Francesca Fioredda

A Prospective Study on the Epidemiology of Febrile Episodes during Chemotherapy-Induced Neutropenia in Children with Cancer or after Hemopoietic Stem Cell Transplantation

BACKGROUND The purpose of our study was to evaluate the incidence and clinical characteristics of febrile episodes during neutropenia following chemotherapy in children with cancer. PATIENTS AND METHODS A prospective, 3-year single-center observational study of periods of neutropenia was performed. Epidemiology and clinical diagnoses of febrile episodes occurring during the neutropenic periods were evaluated, taking into consideration different categories of anticancer treatment based on the type of tumor and phase of therapy. RESULTS A total of 703 febrile episodes were observed during 614 (34%) of 1792 neutropenic periods (34%), for a total of 28,001 days at risk, accounting for a rate of 0.76 episodes per 30 days at risk. The highest proportions of neutropenic periods with primary febrile episodes were observed after autologous hemopoietic stem cell transplantation (58%), aggressive treatment for acute leukemia or non-Hodgkin lymphoma (48%), and allogeneic hemopoietic stem cell transplantation (44%); the lowest proportion (9%) was observed during maintenance chemotherapy for acute leukemia (P<.001). The most frequent clinical diagnosis was fever of unknown origin (in 79% of cases), followed by bacteremia (10%); invasive mycosis was diagnosed in only 2% of cases. CONCLUSIONS The overall incidence of febrile neutropenia and severe infectious complications in children with cancer is low, with differences according to the aggressiveness of chemotherapy. This fact must be considered when designing clinical trials on the management of infectious complications in children with cancer.

HIV-1 transmission through breast-milk: appraisal of risk according to duration of feeding.

ObjectivesTo estimate the risk of HIV-1 transmission through breast-milk in children born to infected mothers, and to determine the relationship between duration of breast-feeding and risk. Design and methodsThe study population included 168 breast-fed and 793 bottle-fed children born to seropositive mothers. All subjects were enrolled and followed-up in the Italian Register for HIV Infection in Children; HIV serostatus was defined in all children. Multivariate analysis was performed using a logistic regression model. Independent variables included biological factors (duration of breast-feeding, gestational age, clinical condition of mother at delivery, mode of delivery, birth-weight and sex). Year of birth and age when HIV infection was diagnosed were also considered in the analysis attempting to control for possible selection biases. ResultsBreast-feeding increased the risk of HIV-1 transmission. The estimated adjusted odds ratio for 1 day of breast- versus bottle-feeding was 1.19 (95% confidence interval, 1.10–1.28). The infection odds ratio of breast- versus bottle-feeding increased with the natural logarithm of the duration of practice. ConclusionsThese results are the first to provide an appraisal of the additional risk of HIV-1 transmission associated with a seropositive mother breast-feeding her child. Biological significance of this route of transmission was supported by demonstration of a relationship between duration of breast-feeding and risk of HIV-1 transmission.

Effects of mode of delivery and infant feeding on the risk of mother-to-child transmission of hepatitis C virus: European Paediatric Hepatitis C Virus Network

OBJECTIVE To investigate the effects of mode of delivery and infant feeding on the risk of mother-to-child transmission of hepatitis C virus. DESIGN Pooled retrospective analysis of prospectively collected data. SAMPLE Data on hepatitis C virus seropositive mothers and their children identified around delivery were sent from 24 centres of the European Paediatric Hepatitis C Virus Network. MAIN OUTCOME MEASURES Hepatitis C virus infection status of children born to hepatitis C virus infected women. RESULTS A total of 1,474 hepatitis C virus infected women were identified, of whom 503 (35%) were co-infected with HIV. Co-infected women were more than twice as likely to transmit hepatitis C virus to their children than women with hepatitis C virus infection alone. Overall 9.2% (136/1,474) of children were hepatitis C virus infected. Among the women with hepatitis C virus infection-only, multivariate analyses did not show a significant effect of mode of delivery and breastfeeding: caesarean section vs vaginal delivery OR = 1.17, P = 0.66; breastfed versus non-breastfed OR = 1.07, P = 0.83. However, HIV co-infected women delivered by caesarean section were 60% less likely to have an infected child than those delivered vaginally (OR = 0.36, P = 0.01) and those who breastfed were about four times more likely to infect their children than those who did not (OR = 6.41, P = 0.03). HIV infected children were three to four times more likely also to be hepatitis C virus infected than children without HIV infection (crude OR = 3.76, 95% CI 1.89-7.41). CONCLUSIONS These results do not support a recommendation of elective caesarean section or avoidance of breastfeeding for women with hepatitis C virus infection only, but the case for HIV infected women undergoing caesarean section delivery and avoiding breastfeeding is strengthened if they are also hepatitis C virus infected.

