Immunosuppressive therapy for transplant-ineligible aplastic anemia patients

Abstract

Aplastic anemia is a rare life-threatening bone marrow failure that is characterized by bicytopenia or pancytopenia in the peripheral blood and a hypoplastic or aplastic bone marrow. The patients are at risk of infection and hemorrhage due to neutropenia and thrombocytopenia and suffer from symptoms of anemia. The main treatment approaches are allogeneic stem cell transplantation and immunosuppression. Here, we review current standard immunosuppression and the attempts that have been made in the past two decades to improve results: review of recent developments also reveals that sometimes not only the advent of new drugs, good ideas and well-designed clinical trials decide the progress in the field but also marketing considerations of pharmaceutical companies. Aplastic anemia experts unfortunately had to face the situation that efficient drugs were withdrawn simply for marketing considerations. We will discuss the current options and challenges in first-line treatment and management of relapsing and refractory patients with an emphasis on adult patients. Some promising new approaches are currently under investigation in prospective, randomized trials.

Association of Human Leukocyte Antigen DRB1*15 and DRB1*15:01 Polymorphisms with Response to Immunosuppressive Therapy in Patients with Aplastic Anemia: A Meta-Analysis

“…The mechanism of activation of cytotoxic T cells is uncertain, but several potential factors related to antigen recognition, susceptibility of immune response, and secretion of cytokines might be involved. Certain human leukocyte antigen (HLA) alleles were suggested to play a role in the activation of autoreactive T-cell clones in patients with AA [2]. Till date, potential roles of HLA-DRB1 polymorphisms have been postulated in many types of autoimmune diseases (e.g., systemic lupus erythematosus and lupus nephritis[3], rheumatoid arthritis[4]).…”

“…Patients with AA have been treated with IST and hematopoietic stem cell transplantation [1, 2]. However, a lack of HLA-matched sibling donors and the cost of transplantation result in most patients with AA tending to accept IST.…”

“…However, a lack of HLA-matched sibling donors and the cost of transplantation result in most patients with AA tending to accept IST. IST contains cyclosporin (CsA), antithymocyte globulin (ATG), and antilymphocyte globulin (ALG) [1, 2, 20]. In addition, androgen and traditional Chinese medicine (TCM) also showed some effect on AA [21, 22].…”

Rapamycin targets several pathophysiological features of immune-mediated bone marrow failure in murine models

“…Moreover, IST is not effective in treating refractory and relapsed AA. [7][8][9][10][11][12] Recently, combined application of eltrombopag, a thrombopoietin mimetic, and standard IST has proven to be very effective in treating patients with refractory and severe AA. However, relapse and clonal evolution remain important post-therapy concerns.…”