158: Clinical outcome of human herpes-6 reactivation after haematopoietic stem cell transplantation in children

Abstract

Background: Although human herpes virus 6 (HHV6) is known to reactivate during haematopoietic cell transplantation (HCT) and is suggested to be associated with severe clinical manifestations in adults, the clinical significance in children remains controversial. In this study we investigated the incidence of HHV6 reactivation and HCT-associated morbidity and mortality in children.Methods: Between 1/2004 and 4/2006 59 patients, median age 6.6y (0.1-18.1), underwent 68 allogeneic HCTs. By quantitative PCR HHV6, EBV, CMV and adenovirus (AdV)-plasma loads were measured once a week. Clinical features, engraftment, number of transfusions, HCT-associated mortality and morbidity (like GvHD) were monitored. Antiviral treatment for HHV-6 reactivation was only given from 4/2005 for those with clinical symptoms assumed to be associated with HHV6. HHV6 reactivations were grouped in group I (no HHV6), group II (loads <1000cp/mL) and group III (loads >1000cp/mL). CMV, EBV and AdV-reactivations were treated according to local guidelines. A risk factor analyses was performed using logistic regression.Results: 36 HLA-id and 23 HLA non-id grafts were used: 44 bone marrow/PBSCs and 15 cord blood grafts. Median follow up was 17 (5-35)mths. HHV6 reactivation occurred in 40/59 (67%) with 33/40 (82%) occurring within the first 30 d post-HCT. 23/59 (39%) had HHV6 loads above 1000cp/mL (group III). Groups did not differ regarding sex, age, donor source or HLA-disparity. In multivariate analysis HHV6 reactivation was associated with a lower survival in group III (OR 0,16; range 0,03-0,89; p=0.035) as well as with more multiple viral reactivations (p=0,049: OR 5,5; range 1,1-29) were seen in this group. In 11/13 multiple viral reactivation HHV6 was the first viral reactivation. There was a non-significant trend for more grade 2-4 acute-GvHD (p=0,058 OR 4,3; range 0,8-18) in group III. HHV6 didnot influence period of neutro-trombocytopenia.Conclusion: HHV6 reactivation is common after HCT in children and is associated with a higher rate of multiple viral reactivations, aGvHD and with a lower survival rate. Although the exact role of HHV6 reactivation in transplantation associated morbidity and mortality has to be elucidated, early detection and initiation of therapy might influence the outcome. Background: Although human herpes virus 6 (HHV6) is known to reactivate during haematopoietic cell transplantation (HCT) and is suggested to be associated with severe clinical manifestations in adults, the clinical significance in children remains controversial. In this study we investigated the incidence of HHV6 reactivation and HCT-associated morbidity and mortality in children. Methods: Between 1/2004 and 4/2006 59 patients, median age 6.6y (0.1-18.1), underwent 68 allogeneic HCTs. By quantitative PCR HHV6, EBV, CMV and adenovirus (AdV)-plasma loads were measured once a week. Clinical features, engraftment, number of transfusions, HCT-associated mortality and morbidity (like GvHD) were monitored. Antiviral treatment for HHV-6 reactivation was only given from 4/2005 for those with clinical symptoms assumed to be associated with HHV6. HHV6 reactivations were grouped in group I (no HHV6), group II (loads <1000cp/mL) and group III (loads >1000cp/mL). CMV, EBV and AdV-reactivations were treated according to local guidelines. A risk factor analyses was performed using logistic regression. Results: 36 HLA-id and 23 HLA non-id grafts were used: 44 bone marrow/PBSCs and 15 cord blood grafts. Median follow up was 17 (5-35)mths. HHV6 reactivation occurred in 40/59 (67%) with 33/40 (82%) occurring within the first 30 d post-HCT. 23/59 (39%) had HHV6 loads above 1000cp/mL (group III). Groups did not differ regarding sex, age, donor source or HLA-disparity. In multivariate analysis HHV6 reactivation was associated with a lower survival in group III (OR 0,16; range 0,03-0,89; p=0.035) as well as with more multiple viral reactivations (p=0,049: OR 5,5; range 1,1-29) were seen in this group. In 11/13 multiple viral reactivation HHV6 was the first viral reactivation. There was a non-significant trend for more grade 2-4 acute-GvHD (p=0,058 OR 4,3; range 0,8-18) in group III. HHV6 didnot influence period of neutro-trombocytopenia. Conclusion: HHV6 reactivation is common after HCT in children and is associated with a higher rate of multiple viral reactivations, aGvHD and with a lower survival rate. Although the exact role of HHV6 reactivation in transplantation associated morbidity and mortality has to be elucidated, early detection and initiation of therapy might influence the outcome.