Prospective long-term study on primary CMV infections in adult liver transplant (D+/R−) patients after valganciclovir prophylaxis

BackgroundCytomegalovirus (CMV) can cause severe infections in transplanted patients. To prevent CMV infection, most liver centers use prophylaxis for CMV-seronegative recipients receiving an organ from a seropositive donor (D+/R−). Valganciclovir is mostly given for 3–6 months after transplantation. However, the patients may develop primary CMV infection after the cessation of prophylaxis and late-onset CMV disease may occur.ObjectivesA prospective long-term follow-up of CMV (D+/R−) adult liver transplant recipients after 3 months valganciclovir prophylaxis was investigated.Study designOf 154 consecutive adult liver recipients transplanted from 2006 to 2009, 20 (13%) were CMV D+/R− and received antiviral prophylaxis up to 3 months after transplantation. After excluding the recipients with incomplete prophylaxis or monitoring, 13 (D+/R−) patients with follow-up of >4 years after the 3-month period of valganciclovir prophylaxis were included in the study.The patients were monitored for CMV by real-time quantitative plasma PCR.ResultsNo break-through CMV infections were recorded during the prophylaxis period. After cessation of valganciclovir prophylaxis 12/13 (90%) patients demonstrated CMV-DNAemia following a post transplantation mean interval of 165 days (range 95–320). Ten patients with high viral loads (peak viral load mean 81,510, range 1900–648950 cps/ml) were successfully treated, 6 with valganciclovir, and 4 with ganciclovir. Two patients with low level CMV-DNAemia (<1000 cps/ml) were asymptomatic and not treated. No intragraft infection was seen, but one patient developed gastrointestinal CMV infection verified from ileum biopsy. During long-term follow-up, 3 patients demonstrated low-level viral replication, but no symptomatic recurrences occurred. One patient died of bacterial sepsis, but no patient or graft was lost due to CMV.ConclusionsPrimary CMV infections after cessation of prophylaxis were common, but were successfully treated with valganciclovir or ganciclovir.     

Risk factors for herpes simplex virus-1/2 viremia and clinical outcomes following unmanipulated haploidentical haematopoietic stem cell transplantation

BackgroundHerpes simplex virus (HSV)-1/2 can still be reactivated after allogeneic haematopoietic stem cell transplantation (allo-HSCT) even when the prophylactic acyclovir is used. However, the risk factors for HSV-1/2 viremia and the clinical outcomes following unmanipulated haploidentical HSCT remain unknown.Objectives and study designNineteen patients with HSV-1/2 viremia and fifty-seven patients without HSV-1/2 viremia which were selected using the case-pair method after undergoing haploidentical HSCT were enrolled. We analysed the risk factors for HSV-1/2 viremia and compared the clinical outcomes between the two groups.ResultsThe risk factors for HSV-1/2 viremia included HLA disparity ≥2 loci (p = 0.049) and cytomegalovirus (CMV) reactivation (p = 0.028). The incidences of platelet engraftment, oral mucositis and severe haemorrhagic cystitis (HC) in patients with and without HSV-1/2 viremia were 77% and 94% (p = 0.003), 78% and 13% (p = 0.000), and 25% and 6% (p = 0.04), respectively. Moreover, the median time to platelet engraftment in patients with and without HSV-1/2 viremia was +25 days (range, +11–+80) and +17 days (range, +8–+67) (p = 0.004), respectively. According to the multivariate analyses, HSV-1/2 viremia was associated with delayed platelet engraftment (p = 0.038), a higher incidence of oral mucositis (p = 0.000) and severe HC (p = 0.038). However, HSV-1/2 viremia was not associated with non-relapse mortality (34.0% vs. 31.5%, p = 0.26), leukaemia-free survival (60.9% vs. 57.9%, p = 0.46) and overall survival (61.2% vs. 60.7%, p = 0.37).ConclusionsBased on our study results, we recommend that HSV-1/2 PCR should be performed upon clinical suspicion of HSV-1/2 infection.     

Epstein-Barr virus DNA load kinetics analysis in allogeneic hematopoietic stem cell transplant recipients: Is it of any clinical usefulness?

