The performance of a plasma real-time PCR (cytomegalovirus [CMV] PCR kit; Abbott Diagnostics) was compared with that of the antigenemia assay for the surveillance of active CMV infection in 42 allogeneic hematopoietic stem cell transplantation (Allo-SCT) recipients. A total of 1,156 samples were analyzed by the two assays. Concordance between the two assays was 82.2%. Plasma DNA levels correlated with the number of pp65-positive cells, particularly prior to the initiation of preemptive therapy. Fifty-seven episodes of active CMV infection were detected in 37 patients: 18 were defined solely by the PCR assay and four were defined on the basis of the antigenemia assay. Either a cutoff of 288 CMV DNA copies/ml or a 2.42-log 10 increase of DNAemia levels between two consecutive PCR positive samples was an optimal value to discriminate between patients requiring preemptive therapy and those not requiring therapy on the basis of the antigenemia results. The real-time PCR assay allowed an earlier diagnosis of active CMV infection and was a more reliable marker of successful clearance of CMV from the blood. Analysis of the kinetics of DNAemia levels at a median of 7 days posttreatment allowed the prediction of the response to CMV therapy. Two patients developed CMV colitis. The PCR assay tested positive both before the onset of symptoms and during the disease period. The plasma real-time PCR from Abbott is more suitable than the antigenemia assay for monitoring active CMV infection in Allo-SCT recipients and may be used for guiding preemptive therapy in this clinical setting.Preemptive antiviral therapy based on the detection of cytomegalovirus (CMV) in blood has been shown to significantly reduce the incidence of CMV disease in the early posttransplant period following allogeneic hematopoietic stem cell transplantation (Allo-SCT) (2, 7). The pp65 antigenemia assay has been adopted by many transplant centers as the "gold standard" for monitoring active CMV infection and guiding preemptive therapy in this clinical setting. The antigenemia assay, however, requires rapid processing of specimens, is labor-intensive, cannot be automated, is subjective in reading, and is unfeasible during periods of severe neutropenia. In addition, it does not reflect the viral load in the blood compartment accurately (12) and sometimes displays negative results in the presence of CMV disease (2,31,32,36).Quantification of CMV DNA in blood by PCR is emerging as an alternative to the antigenemia assay and may soon become the standard for the surveillance of CMV infection in Allo-SCT recipients. Viral load quantification in blood allows early detection of active CMV infection, close monitoring of the response to antivirals, prediction of the risk of viremic relapse, emergence of resistant strains, and eventual development of CMV disease (8,31). In addition, it may be safely used for guiding preemptive therapy (11,16,23,24,32,37). Nevertheless, there is some controversy as to which is the optimal clinical specimen (plasma, whole blood, or leukoc...

Epidemiologic data about coronaviruses (CoVs) and human bocavirus (HBoV) in the setting of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are scarce. We conducted a prospective longitudinal study on respiratory viral infections (RVIs) in allo-HSCT recipients with respiratory symptoms from December 2013 until June 2016. Respiratory virus in upper and/or lower respiratory tract (URT and LRT) specimens were tested using Luminex xTAG RVP Fast v1 assay. Seventy-nine consecutive allo-HSCT recipients developed a total of 192 virologically documented RVI episodes over 30 months. The median follow-up after RVI was 388 days (range, 5 to 923). CoV or HBoV was detected in 27 of 192 episodes (14%); 18 of 79 recipients (23%) developed a total of 21 CoV RVI episodes, whereas 6 recipients (8%) had 1 HBoV RVI episode each. Fourteen CoV RVI episodes were limited to the URT, whereas 7 affected the LRT. Co-pathogens were detected in 8 (38%) CoV cases. Type OC43 CoV was the dominant type (48%) followed by NL63 (24%), KHU1 (19%), and 229E (9%); the CoV hospitalization rate was 19%, whereas mortality was 5% (1 patient without any other microbiologic documentation). Among the 6 recipients with HBoV (3%), only 1 had LRT involvement and no one died from respiratory failure. In 5 cases (83%) HBoV was detected along with other viral co-pathogens. CoV RVIs are common after allo-HSCT, and in a significant proportion of cases CoV progressed to LRT and showed moderate to severe clinical features. In contrast, HBoV RVIs were rare and mostly presented in the context of co-infections.

Purpose Most anemic patients with non-deleted 5q lower-risk myelodysplastic syndromes (MDS) are treated with erythropoiesis-stimulating agents (ESAs), with a response rate of approximately 50%. Second-line treatments, including hypomethylating agents (HMAs), lenalidomide (LEN), and investigational drugs, may be used after ESA failure in some countries, but their effect on disease progression and overall survival (OS) is unknown. Here, we analyzed outcome after ESA failure and the effect of second-line treatments. Patients and Methods We examined an international retrospective cohort of 1,698 patients with non-del(5q) lower-risk MDS treated with ESAs. Results Erythroid response to ESAs was 61.5%, and median response duration was 17 months. Of 1,147 patients experiencing ESA failure, 653 experienced primary failure and 494 experienced relapse after a response. Primary failure of ESAs was associated with a higher risk of acute myeloid leukemia (AML) progression, which did not translate into an OS difference. Of 450 patients (39%) who received second-line treatment, 194 received HMAs, 148 received LEN, and 108 received other treatments (MISC), whereas 697 received RBC transfusions only. Five-year AML cumulative incidence was 20.3%, 20.3%, and 11.3% for those receiving HMAs, LEN, and MISC, respectively ( P = .05). Five-year OS for patients receiving HMA, LEN, and MISC was 36.5%, 41.7%, and 51%, respectively ( P = .21). In a multivariable analysis adjusted for age, sex, revised International Prognostic Scoring System score, and progression at ESA failure, there was no significant OS difference among the three groups. Conclusion In this large, multicenter, retrospective cohort of patients with non-del(5q) lower-risk MDS treated with ESAs, none of the most commonly used second-line treatments (HMA and LEN) significantly improved OS. Early failure of ESAs was associated with a higher risk of AML progression.

