Herpesvirus Viremia and Engraftment Status of Umbilical Cord Blood in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplant
Authors: Al_Harbi Ibrahim , Yau Yvonne , Allen Upton , Schechter Tal , Lau Wendy , Petrich Astrid , Gassas Adam , McDougall Elizabeth , Doyle John J 
Published: October 2019

Abstract
Abstract 3021
Umbilical Cord Blood (UCB) is frequently used as a source of stem cells for children undergoing allogeneic hematopoietic stem cell transplant (HSCT) for both benign and malignant disorders. Despite algorithms using both nucleated cell numbers and HLA typing, the rate of engraftment failure remains higher than rates observed using other stem cell products. We conducted a retrospective review of our centre's experience with HSCT with UCB to evaluate the impact of herpesvirus viremia on the rate of engraftment. Children who underwent allogeneic HSCT with UCB between 06/2005 and 05/2010 inclusive were identified from the program database. Engraftment was defined as the first day of three consecutive absolute neutrophil counts of > 0.5 × 10[exp 9]/L within 42 days of UCB infusion and evidence of donor DNA on chimerism testing. Blood samples were sent for qualitative herpesvirus polymerase chain reaction (PCR) weekly (HHV-6, HHV-7, EBV, CMV, HSV or VZV). If either CMV or EBV results were positive, a quantitative assay was performed as well. Viremia was considered to have occurred if the qualitative assay became positive. Anti-viral therapy was initiated for measurable amounts of either CMV or EBV DNA or selectively for HHV-6 DNA. Eighty-one HSCT utilizing UCB were performed during this period. One child was unevaluable (NRM at day +15) so the analysis was performed using the remaining 80 patients. Thirty HSCT (37.5%) were performed for non-malignant indications and 50 (62.5%) for malignant disorders. Ninety per cent were performed using unrelated UCB; 27 were 6/6 HLA matched UCB, 42 were 5/6 HLA matches and 11 were 4/6 matches. Four children were recovering counts at day +42 but had not reached the threshold neutrophil value. They were considered as delayed engraftment rather than engraftment failure. Eleven (14%) failed to engraft. Forty-two (52.5%) of the transplants were complicated by the detection of 1 or more herpesviruses (24 for only 1 virus, 15 for 2 viruses and 3 for 3 viruses). None of gender, ABO matching, recipient CMV pre-HSCT serostatus, disease category, use of ATG or TBI in the conditioning regimen, use of methotrexate as GVHD prophylaxis or positivity for any single herpesvirus was associated with engraftment failure. Numbers of viable nucleated cells and CD34+ cells were not different between those that engrafted and those that failed to engraft. Transplants complicated by viremia of more than 1 herpesvirus had a significantly poorer engraftment rate than others (0.667 vs 0.933, P=0.007); more specifically viremia due to CMV and any other herpesvirus was associated with a worse engraftment rate than others (0.643 vs 0.921, P=0.006) (table). Notably viremia due to HHV-6 and others or EBV and others were not related to engraftment failure.PCR resultEngraftedFailed to engraftNo CMV516CMV positive185CMV alone90CMV plus:    HHV-632    HHV-721    EBV22    HHV-6 & HHV-710    HHV-6 & EBV10

Conclusion:
A significantly poorer engraftment rate in children undergoing HSCT using UCB was seen in those with CMV viremia in the presence of another herpesvirus. Further research is needed to define cause and effect and the therapeutic strategies to prevent it.

Disclosures:
No relevant conflicts of interest to declare.