The optimal treatment strategy for adult Langerhans cell histiocytosis (LCH) remains unclear. Our previous study demonstrated the remarkable efficacy of combined methotrexate and cytarabine (Ara-C) [MA] therapy in patients newly diagnosed with LCH, with a median follow-up of 2 years. The present article reports long-term follow-up data spanning a median of 78 months (6.5 years) from a single-arm, single-centre, prospective phase 2 clinical trial (NCT02389400) conducted between January 2014 and December 2020. Ninety-five adults with newly diagnosed LCH exhibiting multisystem disease or multifocal single-system involvement underwent MA therapy every 35 days for six cycles. Methotrexate (1 g/m