BK Virus Reactivation After Double Umbilical Cord Blood Transplantation in Adults Correlates with Tregs and Delayed Reconstitution of CD4+ and CD8+ T Effector Cells

• Published in: Blood 2012-11, Vol.120 (21), p.4174-4174
• Main Authors: Satyanarayana, Gowri, Hammond, Sarah, Kim, Haesook T, McDonough, Sean, Brown, Julia, Politikos, Ioannis, Li, Lequn, Viscidi, Raphael, Broge, Thomas, Koralnik, Igor, Cutler, Corey, Ballen, Karen K., Antin, Joseph H., Marty, Francisco M, Ritz, Jerome, Tan, C Sabrina, Boussiotis, Vassiliki A.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V120.21.4174.4174

Abstract 4174 Umbilical cord blood transplantation (UCBT) in adults is associated with impaired immune function and increased infection-related morbidity and mortality due to lack of antigen experienced cells and delayed immune reconstitution. BK virus (BKV) is a human polyomavirus that remains latent in renal epithelial cells and can be reactivated after hematopoietic stem cell transplantation (HSCT), leading to hemorrhagic cystitis. Data regarding BKV reactivation and its association with immune reconstitution after UCBT is lacking. We evaluated the status, cellular mechanisms, and clinical implications of immune reconstitution on BK viremia in adults with hematologic malignancies undergoing double unit cord blood transplantation. Thirty-two patients with a median age of 50 years with hematopoietic malignancies were treated with reduced intensity conditioning (Flu/Mel/rATG) followed by infusion of two sequential UCB grafts and GvHD prophylaxis with tacrolimus and sirolimus. The grafts were at least a 4/6 match with each other and the recipient. The results are based on 27 evaluable patients. Assessments were done prior to transplant and at 1, 2, 3, 6 and 12 months after UCBT. After UCBT, 15 patients had detectable serum BKV DNA, median 2.6×104 copies/ml (range, 2.5×102–7.9×106) with a median time to viremia of 40 days (range, 26–733). The cumulative probability of developing BK viremia by day 100 was 0.52 (95% CI, 0.33–0.71). In 9 of the 15 patients with detectable serum BKV DNA, urinary BKV PCR was also performed. All 9 tested patients had detectable urinary BKV and developed clinical symptoms ranging from dysuria to hemorrhagic cystitis. To determine whether development of BK viremia was related to the immunological status, we analyzed detection of serum BKV DNA in conjunction with parameters of immune reconstitution. At 6 and 12 months after transplantation development of BK viremia displayed a statistically significant inverse correlation with CD4+ and CD8+ T cells (p