BackgroundThere is a lack of clinical information regarding the usefulness of plasma Epstein-Barr virus (EBV) DNA load kinetics analyses in the management of EBV infections in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Namely, it remains unknown whether this type of analysis can help physicians to anticipate the development of high-level EBV DNAemia episodes requiring rituximab treatment or predict the risk of recurrent EBV DNAemia or post-transplant lymphoproliferative disorders (PTLDs).Study designUnicentric, retrospective, observational study including 142 consecutive patients undergoing T-cell replete allo-HSCT. The plasma EBV DNA load was monitored on a weekly basis using the artus^® EBV PCR kit.ResultsFifty-five of the 142 patients (38.7%) developed at least one episode of EBV DNAemia; 13 of the 55 initial EBV DNAemia episodes (23.6%) were preemptively treated with rituximab, 7 patients had a recurrent episode of EBV DNAemia, and biopsy-proven PTLDs were diagnosed in 4 patients. The initial plasma EBV DNA load was not significantly different (P = 0.269) in episodes of self-resolving EBV DNAemia, those requiring rituximab treatment, or those leading to PTLDs. The plasma EBV DNA load doubling times were similar across all the groups (P = 0.799), and the EBV DNA-load half-life was not associated with the occurrence of recurrent EBV DNAemia (P = 0.550).ConclusionPlasma EBV DNA-load kinetics analyses are unlikely to be useful in predicting the occurrence of high-level EBV DNAemia, PTLD, or recurrent EBV DNAemia.     

Analysis of the shedding of three β-herpesviruses DNA in Polish patients subjected to allogeneic hematopoietic stem cell transplantation: Six-year follow up

BackgroundInfections with human β-herpesviruses are common worldwide and are still frequent in patients after hematopoietic stem cell transplantation. Some data suggest that HHV-6 and HHV-7 could take part in CMV reactivation from latency and/or progression of CMV disease in immunosupressed patients.ObjectivesThe aims of this study were: (1) to summarise retrospectively the results of β-herpesviruses DNA detection in a large group of adult allogeneic haematopoietic stem cell transplant recipients; and (2) to find a potential correlation between viruses belonging to this subfamily.Study designAlloHSCT recipients (N = 142) were examined in the early post-transplant period (median = 89 days). The presence of CMV, HHV-6 and HHV-7 was confirmed through detection and quantification of viral DNA, isolated from 1679 sera samples.ResultsCMV DNA alone was detected in 23.9% of patients, while single HHV-6 and HHV-7 were detected in 14.8% and 9.9% of individuals, respectively. The reactivation of more than one virus was identified in 31% of analysed patients. In cases of concurrent infection, HHV-7 was detected at the same time as HHV-6, and both of them were usually reactivated before CMV. The kinetics of virus reactivation and measured viral load may suggest a potential role of HHV-6 and HHV-7 as co-factors in CMV reactivation.ConclusionsThe observed kinetics of virus reactivation may strongly suggest a potential role of HHV-6 and/or HHV-7 as co-factors of CMV reactivation. The co-infection with these β-herpesviruses could predispose patients after hematopoietic stem cell transplantation to a longer and more severe CMV infection.     

Haploidentical haematopoietic stem cell transplantation for the treatment of severe aplastic anaemia patients with high-risk factors who lack an HLA-matched sibling donor

This study aimed to analyse the efficacy of haploidentical donor (HID) haematopoietic stem cell transplantation as a first-line treatment for severe aplastic anaemia (SAA) with high-risk factors (infection or very severe aplastic anaemia,VSAA) in patients who lack an HLA-matched sibling donor (MSD). The patients with infection were treated with anti-infection therapy, and allogeneic haematopoietic stem cell transplantation (HSCT) was carried out after the infection being effectively controlled was in accordance with the stable infection (SI) standard. A total of 44 SAA patients receiving MSD transplantation (n = 19) and HID transplantation (n = 25) were included in this study. There was no significant difference in neutrophil engraftment between the two groups [MSD vs. HID, 19 (11–38) vs. 22 (15–47).P = 0.241], and the difference in platelet engraftment was statistically significant [MSD vs. HID, 11(7–33) vs. 20 (12–69), P = 0.034]. The HID group exhibited a higher incidence of grade II–IV acute graft-versus-host disease (aGVHD) (HID vs. MSD, 48.0% vs10.5%, P = 0.034)and a higher incidence of chronic GVHD (cGVHD) than the MSD group (64.0% vs. 21.1%, P = 0.026). There was no significant difference between overall survival (OS) following HID and MSD transplantation (84.0% vs. 89.5%, P = 0.664) and failure-free survival (FFS)(80.0% vs. 84.2%, P = 0.965). The interval from diagnosis to transplantation (> 50d) and ECOG (> 2) were independent factors associated with OS and FFS. HID HSCT may be an effective and safe option for SAA patients with high-risk factors who lack an MSD.     

