What is the recommended prophylaxis regimen for starting anti-Cytomegalovirus (CMV) medication in high-risk pediatric patients before transplantation?

From the Guidelines

For high-risk pediatric patients requiring anti-CMV prophylaxis before transplantation, the recommended regimen is typically primary prophylaxis with oral or intravenous letermovir, which may be considered for CMV-seropositive recipients who undergo allogeneic HCT, with a dose reduction recommended if coadministered with cyclosporine due to drug interactions 1. The strategy of CMV surveillance testing by PCR followed by pre-emptive anti-CMV therapy for a positive result is favored over universal long-term prophylaxis. Some centers consider the use of letermovir through day 100 post-HCT and continue CMV surveillance for patients at high risk for CMV reactivation. In certain circumstances, up to day 200 can be considered. Key points to consider in the management of CMV prophylaxis include:

• The use of letermovir as a potential option for primary prophylaxis in high-risk patients
• The importance of CMV surveillance testing by PCR to guide pre-emptive therapy
• The need for dose reduction of letermovir when coadministered with cyclosporine
• The consideration of alternative agents, such as valganciclovir or intravenous ganciclovir, in patients who cannot tolerate letermovir or have specific contraindications. Regular monitoring of complete blood counts and renal function is essential due to potential bone marrow suppression and nephrotoxicity associated with anti-CMV medications. High-risk patients typically include CMV-seronegative recipients receiving organs from CMV-seropositive donors (D+/R-), or CMV-seropositive recipients receiving certain immunosuppressive regimens. This prophylactic approach is effective because it maintains therapeutic drug levels during the period of highest immunosuppression, preventing viral replication before infection becomes established. Regular CMV viral load monitoring should accompany prophylaxis to detect breakthrough infections early. It is also important to note that letermovir lacks HSV and VZV coverage, and therefore, HSV/VZV prophylaxis should be continued 1.

From the FDA Drug Label

For pediatric heart transplant patients 4 month to 16 years of age, the recommended once daily mg dose (7x BSA x CrCL) should start within 10 days of transplantation until 100 days post-transplantation The recommended prophylaxis regimen for starting anti-Cytomegalovirus (CMV) medication in high-risk pediatric patients before transplantation is to start valganciclovir within 10 days of transplantation. The dosage is calculated based on body surface area (BSA) and creatinine clearance (CrCl) using the equation: Pediatric Dose (mg) = 7 x BSA x CrCl. The dose should be rounded to the nearest 10 mg increment and should not exceed 900 mg. Valganciclovir for oral solution is the preferred formulation for pediatric patients, as it allows for more precise dosing 2.

• Key points:
  • Start valganciclovir within 10 days of transplantation
  • Calculate dosage based on BSA and CrCl
  • Use valganciclovir for oral solution for pediatric patients
  • Monitor serum creatinine levels regularly and adjust dose as needed
  • Maximum dose: 900 mg

From the Research

Prophylaxis Regimens for High-Risk Pediatric Patients

The recommended prophylaxis regimen for starting anti-Cytomegalovirus (CMV) medication in high-risk pediatric patients before transplantation involves the use of antiviral medications such as ganciclovir and/or oral valganciclovir 3.

Key Considerations

• High-risk patients, particularly those who are CMV seronegative and receive an organ from a CMV seropositive donor, require careful consideration of prophylaxis strategies 3, 4.
• A hybrid strategy bridging prophylaxis and pre-emptive therapy may be effective in preventing CMV disease 3.
• The use of CMV hyperimmune globulin (CMVIG) in addition to antiviral prophylaxis may be beneficial in reducing the risk of CMV infection, but its effectiveness in preventing CMV disease is less clear 5, 6, 7.

Prophylaxis Strategies

• Valganciclovir is the only approved antiviral for CMV prevention in pediatric solid organ transplantation (SOT) 4.
• A multicenter retrospective study found that CMV DNAemia in the first year after prophylaxis or during prophylaxis (breakthrough) was associated with liver transplantation, intermediate or high risk based on donor/recipient serologies, neutropenia, and valganciclovir dose modifications attributed to toxicity 4.
• The use of pp67 NASBA-based pre-emptive ganciclovir therapy combined with CMV hyperimmune globulin prophylaxis in high-risk patients may lead to a lower rate of CMV disease 5.
• CMVIG may be effective in preventing CMV infection, but its use requires further evaluation 6, 7.

Treatment Approaches

• Ganciclovir is commonly used to treat CMV infection and disease 5, 7.
• The combination of intravenous ganciclovir and CMVIg may be effective in treating tissue-invasive disease 7.
• CMVIg monotherapy prophylaxis may be effective in patients with ganciclovir-related toxicity 7.