Cytomegalovirus mismatch still negatively affects patient and graft survival in the era of routine prophylactic and preemptive therapy: A paired kidney analysis

The impact of cytomegalovirus (CMV) serostatus on kidney transplant outcomes in an era when CMV prophylactic and preemptive strategies are used routinely is not clearly established. Using United Network for Organ Sharing/Organ Procurement and Transplantation Network data, recipients with first deceased donor kidney transplant (≥18 years, 2010‐2015) were stratified into 4 groups in the main cohort: CMV‐seronegative donor (D?)/CMV‐seronegative recipient (R?), CMV‐seropositive donor (D+)/R?, D+/CMV‐seropositive recipient (R+), and D?/R+. In a paired kidney cohort, we identified 2899 pairs of D? kidney transplant with discordance of recipient serostatus (D?/R? vs D?/R+) and 4567 pairs of D+ kidney transplant with discordance of recipient serostatus (D+/R? vs D+/R+). In the main cohort, D+/R? was associated with a higher risk of graft failure (hazard ratio [HR] = 1.17, P = .01), all‐cause mortality (HR = 1.18, P < .001), and infection‐related mortality (HR = 1.38, P = .03) compared with D?/R?. In the paired kidney analysis, D+/R? was an independent risk factor for all‐cause mortality (HR = 1.21, P = .003) and infection‐related mortality (HR = 1.47, P = .04) compared with D+/R+. No difference in graft loss between D+/R? and D+/R+. CMV mismatch is still an independent risk factor for graft loss and patient mortality. The negative impact of D+/R? serostatus on mortality persists after fully matching for donor factors.     

Epidemiology,risk factors,and outcomes of infections in patients undergoing liver transplantation for hilar cholangiocarcinoma

The epidemiology of infection after liver transplantation for hilar cholangiocarcinoma has not been systematically investigated. In this study of 124 patients, 255 infections occurred in 105 patients during the median follow‐up of 4.2 years. The median time to first infection was 15.1 weeks (IQR 1.6‐62.6). The most common sites were the abdomen, bloodstream, and musculoskeletal system. Risk factors for any post‐transplant infection were pre‐transplant VRE colonization (Hazard Ratio [HR] 1.9, P=.002), living donor transplantation (HR 6.6, P<.001), longer cold ischemia time (HR 1.05 per 10 minutes, P<.001), donor CMV seropositivity (HR 2.2, P<.001), hepatic artery thrombosis (HR 2.6, P=.005), biliary stricture (HR 3.8, P=.002), intra‐abdominal fluid collection (HR 4.2, P<.001), and re‐operations within 1 month after transplantation (HR 1.7, P=.020). Abdominal infections were independently associated with hemodialysis requirement within 1 month after transplantation (HR 5.6, P=.006), hepatic artery thrombosis (HR 3.3, P=.007), biliary stricture (HR 5.2, P<.001), and abdominal fluid collection (HR 3.7, P=.0002). Bloodstream infections were independently associated with allograft ischemia (HR 17.8, P<.001), biliary stricture (HR 6.5, P=.005), and recipient VRE colonization (HR 4, P<.001). Abdominal infections (HR 2.3, P=.02) and Clostridium difficile infections (HR 4.6, P=.01) were independently associated with increased mortality.     

Management of BK viremia is associated with a lower risk of subsequent cytomegalovirus infection in kidney transplant recipients

