Aims
Multidrug‐resistant (MDR) bacteria are an emerging cause of morbidity and mortality after haematopoietic stem cell transplantation (HSCT). The aim of the study was to analyse the incidence, ...clinical characteristics and survival from bacterial infections (BI) caused by MDR pathogens in paediatric HSCT recipients.
Methods and Results
Among 971 transplanted patients, BI were found in 416 children between the years 2012 and 2017. Overall, there were 883 bacterial episodes, which includes 85·8% after allo‐HSCT and 14·2% after auto‐HSCT. MDR strains were responsible for half of the total number of bacterial episodes. Over 50% of MDR pathogens were Enterobacteriaceae causing mainly gut infections or urinary tract infections.
Conclusions
Regarding HSCT type, we did not find differences in the profile of MDR BI between allo‐ and auto‐HSCT recipients. However, survival in MDR and non‐MDR infections was comparable.
Significance and Impact of the Study
The large sample size enables unique analysis and makes our data more applicable to other paediatric HSCT centres. In the absence of local epidemiological data, presented clinical characteristics of MDR‐caused infections may be used to optimize the prophylactic strategies, early identification of infectious complications of MDR aetiology and thus promptly initiate adequate antibiotic therapy and further improve patients’ outcome.
Clostridium difficile
infection (CDI) is one of the most common causes of nosocomial infectious diarrhea in children during anticancer therapy or undergoing hematopoietic stem cell transplantation ...(HSCT) in Europe. Immunosuppression in these patients is a risk factor for CDI. Malignant diseases, age, acute graft-versus-host disease (aGVHD), HLA mismatch, or use of total body irradiation may play an important role in CDI course. The aim of this study was to evaluate the incidence, course, and outcome of CDI in children treated for malignancy or undergoing HSCT. Between 2012 and 2015, a total number of 1846 patients were treated for malignancy in Polish pediatric oncological centers (PHO group) and 342 underwent transplantation (HSCT group). In PHO group, episodes of CDI occurred in 210 patients (14%). The incidence of CDI was higher in patients with hematological malignancies in comparison to that with solid tumors. Patients with acute myeloblastic leukemia had shorter time to episode of CDI than those with acute lymphoblastic leukemia. Patients over 5 years and treated for acute leukemia had more severe clinical course of disease in PHO group. In HSCT group, CDI occurred in 29 (8%) patients. The incidence of CDI was higher in patients transplanted for acute leukemia. The recurrence rate was 14.7% in PHO and 20.7% in HSCT patients. CDI incidence was highest in patients with hematological malignancies. Most of patients experienced mild CDI. Age < 5 years and diagnosis other than acute leukemia were the positive prognostic factors influencing clinical CDI course.
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.
Highlights
Low incidence of HAdV causing less severe infections not requiring antiviral therapy but with satisfactory outcome within cancer patients.
In allo‐HSCT recipients disseminated disease requiring antiviral drugs and at risk of fatal outcome is more likely to occur.
Monitoring for HAdV in all patients, and especially in those who underwent AdVI prior to HSCT or had MD or MMUD‐HSCT, at early posttransplantation period should be recommended.
We analyzed incidence and profile of infections in children with acute lymphoblastic leukemia (ALL) treated with hematopoietic stem cell transplantation (HSCT) in Polish pediatric HSCT departments, ...over a 2-year period.
Hospital records of 67 patients, who underwent allogeneic HSCT for ALL, were analyzed retrospectively for microbiologically documented infection: bacterial infection (BI), viral infection (VI), and fungal infection (FI). The majority of patients (40/67; 59.7%) underwent HSCT from matched unrelated donors (MUD).
In total, 84 BI in 31 patients, 93 VI in 50 patients, and 27 FI in 22 patients were diagnosed. No differences were found in the frequency of occurrence of BI according to the type of transplant (P = .16); the occurrence of VI was statistically more frequent in MUD transplant recipients as compared with matched sibling donors (MSD) and mismatched related donors (MMFD; P = .001) and there was a trend in MUD patients for the higher occurrence of FI in comparison with MSD and MMFD transplants (P = .08). Regarding disease status, the occurrence of BI, VI, and FI was statistically more frequent in children who underwent transplantation in their first complete remission (CR1), rather than those who underwent transplantation in ≥CR2 (P < .05). In conclusion, infectious complications are an important cause of morbidity in children with ALL treated with allogeneic HSCT and the incidence of infections is high in this group of patients.
