Early Human Herpes Virus Type 6 Reactivation in Patients Undergoing Allogeneic Stem Cell Transplantation (allo-SCT).

Human herpes virus 6 (HHV6) is known to reactivate after allo-SCT. It has been suggested that HHV6 may be associated with severe clinical manifestations, but little is known about its exact role in patients' outcomes following allo-CST.

Here we report our findings in 225 consecutive patients who underwent allo-SCT in our unit between January 2004 and March 2009. The median age was 42 years (3-62). Donors were HLA-identical sibling (n=110), and unrelated (n=115). Source of stem cells was bone marrow (BM; n=124), peripheral blood stem cell (PBCS; n=69) and cord blood (CB; n=32). Conditioning regimen was myeloablative (n=151), or reduced intensity (RIC; n=74). HHV6 plasma loads were measured almost weekly by quantitative PCR. We treated symptomatic patients when no other cause than HHV6 reactivation could explain the symptoms. However, patients with associated CMV reactivation were also treated with anti-viral therapy. At the time of analysis on July 31st 2009, the median follow-up was 33 months (4-68). A total of 105 (46%) patients had early positive HHV6-PCR within the first 100 days following transplantation (group I). In this retrospective study we compared the outcome of patients in group I to those who did not reactivate HHV6 or those who had positive HHV6-PCR after day 100 (group II; n=120).

Patients with PBSC and those who received RIC showed evidence of HHV6 reactivation less often than the others (p=0.049 and p=0.076, respectively). When HHV6-PCR was positive, only 10 patients in group I were asymptomatic while 95 patients experienced either fever (n=55), skin rash (n=51), diarrhea (n=41), pulmonary complications (n=16), neurological disorders (n=12), liver dysfunction (n=8) and/or others (n=7). Of note, 73 patients (70%) experienced more than one symptom concomitant to HHV6 reactivation. Thirty-seven patients received anti-viral therapy for HHV6-reactivation alone (n=18) or associated with CMV reactivation (n=19) resulting in negative HHV6-PCR in 31 of them. Out of the 6 patients who failed to have negative HHV6-PCR, 2 died 25 and 90 days after anti-viral therapy initiation, respectively. Although, there was no significant difference in overall survival or relapse-free survival between the two groups, patients in group II had earlier platelet engraftment (> 50 G/L) than those in group I with a median of 22 versus 28 days (p=0.003). In addition, patients in group I developed more often acute grade III-IV graft-versus-host disease (GvHD) than those in group II (34/105 versus 15/120, p=0.008). Of note, for 53% patients in group I with acute grade III-IV GvHD, HHV6 reactivation was observed before the development of acute GvHD. In multivariable analysis, the most important factors influencing acute grade III-IV GvHD were early HHV6 reactivation, [HR: 2.10; 95%CI, 1.20-3.66] (p=0.011) and unrelated donor, [HR: 1.17; 95%CI 1.04-1.32] (p=0.007).

HHV6 reactivation is common after allo-SCT and is responsible for platelet engraftment delay and high-grade acute GvHD. Careful monitoring of HHV6-PCR is warranted during the early period of transplantation, as symptomatic patients require treatment.

No relevant conflicts of interest to declare.