Benefits of rituximab as a second‐line treatment for autoimmune haemolytic anaemia in children: a prospective French cohort study

Abstract

Childhood autoimmune haemolytic anaemia (AIHA) requires second-line immunosuppressive therapy in 30-50% of cases. It appears that rituximab is indicated in such circumstances. This prospective national study reports the practice, efficacy and tolerance of rituximab in children with isolated AIHA and AIHA in the setting of Evans syndrome (ES). Sixty-one children were given rituximab between 2000 and 2014. The median interval from diagnosis to rituximab was 9·9 [interquartile range (IQR) 1·6-28·5] months. Forty-six patients responded (75%) and the 6-year relapse-free survival (RFS) was 48%. Twenty patients relapsed at a median interval of 10·8 (IQR 3·9-18·7) months, rituximab allowed steroid withdrawal in 44/61 (72%) of children. In isolated AIHA, complete response and 6-year RFS were significantly higher than in ES (P < 0·05). Ten out of 61 patients were infants, seven of who responded with a 6-year RFS of 71%. Among patients without immunoglobulin substitution before rituximab, 4 are still receiving substitutions. Five patients died, including one potentially attributable to rituximab. This large observational series of childhood AIHA established the rituximab benefit-risk ratio, allowing steroid withdrawal, with 37% of long-term responders, mainly in isolated AIHA. All subgroups of patients drew benefit. Our long-term results indicate the baseline to be challenged by new treatment approaches.

Anti-CD20 Treatment of Autoimmune Hemolytic Anemia Refractory to Corticosteroids and Azathioprine: A Pediatric Case Report and Mini Review

“…The preferred scheme is four weekly intravenous infusions (375 mg/m 2 /dose). During the last years, several reports have emerged, along with few single-center uncontrolled studies and one very recent prospective study [ 4 , 7 , 8 , 10 – 15 ]. The basic characteristics of these case reports and studies are presented in Table 2 .…”

“…In a few cases, IVIG supplementation was administrated for six months after rituximab treatment until the hypogammaglobulinemia resolved [ 30 ]. Generally, rituximab is considered a well-tolerated treatment as only a small number of children from the literature needed IVIG and prophylaxis for possible infectious complications [ 4 , 15 ].…”

“…In children, the majority of the available publications are case reports or single-center uncontrolled studies [ 4 , 7 , 8 , 10 – 14 ]. In a recent prospective national French study of 61 children, the 6-year relapse-free survival was 48% [ 15 ].…”

Efficacy and safety of rituximab in autoimmune and microangiopathic hemolytic anemia: a systematic review and meta-analysis

“…The 2nd fatal patient died because of delayed treatment [55]. The 3rd fatal patient died shortly after RTX therapy, which was also claimed to be partially contributing to the death [42]. Importantly, there is a critical issue about hepatitis B virus reactivation (HBVr) regarding AE of RTX.…”

Refractory immune hemolytic anemia in an immunocompetent infant with cytomegalovirus infection

“…To the Editor: Autoimmune hemolytic anemia (AIHA) is a rare phenomenon in children, with estimated annual incidence of 0.2/100 000 . Management with intravenous immunoglobulin (IVIG) and corticosteroids induces complete remission in two‐thirds of patients, with rituximab being used in refractory cases . Albeit rare, cytomegalovirus (CMV) infection can manifest as AIHA in the absence of other typical symptoms .…”