Quantification of adenovirus DNA in unrelated donor hematopoietic stem cell transplant recipients

BACKGROUND: Adenovirus (AdV) infection is a life threatening condition in immunosuppressed patients. Quantitative AdV assays can improve the clinical management of these patients. OBJECTIVES: To evaluate quantitative measurement of AdV DNA with PCR in blood from hematopoietic stem cell transplant (HSCT) recipients. STUDY DESIGN: Quantitative PCR was used to measure viral DNA levels of AdV in consecutive blood samples from 40 HSCT recipients (27 adults and 13 children) during a 1-year post-engraftment period. All patients received grafts from unrelated donors and were given anti-T-cell antibodies in the conditioning regimen. RESULTS: In the group of 40 patients, six (15%) had detectable AdV DNA in blood for different lengths of time. None of these six patients suffered from severe graft-versus-host disease. In three of the patients a high AdV viral load (>10,000copies/mL) was detected, one of whom also had high viral load of EBV and CMV and one of EBV only. These three patients died within 2 months after detection of ADV viremia. A low AdV viral load (<500copies/mL) was detected in three surviving patients and they did not have concomitant high viral load of neither CMV nor EBV. CONCLUSIONS: AdV viremia was present in 15% of the HSCT recipients and a high AdV viral load was associated with fatal outcome. Screening for AdV DNA with quantitative PCR in blood may be of clinical importance in allogeneic HSCT recipients in order to prevent severe clinical virological complications.     

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.     

Infections due to alphaherpesviruses in early post-transplant period after allogeneic haematopoietic stem cell transplantation: Results of a 5-year survey

BackgroundInfections caused by human α-herpesviruses usually have a benign course with recurrencies. However, they may become dangerous in immunocompromised hosts. In this case, molecular methods constitute a reliable diagnostic tool enabling rapid assessment of the efficacy of antiviral treatment strategies.ObjectivesWe estimated the frequency of alphaherpesviral DNAemia and the viral load during early post-transplantation period after alloHSCT; we also analyzed association of the DNAemia and chosen parameters of the patients.Study designA cohort of 190 alloHSCT recipients from two hospitals in Warsaw, Poland, was examined weekly during 100-day early post-transplantation period using quantitative real time PCR assays. A total of 2475 sera samples were evaluated for the presence of α-herpesviral DNA in patients, of whom 117 (62%) received unrelated grafts, while the remaining 73 (38%) received grafts from sibling donors. All patients received standard antiviral prophylaxis with acyclovir. In the examined group, anti-HSV-1, anti-HSV-2 and anti-VZV IgGs were examined prior to transplantation,ResultsWithin the study period, DNA of α-herpesviruses was detected in 44 patients (23.2%). Most patients tested positive for HSV-1 DNA (43 patients, 22.6%), single patient for HSV-2, and no patient positive for VZV. Clinical symptoms such as pneumonia, skin changes, elevated levels of aminotransferases were observed in five patients, four of these patients presented symptoms of GvHD at the same time. (2,6%). Statistics shows that GvHD (P < 0.001) and matched unrelated donor as a source of HSCT (P = 0.048) are associated with the development of HSV-1 DNAemia.ConclusionsAlthough our data demonstrate frequent reactivation of HSV-1 in the early post-transplant period, the rate of symptomatic infections was low. We did not find association between HSV-1 viremia and mortality, but significant association with GvHD and donor source was observed.     

Risk factors and clinical consequences of human herpesvirus 7 infection in paediatric haematopoietic stem cell transplant recipients

Human herpesvirus 7 (HHV-7) is the least studied beta-herpesvirus in transplant settings. This prospective study examined the activity of HHV-7 during the first 12 weeks post-stem cell transplant in 59 paediatric patients. The presence of HHV-7, human cytomegalovirus (HCMV) and human herpesvirus 6 (HHV-6) in blood was monitored weekly by a multiplex nested polymerase chain reaction. Overall, 33 (55.9%) patients had one or more surveillance blood sample(s) positive for HHV-7. In contrast to HCMV and HHV-6, no obvious peak time of reactivation was observed for HHV-7. The occurrence of HHV-7 DNAaemia showed a significant negative association with HHV-6 (P=0.022), but with no association with HCMV. A significant higher positive rate for HHV-7 was found in autologous versus allogeneic (P=0.002), and in peripheral blood versus umbilical cord/marrow (P<0.001) transplant. Acyclovir had no effect, whereas ganciclovir was associated with a lower rate of HHV-7 reactivation (P=0.009). One patient died of HHV-7 associated brain stem encephalitis. The administration of colony stimulating factor, occurrence of acute graft versus host disease, time to neutrophil and platelet engraftment showed no significant association with the occurrence of HHV-7 DNAaemia.     