Diagnostic usefulness of dynamic changes of CMV-specific T-cell responses in predicting CMV infections in HCT recipients

BackgroundCMV-specific cell mediated immune responses before and after hematopoietic stem cell transplantation (HCT) can categorize patients as at high or low risk of CMV development.ObjectivesWe evaluated the usefulness of the CMV-specific T-cell ELISPOT assay for predicting the development of CMV infections after HCT in recipients with donor-positive and recipient-positive CMV serology (D+/R+ ).Study designCMV pp65 and IE1-specific ELISPOT assays were performed before HCT (D0), and at 30 (D30) and 90 (D90) days after HCT.ResultsOf the 84 HCT recipients with D+/R+, 42 (50%) developed ≥ 1 episode of CMV infection. Thirty-nine (64%) of 61 patients with Δ(D30-D0) pp65 < 42 developed CMV infections compared with 3 (14%) of 21 patients with Δ(D30-D0) pp65 ≥ 42 (P < 0.001). Twenty-three (74%) of 31 patients with Δ(D30-D0) IE1 < −4 developed CMV infections compared with 19 (37%) of 51 patients with Δ(D30-D0) IE1 ≥ −4 (P = 0.001). pp65 Δ(D30-D0) ≥ 42 had 93% sensitivity for ruling out subsequent CMV infection, and pp65 Δ(D30-D0) < 42 followed by Δ(D30-D0) IE1 < −4 had 100% specificity for ruling in the subsequent CMV infection. In addition, 10 (53%) of 19 patients with Δ(D90-D30) pp65 < 23 had relapsing CMV infections, compared with 3 (15%) of 20 patients with Δ(D90-D30) pp65 ≥ 23 (P = 0.02). The sensitivity and specificity of Δ(D90-D30) pp65 were 77% (95% CI 50–92) and 65% (95% CI, 46–81).ConclusionDynamic change in the CMV-specific ELISPOT assay before versus after HCT appears to predict the subsequent development of CMV infection and relapsing CMV infection.     

Adenovirus infection among pediatric patients with cancer and in pediatric recipients of hematopoietic stem cell: A multicenter nationwide study

The aim was to evaluate the incidence, clinical course, and outcome of adenoviral infection (AdVI) in pediatric patients diagnosed and treated due to cancer and in pediatric recipients of hematopoietic stem cell. Over a 72-month period, all-in 5599 children with cancer: 2441 patients with hematological malignancy (HM) and 3158 with solid tumors (ST), and 971 patients after transplantation: 741 after allogeneic (allo-HSCT) and 230 after autologous (auto-HSCT) were enrolled into the study. Among cancer patients, 67 episodes of AdVI appeared in 63 (1.1%) children, including 45 (1.8%) with HM and 18 (0.6%; P < .001) with ST. Within transplanted patients, AdVIs were responsible for 88 episodes in 81 (8.3%) children (P < .001), including 78 (10.5%) patients after allo-HSCT and 3 (1.3%) after auto-HSCT. Time to develop AdVI was short, especially after allo-HSCT. The most common clinical manifestation in cancer patients was enteritis diagnosed in 63 (94.0%) cases, while among HSCT recipient asymptomatic adenoviremia was found in 36 (40.9%) cases and the most common clinical manifestation was urinary tract infection. Cancer patients with disseminated disease, as well as HSCT recipients with either asymptomatic viremia or disseminated disease, received antiviral treatment. The most commonly used first-line therapy was cidofovir. None of the cancer patients died due to AdVI, while within HSCT recipients three patients developed disseminated adenoviral disease and died despite antiviral treatment. In cancer patients, AdVIs are rare and associated with very good prognosis even without specific treatment. However, in allo-HSCT recipients, disseminated disease with fatal outcome is more likely to occur.     

