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Therapy for acute rejection in pediatric organ transplant recipients
Dominique Debray1, Válerie Furlan, Véronique Baudouin
1Paediatric Hepatology Unit, University Hospital of Bicêtre, Le Kremlin Bicêtre, France.
Insights
Pediatric organ transplant rejection management involves initial corticosteroid treatment and careful immunosuppression adjustment. Corticosteroid-resistant cases require tailored strategies, balancing efficacy against risks like infection and malignancy.
Area of Science:
- Pediatric Nephrology
- Transplant Immunology
- Clinical Pharmacology
Background:
- Graft rejection remains a significant challenge in pediatric organ transplantation, leading to morbidity and mortality.
- Current immunosuppressive strategies require careful monitoring and adjustment, especially for late-onset or resistant rejection episodes.
Purpose of the Study:
- To review current management strategies for acute graft rejection in pediatric organ transplant recipients.
- To discuss approaches for corticosteroid-resistant and refractory rejection, including drug adjustments and alternative therapies.
Main Methods:
- Review of existing literature on pediatric organ transplant rejection management.
- Analysis of treatment protocols for acute and resistant rejection episodes.
- Discussion of immunosuppressive drug adjustments and alternative treatment options.
Main Results:
- Initial rejection is treated with methylprednisolone pulses and corticosteroid tapering.
- Corticosteroid-resistant rejection management is organ-specific, often involving switching from cyclosporine to tacrolimus or adding mycophenolate mofetil.
- Advanced therapies like antithymocyte globulins, OKT3, plasmapheresis, and IVIG are reserved for refractory cases, with careful consideration of over-immunosuppression risks.
Conclusions:
- Management of pediatric organ transplant rejection necessitates individualized immunosuppression adjustments.
- Balancing the risks of over-immunosuppression (infections, malignancies) with graft survival is crucial in refractory cases.
- Detransplantation or retransplantation may be considered when rejection is refractory to all therapeutic escalations.
Abstract:
Despite the availability of potent immunosuppressive drugs, rejection after organ transplantation in children remains a serious concern, and may lead to significant morbidity, graft loss, and death of the patient. Acute graft rejection in pediatric recipients is first treated with methylprednisolone pulses, followed by progressive taper of corticosteroid doses. After control of the rejection episode, baseline immunosuppression has to be adjusted and closely monitored since rejection (especially late episodes, occurring more than 6 months after transplantation) may be due to a lack of compliance or sub-therapeutic drug concentrations. The management of corticosteroid resistant rejection is not standardized, and depends on the transplanted organ and previous immunosuppressive regimen. In patients experiencing corticosteroid resistant acute rejection while on a cyclosporine-based immunosuppressive regimen, cyclosporine is generally changed to tacrolimus. In case of tacrolimus-based immunosuppression, tacrolimus blood levels may be increased, and/or mycophenolate mofetil (which nowadays tends to replace azathioprine) or sirolimus may be added, although pharmacodynamic data and clinical studies with these agents are still scarce in pediatric recipients. The use of antithymocyte globulins or monoclonal anti-CD3 antibodies, muromonab CD3 (OKT3) is hampered by numerous adverse effects, including a significant risk of over-immunosuppression. These therapies are nowadays indicated in very selected cases. Other treatments such as plasmapheresis and high dose immunoglobulins may be useful in difficult cases. In patients with refractory rejection despite therapeutic escalation, the risks of over-immunosuppression, including opportunistic infections and malignancies (especially the Epstein-Barr virus related post-transplant lymphoproliferative disease) have to be balanced with the consequences of graft loss due to rejection. Detransplantation or retransplantation may, in some instances, be preferable to severe infectious or tumoral complications.