Advances in Preventive Therapies for CMV

Significant reduction in post-transplant infection

This is a considerable reduction from the 20-40% rate seen before the development of antiviral drugs such as ganciclovir, foscarnet and cidofovir. [2] Prior to the advent of these drugs, post-transplant CMV infection and disease led to mortality in nearly 25% of CMV seropositive patients. [1]

Preventive strategies

The first strategy is using only leukoreduced or CMV seronegative blood products in any transfusions received by a CMV seronegative transplant patient in order to prevent transfusion-transmitted CMV.

The second strategy is a prophylactic approach, where ganciclovir or other antivirals are routinely given to transplant patients who test CMV seropositive before transplant. Prophylactic CMV treatment can be administered at various times, depending on a transplant center's protocol:

• Pre-transplant
• For the first 100 days post-transplant
• At the first sign of engraftment
• During periods of high-risk for CMV infection (e.g., during GVHD therapy)

The third and most common pre-emptive therapy approach involves administering a post-transplant CMV diagnostic test weekly, and immediately starting a course of antiviral treatment if the patient tests CMV positive. Sensitive tests are now available that can detect early infection with CMV, including PCR tests and antigenemia assays.

With these three widely employed preventive anti-CMV strategies, CMV is now a rare cause of early mortality after transplant. The incidence of post-transplant CMV interstitial pneumonitis, a potentially life-threatening CMV complication, has been reduced from 10% in 1976 to 3% in 2001. [4] However, with the successful prevention of CMV disease during the first three months after transplantation, there has been a recognition of late-onset CMV disease, especially in patients with GVHD. [3]

New anti-CMV drugs and usage guidelines

Specific dosages and administration schedules for CMV-targeted antiviral drugs have been outlined in several published guidelines, including those produced by the European Group for Blood and Marrow Transplantation (EBMT) and joint guidelines issued by the Centers for Disease Control and Prevention, the Infectious Disease Society of America, and the American Society for Blood and Marrow Transplantation (http://mmserver.cjp.com/gems/bbmt/7-83.pdf). [5]

References

1. Boeckh M, Nichols WG, Papanicolaou G, et al. Cytomegalovirus in hematopoietic stem cell transplant recipients: current status, known challenges, and future strategies. Biol Blood Marrow Transplant. 2003; 9(9):543-558.
   http://www.bbmt.org/article/PIIS1083879103002878/fulltext
2. Zaia JA. Cytomegalovirus infection. In: Blume KG, Forman SJ, Appelbaum FR, eds. Thomas' Hematopoietic Cell Transplantation, 3rd ed. Malden, Mass: Blackwell, 2004: 701-726.
3. Boeckh M, Fries B, Nichols WG. Recent advances in the prevention of CMV infection and disease after hematopoietic stem cell transplantation. Pediatr Transplant. 2004; 8 Suppl 5:19-27.
   http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?
   cmd=Retrieve&db=pubmed&dopt=Abstract&
   list_uids=15125702
4. Horowitz MM. Uses and growth of hematopoietic cell transplantation. In: Blume KG, Forman SJ, Appelbaum FR, eds. Thomas' Hematopoietic Cell Transplantation, 3rd ed. Oxford, Malden, Mass: Blackwell, 2004: 9-15.
5. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients: Recommendations of Centers for Disease Control, the Infectious Disease Society of America, and the American Society of Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2000; 6(6) Suppl:659-713.
   http://www2.us.elsevierhealth.com/inst/serve?action=searchDB&searchDBfor=iss&id=jbbmt000066b