Sirolimus Treatment for Newly Diagnosed Primary Acquired Pure Red Cell Aplasia: a Single Center Prospective Study

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 (CsA) and steroids, the second line therapy are anti-CD20, anti-human thymocyte immunoglobulin, 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. Some case reports and our previous retrospective study showed that sirolimus was effective for refractory/relapse PRCA with good tolerance. However, due to the rare occurrence of PRCA and good response rate to CsA, there are very few studies of sirolimus on newly diagnosed PRCA so far.

In this study, It is anticipated to evaluate the efficacy and safety of sirolimus versus CsA in patients with newly diagnosed PRCA . The side-effects will be documented and plasma concentration of sirolimus will be monitored. Furthermore, an interim analysis will be performed to assess the treatment efficacy and safety of sirolimus versus CsA in primary PRCA patients when a total of 56 eligible participants finished the designed treatment.