Bortezomib As a Treatment for Autoimmune Cytopenia After Bone Marrow Transplant

Immune dysregulation resulting in autoimmune cytopenia is a serious complication of allogeneic stem cell transplants (SCT). There are few treatment options when first-line and second-line therapies such as steroids, rituximab and IVIG fail to work. Bortezomib is toxic to malignant and normal plasma cells, and has been used to decrease allo-antibody titers in sensitized solid organ transplant recipients. We describe a pediatric patient with history of chronic granulomatous disease who underwent a matched unrelated donor bone marrow transplant and developed secondary autoimmune hemolytic anemia (AIHA) 5 months later. The AIHA transiently improved after treatment with steroids, rituximab and IVIG. However, after 4 months there was an exacerbation of AIHA, and evidence of broader autoimmunity with neutropenia, thrombocytopenia, and minimal change nephrotic syndrome. In addition, opportunistic infection with adenovirus and atypical mycobacteria developed. There was no response of the immune cytopenias or nephrosis to high-dose steroids, IVIG, another 4-week course of rituximab, and plasmapheresis. Four doses of bortezomib 1.3mg/m² IV on days +1, +4, +8, +11 were administered, with concurrent steroids and plasmapherisis. Bortezomib was well-tolerated with transient decrease in neutrophil count. Within 1 month, the reticulocyte count, haptoglobin, bilirubin, and direct antiglobulin test normalized, accompanied by a decline in transfusion requirement, resolution of neutropenia, and improvement in nephrosis. Anemia and thrombocytopenia did not completely resolve because of adenoviral hemorrhagic cystitis, and he ultimately died as a result of the opportunistic infections. In patients whose autoimmune cytopenia does not resolve with rituximab, treatment with bortezomib can rapidly eliminate autoantibody producing B-cells and plasma cells. Earlier institution of therapy may result in disease control and avoid the complications of prolonged immune suppression.