This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Invasive aspergillosis (IA) is associated with poor outcomes in patients with hematologic malignancies (HMs) and hematopoietic cell transplantation (HCT). Small studies suggest a role for combination antifungal therapy. To assess the safety and efficacy of voriconazole and anidulafungin compared with voriconazole monotherapy for treatment of IA. Randomized, double-blind, placebo-controlled multicenter trial. (ClinicalTrials.gov: NCT00531479) 93 international sites. 454 patients with HM or HCT and suspected or documented IA were randomly assigned to treatment with voriconazole and anidulafungin or placebo. Primary analysis was done in the modified intention-to-treat population of 277 patients in whom IA was confirmed. The primary outcome was 6-week mortality; secondary outcomes included 12-week mortality, mortality in major subgroups, and safety measures. Mortality rates at 6 weeks were 19.3% (26 of 135) for combination therapy and 27.5% (39 of 142) for monotherapy (difference, −8.2 percentage points [95% CI, −19.0 to 1.5]; P = 0.087). Secondary mortality outcomes favored combination therapy. Multivariable regression analysis suggested that maximum galactomannan value, Karnofsky score, and baseline platelet count had prognostic significance. Most patients (218 of 277 [78.7%]) had IA diagnosis established by radiographic findings and maximum galactomannan positivity. In a post hoc analysis of this dominant subgroup, 6-week mortality was lower in combination therapy than monotherapy (15.7% [17 of 108] vs. 27.3% [30 of 110]; difference, −11.5 percentage points [CI, −22.7 to −0.4]; P = 0.037). Safety measures, including hepatotoxicity, were not different. Mortality at 6 weeks was higher than expected, and the difference in mortality was lower than expected, which reduced power to detect a treatment effect. Enrollment was restricted to patients with HM or HCT, which limited generalizability. Compared with voriconazole monotherapy, combination therapy with anidulafungin led to higher survival in subgroups of patients with IA. Limitations in power preclude definitive conclusions about superiority. Pfizer.

Cytomegalovirus (CMV) infection after hematopoietic stem cell transplantation (HSCT) is one of the critical infectious complications related to host immune recovery. The spectrum of CMV infection is quite extensive, from asymptomatic CMV reactivation presenting mainly as CMV DNAemia to fatal CMV diseases involving gut, liver, lungs, or brain. In addition to organ involvement, CMV reactivation can exert indirect effects such as immunosuppression or graft failure that may result in the development of concurrent infectious complications. Currently, preemptive therapy, which is based on PCR-based monitoring of CMV from blood, is a mainstay enabling improvement in CMV-related outcomes. During the past decades, new antiviral drugs, clinical trials for prophylaxis in high-risk groups, and vaccines for preventing CMV infection have been introduced. In addition, data for immunologic monitoring and adoptive immunotherapy have also been accumulated. Here, we review the current status and recent updates in this field, with future perspectives including immunotherapy in HSCT recipients.

We aimed to identify whether lymphopenia is a reliable prognostic marker for COVID-19. Using data derived from a Korean nationwide longitudinal cohort of 5628 COVID-19 patients, we identified propensity-matched cohorts (n = 770) with group I of severe lymphopenia (absolute lymphocyte counts [ALC]: <500/mm³, n = 110), group II of mild-to-moderate lymphopenia (ALC: ≥500–<1000/mm³, n = 330), and group III, no lymphopenia (ALC: ≥1000/mm³, n = 330). A significantly higher mortality rate was associated with lymphopenia severity: 40% in group I, 22.7% in group II, and 13.0% in group III (p < 0.001). At 28 days, the estimated inferior overall survival associated with intensified lymphopenia: 62.7% in group I, 79.9% in group II, and 89.0% in group III (p < 0.001). Lymphopenia contributed significantly toward a greater need for interventions in all groups but at varying degrees: requirements of invasive ventilation, intensive oxygen supply, or adequate oxygen supply, respectively (p < 0.001). The lymphopenia intensity was independently associated with higher COVID-19 mortality in multivariable analysis; adjusted odds ratios of 5.63 (95% CI, 3.0–10.72), and 2.47 (95% CI, 1.5–4.13) for group I and group II, respectively. Lymphopenia and its severity levels may serve as reliable predictive factors for COVID-19 clinical outcomes; thus, lymphopenia may provide the prognostic granularity required for clinical use in the management of patients with COVID-19.

Choi SM, et al. J Korean Med Sci. 2003 Oct;18(5):631-636. http://dx.doi.org/10.3346/jkms.2003.18.5.631

Lee DG, et al. Korean J Intern Med. 2011 Jun;26(2):220-252. http://dx.doi.org/10.3904/kjim.2011.26.2.220