The long-term clinical efficacy of SARS-CoV-2 vaccines according to antibody response in immunosuppressed patients such as hematological patients has been little explored. A prospective multicenter registry-based cohort study conducted from December 2020 to July 2022 by the Spanish Transplant and Cell Therapy group, was used to analyze the relationship of antibody response over time after full vaccination (at 3–6 weeks, 3, 6 and 12 months) (2 doses) and of booster doses with breakthrough SARS-CoV-2 infection in 1551 patients with hematological disorders. At a median follow-up of 388 days after complete immunization, 266 out of 1551 (17%) developed breakthrough SARS-CoV-2 infection at median of 86 days (range 7–391) after full vaccination. The cumulative incidence was 18% [95% confidence interval (C.I.), 16–20%]. Multivariate analysis identified higher incidence in chronic lymphocytic leukemia patients (29%) and with the use of corticosteroids (24.5%), whereas female sex (15.5%) and more than 1 year after last therapy (14%) were associated with a lower incidence (p < 0.05 for all comparisons). Median antibody titers at different time points were significantly lower in breakthrough cases than in non-cases. A serological titer cut-off of 250 BAU/mL was predictive of breakthrough infection and its severity. SARS-CoV-2 infection-related mortality was encouragingly low (1.9%) in our series. Our study describes the incidence of and risk factors for COVID-19 breakthrough infections during the initial vaccination and booster doses in the 2021 to mid-2022 period. The level of antibody titers at any time after 2-dose vaccination is strongly linked with protection against both breakthrough infection and severe disease, even with the Omicron SARS-CoV-2 variant.

Risk factors (RFs) and mortality data of community-acquired respiratory virus (CARVs) lower respiratory tract disease (LRTD) with concurrent pulmonary co-infections in the setting of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is scarce. From January 2011 to December 2017, we retrospectively compared the outcome of allo-HSCT recipients diagnosed of CARVs LRTD mono-infection (n = 52, group 1), to those with viral, bacterial, or fungal pulmonary CARVs LRTD co-infections (n = 15, group 2; n = 20, group 3, and n = 11, group 4, respectively), and with those having bacterial pneumonia mono-infection (n = 19, group 5). Overall survival (OS) at day 60 after bronchoalveolar lavage (BAL) was significantly higher in group 1, 2, and 4 compared to group 3 (77%, 67%, and 73% vs 35%, respectively, P = .012). Recipients of group 5 showed a trend to better OS compared to those of group 3 (62% vs 35%, P = .1). Multivariate analyses showed bacterial co-infection as a RF for mortality (hazard ratio[HR] 2.65, 95% C.I. 1.2-6.9, P = .017). We identified other 3 RFs for mortality: lymphocyte count <0.5 × 10 /L (HR 2.6, 95% 1.1-6.2, P = .026), the occurrence of and CMV DNAemia requiring antiviral therapy (CMV-DNAemia-RAT) at the time of BAL (HR 2.32, 95% C.I. 1.1-4.9, P = .03), and the need of oxygen support (HR 8.3, 95% C.I. 2.9-35.3, P = .004). CARV LRTD co-infections are frequent and may have a negative effect in the outcome, in particular in the context of bacterial co-infections.

Abbreviations: aGVHD = acute GvHD; cLPS = common lymphoid precursors; D = donor; MDS = myelodysplastic syndrome; R = recipient.Bone Marrow Transplantation (2016) 51, 718-721

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Here we report the applicability of a protocol based on clinical conditions and risk factors (RFs) for managing 35 allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients who developed a total of 52 episodes of respiratory viral infections (RVIs) caused by respiratory syncytial virus (RSV; n=19), human parainfluenza virus (HPIV; n=29), or both (n=4) over a 2-year study period. Risk categories were classified as high risk (cat-1) when the immunodeficiency scoring index was ≥3 and/or ≥3 RFs and/or ≥1 co-infective virus(es) were present; the remaining cases were classified as low risk (cat-0). The presence of two or more signs or symptoms including fever (T>38 °C), sinusitis, otitis, sore throat, tonsillitis, or baseline C-reactive protein increased by >2-fold at the time of the RVI, was considered a clinically-intense episode (CIE). Overall, 34 out of 52 episodes (65%) were limited to upper respiratory tract infections (URTIs). Overall, 26 (50%) received oral ribavirin. Twenty-four of 40 (60%) cat-1 episodes were treated, compared to 2 of 12 (17%) cat-0 RVIs (P=.01), while 17 of the 25 (68%) CIEs were treated compared to 9 of the remaining 27 (33%) episodes (P=.02). Regardless of antiviral therapy, the overall resolution rate was 100% for URTI and 95% for lower respiratory tract infection; the virus-related mortality was low (4%). In conclusion, the use of a risk-adapted protocol to guide therapeutic decisions for allo-HSCT recipients with RSV or HPIV RVIs is feasible and may limit unnecessary antiviral therapy.