HOLLI W. HAYNIE

Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and pneumonia among infants and children under 1 year of age. The majority of children recover in eight to 15 days, but for children with cancer or an otherwise compromised immune system, RSV is generally more prolonged and severe with a greater potential to be fatal. Researchers at St. Jude Children’s Research Hospital sought to find out which children with RSV infection tend to have a more severe RSV infection. The results of their findings were published in the February issue of Pediatrics: children receiving cancer treatment under age 2, and those with a low lymphocyte count, are at higher risk for severe RSV-related disease.

Some immunocompromised children such as those who’ve undergone a hematopoietic stem cell transplant or are receiving chemotherapy, when infected with RSV, tend to develop lower respiratory tract infections (LRTI). While previous studies on RSV in adults has shown up to 60 percent of subjects developing LRTIs, and the mortality rates of RSV LRTIs between 50 and 100 percent; there is scarce data on immunocompromised children.

“This study is a first step towards identifying some risk characteristics which help us focus on patients who are likely to have more severe infection,” explained Dr. Aditya Gaur, assistant member of the St. Jude Department of Infectious Diseases. “Before this study there was no general consensus as to how to approach these kids in particular.”

Clinicians deal with such patients on an individual basis, determining their level of immmunosuppression and the underlying disease to establish the best course of treatment. Children with severe disease may require oxygen therapy and sometimes mechanical ventilation. Ribavirin aerosol, the only FDA-approved drug for RSV, may be used in the treatment of some patients with severe disease. According to the American Academy of Pediatrics, some investigators have used a combination of immune globulin intravenous (IGIV) with high titers of neutralizing RSV antibody (RSV-IGIV) and ribavirin to treat patients with compromised immune systems. Development of an RSV vaccine is a high research priority, but none is yet available. Current prevention options include good infection-control practices, RSV-IGIV, and an anti-RSV humanized murine monoclonal antibody.

The St. Jude team studied clinical and laboratory information from the records of 58 patients who had tested positive for RSV infection. It included patients with acute lymphoblastic leukemia, acute myeloid leukemia; those with solid tumors, severe combined immunodeficiency (SCIDS), or those who had undergone a bone marrow transplant. Researchers only had the numbers for a retrospective study, yet what they did not find was just as important.

“We did not significantly find any association between a low neutrophil count with (increased risk) for the development of the disease,” explained first author of the study, Dr. Chadi El Saleeby, assistant in pediatrics, division of pediatric infectious diseases at Harvard Medical School and MassGeneral Hospital for Children in Boston. “The development of a low respiratory tract infection was actually driven, at least in part, by a low absolute lymphocyte count.”

Oncologists generally use the absolute neutrophil count (ANC) to determine infection risk in cancer patients, a standard tool that identifies a host’s susceptibility to a bacterial or fungal infection. It turns out, according to the findings of this study, that lymphopenia is more the culprit with a viral infection like RSV. In other words, it’s a low absolute lymphocyte count (ALC), not the ANC that is the more significant risk factor for RSV.

This finding will allow clinicians to be more categorical in their risk assessments. However, Gaur maintained, these criteria do not imply that all patients with one or both of those risk factors will develop severe RSV; they simply have a much higher chance of severe disease.

“If we are seeing a patient who has either of these risk factors, we’ll be cognizant of this as a subset of patients who may have lower respiratory tract disease and we will follow them closely and then build on the available treatment options,” said Gaur. “We may tend to use them earlier.”

Efficacy studies for anti-RSV interventions in an immunocompromised patient population are impeded by the need for multi-site participation to attain a meaningful sample size. In the mean time, St. Jude clinicians will continue to approach each patient on a case-by-case basis to evaluate and attribute risk factors.

“This study makes things a little more systematic in the sense that it brings to the clinicians attention (specific) clinical features — age less than 2 and lymphocyte count,” concluded Gaur. “These (guidelines) influence how, in our hospital, patients with RSV are viewed and we can build on this with future studies.”



March 2008