Sirolimus improves lymphoproliferation, autoimmune cytopenias and double negative T cells in patients with ALPS. Four patients were treated with sirolimus for autoimmune cytopenias. Panels depict changes in platelet count (A), ANC (B) and haemoglobin (C). Patients 1 and 3 had autoimmune pancytopenia. Patient 2 only had autoimmune thrombocytopenia. Patient 4 had autoimmune neutropenia and thrombocytopenia. The x-axis depicts time in weeks with data for every 2-week time points if available. NOTE change in scale after 16 weeks demarcated by vertical purple line. Week 0 (zero) is the time sirolimus was initiated. Arrows depict the time points when steroids were stopped. Panel D depicts peripheral blood DNTS (Double negative T cells; T cell phenotype: CD3⁺, CD4⁻, CD8⁻, TCRa/b⁺). DNTs were collected prior to initiating sirolimus and on therapy. All patients demonstrated significant reduction in DNTs. Post-treatment data point represents time 4–8 weeks after steroids stopped except for Patient 5 who had his level obtained on low dose steroids (5 mg every other day). Panel E depicts Fluorodeoxyglucose (FDG) PET–CT imaging, demonstrating a marked improvement in lymphadenopathy and splenomegaly in Patient 1 with ALPS after 3 months of treatment with sirolimus. Improvement was demonstrated in size of lymph nodes and spleen and in FDG-uptake. Upper panels represent pre-treatment (marked by arrows) and lower panels represent post-treatment.