Antifungal Agents for Secondary Prophylaxis Based on Response to Initial Antifungal Therapy in Allogeneic Hematopoietic Stem Cell Transplant Recipients with Prior Pulmonary Aspergillosis

We performed a prospective study to evaluate the efficacy and safety of secondary antifungal prophylaxis (SAP) for patients with a history of invasive pulmonary aspergillosis (IPA) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, the prophylactic agents used were chosen based on treatment response to initial antifungal therapy. One hundred and thirty-six patients undergoing allo-HSCT with prior IPA were enrolled in this multicenter study. The agents of SAP included itraconazole in 24, voriconazole in 74, caspofungin in 32, and liposomal amphotericin B in 6. Eighty-eight patients had stable IPA and 48 had active IPA at the time of transplantation. The success rate of SAP was 91.2%. Twelve patients developed breakthrough invasive fungal disease (IFD), and none discontinued antifungal agents because drug-related adverse events. The incidence of breakthrough IFD was neither different among the different antifungal agents (P = .675) nor between patients with active and stable IPA (P = .080). The 1-year cumulative incidence of IFD and IPA relapse was 27.3% ± 4.5% and 24.7% ± 4.4%, respectively. Our data indicate that SAP with antifungal agents based on initial antifungal therapy has favorable efficacy and safety in allo-HSCT recipients with prior IPA. Active IPA might not increase the risk of breakthrough IFD after transplantation.     

Invasive pulmonary aspergillosis is associated with cytomegalovirus viremia in critically ill patients - A retrospective cohort study

Background/PurposeCytomegalovirus (CMV) viremia is associated with a higher mortality rate and prolonged intensive care unit (ICU) stay for critically ill patients. CMV infection causes transient but substantial immunosuppression for transplant recipients, increasing risk of fungal infection. The association between CMV viremia and invasive pulmonary aspergillosis (IPA) for critically ill patients is still unknown.MethodsWe retrospectively analyzed patients received bronchoalveolar lavage (BAL), galactomannan test, influenza survey and blood CMV viral load test in ICUs of a university hospital between April 2017 and May 2020. Independent risks for IPA were analyzed by multivariable logistic regression.ResultsA total of 136 patients were included. Twenty-one patients had IPA, 48 patients had CMV viremia and 22 patients had influenza. In a multivariable logistic regression model, patients with CMV viremia or influenza had higher IPA risk (adjusted odds ratio, 3.98 and 8.72; 95% CI, 1.26–12.60 and 2.64–28.82; p value = 0.019 and <0.001, respectively.). Patients with detectable CMV in BAL fluid did not have higher IPA risk (crude odds ratio, 0.95; 95% CI, 0.33–2.79; p value = 0.933). After stratifying patients by CMV viral load, the IPA risk is higher for patients with higher viral loads. There is an additive synergistic effect on IPA risk between CMV viremia and influenza infection.ConclusionFor critically ill patients, CMV viremia is an independent risk factor of IPA. Patients with higher blood CMV viral loads have a higher risk of IPA. CMV viremia and influenza have an additive synergistic effect for IPA risk in critically ill patients.     

Considerable decrease in antibodies against hepatitis B surface antigen following kidney transplantation

BackgroundImmunization against hepatitis B virus (HBV) in kidney transplantation (KT) candidates and recipients is recommended. If anti-HBV surface antigen antibody (anti-HBsAb) titer of 10 IU/L is admitted to be protective, the optimal threshold, at and after KT, is unknown. In addition, the natural evolution of anti-HBsAb titers after KT is not reported.ObjectivesTo describe rates of protective immunity to HBV at time of KT (baseline) and evolution of anti-HBsAb titers during the following year.Study designWe retrospectively analyzed HBV serology at baseline, 15 days, and 4 and 12 months post-KT. No patient received vaccination during the study period, but information about previous vaccination was unavailable.ResultsAt baseline 80% of 141 recipients had anti-HBsAb titer ≥10 IU/L. Among these 113 patients, 84 had subsequent HBV serologies at day 15 and month 4, and 67 had also serology at month 12. At month 12, 25% of patients had lost protective anti-HBsAb titers (p < 0.001). The duration of protective anti-HBsAb titers was significantly longer when the initial titer was ≥ 100 IU/L versus <100 IU/L (log-rank test p < 0.0001). Protective titers at month 12 persisted in 93% of patients with initial titer ≥100 IU/L compared to 33% with 10–100 IU/L titer (p < 0.0001). In contrast, duration of protective titers did not differ according to the anti-HBV core antigen antibody status at baseline.ConclusionsDespite a high prevalence of protective anti-HBsAb titer at KT, the loss of protective immunity during the following year was considerable, particularly when initial anti-HBsAb titer was <100 IU/L.     