The risk of subsequent cytomegalovirus infection (CMV) in kidney transplant recipients (KTR) after diagnosis of BK polyomavirus viremia (BKV) is unclear, and current evidence is conflicting. We reviewed all KTR transplanted at our institution between 1/1/2005 and 12/31/2015. Follow-up began 3 months after transplantation to avoid confounding effects of prophylaxis. Clinically significant BKV, defined as detectable BK viremia >1000 copies/mL via molecular diagnostic testing (PCR), was treated as a time-varying exposure with 1-year follow-up. This viral load cutoff was chosen to ensure a more homogenous population that would be considered to have clinically significant BK viremia that necessitated management via immunosuppressive modification. Patients were then screened for subsequent CMV infection. 2435 RTX recipients met inclusion criteria; of these, 314 developed BKV during follow-up (BK+). Lymphocyte depletion, tacrolimus maintenance, and biopsy-proven rejection were significantly higher in the BK+ group. BK+ was associated with lower risk of subsequent CMV infection (BK+ HR 0.45, 95% CI 0.22-0.94, P = .03, relative risk reduction 55%). When adjusted for significant confounding factors, CMV incidence remained reduced in the BK+ population (HR 0.47, 95% CI 0.22-0.98, P = .04). This large series of KTR demonstrates that BKV is associated with lower risk of subsequent CMV infection.     

Prospective randomized study comparing everolimus and mycophenolate sodium in de novo kidney transplant recipients from expanded criteria deceased donor

The optimal immunosuppressive regimen for recipients of expanded criteria donor (ECD) kidneys has not been identified. In this single‐center study, 171 recipients of ECD kidney transplants were randomized to receive antithymocyte globulin induction, and delayed introduction of reduced dose tacrolimus, prednisone and everolimus (r‐ATG/EVR, n = 88), or mycophenolate (r‐ATG/MPS, n = 83). No cytomegalovirus (CMV) pharmacological prophylaxis was used. The primary endpoint was the incidence of CMV infection/disease at 12 months. Secondary endpoints included treatment failure [first biopsy‐proven acute rejection (BPAR), graft loss, or death] and safety. Patients treated with EVR showed a 89% risk reduction (13.6 vs. 71.6%; HR 0.11, 95% CI 0.06–0.220, P < 0.001) in the incidence of first CMV infection/disease. Incidences of BPAR (16% vs. 5%, P = 0.021), graft loss (11% vs. 1%, P = 0.008), death (10% vs. 1%, P = 0.013), and treatment discontinuation (40% vs. 28%, P = 0.12) were higher in the r‐ATG/EVR, leading to premature study termination. Mean glomerular filtration rate was lower in r‐ATG/EVR (31.8 ± 18.8 vs. 42.6 ± 14.9, P < 0.001). In recipients of ECD kidney transplants receiving no CMV pharmacological prophylaxis, the use of everolimus was associated with higher treatment failure compared with mycophenolate despite the significant reduction in the incidence of CMV infection/disease (ClinicalTrials.gov.NCT01895049).     

Cytomegalovirus prevention strategies and the risk of BK polyomavirus viremia and nephropathy

Polyomavirus BK (BKV) is the cause of polyomavirus‐associated nephropathy resulting in premature graft loss. There are limited data regarding the role of cytomegalovirus (CMV) infection and its prevention in developing BKV viremia and PVAN. In a prospective study, we analyzed 207 consecutive renal transplant recipients previously enrolled in 2 randomized trials evaluating different CMV prevention regimens with routine screening for BKV and CMV. Of these, 59 received valganciclovir and 100 valacyclovir prophylaxis; 48 patients were managed by preemptive therapy. At 3 years, the incidence of BKV viremia and PVAN was 28% and 5%, respectively. CMV DNAemia developed in 55% and CMV disease in 6%. Both BKV viremia (42% vs 23% vs 21%, P = .006) and PVAN (12% vs 2% vs 2%, P = .011) were increased in patients treated with valganciclovir prophylaxis compared to valacyclovir and preemptive therapy. Using multivariate Cox proportional hazard regression, valganciclovir prophylaxis was independent predictor of BKV viremia (hazard ratio [HR] = 2.38, P = .002) and PVAN (HR = 4.73, P = .026). In contrast, the risk of subsequent BKV viremia was lower in patients with antecedent CMV DNAemia (HR = 0.50, P = .018). These data suggest valganciclovir prophylaxis may be associated with increased risk of BKV viremia and PVAN. CMV DNAemia did not represent a risk for BKV.     