•We analyzed the incidence and profile of infections in children with ALL following HSCT.•No differences were found between the occurrence of BI and donor type.•Statistically there was a higher occurrence of VI in unrelated donor transplants.•There was a trend of higher occurrence of FI in unrelated donor transplants.•There was a more frequent occurrence of infectious complications in children who underwent transplantation in CR1.
This nationwide multicentre study analysed the epidemiology of bacterial, viral and fungal infections in paediatric haematopoietic stem cell transplantation (HSCT) and paediatric haematology and ...oncology (PHO) patients over a period of 24 consecutive months, including incidence, hazard risk and outcome of infections as well as occurrence of multidrug-resistant bacteria. During this period, 308 HSCTs were performed and 1768 children were newly diagnosed for malignancy. Compared to PHO, the risk in HSCT patients was significantly higher for all infections (hazard ratio (HR) 2.7), bacterial (HR 1.4), fungal (HR 3.5) and viral (HR 15.7) infections. The risk was higher in allo- than auto-HSCT for bacterial (HR 1.4), fungal (HR 3.2) and viral (HR 17.7) infections. The incidence of resistant bacteria was higher in HSCT than in PHO patients for both G-negative (72.5% vs. 59.2%) and G-positive (41.4% vs. 20.5%) strains. Cumulative incidence of bacterial, fungal and viral infections in HSCT patients was 33.9, 22.8 and 38.3%, respectively. Cumulative incidence of viral infections in allo-HSCT was 28.0% for cytomegalovirus, 18.5% for BK virus, 15.5% for Epstein-Barr virus, 9.5% for adenovirus, 2.6% for varicella zoster virus, 0.9% for influenza, 0.9% for human herpesvirus 6 and 0.3% for hepatitis B virus. Survival rates from infections were lower in HSCT than in PHO patients in bacterial (96.0 vs. 98.2%), fungal (75.5 vs. 94.6%) and most viral infections. In conclusion, the risk of any infections and the occurrence of resistant bacterial strains in allo-HSCT patients were higher than in auto-HSCT and PHO patients, while the outcome of infections was better in the PHO setting.
Background
Infectious complications are a significant cause of hematopoietic stem cell transplantation (HSCT) failure, especially allogeneic HSCT (allo‐HSCT) because of delayed immune reconstitution ...and graft‐versus‐host disease (GVHD) occurrence. Identifying the factors responsible for bacterial infections (BI) in patients undergoing HSCT will provide much more effective empirical antimicrobial treatment in this group of patients.
Objective
The aim of this study was to evaluate the epidemiology and profile of BI in patients after HSCT in 5 centers of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation in 2012–2013.
Patients and methods
In 308 HSCT recipients, we retrospectively analyzed 273 episodes of BI in 113 (36.7%) children aged 0.02–22 years (median age: 7 years), 92 after allo‐HSCT and 22 after autologous HSCT (auto‐HSCT). We assessed incidence of BI in different HSCT types by calculating the Index of Bacterial Infection (IBI) as a ratio of patients with at least 1 BI to all patients who underwent this type of HSCT in the analyzed period. We assessed the profile of BI with particular emphasis on multidrug‐resistant organisms, and impact of underlying disease and of graft‐versus‐host disease on BI episodes.
