treatment, leading to seven strata:
Carlos Rodriguez-Galindo, MD, Co-Chair
St. Jude Children's Research Hospital, Memphis, TN USA
Learn more about opening the LCH-IV at your institution.
View more information about this study on ClinicalTrials.gov.