Background: Haploidentical allogeneic hematopoietic cell transplant recipients (allo-HCTr) receiving posttransplant cyclophosphamide (haplo-PTCy) are at higher risk for infectious complications, including viral infections.

Methods: We performed a retrospective, single-center, propensity-score matched-pair study including adult haplo-PTCy and allo-HCTr from human leukocyte antigen (HLA)-matched donors, undergoing transplantation in our institution between 2016 and 2022. For each patient, 4 blood samples (day [D] 0, D30, D90, and D180 posttransplantation) were extracted from the biobank and tested with metagenomic next-generation sequencing (mNGS) to describe the blood virome and identify viral RNA/DNA signatures potentially unrecognized by routinely available tests. Routine and symptom-driven polymerase chain reaction (PCR) test results performed during the study period were reviewed.

Results: Twenty-five matched pairs of haplo-PTCy and HLA-matched allo-HCTr were included in the analysis. Plasma mNGS detected a total of 155 and 190 different viral RNA/DNA signatures in haplo-PTCy and HLA-matched allo-HCTr, respectively between D0 and D180. The number of viral signatures was significantly lower in the haplo-PTCy group compared to HLA-matched allo-HCTr at D90 (-1.0 [95% confidence interval {CI}, -1.7 to -.3]; P = .01) and during the period between D30 and D180 (-1.9 [95% CI, -3.3 to -.5]; P = .01). Certain viral species (Anelloviridae, Epstein-Barr virus) were more prevalent in HLA-matched patients. Symptom-driven PCR tests showed higher infection rates of usual viral pathogens in haplo-PTCy versus HLA-matched allo-HCTr (P = .02).

Conclusions: Frequently deployed, targeted PCR tests showed increased viral infection prevalence in haplo-PTCy patients. Conversely, mNGS testing applied at specific timepoints revealed a lower number of commensal viruses in this patient group. More studies on routine use of mNGS are needed to further assess its clinical relevance and value.