Cytomegalovirus (CMV) viremia after CD34⁺‐selected hematopoietic stem cell transplant (HCT) often requires prolonged antiviral therapy. We report rates and outcomes of resistant CMV in a contemporary cohort of CD34⁺‐selected HCT recipients managed preemptively.

We retrospectively reviewed 220 consecutive, CMV‐seropositive recipients (R+), who received CD34⁺‐selected HCT at Memorial Sloan Kettering Cancer Center between June 2010 and December 2014. Patients were monitored by quantitative CMV PCR and were treated preemptively. CMV resistance was tested by a genotypic assay.

One hundred and sixty‐one (73%) patients developed CMV viremia and 47 (29% of viremic and 21% of total patients) had CMV resistance testing by one‐year from HCT. CMV resistance was confirmed in 19 (12% of viremic and 9% of total) patients and was identified >3 months from HCT in 90% of patients. Twelve patients had mutations in UL97 only; the remaining 7 patients had mutations in UL54 only or UL54 and UL97. By 1 year from HCT, 11 of 19 (58%) patients with mutations had CMV end‐organ disease. CMV‐related mortality in patients with resistance was 42%.

Nine percent of CMV R+, CD34⁺‐selected HCT recipients had resistant CMV by 1 year from HCT. Of 19 patients with resistant CMV, 58% had CMV end‐organ disease and 42% died of CMV. Effective strategies for CMV prevention and restoration of CMV immunity are needed for CD34⁺‐selected HCT.