The risk of cytomegalovirus infection after treatment of acute rejection in renal transplant recipients

The risk of cytomegalovirus infection (CMV) after rejection treatment is poorly understood. To investigate this, we conducted a case/control (1:2) analysis of adult renal transplant recipients between January 1, 2005 and December 31, 2015, via incidence density sampling and survival analysis. Our objective was to evaluate the association of prior acute rejection with subsequent CMV, including epidemiology and outcomes. There were 2481 eligible renal transplants within the study period and 251 distinct CMV infections. Despite the use of antiviral prophylaxis rejection was a significant risk factor for CMV on unadjusted (HR 1.73 [1.34, 2.24] P < 0.05) and adjusted analysis (HR 1.46 [1.06, 2.04] P < 0.05). When matching cases to controls patients with CMV had significantly more rejection prior to CMV diagnosis (26.7% vs 14.2%, P < 0.01). CMV was associated with a twofold increased risk of prior rejection on unadjusted (OR 1.94, 95%CI: 1.28‐2.96, P < 0.01) and adjusted analysis (OR 2.16, 95% CI: 1.31‐3.58, P < 0.01). Patients with rejection preceding CMV had significantly increased graft loss (HR 2.89, 95% CI: 1.65‐5.09, P < 0.01) and mortality (HR 1.82, 95% CI: 1.12‐4.24, P = 0.03) as compared to those CMV cases without rejection. In conclusion, rejection is a risk factor for CMV infection that appears to persist for 1 year. Preceding rejection events increased risk of graft loss and mortality in CMV patients. Given this, prolonged surveillance monitoring for CMV after rejection may be warranted. Studies are needed investigating optimal monitoring strategies.     

ABO desensitization affects cellular immunity and infection control after renal transplantation

The impact of ABO desensitization on overall immunity, infectious control, and alloreactivity remains unknown. We compared 35 ABO‐incompatible kidney transplant recipients (KTRs) to a control of 62 ABO compatible KTRs. Samples were collected before, at +1, +2, +3, +6, and +12 months post‐transplantation. CMV‐, BKV‐specific, and alloreactive T cells were measured using an interferon‐γ ELISPOT assay. The extent of immunosuppression was quantified by enumeration of lymphocyte subpopulations and cytokines. No differences were observed for 5‐year allograft survival and function between both groups (P > 0.05). However, ABO‐incompatible KTRs were more likely to develop CMV infection, BKV‐associated nephropathy, and severe sepsis (P = 0.001). Interestingly, ABO‐incompatible KTRs with poor HLA‐match showed the highest rates of infections and inferior allograft function (P < 0.05). CD3+, CD4+ T‐cell counts, interferon‐γ and IL‐10 levels were lower in ABO‐incompatible KTRs early post‐transplantation (P < 0.05). Likewise, ABO‐incompatible KTRs showed impaired BKV‐ and CMV‐specific T‐cell immunity (P < 0.05). ABO‐incompatible KTRs showed lower frequencies of alloreactive T cells (P < 0.05). Our data suggest T‐cell depletion due to ABO desensitization, which may contribute to the increased risk of T‐cell‐dependent infections. Elimination of B cells serving as antigen‐presenting cells, thereby causing impaired T‐cell activation, plays a significant role in both impaired infection control and reduced alloreactive T‐cell activation.     

Loss of ARID1A expression is associated with poor prognosis in invasive micropapillary carcinomas of the breast: A clinicopathologic and immunohistochemical study with long‐term survival analysis

