Cytomegalovirus (CMV) gB3 Genotype Is Associated with Acute Gvhd and CMV Disease in Allogeneic Hematopoietic Stem Cell Transplant Recipients (HSCT)

Abstract 1958

Based on sequence variation in the UL55 gene that encodes glycoprotein B (gB), human cytomegalovirus (CMV) can be classified into four gB genotypes. Previous studies have suggested an association between CMV gB genotype and clinical outcome in patients who underwent an allogeneic hematopoietic stem cell transplant (HSCT). Objectives: The goals of this study were: identify patients with active infection caused by CMV in recipients of HSCT; determine the prevalence of CMV genotypes in the study group; correlate genotype with the CMV disease, acute GVHD and overall survival. Study design: The diagnosis of active CMV infection after allogeneic HSCT was detected by Antigenemia (AGM) and/or Nested-PCR (N-PCR). Positive samples from patients with active CMV infection were submitted to genotyping using the N-PCR to amplify a region of UL55, followed by restriction analysis based on HinfI and RsaI digestion. Real-time PCR (qPCR) was used to determine the viral load during active CMV infection and antiviral treatment. Results: Were evaluated 63 allogeneic HSCT recipients, 49/63 patients (78%) presented active CMV infection detected by AGM and/or N-PCR, in a median time of 38 days after the transplant. The distribution of CMV gB genotypes in these 49 patients with active CMV infection was as follow: gB1, 19/49 (38.8%); gB2, 17/49 (34.7%); gB3, 3/49 (6.1%); gB4, 7/49 (14.3%) and three patients (6.1%) had mixed infection with gB1+gB3, gB1+gB4 and gB2+gB4. Acute GVHD grade II-IV occurred in 17/49 (34.7%) patients: 8/19 (gB1-42%), 1/17 (gB2 - 5.9%), 4/4 (gB3 - 100%) and 4/9 (gB4 - 44.4%). The distribution of the frequency of acute GVHD grade II-IV between the genotypes was statistically different (p=0.008). CMV disease occurred in 3/49 (6.1%) patients, characterized for gastrointestinal disease and these three patients had infection with CMV gB3 genotype. This genotype of CMV was also associated with higher viral load during antiviral treatment and worse survival. Conclusions: This study demonstrated that the frequency of active CMV infection in HSCT population was high (78%). The most prevalent genotype in patients with active CMV infection was gB1 and gB3 genotype was associated with acute GVHD grade II-IV, CMV gastrointestinal disease, higher viral load during antiviral treatment and worse survival.