The use of reduced-intensity stem cell transplantation in haemophagocytic lymphohistiocytosis and Langerhans cell histiocytosis

Allogeneic stem cell transplant is curative for haemophagocytic lymphohistiocytosis (HLH) and refractory Langerhans cell histiocytosis (LCH). However, patients frequently have significant pre-transplant morbidity and there is high TRM. Because HLH is caused by immune dysregulation, we surmised that a reduced-intensity conditioned (RIC) regimen might be sufficient for cure, while decreasing the TRM. In 2006, we reported the outcome of 12 patients treated with RIC SCT from a matched family/unrelated or haploidentical donor. Here we discuss the update of these patients, including a total of 25 patients treated with RIC SCT for HLH and three for LCH. Twenty-one of the twenty-five patients with HLH (84%) are alive and well with remission at a median of 36 months from SCT. Mortality included pneumonitis (n = 3) and hepatic rupture (n = 1). All three patients treated with RIC SCT for LCH remain alive and in remission at a median of 5.1 years from SCT. Seven of twenty-four survivors (one with LCH) have mixed chimerism but remain disease-free. These data are supported by other groups including 100% survival in seven patients with HLH and 78% survival of nine patients with LCH. In summary, RIC compares favourably with conventional SCT with long-term disease control in surviving patients with both HLH and LCL, despite a significant incidence of mixed chimerism.