Invasive micropapillary carcinoma (IMPC) of the breast is a highly aggressive and a rare subtype of breast cancer. In this study, we aimed to investigate differences between pure and mixed IMPCs of the breast in terms of clinicopathologic features, and also to analyze the significance of expressions of ARID1A and bcl‐2 regarding prognosis. Sixty‐nine of IMPCs consisting of 21 pure and 48 mixed type diagnosed at Pathology Department of Istanbul Medical Faculty between 2000 and 2011, who had complete follow‐up data, were collected to analyze ARID1A and bcl‐2 expressions immunohistochemically with prognosis. The median follow‐up period was 94 months. No significant difference was found between pure and mixed type IMPC, as well as in luminal subgroups in terms of prognostic and clinicopatologic features. ARID1A and human epidermal growth factor receptor‐2 (Her‐2) status were found to be independent prognostic factors of both overall survival (OS) (HR=6.1, 95% CI 1.4‐26.6, P=.02; HR=15.9, 95% CI 3.5‐71.5, P<.0001, respectively) and disease free survival (DFS) (HR=4, 95% CI 1.1‐14.9, P=.04; HR=7.2, 95% CI 2‐25.4, P=.002, respectively) in multivariate analysis using Cox regression. The loss of ARID1A expression was significantly related with 10 year‐OS (P=.001) and 10 year‐DFS (P=.05). Statistically significant effect of ARID1A expression was also stated on DFS and OS in Luminal B group (P=.05 and P=.001 respectively). Pure and mixed type IMPCs are similar in terms of clinicopathologic and prognostic features. The loss of ARID1A expression and Her‐2 positivity have significant adverse effect clinical outcomes of IMPC patients.     

Neutropenia in kidney and liver transplant recipients: Risk factors and outcomes

No studies have directly compared the key characteristics and outcomes of kidney (KTx) and liver transplantation (LTx) recipients with neutropenia. In this single‐center, retrospective, cohort study, we enrolled all adult patients who received a KTx or LTx between 2000 and 2011. Neutropenia was defined as 2 consecutive absolute neutrophil count (ANC) values <1500/mm³ in patients without preexisting neutropenia. The first neutropenia episode occurring during the first year post‐transplantation was analyzed. A total of 663 patients with KTx and 354 patients with LTx met the inclusion criteria. Incidence of neutropenia was 20% in KTx and 38% in LTx, respectively. High‐risk CMV status and valganciclovir (VGCV) use were significant predictors of neutropenia for KTx recipients, but only VGCV use vs nonuse in LTx recipients. Neutropenia was associated with worse survival in KTx recipients (adjusted HR 1.95, 95% CI 1.18‐3.22, P<.01), but not in LTx recipients (adjusted HR 0.75, 95% CI 0.52‐1.10, P=.15). Sixteen acute rejection episodes were associated with preceding neutropenia in KTx recipients (HR 1.77, 95% CI 1.16‐2.68, P=.007) and 24 acute rejection episodes in LTx recipients (HR 1.41, 95% CI 0.97‐2.04, P=.07). Incidence of infection was similar in patients with and without neutropenia among KTx and LTx recipients.     

Increased risk of rejection after basiliximab induction in sensitized kidney transplant recipients without pre‐existing donor‐specific antibodies – a retrospective study

Depleting induction therapy is recommended in sensitized kidney transplant recipients (KTRs), though the detrimental effect of nondonor‐specific anti‐HLA antibodies is not undeniable. We compared the efficacy and safety of basiliximab and rabbit anti‐thymocyte globulin (rATG) in sensitized KTRs without pre‐existing donor‐specific antibodies (DSAs). This monocentric retrospective study involved all sensitized KTR adults without pre‐existing DSAs (n = 218) who underwent transplantation after June 2007. Patients with basiliximab and rATG therapy were compared for risk of biopsy‐proven acute rejection (BPAR) and a composite endpoint (BPAR, graft loss and death) by univariate and multivariate analysis. Patients with basiliximab (n = 60) had lower mean calculated panel reactive antibody than those with rATG (n = 158; 23.7 ± 24.2 vs. 63.8 ± 32.3, P < 0.0001) and more often received a first graft (88% vs. 54%, P < 0.0001) and a transplant from a living donor (13% vs. 2%, P = 0.002). Risks of BPAR and of reaching the composite endpoint were greater with basiliximab than rATG [HR = 3.63 (1.70–7.77), P = 0.0009 and HR = 1.60 (0.99–2.59), P = 0.050, respectively]. Several adjustments did not change those risks [BPAR: 3.36 (1.23–9.16), P = 0.018; composite endpoint: 1.83 (0.99–3.39), P = 0.053]. Infections and malignancies were similar in both groups. rATG remains the first‐line treatment in sensitized KTR, even in the absence of pre‐existing DSAs.     

