• Cincinnati Children's Hospital Medical Center. Evidence-based care guideline for cytomegalovirus prophylaxis following solid organ transplants. Cincinnati (OH): Cincinnati Children's Hospital Medical Center; 2007 Jul 6. 15 p. [68 references]

This is the current release of the guideline.

This guideline updates a previous version: Cincinnati Children's Hospital Medical Center. Evidence based clinical practice guideline for cytomegalovirus prophylaxis following solid organ, blood and marrow transplants. Cincinnati (OH): Cincinnati Children's Hospital Medical Center; 2001 Jun 7. 16 p. [145 references]

Each recommendation is followed by evidence grades (A-X) identifying the type of supporting evidence. Definitions of the evidence grades are presented at the end of the "Major Recommendations" field.

Laboratory Assessment

1. It is recommended that cytomegalovirus (CMV) status of donors and recipients be tested pre-transplant to stratify risk (Badley et al., 1997 [B]; Flechner et al., 1999 [C]; Humar et al., 1999 [C]; Blok et al., 1998 [C]; Sakamaki et al., 1997 [C]; Solans et al., 1995 [C]; Muir et al., 1998 [D]; Abecassis et al., 1996 [D]; Martin, 1995 [S]; Snydman, 1994 [S]).

   Note: The specific laboratory tests are described (see table 3 in the original guideline document).

Prophylactic Approach

Recommendations for CMV disease prophylaxis in solid organ transplant recipients are based on the previously defined risk levels (see table 2 in the original guideline document) and treatment effectiveness (see table 4 in the original guideline document).

Solid Organ (see algorithm 1 in the original guideline document)

Laboratory Evaluation

2. It is recommended that patients receiving prophylaxis for CMV be assessed regularly for evidence of CMV disease by clinical examination (Local Consensus [E]).
3. No specific recommendations regarding laboratory screening for CMV disease in patients receiving prophylaxis are made because of lack of evidence.

Prophylactic Therapy (see table 5 in the original guideline document for specific dosages and duration of therapy)

4. It is recommended that CMV prophylaxis be initiated for all high and intermediate risk solid organ transplant recipients (Hodson et al., 2005 [M]; Lowance et al., 1999 [A]; Merigan et al., 1992 [A]; Macdonald et al., 1995 [B]; Martin et al., 1994 [B]; Nichols & Boeckh, 2000 [S]; Patel et al., 1996 [S]). Such prophylaxis includes intravenous ganciclovir at induction doses for 14 days (Merigan et al., 1992 [A]; Cohen et al., 1993 [B]) followed by oral ganciclovir capsules for three months (Winston & Busuttil, 2003 [B], 2004 [C]; Rubin et al., 2000 [C]; Pescovitz et al., 1997 [C]; Local Consensus [E]).

   Note 1: In adult renal and liver transplant recipients oral ganciclovir therapy has been reportedly used for the entire 3-month period (Gane et al., 1997 [A]; Flechner et al., 1998 [B]; Kletzmayr et al., 2000 [C]; Brennan et al., 1997 [C]).

   • In kidney recipients, oral valganciclovir for 100 days has been shown to be as clinically effective as oral ganciclovir for CMV prevention (Paya et al., 2004 [A]). In heart recipients, valganciclovir is also presumed to be effective, but data are more limited (see Table 6 in the original guideline document, (Paya et al., 2004 [A]).

     Note 1: Oral valganciclovir has been shown to have equivalent bioavailability to intravenous (IV) ganciclovir in adult liver transplant recipients (Pescovitz et al., 2000 [B]). Preliminary data suggest similar results in children (Bouw et al., 2006 [B]).

     Note 2: A higher incidence of neutropenia is reported in patients on valganciclovir, 8.2% versus 3.2% ganciclovir (Paya et al., 2004 [A]).

     Note 3: In the liver transplant subpopulation, there was a higher incidence of overall CMV disease and a significant increase in tissue-invasive CMV disease in the valganciclovir arm vs the ganciclovir arm (14% vs 3%) (Paya et al., 2004 [A]). Accordingly, the U.S. Food and Drug Administration (FDA) has cautioned against the use of valganciclovir in liver recipients (see Table 6 in the original guideline document) (Roche Pharmaceuticals 2003 [E]).

5. If a patient is unable to tolerate the above regimen due to adverse effects of the medication or inability to take capsules, the following options may be considered:
   • Intravenous ganciclovir at induction doses for 14 days, followed by oral ganciclovir suspension for three months (limited data in pediatric patients): (Pescovitz et al., 1997 [C]; Local Consensus [E])
   • Intravenous ganciclovir at induction doses for 14 days in combination with CMV hyperimmune globulin (Ham et al., 1995 [D]; Bonham, 2000 [S]; Martin, 1995 [S])
   • CMV hyperimmune globulin alone (Glowacki & Smaill, 1994 [M]; Snydman et al., 1987 [A]; Saliba et al., 1989 [B]; Kathawalla et al., 1996 [D]; Basadonna et al., 1994 [D]; Arbo et al., 2000 [Q])
   • Intravenous ganciclovir daily for 30 days, followed by intravenous ganciclovir Monday through Friday until day +100 (Glowacki & Smaill, 1994 [M]; Winston et al., 1995 [A])

     Note: Ganciclovir requires a dosage adjustment in patients with renal dysfunction (Taketomo, Hodding, & Kraus, 2000 [O]). (see Tables 7 through 9 in the original guideline document)

6. In low risk solid organ transplant recipients there is insufficient evidence to make specific recommendations regarding the use of antiviral agents for CMV prophylaxis (Local Consensus [E]). Instead, ongoing clinical surveillance for signs and symptoms of CMV disease appears reasonable (Local Consensus [E]).