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.     

Infections in liver and lung transplant recipients: a national prospective cohort

Infections are a major complication of solid organ transplants (SOTs). This study aimed to describe recipients’ characteristics, and the frequency and etiology of infections and transplant outcome in liver and lung SOTs, and to investigate exposures associated to infection and death in liver transplant recipients. The study population included recipients of SOTs performed in Italy during a 1-year period in ten Italian lung transplant units and eight liver transplant units. Data on comorbidities, infections, retransplantation, and death were prospectively collected using a web-based system, with a 6-month follow-up. The cumulative incidence of infection was 31.7% and 47.8% in liver and lung transplants, respectively, with most infections occurring within the first month after transplantation. Gram-negatives, which were primarily multidrug-resistant, were the most frequent cause of infection. Death rates were 0.42 per 1000 recipient-days in liver transplants and 1.41 per 1000 recipient-days in lung transplants. Infection after SOT in adult liver recipients is associated to an increased risk of death (OR?=?13.25; p-value?<?0.001). Given the frequency of infection caused by multidrug-resistant microorganisms in SOT recipients in Italy and the heavy impact of infections on the transplant outcome, the reinforcement of surveillance and control activities to prevent the transmission of multidrug-resistant microorganisms in SOT recipients represents a priority. The implementation of the study protocol in liver and lung transplant units and the sharing of results have increased the awareness about the threat due to antimicrobial resistance in the country.     

Diagnostic value of quantitative PCR for adenovirus detection in stool samples as compared with antigen detection and cell culture in haematopoietic stem cell transplant recipients

Adenovirus (AdV) infections constitute a significant cause of morbidity and mortality during haematopoietic stem cell transplantation. Recent guidelines recommend repeated screening for AdV in whole blood (WB), with quantitative PCR (qPCR) as the reference standard. Despite pre-emptive antiviral treatment based on qPCR in WB, the mortality rate after disseminated AdV infection remains very high. The aim of our study was to advance early screening for AdV, using a standardized method, so as to enable the earlier initiation of antiviral treatment or adoptive immunotherapy. The diagnostic value of AdV DNA quantification in stool samples was investigated retrospectively and compared with antigen detection and cell culture in 21 patients with AdV infection, from 182 patients followed in the Transplant Unit of Nancy University Hospital Centre, including 18 patients with systemic infection. In 16/18 patients with positive AdV viraemia, AdV DNA was present in stool samples earlier than in WB (median, 42 days; range, 3–199 days), whereas both antigen detection and cell culture were still negative for 11/18 patients with systemic AdV infection. The course of AdV viral loads in stool samples was predictive of adenoviraemia (sensitivity, 89%). Very late and lethal AdV infections were observed in cord blood transplant recipients, and would have been detected much earlier with the use of qPCR on stool samples. This study confirmed that quantification of AdV in stool samples by qPCR is beneficial for the management of transplant recipients, with or without antigen detection.     

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.     

Hematopoietic stem cell transplantation with latently infected donors does not transmit virus to immunocompromised recipients in the murine model of cytomegalovirus infection

Hematopoietic stem cell transplantation (HSCT) bears a risk of reactivating latent cytomegalovirus (CMV) in either the transplanted hematopoietic donor cells or in parenchymal and stromal tissue cells of the immunocompromised recipient, or in both. While reactivated human CMV in recipients of organ transplantations is frequently the virus variant of the donor, this is not usually the case in HSCT recipients. Here we have used experimental sex-mismatched HSCT in the BALB/c mouse model to test if latent murine CMV from CMV-immune donors is transmitted with bone marrow cells to naive immunocompromised recipients.     