Risk factors of tuberculosis after liver transplant in a tertiary care hospital

BackgroundTuberculosis (TB) is a serious opportunistic infection in liver transplant (LT) recipients with a high rate of morbidity and mortality. This study aims to clarify the frequency and risk factors for tuberculosis in LT recipients.MethodsA total of 884 LT recipients were investigated retrospectively at China Medical University Hospital, Taichung, Taiwan. We performed a case–control study (1:2) to investigate the potential risk factors and disease onset of TB after LT.ResultsAmong the 884 LT recipients, 25 of TB cases (2.8%) were reported from 2009 to 2016. The overall incidence of TB was 744 cases per 100,000 patient-year, which was 18-fold higher than the general population in Taiwan. The median time to develop TB after liver transplant was 20 months. Of the TB cases, 15 were pulmonary TB and 10 were extra-pulmonary TB. Five cases of those extra-pulmonary TB occurred in the first post-transplant year. Overall five-year survival rate was 63.3%. Multivariate analyses identified apical fibrotic change in pre-transplant computed tomographic (CT) finding and the exposure to mammalian target of rapamycin (mTOR) inhibitors before TB event as independent risk factors for TB development (Odd ratio (OR) 10.79, 95% confidence interval (CI), 1.73–67.49, p = 0.01; OR 3.847, 95% CI 0.80–18.51, P = 0.09, respectively).ConclusionTB incidence in LT recipients is high in this study. Among those post-transplant recipients with long-term immunosuppression, abnormal CT finding and exposure to mTOR inhibitors before liver transplant might be the risk factors for TB.     

Bacterial and fungal bloodstream infections in solid organ transplant recipients: results from a Danish cohort with nationwide follow-up

ObjectivesBloodstream infections (BSI) are prevalent after solid organ transplantation (SOT). In this study, we aimed to investigate the incidence and risk factors for BSI in the first 5 years post-transplantation.MethodsThe study included 1322 SOT (kidney, liver, lung and heart) recipients transplanted from 2010 to 2017 with a total of 5616 years of follow-up. Clinical characteristics and microbiology were obtained from the Centre of Excellence for Personalized Medicine of Infectious Complications in Immune Deficiency (PERSIMUNE) data repository with nationwide follow-up. Incidence was investigated in the different SOT groups. Risk factors associated with BSI were assed in the combined group in time-updated multivariable Cox regressions.ResultsThe cumulative incidence of first BSI in the first 5 years post-transplantation differed in the SOT groups with a lower incidence in heart transplant recipients than in the other SOT groups (heart: 4.4%, CI 0.0–9.7%, vs. kidney: 24.6%, CI 20.9–28.2%, liver: 24.7%, CI 19.4–29.9%, and lung: 19.6%, CI 14.5–24.8%, p <0.001). Age above 55 years (HR 1.71, CI 1.2–2.4, p=0.002) and higher Charlson comorbidity index score (HR per unit increase: 1.25, CI 1.1–1.4, p<0.001) at transplantation, current cytomegalovirus (CMV) infection (HR 4.5, CI 2.6–7.9, p<0.001) and current leucopenia (HR 13.3, CI 3.7–47.9, p<0.001) were all associated with an increased risk of BSI.ConclusionIn SOT recipients, the incidence of BSI differed with the type of transplanted organ. Risk of BSI was higher in older recipients and in recipients with comorbidity, current CMV infection or leucopenia. Thus, increased attention towards BSI in recipients with these characteristics is warranted.     