High-level JCPyV viruria after kidney transplantation—Clinical and histopathological findings

BackgroundThe significance of JC polyomavirus (JCPyV) after kidney transplantation ranges from irrelevant to full-blown nephropathy or PML.ObjectivesTo investigate the clinical significance of high-level JCPyV viruria and JCPyV primary infections after kidney transplantation.Study designJCPyV viruria was detected in routine screening by quantitative real-time PCR in 40/238 kidney transplant recipients and was high-level (>10⁷ copies/ml) in 17 patients. A protocol biopsy at the time of JCPyV viruria was available from 10 patients.ResultsPeak urine viral loads were 1.0 × 10⁷ − 2.5 × 10⁹ copies/ml in the 17 high-level viruria patients. 6/15 (40%) patients with high-level JCPyV viruria with pretransplant sera available were JCPyV IgG negative suggesting that JCPyV viruria resulted from the donor graft in most cases. No acute graft dysfunction was associated with JCPyV viruria. No positive SV40 staining was detected in protocol biopsies, and no specific histopathology was associated with high-level viruria; JCPyV nephropathy was not found. No differences were seen in histopathology or graft function at 3 years in patients with high-level viruria compared to non-JCPyV viruric patients transplanted during the same time period, and outcome was similar in patients with presumably primary and reactivated JCPyV. The mean estimated GFR at last follow-up was 44 ml/min (range 12–60 ml/min). One graft with high-level viruria was lost 9 years posttransplant due to recurrent IgA nephropathyConclusionsHigh-level JCPyV viruria seems to be associated with primary JCPyV infection reflecting the average seroprevalence of 60%, but is not stringently associated with inferior graft function or survival, or histopathological changes.     

Effect of the immunosuppressive regimen on the incidence of cytomegalovirus infection in 378 heart transplant recipients: A single centre,prospective cohort study

BackgroundCytomegalovirus (CMV) infection is a major complication of immunosuppression after heart transplant. Recent studies suggest the actual immunosuppressive regimen may affect the risk of CMV infection.ObjectivesTo evaluate incidence, risk factors and clinical consequences of CMV infection and assess the possible differential effect of distinct immunosuppressive protocols.Study designSingle centre, prospective cohort study of 378 consecutive heart transplant recipients undergoing CMV monitoring. Preemptive treatment was the standard of care. Patients were grouped as follows: group A, without any CMV infection; group B, with CMV infection not requiring pre-emptive treatment; group C, treated for CMV infection or disease.ResultsMost recipients never required antiviral therapy because of no CMV infection/disease (group A, 31%) or CMV levels below the cut-off for pre-emptive treatment (group B, 28%). Group C recipients (41%) were significantly older than group A patients (49.1 ± 13.2 vs. 44.8 ± 15.1 years; p = 0.028). Most cases occurred within the second month post-transplant. CMV viremia was detected in 77% and 62% of patients primed with thymoglobulin or ATG Fresenius, respectively, (OR 2.06, 95% C.I. 1.27–3.34; p = 0.0034). Use of everolimus was associated with a significantly lower rate of CMV infection compared to azathioprine or mycophenolate (OR 0.19, 95% C.I. 0.09–0.39; p < 0.0001). Major opportunistic infections were significantly more common in groups B and C.ConclusionIn a large and homogeneous cohort of heart transplant recipients, we observed a strong relationship between the immune suppressive regimen and CMV infection, as well as an increased incidence of other opportunistic infections in recipients with CMV infection/disease.     

Risk factors for cytomegalovirus DNAemia following haploidentical stem cell transplantation and its association with host hepatitis B virus serostatus