Hepatitis B reactivation in HBsAg-negative/HBcAb-positive allogeneic haematopoietic stem cell transplant recipients: risk factors and outcome

HBsAg-negative/HBcAb-positive haematopoietic stem cell transplant (HSCT) recipients are at high risk of hepatitis B virus (HBV) reactivation. Allogeneic HSCT recipients from years 2000 to 2010 were evaluated in order to study the impact of being HBsAg-negative/HBcAb-positive in this population. Overall, 137 of 764 patients (18%) were HBsAg-negative/HBcAb-positive before HSCT. Overall survival, non-relapse mortality (NRM), acute and chronic graft-vs.-host disease were similar in HBcAb-positive and HBcAb-negative patients. Reactivation occurred in 14 patients (10%) within a median of 19 months after HSCT (range 9-77). Cause-specific hazard for reactivation was decreased in the case of an HBV-immune/exposed donor (HR_adjusted = 0.12; 95% CI, 0.02-0.96; p 0.045) and increased in patients who received rituximab treatment (HR_adjusted = 2.91; 95%CI, 0.77-10.97; p 0.11). Competing risk analyses documented a protective role of an HBV-immune/exposed donor (p 0.041) and an increased probability associated with the length of treatment with cyclosporine (p <0.001) and treatment with rituximab (but not with low-dose rituximab prophylaxis, p <0.001 at each landmark point). No differences in overall survival and NRM were found between patients with and without HBV reactivation. The donor’s immunity was independently and consistently associated with a decreased risk of HBV reactivation, while rituximab and cyclosporine treatments increased the probability.     

获得性免疫缺陷综合征（AIDS）合并播散性弓形虫病尸检的病理学研究

报道美国纽约地区９例播散性弓形虫病尸检材料，均有脑部病变，８例累及心脏，４例累及肺脏，尚见胰腺、消化道、甲状腺、淋巴结、泌尿生殖器官等受累。其中弓形虫性脑炎９例，心肌炎４例，肺炎３例，胰腺炎２例。仅脑炎、肺炎产牛症状，经脑ＣＴ扫描、弓形虫抗体测定提示本病，并经涂片、骨髓活检和尸检证实，以查见弓形虫为依据。临床以神经精神症状和肺部感染症状为主。病变分为静止（潜伏）、组织坏死、炎症反应及增生修复四种状态，强调囊型弓形虫形态学识别的诊断意义。     

A prospective longitudinal study of BK virus infection in 120 Czech renal transplant recipients

Polyomavirus BK (BKV) is a common human polyomavirus that rarely causes clinical symptoms in immunocompetent individuals. However, BK virus reactivation occurs in 20-40% of kidney transplant patients and 1-10% of cases present with BK virus-associated nephropathy (BKVN) and reduced kidney allograft survival. In this study, 120 consecutive renal allograft recipients were monitored for BK virus replication by real-time PCR (qPCR) in the blood and urine during the first year post-transplantation and risk factors for BK viremia, viruria, and polyoma BKV-associated nephropathy were evaluated. Receiver operating characteristic curve analysis was used to determine the cutoff points for assessing the risk of developing BKVN. In total, 1,243 samples were tested. BK-DNAuria >10(7) copies/ml and BK-DNAemia >10(4) copies/ml were found in 25.8% and 5% of the samples screened, respectively, during the 12 month follow-up period. BKVN was confirmed histologically in 3/120 patients and viremic patients were treated with dialysis for longer time periods and had higher levels of panel [corrected] reactive antibodies. Patients with viruria were also treated longer with dialysis and had impaired graft function 12 months post-transplantation. Patients with sustained viruria exhibited more acute rejection episodes than patients with transient viruria. Using receiver operating characteristic curve analysis, the cutoff point for viremia and viruria was redefined to 10(3) copies/ml serum for BK viremia and a cutoff point of 6.7 × 10(7) copies/ml in urine. In conclusion, polyoma BK viremia and viruria are frequent findings in kidney transplant recipients that warrant intensive monitoring as a means of preventing graft failure [corrected].     

Clonotypic analysis of T cell reconstitution after haematopoietic stem cell transplantation (HSCT) in patients with severe combined immunodeficiency

Haematopoietic stem cell transplantation (HSCT) is performed for treatment of a broad spectrum of illnesses. Reconstitution of an intact immune system is crucial after transplantation to avoid infectious complications, and above all, the establishment of T cell receptor (TCR) diversity is the most important goal in the procedure. Until recently, little has been known of the mechanism of T cell reconstitution in the very early period after HSCT. In this study, we analysed TCR repertoires sequentially in four patients with severe combined immunodeficiency (SCID) before and after HSCT. In all patients, the TCR repertoires were extremely abnormal before HSCT, whereas after transplantation there was progressive improvement in TCR diversity, based on analysis of the TCR Vbeta repertoire and CDR3 size distributions. Somewhat unexpectedly, there was a significant but transient expansion of TCR diversity 1 month after transplantation in all cases. Clonotypic analysis of TCRs performed in one case showed that many T cell clones shared identical CDR3 sequences at 1 month and that the shared fraction decreased progressively. These results indicate that early expansion of TCR diversity may reflect transient expansion of pre-existing mature T cells from the donor blood, independent of de novo T cell maturation through the thymus.     

