Sirolimus Treatment for Refractory PRCA
Condition: Pure Red Cell Aplasia
MeSH terms: Red-Cell Aplasia, Pure
Study type: Interventional
Phase: Phase 4

Summary: 
      Pure red cell aplasia (PRCA) is a kind of anemia characterized by severe reticulocytopenia
      and obvious bone marrow erythroblastic cells decreased. Cyclosporine and /or steroids are the
      first line therapy but some patients were refractory or intolerance to the treatment. The
      effects of the second line therapy are also not satisfactory and sometimes not available. The
      investigators aim to explore the efficacy and side-effect of sirolimus for refractory PRCA.
    

Detailed description: 
      Pure red cell aplasia (PRCA) is a rare normocytic normochromic anemia with reticulocytopenia,
      characterized by a reduction of erythroid precursors from the bone marrow, could be divided
      into congenital and acquired PRCA according to pathogenesis. Congenital PRCA, also known as
      Diamond-Blackfan syndrome, has been associated with pathogenic variant in GATA1 and TSR2 and
      gene encode ribosomal proteins. Acquired PRCA can be a primary disease which is usually
      mediated by immunology, or secondary to other diseases, such as lymphoproliferative diseases,
      autoimmune diseases, thymoma, infection, or drugs. The first line therapy of acquired PRCA is
      Cyclosporine A and steroids, the second line therapy are anti-CD20, ATG, immunosuppressive
      drugs like cyclophosphamide, bone marrow transplantation. Unfortunately, some patients did
      not response or tolerate the above treatments.

      Sirolimus (rapamycin) is an agent produced by the bacterium Streptomyces hygroscopicus,
      inhibits the mammalian target of rapamycin (mTOR). mTOR is a serine/threonine kinase that
      regulates cell growth, proliferation, metabolism and survival in eukaryotic cells, and is
      identified as two interacting complex, mTORC1 and mTORC2. Sirolimus primarily inhibits
      mTORC1, has been approved for prevent organ transplant rejection, especially in renal
      transplantation, sirolimus also promises to treat autoimmune, degenerative and
      hyperproliferative disorders. Recently, sirolimus has been reported to be effective and well
      tolerated for many immune-mediated cytopenias, such as autoimmune lymphoproliferative
      syndrome, immune thrombocytopenia, EVANS syndrome, etc. However, due to the rare occurrence
      of PRCA and good response rate to cyclosporine, there are very few studies of sirolimus on
      refractory PRCA so far.

      In this study, It is anticipate to evaluate the effect of sirolimus on 30 patients with
      refractory PRCA, the side-effects was documented and plasma concentration of sirolimus will
      be monitor.
    

Intervention name(s): Sirolimus
Intervention type(s): Drug
Intervention description(s): On refractory PRCA patients, sirolimus was tried. Dosage: 2mg QD for the first day, then 1 mg QD. Medication time should last at least 6 months.
Other intervention name(s): Sirolimus Tablets
Intervention MeSH terms: Sirolimus; Temsirolimus; MTOR Inhibitors
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: sirolimus; refractory pure red cell aplasia; prospective study