Nonmalignant Late Effects in Survivors of Partially Matched Donor Hematopoietic Stem Cell Transplantation

Human leukocyte antigen (HLA) partially matched related donor (PMRD) hematopoietic stem cell transplantation (HSCT) is an effective option for hematological malignancies. In this study, the nonmalignant late effects of PMRD HSCT were evaluated and compared with HLA-identical sibling donor (ISD) HSCT. Three hundred thirteen patients (ISD, n = 160; PMRD, n = 153) who survived at least 6 months and received regular follow-up examinations after their HSCT were enrolled. The 5-year cumulative incidence (±SE) of at least one late effect and multiple late effects was 47.30% ± .17% versus 58.21% ± .16% (P = .134) and 17.97% ± .10% versus 34.28% ± .15% (P = .001) for PMRD HSCT recipients versus ISD HSCT recipients, respectively. The cumulative incidence of keratoconjunctivitis sicca, periodontitis, ankylosis, myalgia, and nephrotic syndrome was lower among PMRD HSCT recipients compared with ISD HSCT recipients. Severe chronic graft-versus-host disease, multiple pre-HSCT chemotherapy cycles, female donor, and older age were risk factors for at least one late effect. Female donor, older age, and long-term immunosuppressive therapy were associated with multiple late effects. In summary, PMRD HSCT recipients have a lower risk of late effects compared with ISD HSCT recipients, possibly due to differences in protocols for graft-versus-host disease prophylaxis, and long-term follow-up after transplantation is recommended.     

Oral decontamination with colistin plus neomycin in solid organ transplant recipients colonized by multidrug-resistant Enterobacterales: a multicentre,randomized, controlled,open-label,parallel-group clinical trial

ObjectivesTo evaluate the efficacy of oral colistin-neomycin in preventing multidrug-resistant Enterobacterales (MDR-E) infections in solid organ transplant (SOT) recipients.MethodsMulticentre, open-label, parallel-group, controlled trial with balanced (1:1) randomization in five transplant units. SOT recipients were screened for MDR-E intestinal colonization (extended-spectrum β-lactamase or carbapenemase producing) before transplantation and +7 and + 14 days after transplantation and assigned 1:1 to receive treatment with colistin sulfate plus neomycin sulfate for 14 days (decolonization treatment (DT) group) or no treatment (no decolonization treatment (NDT) group). The primary outcome was diagnosis of an MDR-E infection. Safety outcomes were appearance of adverse effects, mainly diarrhoea, rash, nausea and vomiting. Patients were monitored weekly until 30 days after treatment. Intention-to-treat analysis was performed.ResultsMDR-E rectal colonization was assessed in 768 SOT recipients; 105 colonized patients were included in the clinical trial, 53 receiving DT and 52 NDT. No significant decrease in the risk of infection by MDR-E was observed in the DT group (9.4%, 5/53) compared to the NDT group (13.5%, 7/52) (relative risk 0.70; 95% confidence interval 0.24–2.08; p 0.517). Four patients (5.6%), three (5.6%) in the DT group and one (1.9%) in the NDT group, developed colistin resistance. Twelve patients (22.7%) in the DT group had diarrhoea, eight related to treatment (15.0%); one patient (1.8%) developed skin rash and another (1.8%) nausea and vomiting. Two patients (3.8%) in the NDT group developed diarrhoea.ConclusionsDT does not reduce MDR-E infections in SOT. Colistin resistance and adverse effects such as diarrhoea are a potential issue that must be taken seriously.     

