Identifying Risk Factors for Cytomegalovirus Antigenemia in Pediatric Patients

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Researchers assessed risk factors for cytomegalovirus antigenemia in pediatric patients.
Researchers assessed risk factors for cytomegalovirus antigenemia in pediatric patients.

A study published in Pediatric Blood and Cancer found that positivity for cytomegalovirus (CMV) antibody and low gamma globulin levels prior to undergoing stem cell transplantation (SCT) were independent risk factors for post-SCT CMV antigenemia. 

Testing for CMV antigenemia is a common method used to identify CMV infection in patients who have undergone SCT. Previous studies have identified allogeneic or cord blood transplantation, unrelated or human leukocyte antigen-mismatched donor, acute graft-versus-host disease (GVHD), and use of steroids as some possible risk factors for CMV antigenemia. However, risk factors for CMV have not been extensively studied in pediatric patients.

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Researchers retrospectively assessed 74 pediatric patients (median age 9.5 years; 57% male) who received allogeneic SCT at Sapporo Hokuyu Hospital in Japan between 2007 and 2018. The transplant donor was unrelated in 51 cases and related in 23 cases. Additionally, 30 patients had acute GVHD, and 24 patients had chronic GVHD.

Patients received 100 mg/kg immunoglobulin concentrate intravenously for prophylaxis of infection, starting at day 6 before SCT until day 85 after SCT. Oral acyclovir was also administered for prophylaxis of herpes virus, starting at day 7 before SCT until day 35 after SCT. Blood was collected weekly until day 100 after SCT and tested for CMV antigenemia through immunological staining of leukocytes; CMV antigenemia was confirmed when 1 or more cells stained positively. Protein electrophoresis was used to assess gamma globulin levels.

The researchers detected CMV antigenemia in 22 (29.7%) patients, 4 of whom had CMV infections. Preconditioning levels of gamma globulin were significantly lower (<.014) in patients with CMV antigenemia, with gamma globulin levels below 655 mg/dL indicating higher risk for CMV antigenemia (hazard ratio 6.46; =.0035).

Presence of CMV antibody was also found to be a risk factor as 91% of patients with CMV antigenemia were positive for CMV antibody prior to SCT (<.001). Of note, other risk factors that had been previously reported, such as unrelated donor, cord blood transplantation, and steroid use, were not linked to CMV antigenemia in this study. 

The authors noted the importance of monitoring gamma globulin levels before SCT in pediatric patients. They also acknowledged the development of the anti-CMV agent letermovir, though they concluded that “strong CMV prophylaxis like letermovir may not be necessary for these patients.”

Reference

1. Kobayashi R, Hori D, Matsushima S, Sano H, Suzuki D, Kobayashi K. Lower gamma globulin level before conditioning is a risk factor for cytomegalovirus antigenemia after pediatric allogeneic stem cell transplantation [published online December 17, 2018]. Pediatr Blood Cancer. doi: 10.1002/pbc.27586

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