Post‐transplant lymphoproliferative disease in lung transplantation: A nested case‐control study

Post‐transplant lymphoproliferative disorder (PTLD) may compromise long‐term outcome of lung transplant (LTx) recipients. A case‐control study was performed, comparing LTx recipients with PTLD (n=31) to matched recipients without PTLD (Controls, n=62). Risk factors for PTLD and post‐transplant outcomes were assessed. PTLD prevalence was 3.9%, time to PTLD 323 (166‐1132) days; and 54.8% had early‐onset PTLD versus 45.2% late‐onset PTLD. At LTx, more Epstein‐Barr virus (EBV)‐seronegative patients were present in PTLD (42%) compared to Controls (5%) (P<.0001); most of whom had undergone EBV seroconversion upon PTLD diagnosis. EBV viral load was higher in PTLD versus Controls (P<.0001). Overall, lower hemoglobin and higher C‐reactive protein levels were present in PTLD versus Controls (P<.0001). EBV status at LTx (P=.0073) and EBV viral load at PTLD (P=.0002) were the most important risk determinates for later PTLD. Patients with PTLD demonstrated shorter time to onset of chronic lung allograft dysfunction (CLAD) (P=.0006) and poorer 5‐year survival post‐LTx (66.6% versus 91.5%), resulting in worse CLAD‐free survival (HR 2.127, 95%CI 1.006‐4.500; P=.0483) and overall survival (HR 3.297 95%CI 1.473‐7.382; P=.0037) compared to Controls. Late‐onset PTLD had worse survival compared to early‐onset PTLD (P=.021). Primary EBV infection is a risk for PTLD; which is associated with worse long‐term outcome post‐LTx.     

Diminished impact of cytomegalovirus infection on graft vasculopathy development in the antiviral prophylaxis era – a retrospective study

Evidence concerning an association between cytomegalovirus (CMV) infection and accelerated cardiac allograft vasculopathy (CAV) is inconclusive. Data were analyzed retrospectively from 297 consecutive heart transplants between 1.1.2002 and 31.12.2012. Patients ≤18 years of age, survival, and follow‐up ≤1‐year post‐transplant and patients with early CAV were excluded. CMV‐infection was diagnosed and monitored closely in the first year. CAV was diagnosed by coronary angiography via left heart catheterization, and results were categorized according to the International Society of Heart and Lung Transplantation (ISHLT) scoring system. Risk factors for CAV were tested in a multivariable model. Median follow‐up was 7.5 years (IQR: 5.6–10.3). CMV infection in the first year after transplantation occurred in 26% of patients (n = 78), CMV disease in 5% (n = 15). CAV ≥1 ISHLT was detected in 36% (n = 108). Incidence of CAV >1 ISHLT and severity of CAV increased over time. No statistically significant association between CMV infection and disease within the first year and risk of CAV after 1‐year post‐HTx was detected in the univariate (P = 0.16) and multivariable [hazard ratio (HR), 1.36; confidence interval (CI), 0.89–2.07; P = 0.16] Cox regression. In the multivariable Cox regression, donor age (HR, 1.04; 95% CI, 1.02–1.06; P < 0.01) and acute cellular rejection (ACR) ≥2R in the first year after HTx (HR, 1.77; 95% CI, 1.06–2.95; P = 0.03) were independent risk factors for CAV development. In our cohort, CMV infection and disease in the first year after transplantation did not significantly influence the risk of CAV in the long‐term follow‐up.     

