Late cytomegalovirus disease after hematopoietic cell transplantation: significance of novel transplantation techniques

Abstract

AbstractPreemptive therapy (PET) and letermovir prophylaxis are effective in preventing cytomegalovirus (CMV) disease within the first 100 days after allogeneic hematopoietic cell transplantation (HCT) but are associated with late-onset CMV disease. We retrospectively examined the clinical manifestations, risk factors, prevention algorithm, and outcome of late CMV disease in day 100 survivors with CMV seropositivity who underwent transplantation between 2001 and 2017 (PET cohort) and 2018 and 2021 (letermovir cohort). There were 187 episodes of late CMV disease among 2469 day 100 survivors, and the estimated cumulative incidence of first late CMV disease was 6.7% (95% confidence interval [CI], 5.6-7.6) with no difference between the PET (6.7%; 95% CI, 5.7-7.8) and the letermovir group (5.4%; 95% CI, 3.2-8.3). Thirty-two patients (1.3%) had a second episode of late CMV disease. In multivariable Cox regression models, posttransplant cyclophosphamide was associated with an increased risk of gastrointestinal CMV disease. CMV viremia detected before day 100, corticosteroid treatment after day 100 at dose ≥1 mg/kg, acute and chronic graft-versus-host disease, lymphopenia, HLA-mismatched related donor status, and recipient age were also associated with late CMV disease. HLA-mismatched donor status and late use of corticosteroids (≥1 mg/kg) were risk factors for late CMV disease recurrence. Late CMV disease occurred most frequently in a setting of prolonged low-level untreated viremia and was independently associated with death by 2 years after HCT. In summary, late CMV disease continues to occur in the present era. Improved prevention strategies for late CMV disease are needed.