Impact of pretransplant CMV-specific T-cell immune response in the control of CMV infection after solid organ transplantation: a prospective cohort study

IntroductionAlthough solid organ transplant (SOT) recipients with pretransplant serology for cytomegalovirus (CMV-R+) are considered at intermediate risk for CMV infection post transplantation, CMV infection remains a major cause of morbidity in this population. We prospectively characterized whether having pretransplant CMV-specific cellular immunity is independently associated with controlling infection after transplantation in R + SOT recipients.MethodsA prospective cohort of consecutive R + SOT recipients that received pre-emptive treatment for CMV infection was monitored after transplantation and variables were recorded during the follow-up. The cytomegalovirus-specific T-cell immune response was characterized by intracellular cytokine staining and viral loads determined using real-time PCR.ResultsOne hundred and thirty-five R + SOT recipients were included (67 kidney, 64 liver, four liver–kidney). Only one-third of the patients (42; 31.85%) had CMV-specific T-cell immunity (CD8⁺CD69⁺INF-γ⁺ T cells >0.25%) before transplantation. Patients with negative pretransplant immunity had more CMV infection (49, 52.7% vs. 15, 35.7%; p 0.07) and received more antiviral therapy than those with immunity (32, 34.4% vs. 6, 14.3%, p 0.016). Having CMV specific immunity was an independent factor for protection from developing viraemia ≥2000 IU/mL (OR 0.276, 95% CI 0.105–0.725, p < 0.01) and lower administration of treatment (OR 0.398, 95% CI 0.175–0.905, p 0.028). Only patients with no pretransplant CMV-specific T-cell response were diagnosed with CMV-disease (8, 8.6% vs. 0, 0%, p 0.05).Discussion.Our results show that having a pretransplant CMV specific T-cell response may be associated with a lower rate of CMV viraemia and less antiviral treatment after transplantation; however, more prospective studies are needed to confirm these findings.     

Incidence,management and outcome of respiratory syncytial virus infection in adult lung transplant recipients: a 9-year retrospective multicentre study

ObjectivesTo analyse functional outcome parameters according to antimicrobial treatments after respiratory syncytial virus (RSV)-confirmed infection in adult lung transplant recipients.MethodsA 9-year retrospective multicentre cohort study (2011–19) included adult lung transplant recipients with RSV-confirmed infection. The first endpoint determined new allograft dysfunction (acute graft rejection and chronic lung allograft dysfunction (CLAD)) 3 months after infection. Then baseline and 3 months' postinfection forced expiratory volume in 1 second (FEV₁) values were compared according to antimicrobial treatment. Univariate logistic regression analysis was performed.ResultsRSV infection was confirmed in 77 of 424 lung transplant recipients (estimated incidence of 0.025 per patient per year; 95% confidence interval 0.018–0.036). At 3 months, 22 recipients (28.8%) developed allograft dysfunction: ten (13%) possible CLAD, six (7.9%) acute rejection and six (7.9%) CLAD. Recipients with the lowest preinfection FEV₁ had a greater risk of developing pneumonia (median (interquartile range) 1.5 (1.1–1.9) vs. 2.2 (1.5–2.4) L/s, p 0.003) and a higher odds of receiving antibiotics (1.6 (1.3–2.3) vs. 2.3 (1.9–2.5) L/s, p 0.017; odds ratio 0.52, 95% confidence interval 0.27–0.99). Compared to tracheobronchitis/bronchiolitis, RSV-induced pneumonia led more frequently to hospitalization (91.7%, 22 vs. 58.0%, 29, p 0.003) and intensive care unit admission (33.3%, 8 vs. 0, p < 10^-3). For ribavirin-treated recipients (24.7%, 19) and azithromycin prophylaxis (50.6%, 39), 3-month FEV₁ values were not different from untreated recipients. The overall mortality was 2.5% at 1 month and 5.3% at 6 months, unrelated to RSV.ConclusionsAt 3 months after RSV-confirmed infection, 22 recipients (28.8%) had new allograft dysfunction. Ribavirin treatment and azithromycin prophylaxis did not prevent FEV₁ decline.     

