Rituximab in the very young: benefits in AIHA, at what risk?

Rituximab, a humanized anti-CD20 antibody, was the first approved therapeutic monoclonal antibody and has rapidly gained an important role in the armamentarium against non-Hodgkin lymphoma. Quite well tolerated, rituximab results in not only a significant antitumor response in many patients, but also a profound and long-lasting depletion of normal B cells. Given the latter effect, interest has grown in its potential utility in the treatment of autoimmune disorders. Initial small studies in immune thrombocytopenic purpura (ITP) have demonstrated responses, often long-lasting, in 30% to 50% of adult patients treated with this agent.

While autoimmune hemolytic anemia (AIHA) often runs a transient course in pediatric patients, it can be much more resistant to treatment than ITP, requiring higher dosing of typical therapies such as IVIG or steroids to achieve control. Furthermore, some patients, especially those with Evans syndrome, have a chronic illness where conventional therapies are often not particularly effective and/or have significant side effects. Initial case reports, many in the post–stem cell transplantation setting, and small series have suggested that rituximab may have efficacy in this autoimmune disorder as well.

The prospective study of rituximab in pediatric patients with AIHA or Evans syndrome reported by Zecca and colleagues (page 3857) represents the largest series to date of such patients of any age, let alone pediatric patients, treated with this approach. Thirteen of 15 patients responded, with 10 remaining off all immunosuppressive agents at last follow-up 10 to 28 months after treatment. These patients, with a median age of 2 years, did not have significant infections despite dramatic depletion of B cells for several months, although they received prophylactic IVIG for 6 months. This report adds to the experience of Quartier et al (Lancet. 2001;358:1511-1513) treating 6 patients with AIHA under 3 years of age with rituximab, all of whom responded with long-lasting complete remissions, and suggests that even very young patients with developing immune systems may tolerate a relatively long-lasting reduction of B-cell numbers. However, scattered reports of opportunistic infections following rituximab therapy in pediatric patients, including Pneumocystis cariniiand varicella pneumonia (Motto et al, Isr Med Assoc J. 2002;11:1006-1008), and enteroviral meningoencephalitis associated with particularly prolonged B-cell depletion (Quartier et al, Clin Infect Dis. 2003;36:e47-e49), are cause for concern. Longer term study of the impact of rituximab-induced B-cell depletion in larger numbers of patients will be required to better define the risk-benefit ratio for rituximab in the treatment of autoimmune disorders, particularly in pediatric patients. The fact that many such patients have already been treated with other immunosuppressive agents, and that in some, their underlying disorder may be associated with immune dysregulation, will make this delineation both more challenging and more pressing.