sirolimus treatment for refractory prca

Conditions: Pure Red Cell Aplasia

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.

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.

Eligibility criteria:
inclusion criteria: 1. refractory pure red cell aplasia. 2. excluding other diseases which might cause hematological abnormalities. 3. no response or intolerant to first and second line therapies. 4. 18-80 years old. 5. all subjects must: agree not to donate blood or be counseled about pregnancy precautions and risks of fetal exposure. 6. written informed consent. exclusion criteria: 1. not refractory pure red cell anemia. 2. response and well tolerate to first or second line therapy. 3. patients who are under 18-year-old or over 80-year-old. 4. pregnant or lactating. 5. patients unwilling to or unable to comply with the protocol.

Keywords: sirolimus refractory pure red cell aplasia prospective study