Haematopoietic stem cell transplantation for refractory Langerhans cell histiocytosis: outcome by intensity of conditioning

Paul A Veys, Vasanta Nanduri, K Scott Baker, Wensheng He, Giuseppe Bandini, Andrea Biondi, Arnaud Dalissier, Jeffrey H Davis, Gretchen M Eames, R Maarten Egeler, Alexandra H Filipovich, Alain Fischer, Herbert Jürgens, Robert Krance, Edoardo Lanino, Wing H Leung, Susanne Matthes, Gérard Michel, Paul J Orchard, Anna Pieczonka, Olle Ringdén, Paul G Schlegel, Anne Sirvent, Kim Vettenranta, Mary Eapen

Patients with Langerhans cell histiocytosis (LCH) refractory to conventional chemotherapy have a poor outcome. There are currently two promising treatment strategies for high-risk patients: the first involves the combination of 2-chlorodeoxyadenosine and cytarabine; the other approach is allogeneic haematopoietic stem cell transplantation (HSCT). Here we evaluated 87 patients with high-risk LCH who were transplanted between 1990 and 2013. Prior to the year 2000, most patients underwent HSCT following myeloablative conditioning (MAC): only 5 of 20 patients (25%) survived with a high rate (55%) of transplant-related mortality (TRM). After the year 2000 an increasing number of patients underwent HSCT with reduced intensity conditioning (RIC): 49/67 (73%) patients survived, however, the improved survival was not overtly achieved by the introduction of RIC regimens with similar 3-year probability of survival after MAC (77%) and RIC transplantation (71%). There was no significant difference in TRM by conditioning regimen intensity but relapse rates were higher after RIC compared to MAC regimens (28% vs. 8%, P = 0·02), although most patients relapsing after RIC transplantation could be salvaged with further chemotherapy. HSCT may be a curative approach in 3 out of 4 patients with high risk LCH refractory to chemotherapy: the optimal choice of HSCT conditioning remains uncertain.