Different risk factor profiles distinguish early‐onset from late‐onset BKV‐replication

Two of three reactivations of latent BKV‐infection occur within the first 6 months after renal transplantation. However, a clear differentiation between early‐onset and late‐onset BKV‐replication is lacking. Here, we studied all kidney transplant recipients (KTRs) at our single transplant center between 2004 and 2012. A total of 103 of 862 KTRs were diagnosed with BK viremia (11.9%), among which 24 KTRs (2.8%) showed progression to BKV‐associated nephropathy (BKVN). Sixty‐seven KTRs with early‐onset BKV‐replication (65%) and 36 KTRs with late‐onset BKV‐replication (35%) were identified. A control group of 598 KTRs without BKV‐replication was used for comparison. Lymphocyte‐depleting induction, CMV‐reactivation, and acute rejection increased the risk of early‐onset BKV‐replication (P < 0.05). Presensitized KTRs undergoing renal retransplantation were those at increased risk of late‐onset BKV‐replication (P < 0.05). Among KTRs with BK viremia, higher doses of mycophenolate increased the risk of progression to BKVN (P = 0.004). KTRs with progression to BKVN showed inferior allograft function (P < 0.05). KTRs with late‐onset BK viremia were more likely not to recover to baseline creatinine after BKV‐replication (P = 0.018). Our data suggest different risk factors in the pathogenesis of early‐onset and late‐onset BKV‐reactivation. While a more intensified immunosuppression is associated with early‐onset BKV‐replication, a chronic inflammatory state in presensitized KTRs may contribute to late‐onset BKV‐replication.     

Influence of epidemiology,immunosuppressive regimens,clinical presentation,and treatment on kidney transplant outcomes of patients diagnosed with tuberculosis: A retrospective cohort analysis

Tuberculosis (TB) mortality is high among kidney transplant (KT) recipients. Although local epidemiology is an important factor, diagnostic/therapeutic challenges and immunosuppressive therapy (ISS) may influence outcomes. We analyzed the cumulative incidence (CumI) of TB in KT recipients receiving a variety of ISS with long‐term follow‐up. Our retrospective single‐center cohort study included all KT procedures performed between January 1, 1998, and August 31, 2014, with follow‐up until August 31, 2014. Induction therapy was based on perceived immunological risk; maintenance ISS included prednisone and calcineurin inhibitor (CNI) plus azathioprine (AZA), and mycophenolic acid (MPA) or mechanistic target of rapamycin inhibitor (mTORi). Thirty‐four patients received belatacept/MPA. KT was performed on 11 453 patients and followed for 1989 (IQR 932 to 3632) days. Among these, 152 patients were diagnosed with TB (CumI 1.32%). Median time from KT to TB was 18.8 (IQR 7.2 to 60) months, with 59% of patients diagnosed after the first year. Unadjusted analysis revealed an increasing confidence interval (CI) of TB (0.94% CNI/AZA vs 1.6% CNI/MPA [HR = 1.62, 95% CI = 1.13 to 2.34, P = .009] vs 2.85% CNI/mTORi [HR = 2.45, 95% CI = 1.49 to 4.32, P < .001] vs 14.7% belatacept/MPA [HR = 13.14, 95% CI = 5.27 to 32.79, P < .001]). Thirty‐seven (24%) patients died, and 39 (25.6%) patients experienced graft loss. Cytomegalovirus infection (P = .02) and definitive ISS discontinuation (P < .001) were associated with death. Rejection (P = .018) and ISS discontinuation (P = .005) occurred with graft loss. TB occurred at any time after KT and was influenced by ISS.     

A prospective multicenter observational study of cell‐mediated immunity as a predictor for cytomegalovirus infection in kidney transplant recipients

T cell immunity is essential for the control of cytomegalovirus (CMV) infection after transplantation. We evaluated a CMV‐specific peptide‐based enzyme‐linked immunosorbent spot (ELISPOT) assay to determine whether assay results could predict subsequent CMV events. Adult kidney transplant recipients at 43 centers underwent ELISPOT testing to enumerate interferon gamma (IFN‐γ) binding spot‐forming units (sfu) after stimulation of cells with an overlapping peptide pool of CMV phosphoprotein 65 (pp65) and immediate early‐1 (IE‐1) protein at the end of antiviral prophylaxis (EOP) and various time points thereafter. The primary outcome was a CMV event in the first posttransplant year. In 583 kidney transplant recipients (260 seropositive donor [D+]/seronegative recipient [R?] and 277 R+), CMV events occurred in 44 of 368 eligible patients (11.8%) at a median of 227 days (range 92‐360) posttransplant. A cutoff value of >40 sfu/2.5 × 10⁵ cells for either IE‐1 or pp65 was derived as a threshold for positivity, with a negative predictive value of >97% for CMV events. CMV events were significantly lower in assay positive vs assay negative patients (3.0% vs 19.5%, P < .0001 for pp65). Time to CMV event post‐EOP was significantly greater in those with sfu >40 at EOP (P < .0001). In this large, multicenter trial of kidney transplant recipients, we show that an assessment of CMV‐specific immunity using a novel ELISPOT assay is able to predict protection from CMV infection.     

