Early Human Herpesvirus Type 6 Reactivation in Umbilical Cord Blood Allogeneic Stem Cell Transplantation

Human Herpesvirus Type 6 (HHV-6) reactivation occurs in 38%-67% of hematopoietic stem cell transplant (HSCT) recipients –usually within the first month post-transplant. Studies have shown that HHV-6 reactivation after allogeneic HSCT delays engraftment, has myelosuppressive effects, and potentially increases the risk of developing acute graft-versus-host disease (aGVHD). An increased incidence of HHV-6 reactivation in umbilical cord blood (UCB) HSCTs has been previously described.

In June 2012, Weill Cornell Medical Center began performing allogeneic HSCTs with haploidentical stem cells followed by UCB (Haplo-Cord). No published studies have examined HHV-6 reactivation and its sequelae in Haplo-Cord HSCTs.

The purpose of this study was to retrospectively assess for risk factors and sequelae of HHV-6 reactivation in UCB HSCTs. The objectives were to determine the impact of early HHV-6 reactivation (within 60 days of transplant) on overall survival and incidence of aGVHD at 100 days post-transplantation.

Fifty-seven adult transplants between August 2010 and June 2013 utilizing UCB with ≥ 1 HHV-6 PCR level reported were included: 29 double UCB HSCTs, 26 Haplo-Cord HSCTs, and 2 single UCB HSCTs.

HHV-6 reactivation occurred in 35/57 (61.4%). No baseline factors (age, ASBMT RFI disease classification, conditioning regimen, immunosuppressive regimen, stem cell source, time to engraftment, and underlying disease) predicted for HHV-6 reactivation.

Comparing HSCTs with HHV-6 reactivation and those without, survival at 100 days (77% v. 73%, p=0.706) and development of aGVHD (57% v. 32%, p=0.062) were not significantly different. HHV-6 reactivation with > 1000 copies/mL trended towards increased development of aGVHD (63% v. 36%, p=0.051). Notably, aGVHD developed significantly less often in Haplo-Cord HSCTs compared to HSCTs only using UCB (31% v. 61%, p=0.022).

Based on preliminary analysis, early HHV-6 reactivation after UCB HSCT occurs indiscriminately and does not influence survival or incidence of aGVHD at 100 days post-transplantation.