Norovirus Infections in Patients with Hematological Diseases and After Stem Cell Transplantation; Epidemiological and Clinical Aspects.

Abstract 2661

Poster Board II-637

Norovirus infections have become a major practical clinical problem during the last few years causing outbreaks in many different situations including in hospitals infecting both patients and staff. These infections have also been associated with prolonged virus excretion in renal transplant recipients and a risk of mortality in the elderly. Little is known about the clinical impact of norovirus infections on patients who are severely immunosuppressed. The aim of this study was to analyze the impact of norovirus infections in patients with hematological diseases and after hematopoietic stem cell transplantation (HSCT). The laboratory records from the Clinical Microbiological Laboratory at Karolinska University Hospital were examined in order to identify patients with proven norovirus infection hospitalized on the haematology or allogeneic stem cell transplant wards from 2006 to 2009. The diagnostic methodology was based on an accredited protocol including a reverse transcription real- time PCR procedure with the use of oligonucleotide primers specific for detection of norovirus genotype 1 or 2 in separate wells. After identification of cases, the patient charts were reviewed to assess outcome, possible norovirus associated clinical complications, and delay of antitumor therapy. The duration of virus excretion was defined as the time from the first to the last positive sample.

65 patients were identified. 19 patients had NHL, 14 AML, 8 multiple myeloma, 8 non-malignant hematological disorders, 5 ALL, 5 CLL, 4 MDS, and one patient had CML. 24 patients had undergone HSCT; 22 allogeneic and 2 autologous. The median age was 63.1 (1.1–84.2). The cases occurred in two major and 3 minor clusters over the 3 year period with some additional sporadic cases occurring between the clusters. One of the haematology wards had to be closed for admission twice and one ward once since also several cases occurred among the staff. 17 of the detected viruses were typed to genogroup 2, 2 to genogroup 1, and 46 were not typed. 29 patients had only one positive sample of which 11 had a negative follow-up sample. The median duration of viral detection in the entire cohort was 2 days (1–216 days). Among the patients with more than one positive sample, the median duration was 15 days (2–216 days). 25/65 (38%) patients were PCR positive more than one week, 18 (28%) for more than two weeks, and 9 (14%) for more than four weeks. The majority of patients had minor and quickly resolved gastrointestinal symptoms. Five patients died in close temporal association with the norovirus infection (within a week). Three patients had fluid balance and electrolyte abnormalities and in of these a pre-existing renal failure worsened and the patient required dialysis. One patient died from pneumonia and one patient died from multiple causes with an end-stage malignancy. Seven patients (11%) had planned cytotoxic chemotherapy postponed; one of these patients had a delay in a planned allogeneic HSCT.

We conclude that norovirus infection is a significant clinical complication to management of patients with hematological malignancies and stem cell transplant patients. Fatal outcome is possible primarily in patients with severe underlying conditions. Delay in planned chemotherapy was common and in addition the required closing of the ward presumably delaying chemotherapy for other non-infected patients.