Blood, 15 May 2003, Vol. 101, No. 10, pp. 3761-3761
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 carinii
and 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.
Dana C. Matthews
University of Washington; Fred Hutchinson Cancer
Research
