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.
Four hundred and ninety‐five patients (390 and 105 grafted from unrelated and sibling (SIB) donors, respectively) and their donors were analyzed for the impact of interleukin‐10 (IL‐10) promoter ...genotype rs18000896 (−1082 G/A), rs18000871 (−819 C/T) and rs18000872 (−592 C/A) on the outcome of hematopoietic stem cell transplantation (HSCT). Patients having ACC haplotype were at a lower risk of acute graft versus host disease (aGvHD, grade > I) if transplanted from human leukocyte antigen (HLA) well‐matched (10/10) unrelated donors (20/135 vs 39/117, P < 0.001, Pcorr = 0.002), which was not seen if patients were transplanted from either sibling (SIB) or poorly matched (<10/10) unrelated donors (MUD). In addition, GCC haplotype positive recipients of unrelated donor transplants tended to be more susceptible to aGvHD (68/199 vs 39/169, P = 0.019, Pcorr = 0.057). Multivariate logistic regression analysis in the MUD transplanted group showed that donor–recipient human leukocyte antigen (HLA) mismatch odds ratio (OR) = 3.937, P = 0.001 and a lack of ACC haplotype in recipients (OR = 0.417, P = 0.013) played a significant role as independent risk factors of aGvHD grade > I. ACC carriers had higher proportions of FoxP3+ lymphocytes gated in CD4+ lymphocytes as compared with patients with other IL‐10 haplotypes. It was seen at the time of hematological recovery (mean ± SEM: 3.80 ± 0.91% vs 2.06 ± 0.98%, P = 0.012) and 2 weeks later (5.32 ± 0.87% vs 2.50 ± 0.83%, P = 0.013); −592 C/A polymorphism was separately analyzed and it was found that AA homozygotes tended to have a higher incidence of aGvHD (8/15 vs 116/456, P = 0.034) and low proportions of FoxP3 CD4+ lymphocytes in blood (0.43 ± 0.22% vs 4.32 ± 0.71%, P = 0.051) measured 2 weeks after hematological recovery. Functional IL‐10 polymorphism associated features influenced the risk of aGvHD with a positive effect of ACC on the pool of Treg in blood.
Allogeneic or autologous haematopoietic stem cell transplantation (HSCT) is an established mode of treatment of different diseases. Loss of protective immunity to pathogens has been consistently ...demonstrated in patients referred to HSCT. Impairment of humoral and cell-mediated immunity is commonly seen after transplantation. The degree of immunodeficiency is determined by many factors, particularly by the type of disease and transplant, the presence of graft-versus-host disease (GvHD) or ongoing immunosuppressive treatment. The aim of the study was to evaluate 1) immunogenicity of a revaccination schedule in pediatric HSCT recipients 2) quality of recipient immune reconstitution and protection against ordinary pathogens. Patients and methods: Twenty one patients (pts) 1.4-22 (average 7.8) years old, 13 boys and 8 girls after autologous (11, 52%) and allogeneic (10, 48%) HSCT were included in revaccination program. Indications to HSCT were: solid tumors--11, hematological malignancies-5, immunodeficency states--3 and aplastic anemia 2 pts. Time interval between HSCT and begining of vaccination protocol was 0.8-4 (av. 1.5) years. Vaccines used in protocol were as follows: diphtheria and tetanus toxoids, pertussis (for patients <7 years old), HBV, VZV, Haemophilus influenzae type b conjugate, 23-valent pneumococcal polysaccharide, inactivated influenza, inactivated polio and attenuated measles-mumps-rubella vaccines. Plasma samples to determine specific antibodies by ELISA tests were collected before and after vaccinations. Results: With the exception of one patients presented with repeated fevers, lymph nodes enlargement, muscles and joints pain, no important side effects of vaccinations were observed. A meningococcial meningitis developed in one patient who refused vaccinations. Plasma antibody concentrations before and after vaccinations were as follows: antidiphteria (0-300, mean 62.5; 100-5800, mean 1838), antitetanous (0-500, mean 133; 826-5500, mean 3483) and antiHBV (0-135, mean 33; 317-1000, mean 532) IU/ml. Conclusions: 1) systemic immunization is necessary at appropriate time intervals following transplantation to re-establish immunity. 2) a significant increase of antibodies titer after HBV, diphtheria and tetanus toxoids was detected. 3) vaccinations in patients after HSCT are efficient and well tolerated. 4) a delay in begining of vaccination can result in life threatening complications. Ministry of Science RP, grant number 501/G/640.
