Introduction to Muromonab

Muromonab-CD3 (trade name Orthoclone OKT3) is a murine monoclonal antibody specific for the CD3 receptor on T cells. It was the first monoclonal antibody approved for clinical use in humans by the FDA in 1986. Originally used for preventing acute rejection in organ transplantation, its use has declined due to the development of newer immunosuppressive agents with better side effect profiles.

Mechanism of Action

Muromonab-CD3 works through several mechanisms:

• Binds to the CD3 protein complex on T lymphocytes
• Initially activates T cells, leading to cytokine release
• Subsequently causes internalization of the CD3 receptor, rendering T cells unable to respond to antigens
• Leads to a temporary depletion of T cells from the circulation
• Induces immunosuppression by interfering with T cell function and proliferation

Clinical Applications

While its use has decreased, muromonab-CD3 still has some applications in pediatrics:

• Treatment of acute, steroid-resistant rejection in organ transplantation, particularly:
  • Kidney transplants
  • Liver transplants
  • Heart transplants
• Management of graft-versus-host disease (GVHD) in stem cell transplantation
• Research applications in autoimmune diseases like type 1 diabetes

Dosage and Administration

Dosing in pediatrics is based on body weight:

• Typical dose: 5 mg/day for patients weighing ≥ 30 kg
• For patients < 30 kg: 2.5 mg/day
• Usually administered for 10-14 days

Administration:

• Given as an intravenous bolus injection over 2-5 minutes
• First dose should be given under close medical supervision due to risk of cytokine release syndrome
• Premedication with corticosteroids, antihistamines, and acetaminophen is typically given to reduce side effects

Adverse Effects

Common adverse effects include:

• Cytokine release syndrome (fever, chills, rigors, headache, nausea, vomiting)
• Diarrhea
• Tremor
• Aseptic meningitis
• Increased risk of infections, including opportunistic infections

Rare but serious adverse effects:

• Anaphylaxis
• Pulmonary edema
• Cardiac arrhythmias
• Seizures
• Post-transplant lymphoproliferative disorder (PTLD)

Considerations in Pediatrics

When using muromonab-CD3 in pediatric patients, consider:

• Higher risk of cytokine release syndrome in children, necessitating close monitoring
• Potential for development of human anti-mouse antibodies (HAMA), which can reduce efficacy with repeated use
• Long-term immunosuppression and its impact on the developing immune system
• Increased risk of infections, particularly in the post-transplant setting
• Need for vaccination planning, as live vaccines are contraindicated during and for several months after treatment
• Potential impact on growth and development due to immunosuppression