Background: Autoimmune cytopenias are defined by immune-mediated destruction of distinct hematopoietic lineages, including white blood cells, red blood cells, and platelets. The destruction of a single lineage in response to an unknown stimulus is known as a primary or idiopathic autoimmune cytopenia. These include immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and autoimmune neutropenia (AIN). The primary treatment modality for all autoimmune cytopenias are drugs that suppress or modulate the immune system. Typically first-line treatment involves the use of corticosteroids. However, this treatment modality often requires prolonged use of steroids, which impacts the quality of life of affected patients and causes multiple adverse side effects. For the treatment of pediatric autoimmune cytopenias, the goal of therapy is to modulate the immune system and hence stabilize counts, while also preventing adverse side effects secondary to medications. Mycophenolate mofetil (MMF) is an immunosuppressive drug that inhibits lymphocyte proliferation and limits the mobilization of leukocytes to sites of inflammation. Here, we propose a novel combination therapy of MMF, an adjunct immunosuppressive, and corticosteroids. This combination may allow for rapid decrease of steroid usage as well as prolonged count stabilization in pediatric patients with autoimmune cytopenias.
Objective: To evaluate the efficacy of Mycophenolate mofetil and corticosteroids as a novel combination therapy for stabilizing counts and rapid weaning of steroid usage in pediatric patients with autoimmune cytopenias.
Design/Method: Prospective case series of 5 patients, 4 with AIHA and 1 with ITP, between the ages of 2 and 16 that are being treated with the combination therapy of corticosteroids and MMF.
Results: All patients (Patients 1-4 with AIHA and Patient 5 with ITP) reached minimal to no corticosteroid use after a few months of being on combination therapy, as seen in Figure 1. Patient 1 sustained Hgb levels above 13g/dl after 20 days of combination therapy and an improvement in IgG mediated AIHA, with a decrease in titers from 4+ to 2+ after five months of therapy. In addition, Patient 1 had a decrease in reticulocyte counts from 21.4% to 0.2% after five months of therapy, as well as a decrease in LDH levels from 714 IU/L to 551 IU/L after two months of therapy. Patient 2 sustained Hgb levels above 13g/dl after one month of combination therapy as well as a normal reticulocyte count of 0.8%. Patient 3 has been on combination therapy for one month and has improved Hgb levels from 11g/dl to 11.4g/dl as well as had a significant reduction in steroid usage. Patient 4 sustained Hgb levels above 12g/dl after six months of combination therapy, an improvement in IgG mediated AIHA, with a decrease in titers from 4+ to 3+ after 16 months of therapy, and a decrease in reticulocyte counts from 43.2% to less than 2% after 12 months of therapy. Patient 5 with ITP had a marked increase in platelet counts from 9k/μl to 418k/μl after only 8 days of combination therapy and has maintained normal platelet counts thereafter. All patients have rapidly decreased steroid doses, maintained targeted MMF doses without toxicities or secondary infections, and not had recurrences of autoimmune cytopenias.
Conclusions: Mycophenolate mofetil has been utilized as an adjunct immunosuppressive in a small number of autoimmune diseases and for the treatment of graft-versus-host disease in allogeneic hematopoietic stem cell transplantation. Never before has the combination of MMF and corticosteroids been used to treat pediatric patients with autoimmune cytopenias. The novel combination of MMF and corticosteroids may be an optimal treatment option for pediatric patients with autoimmune cytopenias such as AIHA and ITP. This unique combination of high dose steroids with rapid weaning, coupled with the continued use of MMF mediated immunosuppression allows for prolonged count stabilization with minimal adverse side effects.
*Patient 1's baseline total daily dose of prednisone is 120mg at time 0 months
Off Label Use: Mycophenalate mofetil is an immunosuppressive medication initially utilized in transplantation medicine, and now has been used in a variety of autoimmune diseases. .
Asterisk with author names denotes non-ASH members.