BackgroundThe risk factors associated with CMV DNAemia are not well known after haploidentical stem cell transplantation (SCT).ObjectivesThis study investigated the risk factors and prognosis for CMV DNAemia among CMV seromatched donors and recipients (D+/R+).Study designA retrospective study of patients undergoing haploidentical stem cell transplantation (SCT) between January 2010 and January 2012 was conducted. Cox regression analysis was performed to identify the risk factors for CMV DNAemia. These possible factors included recipient/donor age, recipient/donor gender, gender disparity, recipient HBsAg serostatus, diagnosis, risk stratification, anti-thymocyte globulin (ATG) dose (6 mg/kg,10 mg/kg), early neutrophil engraftment (≤12 days, >12 days), absolute lymphocyte count on day 30 (ALC30) and the occurrence of acute GVHD before CMV DNAemia.ResultsThe total number of patients was 248 with median age of 31 years (range, 14–56). The cumulative incidence of CMV DNAemia (146/248) was 59.5%. CMV DNAemia was first detected after a median of +35 days (range,12–82). Seventeen patients (17/146, 11.6%) developed CMV disease. Multivariate analysis identified HBsAg seropositivity (P = 0.002, hazard ratio (HR) = 1.833; 95%CI = 1.257–2.673) and the occurrence of acute GVHD before CMV DNAemia (P = 0.014; HR = 1.520; 95%CI = 1.088–2.124) as risk factors for CMV DNAemia. CMV DNAemia was associated with subsequent II-IV acute graft-versus-host disease (GVHD) (P = 0.014), III-IV aGVHD (P = 0.013) and chronic GVHD (P = 0.008). Totally, CMV DNAemia was found to be a poor prognostic factor in terms of non-relapse mortality (NRM) (P = 0.003, HR = 2.730; 95%CI = 1.406–5.197), and overall survival (OS) (P = 0.045, HR = 1.654; 95%CI = 1.012–2.701).ConclusionsOur data showed HBsAg seropositivity was associated with an increased risk of cytomegalovirus DNAemia. Detection of CMV DNAemia proved to be a poor prognostic factor for haploidentical patients.     

Cytomegalovirus reactivation in lymphoma and myeloma patients undergoing autologous peripheral blood stem cell transplantation

BackgroundCytomegalovirus reactivation is often diagnosed in allogeneic hematopoietic cell transplant recipients and therefore could lead to CMV-related disease, involving many organs in these immunocompromised patients. In contrast, few studies investigated CMV reactivation and end-organ disease in patients undergoing Autologous Peripheral Blood Stem Cell Transplant (ASCT) since they are considered at low risk for both reactivation and disease.ObjectivesThe primary outcome of the analysis was to understand the difference in incidence of CMV reactivation between MM and Lymphoma patients. Secondary outcomes included the difference between MM and Lymphoma patients when considering the effect of CMV reactivation on transplant related mortality (TRM) overall survival (OS) progression free survival (PFS), risk factors for reactivation, and median time to reactivation.Study designIn this report, we retrospectively compared the incidence, risk factors, and outcome of CMV reactivation in adult patients with Myeloma (MM) and Lymphoma undergoing ASCT at the American university of Beirut Medical Center in Lebanon (AUBMC). A total of 324 consecutive ASCT were performed between January 2005 and March 2016. Serial weekly monitoring for CMV quantification was done using a quantitative PCR, starting from transplantation until the hospital discharge and afterwards based on the clinical symptoms in cases of clinical suspicion of reactivation after discharge from the hospital.ResultsThe cumulative incidence of CMV reactivation was 16% (n = 53) with a median time of 16 (range, 4–242) days after ASCT. The incidence of reactivation was significantly higher in the MM (22%) and NHL (20%) groups, when compared to the HL (4%) (P = 0.001). There was a higher incidence of CMV reactivation according to age (≥50 vs ≤50 years) with higher incidence in the older population 24% vs 10% respectively (p = 0.0043). The mean time to CMV reactivation was significantly higher in the NHL group with a mean of 53.7 days when compared to the HL and MM groups with mean 19.75 days and 12.66 (range, 4–34) days respectively (P = 0.003). Twenty-two patients (76%) and three patients (75%) patients required specific antiviral therapy in the MM group and HL groups respectively; which was significantly higher (P < 0.001) then the NHL group with 13 (65%) patients requiring specific antiviral therapy.Five patients (1.5%) developed CMV disease at a median of 60 days (range, 7–107) post ASCT: there was significant difference in the mean-time to reactivation based on disease type MM versus lymphoma 10 versus 33 days (P = 0.007).In multivariate analysis, a higher age was associated with an increased risk of CMV reactivation; MM and NHL had higher risk of CMV reactivation when compared to HL, and progressive disease at transplant was associated with increased risk of CMV reactivation.After a median follow-up of 21.5 months (range: 1–125), there was no significant impact on PFS, however there was significant decrease in OS of lymphoma patients who had CMV reactivation when compared to those without CMV reactivation (204 and 112 days respectively P = 0.045). TRM increased from 1.1% in patients with no CMV reactivation to 13% in patients with CMV reactivation (P = 0.003).ConclusionOur data suggests that CMV reactivation is not uncommon in ASCT recipients and may contribute to increase TRM. MM patients may have a higher incidence, of CMV reactivation with more anti-viral treatment requirements when compared to lymphoma patients, especially in older population.     