Conventional chemioterapy for non-Hodgkin's lymphoma (NHL) are very successful-up to 70-90% children make a full recovery. However, prognosis for patients with refractory and recurrent disease are ...not so much promising. Objective: we retrospectively analyzed the therapeutic efficancy and safety of allo SCT in children with recurrent or resistant NHL. Patients: In four pediatric BMT centers in Poland, between 2000 and 2008, twenty three children with NHL received allo SCT. There were 17 males and 6 girls, aged from 6,1 to-17,2 years (median 13,5). Among those children 13 suffered from B-NHL, 7 -from T-NHL and 3 children had Large Cell Anaplastic Lymphoma (LCAL). At the moment of SCT 10 patients were in second complete remision (2CR), 4- in 1 CR, 3 children--in greater than or equal to 2 CR, 5 patients had partial remision (PR) and one boy had progressive disease resistant to therapy. Conditioning before SCT was myeloablative in all and consisted of total body irradiation (TBI) with chemotherapy in 16 children and only chemotherapy--in 7 procedures. Thirteen children were transplanted from matched sibling donors (MSD) and ten-from matched unrelated donors (MUD). Results: 22/23 patients engrafted, and in 1 child autologous recovery was observed. 11/23 children are alive (48%) and they are still in CR. Among those patients: 8 were in 2CR, 2-in 1CR and 1-in 1PR befor SCT. 12/23 patients died: 4 children (17%) died due to relapse, 3-due to progression and 5 children (22%)- due to transplantation-related complications (TRM). Overall survival (OS) was 48%, with the observation time from 14 to 104 months (median 40). Conclusions: Our study suggests, that allo SCT may improve prognosis in children with recurrent NHL, when transplantation is being performed in status CR of disease. However, allo SCT doesn't improve results in patients with partial remision. The conclusion should be evalueted in a larger series of patients. Allo SCT in children with resistant or recurrent NHL is burdened with high risk of complications in those heavily pre-treated patients.
A Pleistocene valley-fill alluvial succession deposited in the Kleszczow Graben, central Poland, has been studied in the Belchatow openpit mine. The succession, palynologically documented to ...represent the Drenthe/Warthe interstadial, consists of three alluvial complexes whose component lithofacies associations indicate a fluvial system evolving from temperate-climate meandering river to transitional-type shallow braided network, to periglacial well-developed braided river influenced by aeolian sand supply. The study suggests that the abundance of fine-grained overbank deposits, occurrence of peats/palaeosols and fining-upward cyclothems are diagnostic attributes of perennial meandering river alluvium, which may indicate temperate climatic conditions. Periglacial braided river alluvium is recognizable by an admixture of wind-derived sand grains with aeolian surface textures and by the occurrence of ice-wedge features, indicative of cold climatic conditions. The distinction between the two basic types of alluvium is aided by the analysis of architectural elements and palaeocurrent directional data. The study demonstrates that sedimentological facies analysis can be a useful tool for the recognition of palaeoclimatic changes in Pleistocene alluvial successions.
The effects of an intravenous infusion of physiological saline on plasma atrial natriuretic peptide (ANP), guanosine 3' 5' monophosphate (cGMP) concentrations, and on urinary cGMP and sodium ...excretion were studied in 13 patients with essential hypertension, class I according to WHO criteria, and in 10 healthy subjects. It was found that the groups did not differ as to basal and infusion-induced plasma ANP and cGMP and basal urinary cGMP and sodium excretion, but the sodium chloride infusion resulted in a significantly greater urinary cGMP and sodium excretion and creatinine clearance in hypertensive than in control subjects. The results of this study demonstrate that patients with essential hypertension respond to an intravenous sodium chloride load not only with exaggerated natriuresis, but also with augmented urinary cGMP excretion. The latter finding may in part be due to a greater glomerular filtration of cGMP, but increased renal contribution cannot be excluded. Apart from the possible stronger intrarenal effect of ANP on cGMP production in patients with hypertension, independent direct effect of volume expansion on cGMP excretion and modified activity of other cGMP generating systems may all be responsible for the higher urinary cGMP excretion in essential hypertension.
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.
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.
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