Results
In the studied group, 273 episodes of BI were diagnosed, including 237 episodes after allo‐HSCT and 36 after auto‐HSCT. Among allo‐HSCT recipients diagnosed with at least 1 BI, the IBI was 0.4 (matched sibling donor‐HSCT 0.3; matched donor‐HSCT 0.4; mismatched unrelated donor MMUD‐HSCT 0.8; P = 0.027) and after auto‐HSCT 0.3 per 1 transplanted patient. In patient after allo‐HSCT because of myelo‐ or lymphoproliferative diseases and bone marrow failures, the major cause of infections was Enterobacteriaceae, while gram‐positive bacteria predominated in the group with primary immunodeficiencies. In all patients after auto‐HSCT, the dominant pathogen of BI were Enterobacteriaceae (P = 0.011). Time from each type of HSCT to infection caused by different pathogens did not differ significantly.
Conclusions
The risk of BI does not depend on the underlying disease, but only on HSCT donor type and is the highest after MMUD‐HSCT procedure. The profile of BI depends on the underlying disease and HSCT donor type, but does not depend on the occurrence of acute GVHD. Gram‐negative bacteria predominated in patients with myelo‐ and lymphoproliferative diseases, while in patients with primary immunodeficiencies gram‐positive strains were predominant.
The analysis of epidemiology, risk factors and outcome of viral infections in children and adolescents after hematopoietic cell transplantation (HCT).
In this multicenter nationwide study a total of ...971 HCT procedures (741 allo-HCT; 230 auto-HCT) over a period of 6 years were analyzed.
During this period 801 episodes of viral infections were diagnosed in 442 patients. The incidence of viral infections was 57.9% in allo-HCT and 4.8% in auto-HCT patients. The most frequent infections after allo-HCT were caused by cytomegalovirus (CMV), polyoma BK virus (BKV) and Epstein-Barr virus (EBV). The majority of infections occurred within the first 4 months after allo-HCT and over 80% required pharmacotherapy or symptomatic therapy. The median time of treatment of specific viral infection ranged from 7 (for EBV) to 24 (for CMV) days. The highest mortality was observed in case of CMV infection. The risk factors for viral infections were allo-HCT, acute leukemia, acute and chronic graft versus host disease (a/cGVHD), and matched unrelated donor (MUD)/mismatched unrelated donor (MMUD)-HCT. The risk factor for death from viral infection were CMV-IgG seropositivity in acute lymphoblastic leukemia recipient, and MUD/MMUD-HCT. The incidence of EBV infection requiring pre-emptive treatment with rituximab in allo-HCT children was 19.3%. In 30.8% cases of EBV infection, these episodes were preceded by other viral infection and treated with antivirals, which did not prevent development of EBV-DNA-emia with need of rituximab treatment in 81.5% cases. In 47.7% of these cases, GVHD was a factor enabling development of significant EBV-DNA-emia during antiviral therapy of other infection.
We have shown that antiviral drugs do not prevent EBV reactivation in allo-HCT pediatric patients.
The analysis of epidemiology, risk factors and outcome of infections in children with malignant bone tumors (MBT) undergoing chemotherapy.
In this retrospective nationwide multicenter cross-sectional ...study, a total number of 126 children with MBT including 70 with Ewing sarcoma (ES) and 56 with osteosarcoma (OSA) were screened for infections over a period of 72 consecutive months.
The risk of infection was 7.15-fold higher in patients with ES as compared to the OSA group, especially concerning bacterial infections (4.1-fold increase risk). Bacterial infections occurred in 74.3% patients with ES and in 41.1% with OSA. The median time from diagnosis to first infection was 4.9 months. 33.0% of bacterial episodes were diagnosed as bloodstream (BSI), 31.1% as gastrointestinal tract, 30.1% as urinary tract infection. Infection-related mortality (IRM) from bacterial infection was 6% and 15% in ES and OSA patients, respectively. Cumulative incidence was 7.1% for invasive fungal disease and 6.3% for viral infections. The only significant risk factor for IRM was time to infection ≥5 months since the beginning of chemotherapy. All patients who have died from infection had BSI and were in neutropenia.
Infections in the children with MBT in our study occurred with high frequency, especially in patients with ES. The most frequent were bacterial infections, while fungal and viral infections were episodic. Among the bacterial infections, bloodstream, urinary tract and gastrointestinal tract infections occurred with similar frequency. All deceased patients died due to BSI. Bacterial infection occurring ≥5 months since the beginning of chemotherapy was a risk factor for death.