A pilot study of tacrolimus and mycophenolate mofetil graft-versus-host disease prophylaxis in childhood and adolescent allogeneic stem cell transplant recipients.

Tacrolimus (FK506)/mycophenolate mofetil (MMF) has been demonstrated to be an effective salvage therapy for steroid-resistant chronic graft-versus-host disease (GVHD), but its effectiveness as prophylaxis for acute GVHD (aGVHD) is unknown. We investigated the safety and efficacy of FK506/MMF in preventing aGVHD and sparing the use of methotrexate and methylprednisolone in childhood and adolescent allogeneic stem cell transplant (AlloSCT) recipients. Thirty-four childhood and adolescent patients (median age, 7 years; range, 0.5-21 years; 24 males and 10 females) undergoing 37 AlloSCTs for malignant (n = 22) and nonmalignant (n = 12) disorders received FK506 (0.03 mg/kg/d by continuous intravenous infusion) and MMF (15 mg/kg per dose orally or intravenously twice daily). Stem cell sources included 22 umbilical cord blood donors (21 unrelated and 1 related), 6 related bone marrow donors, and 9 related peripheral blood donors. Malignant diagnoses included 7 acute lymphoblastic leukemias, 3 acute myeloid leukemias, 1 acute promyelocytic leukemia, 2 non-Hodgkin lymphomas, 4 Hodgkin diseases, 3 chronic myeloid leukemias, and 2 neuroblastomas; nonmalignant diagnoses included 2 beta-thalassemias, 1 sickle cell disease, 4 aplastic anemias, 1 Wiskott-Aldrich syndrome, 1 Hurler syndrome, 2 hemophagocytic lymphohistiocytoses, and 1 myelodysplastic syndrome. The probability of developing grade > or =II aGVHD was 45.4% +/- 9.7% (7 related bone marrow/related peripheral blood; 5 umbilical cord blood), and for chronic GVHD it was 38.1% +/- 19.7%. FK506/MMF was well tolerated. Three patients had grade III to IV neurotoxicity (disorientation and leukoencephalopathy); 4 patients developed grade III to IV nephrotoxicity (all received concomitant nephrotoxins). Patients who achieved target mycophenolic acid levels (1.0-3.5 microg/mL) before day +30 had a significantly reduced incidence of developing grade >/=II aGVHD (16.7% +/- 15.2% versus 100%; P <.02). These results suggest that FK506/MMF is well tolerated and may be a safe and effective methotrexate- and methylprednisolone-sparing alternative GVHD prophylaxis regimen after AlloSCT. Further pharmacokinetic and pharmacodynamic studies are ongoing in pediatric and adolescent AlloSCT recipients to define optimal MMF dosing.     

Effectiveness of second-dose varicella vaccination as post-exposure prophylaxis: a prospective cohort study

ObjectivesAlthough administration of a second dose of varicella vaccine (2^nd-dose VarV) to individuals who have previously received one-dose VarV has been recommended as a post-exposure prophylaxis (PEP) strategy for outbreak control, the effectiveness of this strategy remains unclear. We evaluated the vaccine effectiveness (VE) of 2^nd-dose VarV as PEP among students involved in 129 varicella outbreaks in Shanghai, China from 2013 to 2016.MethodsStudents who had received one-dose VarV more than 5 years prior to varicella exposure were eligible to receive 2^nd-dose VarV as PEP. We evaluated the VE using the following formula: VE = (1 – hazard ratio (HR)) × 100%.ResultsA total of 6762 students were eligible for 2^nd-dose VarV, of whom 58.6% accepted PEP after varicella exposure. The adjusted VE of 2^nd-dose VarV as PEP was 77% (95% confidence interval 64–85%). In addition, the adjusted VE of 2^nd-dose VarV as PEP in affected classrooms with high vaccine uptake was higher than that in classrooms with lower vaccine uptake (87% vs. 69%). The adjusted VE was also higher in students who received 2^nd-dose VarV within 3 days of exposure than those who received it more than 3 days post exposure (77% vs. 64%).ConclusionsThese Results suggest that administration of 2^nd-dose VarV as PEP is an appropriate intervention for outbreak control in countries where two-dose VarV has not been adopted.     

