Hematopoietic stem cell transplantation for Langerhans cell histiocytosis: clinical findings and long-term outcomes

ABSTRACT Introduction Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia characterized by accumulation of bone marrow-derived immature dendritic cells harboring oncogenic mutations in mitogen-activated protein kinase (MAPK) pathway genes, such as BRAF V600E, and various reactive inflammatory cells. Infants with chemo-resistant multisystem disease with risk organ involvement [MS-RO(+)] have poor prognosis. Further, relapsed infants have a significant risk of developing disastrous neuro-degenerative central nervous system disease. Areas covered This review covers published papers on hematopoietic stem cell transplantation (HSCT) for LCH selected through a literature search on PubMed between years 1985 and 2019. Expert opinion: Infants with refractory MS-RO(+) disease or with frequent treatment-resistant relapses can benefit from allogeneic HSCT (allo-HSCT). Selection of an HLA-matched sibling or unrelated cord blood (UCB) stem cell source and use of reduced intensity conditioning (RIC) preparative regimens, based on the combination fludarabine with melphalan, are preferable. Most deaths after HSCT occur within 3 months, due to transplantation-related complications. LCH disease activity usually regresses over 3 months after allo-HSCT in survivors. The disease activity at HSCT is the most important prognostic factor. Prior to HSCT, the disease activity should be reduced by treatment.