Clinical significance of the single nucleotide polymorphism TLR2 R753Q in heart transplant recipients at risk for cytomegalovirus disease

BackgroundThe toll-like receptor 2 (TLR2) is a significant component of innate immunity against cytomegalovirus (CMV) infection but information on the clinical significance of the single nucleotide polymorphism (SNP) (R753Q) is conflicting.ObjectivesThe inconsistent observations of the immunological and clinical significance of the TLR2 R753Q polymorphism for CMV infection indicates the influence of confounders.Study designThe presence of the TLR2 polymorphism was determined by a genotyping assay of 175 HTX patients and 281 healthy blood donors and evaluated in relation to selected virological and clinical parameters.ResultsRelative frequency of TLR2 polymorphism was similar in HTX patients and blood donors (homozygous wild-type, 94.3% vs. 94.0%; heterozygous, 5.1% vs. 5.7%; homozygous mutated, <1%). CMV viremia was detectable in 108 (61.7%) of HTX patients. The TLR2 polymorphism was neither associated with occurrence or level of CMV infection nor with survival, graft failure or rejection, or CMV serostatus of patient before transplantation. Nevertheless, CMV viremia occurred in 83.1% of R+/D+, 77.1% of R+/D-, and 64.3% of R-/D+ patients. Time of first CMV viremia was in R-/D+ patients later than in CMV-seropositive patients (median, 182 days versus 23 days; P < 0.001) corresponding to the duration of antiviral prophylaxis in R-/D+ patients.ConclusionsThe TLR2 R753Q polymorphism is extremely rare in the general population and HTX patients. Screening for this risk factor of CMV disease may not be cost-effective in contrast to testing for CMV viremia.     

Association of HHV-6 and HHV-7 reactivation with the development of chronic allograft nephropathy

BackgroundThe long-term effect of HHV-6 and HHV-7 infections on chronic allograft nephropathy (CAN) development after renal transplantation is uncertain.ObjectivesTo determine HHV-6 and HHV-7 reactivation during the post-transplantation period and to evaluate its effect on CAN development in renal transplant patients.Study designEighty-one renal allograft recipients (28 with CAN, 53 with normal transplant function) were studied to determine the frequency of HHV-6 and HHV-7 reactivation during 36.4 ± 7.8 months after renal transplantation using nested PCR. HHV-6 variants were identified using restriction endonuclease analysis. Patients were monitored for the development of CAN.ResultsThe frequency of HHV-6 and/or HHV-7 plasma DNA was significantly higher in CAN patients (25/28, 89.3%) compared to control patients (15/50, 30.0%, p = 0.0001). CAN patients also had an increased incidence of dual active infections (20/25, 80% and 2/15, 13.3%, p = 0.007, respectively). In all 34 HHV-6 positive cases, the HHV-6B variant was identified. The presence of HHV-7 DNA in plasma preceded the presence of HHV-6 DNA. Early development of CAN and graft loss was detected only in patients with simultaneous HHV-6 and HHV-7 plasma DNA.ConclusionsReactivation of HHV-6 and HHV-7 in renal graft recipients is a risk factor for CAN development. The presence of concurrent HHV-6 and HHV-7 DNA in the plasma is an unfavorable prognostic factor.     

Soluble HLA-G pre-transplant levels to identify the risk for development of infection in heart transplant recipients

Infection is still a leading cause of death during the first year after heart transplantation. We evaluated the pre-transplant levels of HLA (Human Leukocyte antigen) – G molecules as a means of identifying heart recipients at risk of serious infections. We prospectively analyzed 122 adult heart transplant (HT) recipients. Serum samples were collected before transplantation and analyzed for sHLA-G levels by ELISA assay. The clinical follow-up period lasted 5 years. Clinical outcomes were bacterial infections requiring intravenous anti-microbial agents, cytomegalovirus (CMV) disease, and fungal infections requiring therapy. We found that 39 patients (32%) developed at least 1 serious bacterial infection. Higher pre-transplant sHLA-G levels were a risk factor for serious infection (above median value 5.4 ng/ml; relative risk 3.70; 95% confidence interval 1.03–12.64; p = 0.043). Patients with high levels of pre-transplant sHLA-G are also characterized by a lower overall survival at 5 years (p = 0.017), with microbial infections as major causes of death. No association was observed with the development rejection episode. Early monitoring of sHLA-G molecules proved useful for the identification of heart recipients who are at risk of serious infections.     