Human herpesvirus 6 infection in autologous bone marrow transplant recipients: a prospective study

After primary infection in early life, human herpesvirus 6 (HHV-6) remains latent in the body and may reactivate in subjects with poor immune status. A 180-day longitudinal study of HHV-6 infection was carried out in 23 autologous bone marrow transplant recipients to evaluate reactivation of HHV-6; two of these patients underwent a double transplant. The patients were monitored prospectively for HHV-6 DNA in peripheral blood mononuclear cells (PBMC) by hot start nested PCR. Positive samples were typed by the enzymatic restriction protocol. Positive plasma samples were also tested for HHV-6 DNA. Antibodies against HHV-6 were measured by immunofluorescence. Five and two out of 23 patients had intermittent and persistent positivity to HHV-6 DNA in PBMCs, respectively; four patients carried variant B, and the other three patients both A and B. None of the respective plasma samples were positive. Two patients were positive for HHV-6 antibodies. Since the significance of HHV-6 DNA in PBMCs is unclear, these findings do not necessarily indicate active infection but may be due to mild immunosuppression in autologous BMT recipients.     

Virus infections in bone marrow transplant recipients: a three year prospective study.

Over three years 81 consecutive bone marrow transplant recipients (32 allogeneic and 49 autologous) who received prophylaxis with acyclovir, were studied for symptomatic virus infection. Thirty nine infections were documented in a total of 28 patients. Thirty two infections were mild, five were moderately severe, and two were severe. Cytomegalovirus infection occurred in only six allogeneic recipients. Herpes simplex virus and varicella zoster virus infections occurred infrequently. Seven patients who were considered at the time of death to have died due to an infectious cause were studied virologically at necropsy. In only one patient was a virus infection thought to have been the cause of death. Prophylaxis with acyclovir may have influenced the rate and clinical prominence of herpes virus infections. In this study viruses were considered to have had a relatively minor role in causing morbidity and mortality.     

The association of cytomegalovirus infection and cytomegalovirus serostatus with invasive fungal infections in allogeneic haematopoietic stem cell transplant recipients: a systematic review and meta-analysis

BackgroundIn allogeneic haematopoietic stem cell transplant (allo-HSCT) recipients, the inter-relationship between post-transplant cytomegalovirus (CMV) and subsequent invasive fungal infections (IFIs) is conflicting and the association of CMV serostatus with IFIs has not been evaluated.ObjectivesTo determine the relationship between CMV infection/serostatus and IFIs in allo-HSCT populations.Data sourcesA systematic literature search was conducted from existence until 11 July 2021 using Medline, Embase and ISI Web of Science databases.Study eligibility criteriaCross-sectional, prospective cohort, retrospective cohort and case–control studies that reported allo-HSCT recipients with CMV and without CMV who developed or did not develop IFIs after CMV infection.ParticipantsAllo-HSCT recipients.InterventionsNot applicable.MethodsA systematic search, screening, data extracting and assessing study quality were independently conducted by two reviewers. The Newcastle–Ottawa scale was used to assess risk of bias. data were analysed using the pooled effect estimates of a random-effects model.ResultsA total of 18 and 12 studies were included for systematic review and meta-analysis, respectively. Post-transplant CMV infection significantly increased the risk of IFIs with a pooled hazard ratio (pHR) of 2.58 (1.78, 3.74), I² = 75%. Further subgroup analyses by timing of IFIs, CMV definitions, study continents, study design and adjustment of effect estimates showed that post-transplant CMV infection consistently increased the risk of subsequent IFIs. High-risk CMV serostatus (D–/R+) increased the risk of IFIs with a pooled odds ratio (OR) of 1.33 (1.04, 1.71), I² = 0%, but low-risk CMV serostatus (D–/R–) decreased the risk of IFIs with a pOR of 0.69 (0.55, 0.87), I² = 0%.ConclusionsPost-transplant CMV infection and high-risk CMV serostatus increased the risk of IFIs, but low-risk CMV serostatus decreased risk of IFIs among allo-HSCT recipients. Further studies are needed to identify at-risk allo-HSCT recipients as well as to focus on fungal diagnostics and prophylaxis to prevent this fungal-after-viral phenomenon.     

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.