Sirolimus is effective in relapsed/refractory autoimmune cytopenias: results of a prospective multi-institutional trial

Blood. 2016 Jan 7;127(1):17-28. doi: 10.1182/blood-2015-07-657981. Epub 2015 Oct 26.


Patients with autoimmune multilineage cytopenias are often refractory to standard therapies requiring chronic immunosuppression with medications with limited efficacy and high toxicity. We present data on 30 patients treated on a multicenter prospective clinical trial using sirolimus as monotherapy. All children (N = 12) with autoimmune lymphoproliferative syndrome (ALPS) achieved a durable complete response (CR), including rapid improvement in autoimmune disease, lymphadenopathy, and splenomegaly within 1 to 3 months of starting sirolimus. Double-negative T cells were no longer detectable in most, yet other lymphocyte populations were spared, suggesting a targeted effect of sirolimus. We also treated 12 patients with multilineage cytopenias secondary to common variable immunodeficiency (CVID), Evans syndrome (ES), or systemic lupus erythematosus (SLE), and most achieved a CR (N = 8), although the time to CR was often slower than was seen in ALPS. Six children with single-lineage autoimmune cytopenias were treated and only 2 responded. Sirolimus was well tolerated with very few side effects. All of the responding patients have remained on therapy for over 1 year (median, 2 years; range, 1 to 4.5 years). In summary, sirolimus led to CR and durable responses in a majority of children with refractory multilineage autoimmune cytopenias. The responses seen in ALPS patients were profound, suggesting that sirolimus should be considered as a first-line, steroid-sparing treatment of patients needing chronic therapy. The results in other multilineage autoimmune cytopenia cohorts were encouraging, and sirolimus should be considered in children with SLE, ES, and CVID. This trial was registered at as #NCT00392951.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / mortality
  • Autoimmune Diseases / pathology
  • Child
  • Child, Preschool
  • Drug Resistance, Neoplasm / drug effects*
  • Female
  • Follow-Up Studies
  • Hematologic Diseases / drug therapy*
  • Hematologic Diseases / mortality
  • Hematologic Diseases / pathology
  • Humans
  • Immunosuppressive Agents / pharmacokinetics
  • Immunosuppressive Agents / therapeutic use*
  • Infant
  • Male
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Prognosis
  • Prospective Studies
  • Salvage Therapy*
  • Sirolimus / pharmacokinetics
  • Sirolimus / therapeutic use*
  • Survival Rate
  • Tissue Distribution
  • Young Adult


  • Immunosuppressive Agents
  • Sirolimus

Associated data