Autoimmune hemolytic anemia (AIHA): AIHA in
childhood can be a primary autoimmune disease or it can be secondary to
immunodeficiency, malignancy or infection. First line treatment is with
high dose steroids followed by immunosuppressants and splenectomy, which
have limited efficacy.
Cohort studies have described the use of weekly
rituximab for AIHA in a total of 25 children, all of whom had failed
conventional treatments with 92% children having a complete sustained
response for 7-28 months [13,14]. It has also proved useful in the
treatment of autoimmune hemolytic anemia in the setting of Evan’s
syndrome, SLE and autoimmune lympho-proliferative syndrome [15-17].
Hemophilia with inhibitors: Patients with
hemophilia who develop inhibitory antibodies to factor VIII and IX, need
treatment with bypassing agents for acute bleeds and immune tolerance
therapy to eliminate the inhibitors. Rituximab has been used for treating
hemophiliacs with inhibitors with upto 63% response. A national cohort in
the UK suggested the use of rituximab combined with factor VIII as
potentially useful treatment for patients with inhibitors resistant to
standard immune tolerance .
Primary systemic vasculitis (PSV): Primary
vasculitic syndromes include Henoch-Schonlein purpura (HSP), Kawasaki
disease (KD), polyarteritis nodosa (PAN), Takayasu disease (TD) and the
ANCA-associated vasculitides (AAV). The current first line treatment for
severe PSV (excluding KD and HSP) includes therapy with corticosteroids
and cyclophos-phamide, sometimes needing plasmapheresis. Use of rituximab
has proved beneficial in the treatment of the PSV conditions with lesser
toxicity and enduring remissions .
Juvenile idiopathic arthritis (JIA):
Rituximab was approved for treatment of rheumatoid arthritis in adults in
1998 but its usefulness in the treatment of children with severe
refractory JIA is anecdotal and limited.
Systemic lupus erythematosus (SLE):
Childhood-onset systemic lupus erythematosus (SLE) a multisystem
autoimmune disease associated with severe hematologic and renal
involvement, has been treated with rituximab .
In the largest long-term experience in children treated
with rituximab for severe SLE, Nwobi, et al. have reported over 90%
response rate in lupus nephritis with control of proteinuria and a fall in
auto antibodies .
Kumar, et al.  have reported a series of 9
patients with pediatric SLE related autoimmune thrombocytopenia (AITP) and
autoimmune hemolytic anemia (AIHA) with 100% of the patients responding to
rituximab with median time to remission being 2-4 weeks. Complete B cell
depletion was seen in all patients for a prolonged period but without any
Nephrotic syndrome: Rituximab has been used
in the treatment of frequently relapsing steroid or cyclosporine dependant
or resistant nephrotic syndrome patients, who needed intensive multiple
agent immunosuppressive therapy [22,23].
In the French multicenter trial, of the 22 patients
with long standing steroid dependant nephrotic syndrome treated with
rituximab, 15 were proteinuria-free at the time of rituximab use and the
remaining 7 patients were nephrotic. Of the 7 nephrotics, 3 achieved
remission with the addition of rituximab. One or more immunosuppressive
treatments could be withdrawn in majority of the patients and complete
withdrawal was achieved in 23% patients. Thus, rituximab was effective in
all patients when administered during a proteinuria-free period in
association with other immunosuppressive agents.
In patients with steroid resistant nephrotic syndrome,
mostly with focal segmental glomerulosclerosis (FSGS), the response rate
to addition of rituximab to ongoing immunosuppressive therapy was 80%. It
has also been used in treatment of recurrent FSGS after renal
Neuromuscular disorders: Rituximab
has been successfully used in many autoimmune neurological disorders in
adults. In children opsoclonus-myoclonus-ataxia syndrome (OMS), may be
idiopathic or secondary to neuroblastoma or ganglio-blastoma. Children
with OMS treated with rituximab in addition to the ongoing therapy with
ACTH and IVIG showed a 80% clinical improvement, thus proving it to be a
safe and efficacious adjunct to the treatment of OMS .
Organ Transplantation: Rituximab has been
used in the setting of solid organ transplantation for prevention of
hyperacute rejection, ABO incompatible transplants, treatment of acute and
chronic rejection, and treatment of post-transplant lymphoproliferative
PTLD are usually EBV related neoplastic disorders
occurring after transplantation, which are treated by reducing the
immunosuppression. Severe cases need chemotherapy. Incorporation of
rituximab in the treatment of PTLD has led to the decreased use of
chemotherapy agents and better outcomes .
In a randomized prospective study in the treatment of
acute rejection in pediatric renal transplantation, rituximab proved safe
and efficacious with recovery of graft function and improvement of biopsy
rejection scores at both the 1- and 6-month follow-up biopsies .
Chronic antibody mediated rejection in pediatric renal transplant patients
has also been successfully treated with a combination of IVIG and
rituximab therapy .
Dose and Administration
The recommended dose of rituximab in the treatment of
lymphoma is 375mg/m
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