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

Abstract

Background: Warm-antibody AIHA is known to complicate solid organ (SOT) and HSCT, the disease maybe refractory to standard therapy. Immunosuppressive therapies as well as IVIG, and rituximab have been the main stay of treatment. Over the past decade, B-lymphocyte targeted, anti-CD-20 antibody has been recognized in the treatment of autoimmune diseases and utilized in AIHA. Bortezomib, a proteasome inhibitor that causes apoptosis of plasma cells, is an appealing targeted therapy in secondary AIHA and has demonstrated efficacy in HSCT patients. From our experience, we advocate for early targeted therapy that combines B cell with plasma cell depletion.Case Report: We describe a 4-year-old-girl with stage III neuroblastoma, complicated with intestinal necrosis needing multivisceral transplant developed warm AIHA 1-year after transplantation, and following an adenovirus infection. She received immunoglobulin therapy, rituximab, sirolimus, plasmapheresis, and long-term prednisolone with no sustained benefit while developing spinal fractures related to the latter therapy. She received bortezomib for intractable AIHA in combination with rituximab with no appreciable adverse effects. Three years later the child remains in remission with normal reticulocyte and recovered B cells. In the interim, she required chelation therapy for iron overload related to blood transfusion requirement during the treatment of AIHA. Conclusion:We propose early targeted anti-plasma cell therapy with steroid burst, IVIG, rituximab, and possible plasmapheresis may reduce morbidity in secondary refractory w-AIHA. K E Y W O R D Santi-plasma cells, bortezomib, child, multivisceral transplant, refractory autoimmune hemolytic anemia AIHA data.From our experience and understanding of the immunopathogenesis mechanism that leads to secondary AIHA, we emphasize the need for early targeted therapy with combination of anti Blymphocyte and anti-plasma cell therapy in transplanted pediatric patients along with prednisolone and IVIG. This will reduce morbidity related to protracted therapies.

End-organ damage due to iron overload related to blood transfusion in an 11-year-old male

“…Iron Overload induced by AIHA crisis in paediatrics is not well reported in the literature, Menchetti and colleagues described iron overload as a result of an AIHA crisis in a 66-year-old male patient with Evans syndrome. Ghobrial and colleagues described a refractory AIHA and iron overload related to blood transfusion in a child with a multi-visceral transplant 12 , 13 .…”

Development of New Drugs for Autoimmune Hemolytic Anemia

“…Bortezomib has been reported to be effective in the setting of hematopoietic and solid organ transplant-associated AIHA in a number of case reports [ 162 , 163 , 164 , 165 , 166 , 167 ]. In retrospective case series and case reports on relapsed refractory wAIHA, bortezomib in combination with dexamethasone had an overall response rate of 85%, with five CR (35%) and seven PR (50.0%) [ 168 , 169 , 170 ] ( Table 2 ).…”