Toxoplasmosis after allogeneic haematopoietic cell transplantation: experience using a PCR-guided pre-emptive approach

ObjectivesProphylaxis with trimethoprim–sulphamethoxazole (TMP-SMZ) is recommended in Toxoplasma-seropositive allogeneic haematopoietic cell transplant (HCT) recipients to prevent reactivation, but it is associated with numerous side effects. We report our experience of a pre-emptive approach guided by a polymerase chain reaction (PCR) in patients not receiving prophylaxis.MethodsIn this retrospective, single-centre experience, seropositive recipients and seronegative recipients receiving a graft from a seropositive donor were screened by PCR for the presence of Toxoplasma gondii DNA in peripheral blood until at least 6 months after transplantation. Confirmed PCR positivity triggered a pre-emptive anti-Toxoplasma therapy. Cases of Toxoplasma reactivation (using the European Society for Blood and Marrow Transplantation definitions) were compared with four controls (without reactivation), matched in time and recipient serostatus, to identify risk factors for reactivation by multivariate analysis.ResultsFrom November 2001 to August 2020, 1455 consecutive adult patients (59 cases and 1396 controls) were screened. The overall 1-year cumulative incidence of toxoplasmosis was 4.1% and the 1-year cumulative incidence in the seropositive recipients was 8.8%. Reactivation was associated with second transplant (OR 2.51, 95%CI 1.28–4.94, p 0.011), myeloablative conditioning (OR 2.24, 95%CI 1.17–4.41, p 0.011), total body irradiation (OR 2.29, 95%CI 1.17–4.44, p 0.010), acute graft-versus-host disease (GvHD) (OR 2.27, 95%CI 1.26–4.08, p 0.008) and use of high-dose corticosteroids (OR 2.08, 95%CI 1.14–3.78, p 0.018). In multivariate analysis only acute GvHD remained significant (adjusted OR 2.54, 95%CI 1.16–5.71, p 0.021).ConclusionsA PCR-based pre-emptive approach might serve as an acceptable alternative for patients unable to start with or to continue TMP-SMZ prophylaxis. Acute GvHD was identified as the single independent predictor for reactivation.     

Varicella Zoster Virus Infection in Children with Autologous Hematopoietic Cell Transplantation: A Retrospective,Single-Center Study in Korea

Although long-term antiviral prophylaxis is recommended to prevent varicella zoster virus (VZV) infection in seropositive recipients of allogeneic and autologous (auto-) hematopoietic cell transplantation (HCT), studies of VZV infections in pediatric auto-HCT recipients are rare. This study aimed to investigate the incidence and characteristics of VZV infection in pediatric auto-HCT recipients and explore the risk factors of VZV infection and its effect on survival outcomes. This study included all pediatric patients who underwent auto-HCT at Samsung Medical Center, Seoul, Korea, between January 1998 and December 2013. Before 2006, short-term acyclovir prophylaxis was provided until neutrophil engraftment; thereafter, routine prophylaxis was not provided. Patients who developed either herpes zoster or chickenpox within 2 years from transplantation were identified, and a chart review was performed. A total of 413 recipients and 698 auto-HCTs were included. Sixty-one episodes of VZV infections were identified in 54 patients. Fourteen cases of VZV infection (23%; 14 of 61) occurred within 30 days after auto-HCT. The cumulative incidence of the first episode of VZV infection at 2 years after transplantation was 14% (95% confidence interval [CI], 7.9% to 22.8%) in all recipients and 9% (95% CI, 1.0 to 26.6) in VZV-seronegative patients. Notably, the VZV infection rate increased with age and the VZV infection rate in patients age 15 to 19 years was almost three times higher than in patients age 0 to 4 years (28% versus 10%; P = .003). However, there was no difference in the VZV infection rate between recipients of single auto-HCT and recipients of tandem auto-HCT. Two patients died of disseminated VZV infection. VZV infection is a considerable risk in auto-HCT recipients with or without short-term prophylaxis. Universal antiviral prophylaxis might be considered, particularly in older children, regardless of VZV serologic results. To our knowledge, this is the largest study of VZV infection in pediatric auto-HCT recipients reported to date.     

