Patients with refractory cytomegalovirus (CMV) infection following allogeneic haematopoietic stem cell transplantation are at high risk for CMV disease and non-relapse mortality

Abstract

Pre-emptive therapy is an effective approach for cytomegalovirus (CMV) control; however, refractory CMV still occurs in a considerable group of recipients after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Until now, hardly any data have been available about the clinical characteristics and risk factors of refractory CMV, or its potential harmful impact on the clinical outcome following allo-HSCT. We studied transplant factors affecting refractory CMV in the 100 days after allo-HSCT, and the impact of refractory CMV on the risk of CMV disease and non-relapse mortality (NRM). We retrospectively studied 488 consecutive patients with CMV infection after allo-HSCT. Patients with refractory CMV in the 100 days after allo-HSCT had a higher incidence of CMV disease and NRM than those without refractory CMV (11.9% vs. 0.8% and 17.1% vs. 8.3%, respectively). Multivariate analysis showed that refractory CMV infection in the 100 days after allo-HSCT was an independent risk factor for CMV disease (hazard ratio (HR) 10.539, 95% CI 2.467-45.015, p 0.001), and that refractory CMV infection within 60-100 days after allo-HSCT was an independent risk factor for NRM (HR 8.435, 95% CI 1.511-47.099, p 0.015). Clinical factors impacting on the risk of refractory CMV infection included receiving transplants from human leukocyte antigen-mismatched family donors (HR 2.012, 95% CI 1.603-2.546, p <0.001) and acute graft-versus-host disease (HR 1.905, 95% CI 1.352-2.686, p <0.001). We conclude that patients with refractory CMV infection during the early stage after allo-HSCT are at high risk for both CMV disease and NRM.

The clinical and economic impact of cytomegalovirus infection in recipients of hematopoietic stem cell transplantation

“…In addition to CMV D/R serostatus, previous studies have identified the following risk factors for CMV‐I: age, GVHD, HLA mismatch, T‐cell depletion, mycophenolic acid, lymphopenia, and corticosteroids . In both multivariable regression analysis and random forest analysis, we confirmed that CMV D/R serostatus was the most important risk factor for CMV‐I.…”

“…In the era of World Health Organization (WHO)‐standardized PCR surveillance and preemptive antiviral therapy, our observations add to the current knowledge base regarding the characteristics, complications, and clinical and economic impact of CMV‐I. In this cohort, the incidence of CMV‐I in allogeneic HSCT recipients was lower than in other studies . It is possible that the lower incidence of CMV‐I may be attributable to differences in CMV assays and host characteristics or perhaps to the initial IV dose of acyclovir prophylaxis administered.…”

CMV viral load in bronchoalveolar lavage for diagnosis of pneumonia in allogeneic hematopoietic stem cell transplantation

“…In this study, 10.7% of patients who received an AHSCT were diagnosed with probable CMV pneumonia with a high percentage of mortality (50%) with a specific treatment. As described in other studies, 15 the factor associated with increased mortality was the persistent CMV DNAemia for more than 2 weeks in spite of antiviral therapy, which could be related to ganciclovir resistance, although we could not analyze this fact. In two patients who died, the treatment was changed to foscarnet very late (after 20 days of ganciclovir treatment, the plasma VL did not become negative).…”

Viral encephalitis after haplo‐identical hematopoietic stem cell transplantation: Causative viral spectrum, characteristics, and risk factors

“…Acyclovir was given daily from the conditioning to engraftment, and then, it was administered daily for 7 days every 2 weeks until 1 year post‐transplants for virus infection prophylaxis. For cytomegalovirus (CMV) prophylaxis, patients received acyclovir from day 1 to day 30 and ganciclovir from day ‐10 to day ‐2 as previously reported . Preemptive therapy with either intravenous ganciclovir or intravenous foscarnet was given when the PCR tests were positive.…”

“…For cytomegalovirus (CMV) prophylaxis, patients received acyclovir from day 1 to day 30 and ganciclovir from day -10 to day -2 as previously reported. 22,23 Preemptive therapy with either intravenous ganciclovir or intravenous foscarnet was given when the PCR tests were positive. Treatment was administered for 2 weeks at the full dose and as maintenance for another 2 weeks until CMV DNA was no longer detected.…”