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

Karen L. Bride, Tiffaney Vincent, Kim Smith-Whitley, Michele P. Lambert, Jack J. Bleesing, Alix E. Seif, Catherine S. Manno, James Casper, Stephan A. Grupp and David T. Teachey

Key points

  • Sirolimus monotherapy is a safe and effective, steroid-sparing agent, improving autoimmune cytopenias in highly refractory patients.

  • Sirolimus is particularly active in ALPS and should be an early therapy option for patients who require chronic therapy.


Patients with autoimmune multi-lineage 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, including rapid improvement in autoimmune disease, lymphadenopathy, and splenomegaly within 1-3 months of starting sirolimus. Double negative T (DNT) 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 multi-lineage cytopenias secondary to common variable immune deficiency (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 two responded. Sirolimus was well tolerated with very few side effects. All of the responding patients have remained on therapy for over one year (median 2 years, range 1–4.5 years). In summary, sirolimus led to complete and durable responses in a majority of children with refractory multi-lineage autoimmune cytopenias. The responses seen in ALPS patients were profound suggesting that sirolimus should be considered as a first-line, steroid-sparing treatment for patients needing chronic therapy. The results in other multi-lineage autoimmune cytopenia cohorts were encouraging and sirolimus should be considered in children with SLE, ES, and CVID.

  • Submitted July 30, 2015.
  • Accepted September 22, 2015.