Limited impact of cytomegalovirus infection in the long-term outcome of renal and liver transplant

BackgroundThe strength of the assumed association of CMV and long term deleterious events in solid organ transplant recipients (SOT) is controversial.ObjectivesThe aim of the present study was to evaluate whether viral replication dynamics during CMV infection or CMV disease may correlate not only with graft dysfunction and survival, but also with other potentially related late events in a long-term followed cohort of kidney (KT) and liver (LT) transplant recipients.Study design162 SOT (104 kidney, 58 liver) at our institution (2003–2005) with survival over 180 days and a median follow-up of 71 months (9–86) were analyzed. Using a Cox proportional hazard model, CMV infection (including area under the curve of DNAemia[AUC]) and CMV disease in the first 180 days were evaluated as potential predictors of the following late events (>180 days): mortality, graft dysfunction (GD), graft loss (GL), cardiovascular events (CVE), malignant tumors (MT).ResultsCMV infection occurred in 59% and CMV disease in 8%. Late death occurred in 17%, GD in 45.6%, GL in 14.2%, CVE in 10.5% and MT in 9.9%. We found no significant association between the intensity or duration of CMV viremia (AUC, persistent viremia or untreated CMV viremia) or CMV disease and the development of evaluated late events. According multivariate analysis neither CMV infection (hazard ratio [HR] 2.18 95% CI 0.949–5 p = 0.066) nor CMV disease (HR: 1.72; 95% CI 0.59–5 p = 0.31) were significantly correlated with late mortality.ConclusionsOur data do not support that CMV infection or CMV disease contribute significantly to long-term deleterious events in SOT.     

Mycobacterial infections in adult recipients of allogeneic hematopoietic stem cell transplantation: A cohort study in a high endemic area

BackgroundMycobacterial infections are important and potentially life-threatening complications after organ transplantations. Notably, for the recipients of allogeneic hematopoietic stem cell transplantation (HSCT), there are a few supporting results to explore post-transplant mycobacterial infections. Taiwan is a high endemic area of the infection. We aim to investigate the incidence, risk factors, and survival of post-transplant mycobacterial infections, including mycobacterium tuberculosis (MTB) and non-tuberculous mycobacterium (NTM).MethodsWe included 422 adult patients undergoing allogeneic HSCT at an Asian tertiary medical center between January 2003 and December 2014. A total 26 subjects developed post-transplant mycobacterial infections. Risk factors, clinical features, and survival for post-transplant mycobacterial infections were collected and analyzed.ResultsPost-transplant mycobacterial infections occurred in 26 (6.2%) of 422 HSCT patients. Two-year cumulative incidences in MTB and NTM were 1.4% and 5.4%. In the multivariate analysis, being age >45 years (adjusted HR 2.21, 95% CI 1.01–4.83) and extensive chronic graft-versus-host disease (cGVHD) (adjusted HR 4.95, 95% CI 2.14–11.46) were identified as independent risk factors of infections. There was a trend as a risk factors in relapsed patients (P = 0.088). For patients with cGVHD, there was a significant difference of post-transplant survival between mycobacterial infections and none (P = 0.036). Pneumonia contributed most to mortality (n = 11, 42.3%).ConclusionMycobacterial infections are worth to note in a high endemic area. Once a high-risk group is identified, much effort is required to target new approaches for prevention, early detection and treatment of infections.     

Antibody response to SARS-CoV-2 mRNA vaccine among kidney transplant recipients: a prospective cohort study

ObjectivesWe aimed to evaluate the rates of antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine among kidney transplant recipients, and to identify factors associated with reduced immunogenicity.MethodsThis was a prospective cohort study including consecutive kidney transplant recipients in a single referral transplant centre. Participants were tested for anti-spike (anti-S) antibodies 2–4 weeks after a second vaccine dose. Primary outcome was rate of seropositivity. Univariate and multivariate analyses were conducted to identify factors associated with seropositivity.ResultsOf 308 kidney transplant recipients included, only 112 (36.4%) tested positive for anti-S antibodies 2–4 weeks after receiving the second dose of BNT162b2 vaccine. Median antibody titre was 15.5 AU/mL (interquartile range (IQR) 3.5–163.6). Factors associated with antibody response were higher estimated glomerular filtration rate (eGFR) (odds ratio (OR) 1.025 per mL/min/1.73 m², 95% confidence interval (CI) 1.014–1.037, p < 0.001), lower mycophenolic acid dose (OR 2.347 per 360 mg decrease, 95%CI 1.782–3.089, p < 0.001), younger age (OR 1.032 per year decrease, 95%CI 1.015–1.05, p < 0.001) and lower calcineurin inhibitor (CNI) blood level (OR 1.987, 95%CI 1.146–3.443, p 0.014). No serious adverse events resulting from the vaccine were reported.ConclusionsKidney transplant recipients demonstrated an inadequate antibody response to SARS-CoV-2 mRNA vaccination. Immunosuppression level was a significant factor in this response. Strategies to improve immunogenicity should be examined in future studies.     

