Recipient CMV Seropositivity Predicts Relapse Post Allogeneic Transplantation in Children.
Authors: Zuha Roslin , Gatt Alex , Alvares Caroline , Horton Clive , Patel Gita , Ethell Mark , Potter Michael 
Published: October 2019

Abstract
The importance of recipient CMV status is established as a major determinant of post transplantation infection risk, however studies to date have so far not demonstrated an influence on relapse. CMV is one of the key human pathogens known to induce immunosuppression.This has been attributed to the potential of the virus to infect bone marrow progenitors, thus interfering with haematopoiesis, but there is also evidence that CMV can infect dendritic cells resulting in an impairment of adequate generation and maintenance of immune responses,leading to delayed activation of T cell responses.We hypothesised that CMV positive patients undergoing transplantation, have impaired Tcell recovery and this subsequently has a detrimental impact on the immune response required for an effective graft versus leukaemia effect, leading to a potential increase in post transplantation relapse. We retrieved data on 429 allogeneic stem cell transplant patients treated at the Royal Marsden hospital (129 unrelated, 289 sibling,11 haploidentical). The donor and recipient CMV serology status was documented pre transplant.Of the recipients ,191 were positive and 238 were negative.We analysed the influence of patient and donor CMV serlogy status on the probablity of relapse, event free survival (EFS) and overall survival (OS). Univariate and multivariate analysis were conducted to establish other factors that could have had an impact on relapse.
RESULTS ; CMV seropositive recipients (n=191) showed a significantly higher probability of relapse at ten years follow up (p=0.0107). Patient CMV serostatus also had an influence on EFS (p=0.0497) but not OS (p=0.08). Donor/patient CMV match did not appear to have an impact on EFS , OS or probabilty of relapse (p 0.23 v 0.3 v 0.17 respectively).In contrast to published studies, post transplant CMV reactivation which occurred in 116 patients, did not appear to impact on post transplantation relapse rate.( p=0.63). On subanalysis of CMV positive recipients into children (n=133, positive=38, negative=95) and adults (n=296, positive=153 ,negative= 143), the probability that this was associated with relapse appeared to apply to children only (p 0.028 v 0.12). EFS was higher in children than adults.(p=0.0001).The diagnosis had a significant influence in relapse rate (P=0.048) The acute leukaemias represented over half of the patient cohort, with ALL being the most common malignant diagnosis in children.( ALL n=140 of which 87 were aged <17yrs ,AML n= 120, MYL/CML n=101, other n=46 ).Previous autograft decreased both the EFS and OS (P<0.00001).Prior treatment with CAMPATH did not appear to impact on either of these survival outcomes.(p=0.4 v 0.34). CD34 and GVHD information was excluded from analysis due to incomplete availability of data.In conclusion , a positive CMV status in the recipient, prior to transplantation appears to result in a significantly higher relapse rate in children. This may relate to the delayed and incompetent immune reconstitution leading to a suboptimal graft versus disease effect. The difference in adults and children remains unclear although this may be related to the variation in disease subgroups.