Salvage treatment of relapsed/refractory LCH.

Abstract

The Langerhan's cell histiocytosis (LCH) is a rare hematologic disorder of all age group, and the classification of LCH as a neoplasm of myeloid origin was introduced with the current observation of recurrent BRAFV600E mutation in LCH patients. LCH shows broad spectrum of clinical manifestations from single system involvement to wide spread multi-system (MS) disease, and this clinical variety is assumed to be determined by the differentiation stage of myeloid dendritic cells in which the mitogen-activated protein kinase (MAPK) pathway is aberrantly activated. The lesions of LCH typically show clonal proliferation of CD1a+/CD207+ cells with significant infiltration of inflammatory cells, and the documentation of this CD1a+ or CD207+ cell in biopsy specimen is required for the diagnosis of LCH. The survival of relapsed/refractory (R/R) high risk LCH patients was significantly improved with intensification of therapy, and the disease reactivation rate was somewhat reduced overtime due to prolongation of therapy during last two decades. Despite this improvements in survival and reactivation rate, the risk of permanent consequences of LCH was only marginally reduced [1]. Although most of the relapsed patients without risk organ involvement (RO−) can be salvaged successfully with less intensive chemotherapies, they are more likely to develop permanent consequences. The poor survival rate of MS LCH patients with RO involvement (RO+) who are refractory to or relapsing after standard chemotherapy was much improved with the introduction of salvage chemotherapy using 2CdA and Ara-C [2], but still there are patients not responding and dying with R/R disease. Therefore, the intensity and duration of second line treatment for these R/R MS LCH patients should be decided according to the status of RO involvement. LCH-IV protocols of the Histiocyte Society also employ the strategies of salvage therapy for patients with R/R LCH according to the status of RO involvement. The second line treatment for R/R RO− LCH patient needs to achieve disease resolution, prevent further reactivations and permanent consequences. Moreover, the goal of second line treatment for R/R RO+ LCH patient needs to include further reduction of mortality due to disease progression as well.