Different sensitivity of rituximab-treatment to B-cells between ABO-incompatible kidney and liver transplantation

A desensitization protocol with rituximab is currently widely used for kidney transplantation (KT) and liver transplantation (LT) across the ABO blood group-incompatible (ABO-I) barrier. However, it remains to be elucidated whether rituximab is equally effective for B-cell and T-cell immune responses in both KT and LT recipients. To clarify these effects of rituximab, we enrolled 46 KT and 77 LT recipients in this study. The proportion of peripheral blood B-cells was determined at the perioperative period. T-cell responses to allostimulation were evaluated by a mixed lymphocyte reaction (MLR) assay. One week after rituximab administration, peripheral B-cells became undetectable in ABO-I KT recipients but remained detectable in some of the ABO-I LT recipients; B-cells were undetectable in both groups by week 2. B-cells remained below the detection limit throughout the first year in the ABO-I KT recipients, whereas they reappeared in the periphery after 6 months in the ABO-I LT recipients. There were no significant differences in alloreactive T-cell responses based on MLR analyses between ABO-I and ABO-compatible groups. This study indicates that rituximab has differing B-cell sensitivity between KT and LT recipients and a minimal effect on the alloreactive T-cell responses in KT and LT recipients.     

Impact of persistent and cleared preformed HLA DSA on kidney transplant outcomes

Preformed HLA donor-specific antibodies (DSA) only detected with Luminex have been associated with increased risk of antibody-mediated rejection (ABMR) and graft failure after kidney transplantation (KT). Their evolution after KT may modify this risk. We analyzed postransplant evolution of preformed DSA identified retrospectively and their impact on outcomes of 370 KT performed 2006–2014. Antibodies were monitored prospectively at 1-3-5?years after KT and if any dysfunction. Early acute ABMR was more frequent among patients with preformed DSA class-I or I?+?II than isolated class-II (29.4% vs 4.5%, p?=?0.02). One year post-KT, 20 of 34 patients with functioning KT had persistent DSA. Preformed DSA class-II persisted more frequently than class-I/I?+?II (66.7% vs 33.3%; p?=?0.031). The only risk factor independently associated with persistence was pretransplant MFI. Patients with de novo DSA had the highest risk of ABMR (HR 22.2 [CI 6.1–81.2]). Although recipients with persisting preformed DSA had significantly increased ABMR risk (HR 14.7 [CI 6.5–33.0]), those with cleared preformed DSA also had a higher risk than those without DSA (HR 7.01 [CI 2.2–21.8]).Preformed DSA are a very important risk factor for ABMR and graft loss. Patients who clear preformed DSA still show an increased risk of ABMR and graft loss after KT.     

Chlorhexidine alcohol versus povidone-iodine: The comparative study of skin disinfectants at the blood transfusion centers of Iran

ObjectivesThe skin disinfection in the blood donor's arm is a key step to minimize the risk of microbial contamination at blood donation sessions. Current study aimed to compare the efficacy of 2% chlorhexidine gluconate in 70% isopropyl alcohol (CHG/IPA) with povidone-Iodine (PI) at blood transfusion centers (BTCs) of Iran.Material and methodsBlood donors were selected to evaluate three commercial CHG/IPA disinfectants (N = 300), prior the application at BTCs, and to compare the rate of positive skin cultures between CHG/IPA and PI in 31 BTCs (N = 8578). The rate of positivity for PI over a 5-year period was also investigated. After application of a two-step disinfection procedure, the biochemical characteristics were checked in accordance with the conventional bacteriological methods. The Z-test analysis was used to compare the deviation between the positive microbial culture ratios.ResultNo donors had a positive culture after disinfection during the evaluation study. There was no difference in the rate of positivity between PI and CHG/IPA after disinfection (P > 0.05). The rate of positivity for PI from 2012 to 2017 showed a decreasing trend. The rate of positivity was significantly higher in winter rather than summer (P < 0.05).ConclusionThe disinfection efficacy of CHG/IPA was equivalent to that of PI. The 5-year monitoring of PI at BTCs showed that the improvement in the rate of positive skin cultures possibly due to effectiveness of correcting actions.     

