Bortezomib as plasma cell – directed therapy in pediatric refractory autoimmune haemolytic anaemia: A report of two cases

Paediatric autoimmune haemolytic anaemia (AIHA) is a rare but potentially life-threatening disorder. Its clinical course ranges from acute, self-limiting episodes to chronic, relapsing disease. First-line therapy with corticosteroids works initially in most cases but some tend to relapse and they require prolonged administration of immunomodulators. A subset of children remain refractory to the commonly used immunomodulators, posing significant management challenges. In such cases, novel agents such as proteasome inhibitors, including Bortezomib, are being explored to target autoantibody-producing plasma cells. We report two cases of chronic refractory AIHA where Bortezomib achieved sustained hemoglobin improvement and transfusion independence, supporting its role as a salvage option. In this communication we report two cases of refractory AIHA . A 6-year-old boy and a 10-year-old girl with relapsing AIHA since the duration of 2 years and 2.5 years respectively, initially responded to methyl-prednisolone and intravenous immunoglobulin (IVIG) but later became steroid-resistant. They subsequently received Rituximab, Mycophenolatemofetil (MMF), and Azathioprine sequentially, but remained refractory and required frequent transfusions. Evaluation for inborn errors of immunity was negative for both. They were eventually put on Bortezomib, to which both showed an excellent response. After 10 doses for the first case and 8 doses for the second case, their hemoglobin stabilized at 11 g/dL in case 1 and 10.6 in case 2, and they have remained transfusion-independent for the past 3 months and 2 months respectively. This case report illustrates the successful use of Bortezomib in a child with chronic, refractory AIHA unresponsive to conventional therapies