A 3-month course of ciprofloxacin does not prevent BK virus replication in heavily immunosuppressed kidney-transplant patients

BackgroundIn vitro and retrospective studies of kidney-transplant patients have shown that quinolones can efficiently prevent BK virus (BKV) replication. However, in a prospective study, a 3 month-course of levofloxacin did not decrease the rate of BK viruria in kidney-transplant patients treated with standard immunosuppression.ObjectivesThe aim of this study was to assess the effect of a 3-month course of ciprofloxacin prophylaxis on BKV replication in kidney-transplant patients that had received heavy immunosuppression (plasma exchange or immunoadsorption and rituximab) to achieve desensitization before undergoing HLA- and/or ABO-incompatible (ABOi) transplantation.Study designTwenty-nine patients were given ciprofloxacin (500 mg/d) for 3 months, starting immediately after transplantation. The results were compared with results from a previous study where patients had received a similar immunosuppression regimen without ciprofloxacin prophylaxis (n = 43). Around 60% of patients had undergone a retransplantation. After transplantation, all patients were given induction therapy, tacrolimus, mycophenolic acid and steroids. BK viruria and viremia were monitored at months 1, 3, 6 and 12 post-transplantation.ResultsThe rates of BK viruria, BK viremia, and BKV-associated nephropathy did not differ between patients who were given or not given ciprofloxacin prophylaxis. These rates were also identical when patients received quinolones at any time within the first year after transplantation compared to those that had not. The rate of bacterial infection was also similar in patients who had or had not received ciprofloxacin.ConclusionThe use of quinolones seemed to not have any beneficial effect in preventing BKV replication in kidney-transplant patients receiving heavy immunosuppression.     

Human Leukocyte Antigen-G Polymorphisms Association With Cancer Post-Heart Transplantation

BackgroundPost transplantation, a major complication is the development of malignancies. Human Leukocyte Antigen (HLA)-G is a molecule that inhibits the immune system and it is utilized by malignant cells to hide from the immune system. Expression of HLA-G from the donor and recipient cells in transplant patients is regulated by gene variations however, the association between genotype and cancer remains unknown. Our objective was to determine the association between genotype and outcome.MethodsHeart transplant recipients (251) and available corresponding donors (196) samples were genotyped for polymorphisms and the association of polymorphisms to outcome was evaluated with parametric hazard regression models.ResultsRisk of cancer was 22% at 10 years post-transplantation. The mean follow-up was of 4.9 ± 3.6 years. In a multivariable analysis, donor–recipient SNP 3187 matching was identified as a protective factor for cancer (hazard ratio 0.43; 95% confidence interval 0.19–0.93; p = 0.03). While coding region allele (haplotype 6) was identified as an independent risk factor (hazard ratio 3.7; 95% confidence interval 1.36–10.06; p = 0.01).ConclusionIn this investigation, we identified an association between cancer post-transplantation and HLA-G polymorphisms, which may reveal a pathway for potential diagnostic and therapeutic strategies for cancer post-transplantation.     

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.     

Przeszczepianie krwi pępowinowej w polskich ośrodkach pediatrycznych: raport Polskiej Pediatrycznej Grupy ds. Transplantacji Komórek Krwiotwórczych