Occurrence,risk factors and outcome of adenovirus infection in adult recipients of allogeneic hematopoietic stem cell transplantation

BackgroundAdenovirus (ADV) infections can have a high mortality in immunocompromised patients and are difficult to treat.Objectives and study designWe retrospectively analyzed occurrence and risk factors of ADV infection in 399 adults with hematological disorders undergoing hematopoietic stem cell transplantation (allo-HSCT), focusing on alternative donor transplantation (ADT) and disseminated disease.ResultsADV infection occurred in 42 patients (10.5%). Disease was localized in 18 and disseminated in 6 patients. ADV infection was observed in 15% after ADT, performed in 29% of all recipients, and was less frequent (6%) in T-cell-replete (TCR) haploidentical transplantation using post-transplantation cyclophosphamide (PTCY) than in other ADT protocols. Lower age, the use of alternative donor grafts and acute graft-versus-host disease (GvHD) ≥ grade II were risk factors for ADV infection.After failure of standard antiviral treatment, three patients with disseminated ADV disease received one dose of ADV-specific T cells, resulting in virological response in 2/3 patients, clearance of ADV viremia in 2/2 patients, and survival of 1/3 patients; both patients with pneumonia died.ConclusionsADV infection was of moderate occurrence in our adult recipients of allo-HSCT despite a high proportion of potential high-risk patients receiving ADT. TCR strategies using PTCY might limit ADV complications in haploidentical transplantation. Despite feasible adoptive therapy strategies, outcome of disseminated disease remains dismal.     

Positive follow-up blood cultures identify high mortality risk among patients with Gram-negative bacteraemia

ObjectivesThe role of follow-up blood cultures (FUBCs) in the management of Gram-negative bacteraemia (GNB) is poorly understood. We aimed to determine the utility of FUBCs in identifying patients with increased mortality risk.MethodsAn observational study with a prospectively enrolled cohort of adult inpatients with GNB was conducted at Duke University Health System from 2002 to 2015. FUBCs were defined as blood cultures performed from 24 hours to 7 days from initial positive blood culture.ResultsAmong 1702 patients with GNB, 1164 (68%) had FUBCs performed. When performed, FUBCs were positive in 20% (228/1113) of cases. FUBC acquisition was associated with lower all-cause in-hospital mortality (108/538, 20%, vs. 176/1164, 15%; p 0.01) and attributable in-hospital mortality (78/538, 15%, vs. 98/1164, 8%; p < 0.0001). Propensity score–weighted Cox proportional hazards models revealed that obtaining FUBCs was associated with reductions in all-cause (hazard ratio (HR) 0.629; 95% confidence interval (CI), 0.511–0.772; p < 0.0001) and attributable mortality (HR 0.628; 95% CI, 0.480–0.820; p 0.0007). Positive FUBCs were associated with increased all-cause mortality (49/228, 21%, vs. 110/885, 11%; p 0.0005) and attributable mortality (27/228, 12%, vs. 61/885, 7%; p 0.01) relative to negative FUBCs. Propensity score–weighted Cox proportional hazards models revealed that positive FUBCs were associated with increased all-cause (HR 2.099; 95% CI, 1.567–2.811; p < 0.0001) and attributable mortality (HR 1.800; 95% CI, 1.245–2.603; p 0.002). In a calibration analysis, a scoring system accurately identified patients at high risk of positive FUBCs.ConclusionsRates of positive FUBCs were high and identified patients at increased risk for mortality. Clinical variables can identify patients at high risk for positive FUBCs. FUBCs should be considered in the management of GNB.