Human herpes virus 6 infection is a hallmark of cord blood transplant in adults and may participate to delayed engraftment: a comparison with matched unrelated donors as stem cell source

Abstract

Occurrence of CMV, EBV and human herpes virus 6 (HHV6) infections and immune reconstitution were compared in 15 adult patients receiving a cord blood transplantation (CBT) and 40 patients who received an allogeneic transplantation from a matched unrelated donor (MUD). Herpes virus DNA quantifications in the blood (459 samples) were performed before and then monthly up to 9 months after transplant and the main lymphocytes populations were counted at 3, 6 and 9 months. Incidence of HHV6 infection was significantly higher in the CBT group (80 vs 42.5%; Po0.0001), with higher viral load (Po0.0001). In multivariate analysis, the use of a CBT and a myeloablative conditioning regimen were found to increase the risk of HHV6 infection (odds ratio (OR) ¼ 5.4, P ¼ 0.02 and OR ¼ 3.5, P ¼ 0.04, respectively). Incidences of CMV were similar between the two groups whereas MUD increased the risk of EBV infection, in univariate analysis only. HHV6 reactivation translated toward delayed neutrophils and plts engraftment in the two groups. MUD and CBT do not share the same immune reconstitution patterns, notably for B and CD8 lymphocytes and NK cells. There is a strong and specific relationship between HHV6 infection and the use of cord blood cells.

HHV-6 encephalitis in umbilical cord blood transplantation: a systematic review and meta-analysis

“…[41][42][43][44] Interestingly, a higher expression of CD46 is observed on the surface of untreated CB cells compared with G-CSF-mobilized hematopoietic progenitor cells used in HSCT, which may contribute to the increased prevalence of post-CBT HHV-6 reactivation. 10,45,46 However, several lines of evidence suggest that other cellular factors in addition to CD46 are crucial to the establishment of active HHV-6 infection in vivo. 41 Ogata et al 47 demonstrated that serum IL-6 levels increase dramatically in patients experiencing HHV-6 reactivation, showing a correlation between high levels of IL-6 in serum and CSF and the development of encephalitis.…”

“…Forest plots were built using STATA's user-developed 'metan' procedure. 33 63 Mixed 4500 copies per mL detected in whole blood 68.5% (37/54) 32.1% (9/28) Ishiyama et al 66 Adult 4100 copies per mL detected in plasma 80% (12/15) 0% (0/5) a Chevallier et al 10 Adult Defined by either one positive PCR test of 41000 copies per mL detected in whole blood or two consecutive positive PCR tests of 4100 copies per mL detected in whole blood 80% (12/15) 42.5% (17/40)…”

“…In particular, a distinct increase in HHV-6 reactivation and encephalitis following CBT (compared with HSCT with other stem cell sources) has emerged in the recent literature. 10,11 HHV-6 is the collective name for HHV-6A and HHV-6B, 12,13 two closely related beta-herpesviruses that establish primary infection in early childhood and maintain lifelong persistent infection with a combined seroprevalence of 490% in adults. [14][15][16][17] Of the two, HHV-6B is the variant implicated in nearly all documented cases of HHV-6 reactivation following HSCT, which typically occurs within 30 days of HSCT.…”

The impact of CD34+ cell dose on engraftment after SCTs: personalized estimates based on mathematical modeling

“…This has to be a subject of further research. Up to now, several risk factors for delayed engraftment have been identified, including HHV6 infection, 44 gene polymorphisms, 45 splenomegaly 46,47 and others. 3,[44][45][46][47][48][49][50][51][52][53] The current results underline that further investigation of this topic Figure 4.…”

Features of EBV reactivation after reduced intensity conditioning unrelated umbilical cord blood transplantation

“…CMV, EBV, adenovirus and Human Herpes Virus 6 were routinely screened by quantitative PCR. 13 EBV monitoring and therapy During the first 6 months after UCBT and in patients treated for GVHD, weekly DNA-PCR screening was performed in the peripheral blood for EBV reactivation and all patients were clinically monitored for clinical features attributable to EBV. After the first 6 months, if no reactivation occurred, the screening for EBV was regularly performed (usually monthly) and whenever clinically relevant, until full immune reconstitution of the patient was achieved.…”