Background: Allogeneic hematopoietic cell transplant recipients (allo-HCTR) with positive CMV serology may have false positive results due to blood product transfusions associated passive immunity.

Methods: This is a single-center cohort study including consecutive adult allo-HCTR (01.01.2018-31.12.2022) with negative baseline (at hematologic malignancy diagnosis) and indeterminate or low-positive (CMV-IgG-titer: ≥ 0.6-<50 U/mL) pretransplant CMV-serology with negative pretransplant plasma CMV DNAemia. The CMV serology status of those patients was reclassified from R + to R- (CMVR- reclassification group). We compared those patients to allo-HCTR with negative (CMV-IgG-titer < 0.6 U/mL) pretransplant CMV IgG serology (CMVR- group). We describe the number and type of patients, whose pretransplant CMV serology status was reclassified from indeterminate/positive to negative. Moreover, we reviewed all plasma CMV DNAemia tests performed during the first 6 months posttransplant in both groups, to assess the safety of this approach.

Results: Amongst 246 (84.5%) of 291 transplanted patients identified as CMVR + pretransplant, 60/246 (24.4%) were reclassified from CMV serology indeterminate (N:10) or low-positive (N:50) to R-. Only 1/60 (1.67%) patient in the CMVR- reclassification group vs 3/44(6.8%; p = 0.30) in the CMVR- group developed CMV-DNAemia during the 6-month posttransplant follow-up period. There were no significant differences in the number of CMV-DNAemia tests performed, CMV-DNAemia range and time posttransplant between the two groups.

Conclusion: One out of four allo-HCT CMVR + may be falsely flagged as R+, with significant impact on donor selection and prophylaxis administration. A 2-step approach including CMV-serology testing at hematologic malignancy diagnosis in allo-HCTR candidates and careful review of pretransplant CMV IgG-titers may help correctly classify CMV-serology status.