Daratumumab in life-threatening autoimmune hemolytic anemia following hematopoietic stem cell transplantation

Abstract

New-onset autoimmune hemolytic anemia (AIHA) occurs in 2% to 6% of pediatric patients post–hematopoietic stem cell transplantation (HSCT) and is a significant complication. Incomplete immune recovery following HSCT may predispose to immune dysregulation including autoimmune cytopenias. We describe an innovative therapy for AIHA refractory to proteasome inhibition. In potentially life-threatening AIHA in the context of HSCT, daratumumab may be an effective rescue therapy.

Successful treatment with daratumumab for post‐HSCT refractory hemolytic anemia

“…It is hard to say how long it may take for the humoral immunity to fully reconstitute, but according to previous reports B cell reconstitution could be delayed by up to 1 year post daratumumab treatment. 6 In summary, we report a pediatric case of refractory post-HSCT AIC who completely recovered following treatment with daratumumab, without significant AEs other than prolonged hypogammaglobulinemia. We suggest that daratumumab may be a valid treatment option for refractory post-HSCT AIC.…”

“…Recently, treatment with daratumumab for post-HSCT AIC was reported in three patients, two of whom were cured. 6 Additionally, two case reports of successful treatment with daratumumab for delayed red cell engraftment following HSCT were recently published. 7,8 No significant adverse effects were noted in these cases except for delayed recovery of humoral immunity necessitating substitution with IVIG.…”

“…Recently, there have been reports of successful treatment of resistant post-HSCT AIHA and of post-HSCT pure red cell aplasia with daratumumab. [6][7][8] We present here a case of a pediatric patient with primary myelofibrosis of infancy caused by VPS45 protein deficiency, who developed severe refractory post-HSCT hemolytic anemia and thrombocytopenia and was successfully treated by daratumumab with complete resolution of symptoms and normalization of blood counts.…”

Autoimmune hemolytic anemia and immune thrombocytopenia following hematopoietic stem cell transplant: A critical review of the literature

“…31,33-37 A recent report described three highly refractory patients with life-threatening post-HSCT AIHA treated successfully with daratumumab, an anti-CD38 monoclonal antibody. 38 Treatment for ITP can also include thrombopoietin receptor agonists, which stimulate platelet production by bone marrow megakaryocytes. These agents have been shown to successfully overcome the rate of platelet destruction in ITP, and their use has been reported in the post-HSCT setting.…”

Daratumumab in combination with standard treatment for autoimmune hemolytic anemia in a pediatric patient

“…B‐cell depleting therapy, anti‐CD20 or anti‐CD22, are commonly used in autoimmune disorders, however, long‐lived plasma cells resist these therapies and continue to produce autoantibodies . The use of daratumumab (DARA) in ABO mismatched stem cell recipients has demonstrated a decrease of antibody mediated hemolysis when used in conjunction with conventional treatments . One study, using human blood specimens, suggests anti‐CD38 therapy should be evaluated for the reduction in plasma cells producing autoantibodies in RA and SLE .…”