Bortezomib for autoimmune hemolytic anemia after intestinal transplantation

Abstract

AIHA is rare in the general population and associated with a mortality of 8%. In contrast, AIHA occurs in up to 12.2% of cases after intestinal transplantation and is associated with mortality up to 50%. Treatment entails a "step-up" approach including corticosteroids, IvIg, plasmapheresis, and rituximab. However, AIHA after transplantation often is refractory to this strategy, contributing to a poor outcome. We describe a child with microvillous inclusion disease who developed AIHA 1 year after multivisceral transplantation that was refractory to standard therapy and was subsequently treated with bortezomib.We observed remission of AIHA within 1 week after the start of bortezomib. Bortezomib was associated with transient diarrhea, leucopenia, and elevated liver enzymes. Three years later, he remains in remission without important complications. Published data on bortezomib for autoimmune cytopenias outside SOT are discussed. This is the first report to support bortezomib as an important therapeutic alternative for AIHA after SOT. The occurrence and treatment of AIHA after SOT, and specifically intestinal transplantation, should be the subject of future registry studies to collect additional experience and explore the optimal therapeutic approach.

Transplant‐associated thrombotic microangiopathy and immune haematological complications following intestine‐containing organ transplantation: experience from over 100 consecutive cases

“…Our protocol now involves the early use of rituximab in order to minimise corticosteroid exposure (typically patients may receive at least eight weeks of corticosteroids) and based on our experience of needing to recourse to its use in the majority of cases due to a lack of efficacy of steroids alone. Notably, one patient that had seven previous lines of therapy for immune haemolytic anaemia also received bortezomib, a proteasome inhibitor, which appeared to be successful after two doses and has previously been described with success in a small case series of patients with autoimmune haemolytic anaemia outside of solid organ transplant and in one patient with immune haemolytic anaemia after intestine transplant who, as in our case, had a remission within one week of starting bortezomib 25,26 . Bortezomib warrants further studies in this patient group.…”

“…Notably, one patient that had seven previous lines of therapy for immune haemolytic anaemia also received bortezomib, a proteasome inhibitor, which appeared to be successful after two doses and has previously been described with success in a small case series of patients with autoimmune haemolytic anaemia outside of solid organ transplant and in one patient with immune haemolytic anaemia after intestine transplant who, as in our case, had a remission within one week of starting bortezomib. 25,26 Bortezomib warrants further studies in this patient group. Of note, only one patient had an attempted switch from tacrolimus to ciclosporin (and was then switched back to tacrolimus as the immune haemolysis continued unabated); this is relevant because tacrolimus has been described as a cause of late ITP after renal transplant, resolving when it is replaced by ciclosporin.…”

Anti‐plasma cell treatment in refractory autoimmune hemolytic anemia in a child with multivisceral transplant

“…10 A study by Khandelwal et al 11 demonstrated that bortezomib is beneficial in the treatment of refractory autoimmunity in HSCT children. Similarly, Knops et al 12 report the successful use of bortezomib for treatment of AIHA in an intestinal transplant patient. Here we report a refractory case of secondary AIHA that was effectively treated with bortezomib and propose that earlier implementation of this treatment may reduce morbidity related to protracted therapies.…”

Role of Proteasomes in Inflammation

“…This effect is unfortunately not limited to pathogenic PCs but also depletes protective PCs [ 164 ]. Bortezomib has furthermore successfully been used in different cases of autoimmunity including autoimmune cytopenia, refractory primary SjS and encephalitis [ 165 , 166 , 167 , 168 ]. As all beneficial effects of bortezomib on the SLE disease course cannot be attributed to the reduction in autoantibodies [ 162 ], an additional anti-inflammatory effect is suspected.…”