Clinical Assessment

7. It is recommended that patients with any of the following clinical conditions be considered at risk for primary infection or reactivation of CMV disease and be treated accordingly.
   • Fever
   • Hepatitis
   • Muscle pain
   • Gastroenteropathy
   • Leukopenia
   • Pneumonitis
   • Thrombocytopenia
   • Retinitis

8. Quantitative Polymerase Chain Reaction (PCR)

   Note 1: Measurement of quantitative CMV viral load (PCR) may have the potential to identify patients at imminent risk of CMV disease and may be a useful monitoring tool during antiviral treatment, a determinant of adequacy of treatment, and a predictor of CMV relapse (Emery et al., 2000 [C]; Sia et al., 2000 [C]).

Definitions:

Evidence Based Grading Scale:

M: Meta-analysis or systematic review
A: Randomized controlled trial: large sample
B: Randomized controlled trial: small sample
C: Prospective trial or large case series
D: Retrospective analysis
O: Other evidence
S: Review article
E: Expert opinion or consensus
F: Basic laboratory research
L: Legal requirement
Q: Decision analysis
X: No evidence

A clinical algorithm is provided in the original guideline document for "Solid Organ Transplant Prophylactic Approach."

The type of evidence is identified and classified for each recommendation (see "Major Recommendations") using the following scheme:

Evidence Based Grading Scale:

M: Meta-analysis or systematic review
A: Randomized controlled trial: large sample
B: Randomized controlled trial: small sample
C: Prospective trial or large case series
D: Retrospective analysis
O: Other evidence
S: Review article
E: Expert opinion or consensus
F: Basic laboratory research
L: Legal requirement
Q: Decision analysis
X: No evidence

• Cincinnati Children's Hospital Medical Center. Evidence-based care guideline for cytomegalovirus prophylaxis following solid organ transplants. Cincinnati (OH): Cincinnati Children's Hospital Medical Center; 2007 Jul 6. 15 p. [68 references]

Not applicable: The guideline was not adapted from another source.

2001 Jun 7 (revised 2007 July 6)

Cincinnati Children's Hospital Medical Center - Hospital/Medical Center

Cincinnati Children's Hospital Medical Center

Cardiac Clinical Pathway Team, Renal & Liver Transplant Teams 2007 Revision

Cincinnati Children's Hospital Medical Center Physicians: Peter Manning, MD, Cardiac Surgery; Catherine Dent, MD, Cardiac Intensive Care/Transplant; William Border, MD, Cardiology; James Spaeth, MD, Anesthesia; Michael Alice Moga, MD, Cardiology/Fellow; Jeffrey Anderson, MD, Cardiology/Fellow; Pirooz Eghtesady, MD, Cardiac Surgery/Transplant; Jens Goebel, MD, Nephrology/Transplant; Kathleen Campbell, MD, Liver Transplant

Patient Services: Karen Uzark, PhD, CPNP, Cardiology/Transplant; Joyce Slusher, CPNP, Cardiology/Transplant; Christa Barlow, CNP, Cardiac Surgery; Melissa Magness, RN, Cardiac ICU; Tammy Lingsch, RN, A6 Central; Cynthia Wedekind, Pharm D, Clinical Pharmacy; Jenni Raake, RRT, Respiratory Care; Shawna Kirkendall, RN, Manager, A 6 Central

Clinical Effectiveness Services: Eduardo Mendez, RN, MPH, Dir. Evidence-Based Care, Facilitator; Eloise Clark, MPH, Guideline Program Administrator; Danette Stanko, MA, MPH, Epidemiologist; Kate Rich, Lead Decision Support Analyst; Carol Frese, RN, Medical Reviewer; Edward Donovan, MD, Medical Director, Clinical Effectiveness; Carol Tierney, MSN, RN, Education Specialist

The guideline was developed without external funding.  All Team Members and Clinical Effectiveness support staff listed have declared whether they have any conflict of interest and none were identified.

This is the current release of the guideline.

This guideline updates a previous version: Cincinnati Children's Hospital Medical Center. Evidence based clinical practice guideline for cytomegalovirus prophylaxis following solid organ, blood and marrow transplants. Cincinnati (OH): Cincinnati Children's Hospital Medical Center; 2001 Jun 7. 16 p. [145 references]

None available

This NGC summary was completed by ECRI on March 11, 2004. This NGC summary was updated by ECRI Institute on February 26, 2008.