Prognostic factors in kidney transplantation in the septuagenarian: a multicenter analysis

Kidney transplant (KT) programs have extended recipient eligibility to those who were previously excluded due to advanced age. We aimed to determine the outcomes of the patients ≥70 years undergoing KT and investigate factors predicting survival. Two thousand six hundred and twenty‐four KT patients between 2003 and 2013 at two institutions were divided into two groups; those ≥70 years (n=300) and those <70 years (n=2324) at the time of KT. Patient survival at 1, 3, and 5 years was 95%, 86%, and 77% in ≥70 years of age group and 98%, 95%, and 90% in the <70 years group (P<.001). When graft loss due to death was censored, graft survival was not significantly different between the two groups (P=.18). On multivariable analysis, the significant predictors of inferior survival in patients ≥70 years included: body mass index (BMI)>30 kg/m² (hazard ratio [HR] 1.07; P=.01), panel reactive antibody (PRA)>20% (HR 2.38; P=.01), previous coronary artery bypass grafting (CABG; HR 1.95; P=.03) and peripheral vascular disease (PVD; HR 2.60; P=.04). Acceptable outcomes can be achieved in KT recipients ≥70 years. Caution should be used when listing these patients if they have BMI>30 kg/m², PRA>20%, CABG or PVD.     

Cervical human papillomavirus infection in the early postoperative period after liver transplantation: Prevalence,risk factors,and concordance with anal infections

Solid organ transplant recipients are at increased risk of developing several human papillomavirus (HPV)‐related malignancies, including cervical and anal cancers. The purpose of this prospective study was to assess the initial prevalence and risk factors for high‐risk HPV (HR‐HPV) cervical infections in liver transplant recipients, as well as their concordance with anal infections. A total of 50 female patients were enrolled in the Department of General, Transplant and Liver Surgery at the Medical University of Warsaw (center with >1600 liver transplantations). The initial prevalence of cervical HR‐HPV infection was 10.0% (5/50). The only significant risk factor for cervical HR‐HPV infection was ≥4 lifetime sexual partners (P=.037). Statistical tendencies toward higher prevalence of cervical HR‐HPV infections were found for patients with hepatitis B virus (HBV, P=.082) and with model for end‐stage liver disease (MELD) score ≤8 (P=.064). Cervical cytology was abnormal in 10 patients, including three with HR‐HPV. Out of 12 patients with available data on anal HR‐HPV, one had concordant HPV 16 infection. In conclusion, the initial prevalence of high‐risk HPV infection is relatively low, except for patients with ≥4 previous sexual partners and potentially in those with HBV and/or low MELD score.     

Reduced Incidence of Cytomegalovirus Infection in Kidney Transplant Recipients Receiving Everolimus and Reduced Tacrolimus Doses

