Sirolimus Combined With ATRA for the Treatment of Auto-Immune Anemia
Status:
Not yet recruiting
Trial end date:
2022-12-01
Target enrollment:
Participant gender:
Summary
Autoimmune anemia (AIA), including autoimmune hemolytic anemia (AIHA), EVENs' syndrome (ES),
acquired pure red aplastic anemia (PRCA), is a kind of anemia disease mediated by
autoimmunity, which can be primary or secondary to other diseases including autoimmune
disease, malignant tumor, infection, etc. Glucocorticoid is the first-line treatment.
However, the recurrence rate is very high and some patients may not response to steroids, the
latter defined as refractory autoimmune anemia (RAIA). Second-line therapies include
cyclosporine A (CSA), cyclophosphamide, 6-mercaptopurine, CD20 monoclonal antibody, anti
human lymphocyte immunoglobulin (ATG), and even splenectomy. Cyclosporine A is easy to accept
while some patients may have side effects such as renal function damage, gingival
hyperplasia, hypertension and so on. Other second-line drugs also have many problems, such as
low effective rate, slow onset, expensive price, and large side effects, and some patients do
not response to these treatments. The refractory/relapsed AIA patients have increased
cardiovascular events, increased opportunities for infections, decreased quality of life, and
even death. At present, there is still no effective treatment for these patients. Our
previous retrospective study showed that sirolimus was effective in cyclosporine refractory
PRCA with an effective rate of 70% and slight side effects. In addition, we used sirolimus in
refractory AIHA and ES, with an effective rate of 60-70%. However, there are still some
non-responsive patients. Recently, it has been reported that all trans retinoic acid (ATRA)
combined with danazol was effective in the treatment of refractory immune thrombocytopenic
purpura (ITP). Therefore, we plans to combine sirolimus and ATRA in the treatment of
refractory AIA to improve the efficacy. Since both sirolimus and ATRA are cheap and have
slight side effects, this combination may reduce the economic burden of patients and reduce
the side effects related to treatment.