This nationwide multicentre study analysed the epidemiology of bacterial, viral and fungal infections in paediatric haematopoietic stem cell transplantation (HSCT) and paediatric haematology and ...oncology (PHO) patients over a period of 24 consecutive months, including incidence, hazard risk and outcome of infections as well as occurrence of multidrug-resistant bacteria. During this period, 308 HSCTs were performed and 1768 children were newly diagnosed for malignancy. Compared to PHO, the risk in HSCT patients was significantly higher for all infections (hazard ratio (HR) 2.7), bacterial (HR 1.4), fungal (HR 3.5) and viral (HR 15.7) infections. The risk was higher in allo- than auto-HSCT for bacterial (HR 1.4), fungal (HR 3.2) and viral (HR 17.7) infections. The incidence of resistant bacteria was higher in HSCT than in PHO patients for both G-negative (72.5% vs. 59.2%) and G-positive (41.4% vs. 20.5%) strains. Cumulative incidence of bacterial, fungal and viral infections in HSCT patients was 33.9, 22.8 and 38.3%, respectively. Cumulative incidence of viral infections in allo-HSCT was 28.0% for cytomegalovirus, 18.5% for BK virus, 15.5% for Epstein-Barr virus, 9.5% for adenovirus, 2.6% for varicella zoster virus, 0.9% for influenza, 0.9% for human herpesvirus 6 and 0.3% for hepatitis B virus. Survival rates from infections were lower in HSCT than in PHO patients in bacterial (96.0 vs. 98.2%), fungal (75.5 vs. 94.6%) and most viral infections. In conclusion, the risk of any infections and the occurrence of resistant bacterial strains in allo-HSCT patients were higher than in auto-HSCT and PHO patients, while the outcome of infections was better in the PHO setting.
Background
Hodgkin (HL) and non‐Hodgkin lymphoma (NHL) represent a spectrum of lymphoid malignancies that are often curable with currently applied treatment regimens; however, 15%‐30% of lymphoma ...patients still suffer from relapsed or refractory (rel/ref) disease. Although hematopoietic stem cell transplantation (HSCT) improves outcomes of second‐line therapy for lymphoma in childhood, the complication rates in this group of patients, especially infectious complications (IC), remain unclear.
Objective
The aim of this population‐based cohort study was a retrospective analysis of incidence, epidemiology and profile of bacterial infections (BI), invasive fungal disease (IFD), and viral infections (VI) in primary or rel/ref lymphoma patients, both HL and NHL.
Patients and methods
We subdivided lymphoma patients into three groups: patients with primary conventional chemotherapy/radiotherapy regimens (group A), patients with rel/ref lymphoma treated with second‐line chemotherapy (group B), and rel/ref lymphoma patients who underwent HSCT (group C). The medical records of the patients were biannually reported by each pediatric oncology center, and the data were analyzed centrally.
Results
Within 637 patients with primary lymphoma, at least one IC was diagnosed in 255 (40.0%), among 52 patients with rel/ref lymphoma 24 (46.2%) ICs were observed, and in transplanted group, 28 (57.1%) out of 49 children were diagnosed with IC (P = .151). The distribution of etiology of IC differed between the patient groups (A, B, C), with a predominance of BI in group A (85.6% vs 72.0% and 47.9%, respectively), VI in group C (9% and 16.0% vs 46.6%, respectively), and IFD in group B (5.4% vs 12.0% vs 5.5%, respectively). Overall, 500 (68.0%) episodes of bacterial IC were diagnosed in the entire group. Apart from HL patients treated with chemotherapy, in all the other subgroups of patients Gram‐positives were predominant. The rate of multidrug‐resistant bacteria was high, especially for Gram‐negatives (41.1% in group A, 62.5% in group B, and 84.6% in group C). The infection‐related mortality was comparable for each group.
Conclusions
The incidence of IC was comparable during first‐ and second‐line chemotherapy and after HSCT, but their profile was different for primary or re/ref lymphoma and depended on the type of therapy.
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