CMV in Transplant (2013)
Leucodepleted blood products means CMV product selection no longer indicated
CMV is a herpes virus
Causes a primary infection followed by life-long latency
Primary CMV infection = infection occurring in a CMV IgG-negative patient
CMV Reactivation = infection occurring when patient or donor is known to be CMV IgG positive
Uncomplicated CMV infection = Infection + non-specific signs/symptoms without end organ dmg
CMV Disease = CMV infection + signs/symptoms of end organ damage
CMV disease most commonly affects the lung, GI tract, eye, liver or CNS
CMV pneumonia is the most serious complication with a 50% mortality.
CMV also has indirect immunosuppressive effects leading increased susceptibility to other fungal and bacterial infections, and an increased risk of acute and chronic GvHD.
Risk Factors for CMV infection
Preventing CMV reactivation post transplant is dependent on T-cell immune response
Therefore, RF include:
- Unrelated / HLA-mismatched donor transplants as increased immunosuppression used
- ATG or Alemtuzumab use
- Prolonged use of immunosuppression to treat GvHD
Impact of host and donor CMV serology
CMV IgG-negative donor-recipient pairs (R-/D-)
- Rarely develop major CMV-related complications
- CMV- donors should be sought for CMV- recipients wherever possible
- CMV status may be more important for transplant outcome than HLA DQ or DP matching
- CMV- recipients should be re-screened pre-transplant to look for passive antibody transfer from blood products (IgM-, PCR-) or seroconversion following primary infection
- CMV infection occurring in R-/D- pairs must be reported to SHOT
CMV IgG-positive donor or recipient
- CMV+ in either donor or recipient associated with increased non-relapse mortality
- CMV+ donor into a CMV- recipient results in CMV infection in 20-30%
- CMV+ recipients are at greater risk of reactivation (80%) irrespective of donor status, but complications are greater if CMV- donor
Aciclovir or valaciclovir is used but efficacy in T-cell depleted transplants is limite
Ganciclovir is used in solid organ transplants but myelosuppressive SE preclude use in HSCT
Consider for patients with previous CMV disease prior to transplant or with recurrent episodes of CMV infection post-transplant. Use valganciclovir or valaciclovir.
Principle of CMV management post transplant is rapid introduction of therapy based on CMV viral loads detected by real time quantitative PCR.
CMV PCR can be performed on plasma or whole blood.
Should be tested weekly for first 3-6 months post-transplant
Threshold for treatment must be decided at each centre because of Inter-lab variability
Similarly, same lab should be used each time for an individual patient.
- Virustatic. Inhibits viral replication by competing with deoxyguanosine triphosphate (a required substrate for viral DNA polymerase)
- 5mg/kg IV BD for 14 days
- SE: Myelosuppression
- Valine ester of ganciclovir
- 900mg BD
- SE: Haemolysis, Nausea, Fever, Rash, Mental state change, Urinary Sx
- Virustatic. Inhibits viral DNA polymerase
- 90mg/kg BD
- SE: Electrolyte abnormalities, Renal impairment, Nausea, GU symptoms
- Nucleotide analogue
- 5mg/kg weekly
- SE: Renal impairment, nausea, ocular
Uncommon in transplant patients
Resistance estimated at 2-8% of patients after 2-3 months of prolonged therapy
De Novo CMV Disease
MDT approach required (Resp, ophthalmology)
Ganciclovir or Foscarnet for 2 weeks followed by maintenance
Immunosuppression should be reduced or stopped, particularly steroids.