This study compared the incidence of CMV infection/disease in de novo kidney transplant recipients receiving everolimus or mycophenolate and no CMV pharmacological prophylaxis. We randomized 288 patients to receive a single 3 mg/kg dose of antithymocyte globulin, tacrolimus, everolimus, and prednisone (r‐ATG/EVR, n = 85); basiliximab, tacrolimus, everolimus, and prednisone (BAS/EVR, n = 102); or basiliximab, tacrolimus, mycophenolate, and prednisone (BAS/MPS, n = 101). The primary end‐point was the incidence of first CMV infection/disease in the intention‐to‐treat population at 12 months. Patients treated with r‐ATG/EVR showed a 90% proportional reduction (4.7% vs. 37.6%, HR 0.10, 95% CI 0.037–0.29; p < 0.001), while those treated with BAS/EVR showed a 75% proportional reduction (10.8% vs. 37.6%, HR 0.25, 95% CI 0.13–0.48; p < 0.001) in the incidence of CMV infection/disease compared to BAS/MPS. There were no differences in the incidence of acute rejection (9.4 vs. 18.6 vs. 15.8%, p = 0.403), wound‐healing complications, delayed graft function, and proteinuria. Mean estimated glomerular filtration rate was lower in BAS/EVR (65.7 ± 21.8 vs. 60.6 ± 20.9 vs. 69.5 ± 21.5 ml/min, p = 0.021). In de novo kidney transplant recipients receiving no pharmacological CMV prophylaxis, reduced‐dose tacrolimus and everolimus was associated with a significant reduction in the incidence of CMV infection/disease compared to standard tacrolimus dose and mycophenolate ( ClinicalTrials.gov NCT01354301).     

Outcomes of patients with detectable CMV DNA at randomization in the phase III trial of letermovir for the prevention of CMV infection in allogeneic hematopoietic cell transplantation

Letermovir, a cytomegalovirus (CMV) terminase‐complex inhibitor, is indicated for prophylaxis of CMV infection and disease in adult CMV‐seropositive recipients of allogeneic hematopoietic cell transplantation (HCT). In a phase III, double‐blind, randomized trial, letermovir significantly reduced the risk of clinically significant CMV infection (CS‐CMVi) vs placebo through Week 24 post‐HCT. This analysis investigated outcomes in participants with detectable CMV DNA at randomization, who were excluded from the primary efficacy analysis. In total, 70 of 565 randomized participants had detectable CMV DNA at randomization (letermovir 48; placebo 22). Study treatment completion rates were greater in letermovir‐treated participants compared with placebo (52.1% vs 9.1%). The incidence of CS‐CMVi or imputed primary endpoint events through Week 24 were 64.6% and 90.9% in the letermovir and placebo groups, respectively (treatment difference ?26.1%; P = .010). Kaplan‐Meier event rates for CS‐CMVi onset through Week 14 (end‐of‐treatment period) were 33.1% for letermovir and 86.6% for placebo (P < .001). Median viral loads at the CS‐CMVi events was similar in both treatment arms. All‐cause mortality through Week 24 posttransplant was 15.0% for letermovir and 18.2% for placebo; through Week 48, mortality rates were 26.5% and 40.9%, respectively (P = .268). Overall, clinical outcomes were similar to those reported for participants with undetectable CMV DNA at randomization.     

Delayed vs initial cytomegalovirus prophylaxis after kidney transplantation

It is recommended to start cytomegalovirus (CMV) prophylaxis within 10 days of solid organ transplant, if indicated. Our center underwent a cost-savings initiative to delay CMV prophylaxis initiation from postoperative day zero to postoperative day 7 or upon discharge, hypothesizing this would not affect clinical outcomes but could impact costs. The purpose of this retrospective study was to determine the effects of early vs delayed (<72 vs >72 hours after transplant) CMV prophylaxis in kidney and kidney/pancreas transplant recipients transplanted between June 2014 and January 2017. The primary endpoint was incidence of CMV infection within 1 year. Secondary endpoints included CMV disease, CMV testing, and valganciclovir cost during index hospitalization. A total of 173 patients (114 early, 59 delayed) were included. CMV infection occurred in 61% vs 54% in the early vs delayed group (P = .5). Excluding low-level DNAemia (QNAT < 200 IU/mL), infection occurred in 30% vs 22% in the early vs late group (P = .4). The median days to starting prophylaxis were 0 and 6 in the early and delayed group (P < .05), which led to a median cost savings of $497.00 per patient during index hospitalization (P < .05). Delaying prophylaxis initiation did not impact CMV outcomes in this cohort and decreased costs.