Vaccine and Infectious Disease Division

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Cytomegalovirus viral load predicts post-HSCT mortality

After undergoing hematopoietic stem cell transplantation (HSCT), patients are severely immunocompromised. This makes them susceptible to infections that do not normally cause disease in healthy individuals, such as cytomegalovirus (CMV). The most common manifestations of CMV are gastrointestinal disease (esophagitis, gastritis, enteritis, colitis) and pneumonia. Patients can be given antiviral medication when viral replication is detected in the blood (“pre-emptive”) to prevent CMV end organ disease. Because of high mortality in this population, CMV is one of several closely monitored infections in HSCT patients.

VIDD researchers Drs. Maggie Green, Keith Jerome and Michael Boeckh recently published a study of HSCT patients that analyzed CMV viremia as a marker for post-transplant mortality. This retrospective cohort study included 926 patients who underwent HSCT at Fred Hutch between 2007 and 2013. Plasma CMV viral load was measured on a weekly basis and the authors recorded CMV disease and other clinical diagnoses documented in the medical record.

CMV predicts mortality

Within the first year post-transplant, 70% of the patients tested positive for CMV viremia and 11% developed CMV disease. The authors categorized death as either due to relapse (of cancer) or non-relapse, such as from an infection or organ failure. After the first year post-transplant, 45% (118/263) of total deaths were from relapse; 55% (145/263) from non-relapse causes. Even though only 1% of any deaths in the first year (3/263) was attributable to CMV disease specifically, the authors found that CMV viral load was associated with mortality, regardless of the cause of death. The authors split patients into bins according to the level of viremia: low, medium, high. The hazard ratio (i.e., risk) of mortality increased with higher CMV viral load, and this risk was higher within the first 60 days post-transplant. Patients with a medium viral load (more than 500 IU/mL) within the first 60 days had a 20-fold higher risk of mortality than patients with low viremia; this risk lowered to less than 2-fold after day 60 (see figure). This increased risk of first-year mortality was in spite of aggressive pre-emptive anti-viral therapy for CMV viremia. This study shows that CMV viremia may be a useful predictor of clinical outcome within the first year post-HSCT.

 


Green ML, Leisenring W, Xie H, Mast TC, Cui Y, Sandmaier BM, Sorror ML, Goyal S, Ozkok S, Yi J, Sahoo F, Kimball LE, Jerome KR, Marks MA, Boeckh M. (2016). Cytomegalovirus viral load and mortality after haemopoietic stem cell transplantation in the era of pre-emptive therapy: a retrospective cohort study. Lancet Haematol, 3(3), e119-27.


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