BackgroundCord blood transplantation (CBT) is accepted therapeutic method in transplantology since 1988. The first isolated CBT was performed on 12 October 2000 in Poznań.ObjectiveAnalysis of results of CBT in Polish pediatric centers.Patients and methodsA total numer of 19 patients (5 female, 14 male), aged 0.1–10 years (median 4.3 yrs) transplanted with cord blood between 2000–2011 in Polish pediatric centers. The initial diagnosis was: acute lymphoblastic leukemia (n = 6), acute myeloid leukemia (n = 1), myelodysplstic syndrome (n = 2), Wiskott-Aldrich syndrome (n = 3), Fanconi anemia (n = 2), adrenoleukodystrophy (n = 1), Langerhans cell histiocytosis (n = 1), chronic granulomatous disease (n = 1), Kostmann syndrome (n = 1), Sandhoff syndrome (n = 1). Pre-transplant conditioning was myeloablative in 9 patients and reduced-intensity in 10 patients. The source of cord blood was family donor in 8 cases or unrelated donor in 11 cases. Histocompatibility 6/6 HLA between donor-recipient was present in 10 cases.Results10/19 (52.6%) children stay alive, median survival 3.1 years (95%CI = 1.4–4.7), probability of 2-year survival was 0.409 ± 0.133. The cause of death was primary graft failure (n = 2), infectious complications (n = 3) or relapse (n = 4). Two children with primary graft failure had subsequent haploidentical transplantation. In multivariate analysis, generalized documented infection was the only predictive adverse factor of overall survival.ConclusionCBT is an important therapeutic option for patients lacking matched donor, offering positive outcome for a half of patients.     

Hepatitis B virus reactivation after heart transplant: Incidence and clinical impact

BackgroundOccult hepatitis B infection consists of persistence of HBV genomes in hepatocytes,absence of serum HBsAg, low/undetectable serum HBVDNA. Reactivation of HBV infection may occur during immunosuppression, but few data are available in heart transplant.ObjectivesWe followed-up heart recipients with or without markers of previous HBV infection,evaluating prevalence of HBV markers, incidence of HBV reactivation and its virological and clinical features.Study designHeart failure patients listed for heart transplant (2007–2013) were screened for current or past HBV infection. Transplanted patients with past HBV infection (anti-HBc+/±anti-HBs+/HBVDNA−) were followed up as cases, and an equal number of HBV negative patients as controls. Virological reactivation was detected by standard real-time and home-made highly sensitive PCR (surface/core HBVDNA regions). Clinical status and progression were assessed by liver histology, ultrasound or elastography.Results67 patients underwent heart transplant, including 4 (5.9%) HBsAg+ subjects. Cases were 11/67 (16.4%). During a median follow-up of 30 months, only one of these 11 patients presented viral reactivation (HBVDNA 209 IU/mL) at month 22, and started antiviral treatment. Four other recipients showed virological events of uncertain significance (sensitive PCR-only intermittently positive). Clinical signs of liver disease were observed in only one case at the last follow-up. A nonsignificant difference in survival was observed between cases and all other heart recipients without prior HBV contact (death rate 5/11 vs 15/52, respectively; p = 0.097).ConclusionsHBV genotypic reactivation in HBsAg−/anti-HBc+/HBVDNA− heart recipients is uncommon. Virological events of uncertain significance occur more frequently; their clinical impact seems to be negligible.     

The detection,treatment of parvovirus B19 infection induced anemia in solid organ transplants: A case series and literature review of 194 patients

BackgroundThere are no optimal diagnostic, treatment and post-infection surveillance strategies for parvovirus B19 infection in solid organ transplantation (SOT) recipients.MethodsWe conducted a retrospective review of all PVB19 infected cases confirmed by qPCR among SOT recipients at our institution over a 3-year period and reviewed the literature from 1990 to 2021.ResultsEight kidney and two heart transplant patients with refractory anemia had PVB19 infection. The viral DNA load in peripheral blood ranged from 2.62 × 10² to 8.31 × 10⁶ copies/mL. Two patients with the lowest PVB19 DNA load only reduced the use of immunosuppressants and anemia was relieved. Eight received intravenous immunoglobulin (IVIG) (ranging from 0.25 to 0.5 g/kg/day). The median time to anemia improvement (hemoglobulin > 100 g/L) was 16 days (8–70 days) after treatment. One patient had a PVB19 relapse and viral DNA load > 1.00 × 10⁸ copies/mL at diagnosis. A total of 86 studies involving 194 SOTs were screened from the literature, and the most common symptom was anemia and low reticulocyte count. PVB19 DNA was detected in all cases. Of that, 91.4% of cases received IVIG, 53.8% received IVIG and immunosuppression reduction, 6.5% of cases showed reduced immunosuppression without IVIG, and 2.1% did not receive any special treatment. The recurrence rate was 17.5%.ConclusionPVB19 infection is a cause of anemia after SOT, and treatment mainly relies on IVIG and/or immunosuppression reduction.