Prevention of life‐threatening infections due to encapsulated bacteria in children with hyposplenia or asplenia: a brief review of current recommendations for practical purposes

Abstract: The aim of the present work was to summarise in a single paper all the options for prevention of life‐threatening infections due to encapsulated bacteria in patients with hyposplenism or asplenia. Prevention of these infections should be obtained in all patients with 1) patient and family education, 2) prophylaxis by means of vaccination against Haemophilus influenzae and Streptococcus pneumoniae, 3) antibiotic prophylaxis, based primarily on penicillin, 4) delay of elective splenectomy or use methods of tissue salvage in splenic trauma. Vaccination is not effective against all serotypes of S. pneumoniae and Neisseria meningitidis causing life‐threatening infections in hypo/asplenic patients. Moreover, antibacterial prophylaxis could select antibacterial‐resistant pathogens and is highly conditioned by patients compliance. Therefore, empirical antibacterial therapy of fever and/or suspected infection should be recommended to all splenectomised patients independently from time elapsing from splenectomy, vaccinal status and assumption of antibacterial prophylaxis.

Rapid disease progression in HIV-1 perinatally infected children born to mothers receiving zidovudine monotherapy during pregnancy The Italian Register for HIV Infection in Children*

OBJECTIVE To investigate the outcome in children perinatally infected with HIV-1 whose mothers received zidovudine (ZDV) monotherapy in pregnancy. DESIGN Observational retrospective study of a prospectively recruited cohort. SETTING Italian Register for HIV Infection in Children. PATIENTS A group of 216 children perinatally infected with HIV-1, born in 1992-1997 and derived prospectively from birth: 38 children had mothers receiving ZDV monotherapy and for 178 children the mothers received no antiretroviral treatment during pregnancy. MAIN OUTCOME MEASURES The estimated probability of developing severe disease or severe immune suppression, survival probability [95% confidence interval (CI)] within 3 years, and the hazard ratio (95% CI), adjusted for year of birth, maternal clinical condition at delivery, birthweight and treatments (Pneumocystis carinii pneumonia chemoprophylaxis and/or antiretroviral therapy before the onset of severe disease, severe immune suppression or death) were compared. RESULTS Comparison of HIV-1-infected children whose mothers were treated with ZDV with children whose mothers were not treated showed that the former group had a higher probability of developing severe disease [57.3% (95% CI 40.9-74.3) versus 37.2% (95% CI 30.0-45.4); log-rank test 7.83, P = 0.005; adjusted hazard ratio 1.8 (95% CI 1.1-3.1)] or severe immune suppression [53.9% (95% CI 36.3-73.5) versus 37.5% (95% CI 30.0-46.2); log-rank test 5.58, P = 0.018; adjusted hazard ratio 2.4, (95% CI: 1.3-4.3)] and a lower survival [72.2% (95% CI 50.4-85.7) versus 81.0% (95% CI 73.7-86.5); log-rank test 4.23, P = 0.039; adjusted hazard ratio of death 1.9 (95% CI 1.1-3.6)]. CONCLUSIONS This epidemiological observation could stimulate virologic studies to elucidate whether this rapid progression depends on in utero infection or transmission of resistant virus. Findings may suggest a need to hasten HIV-1 diagnosis in infants of ZDV-treated mothers and undertake an aggressive antiretroviral therapy in those found to be infected.

Performance of the galactomannan antigen detection test in the diagnosis of invasive aspergillosis in children with cancer or undergoing haemopoietic stem cell transplantation

Serum galactomannan (GM) antigen detection is not recommended for defining invasive aspergillosis (IA) in children undergoing aggressive chemotherapy or allogeneic haemopoietic stem cell transplantation (HSCT). The ability of the GM test to identify IA in children was retrospectively evaluated in a cohort of children. Test performance was evaluated on samples that were collected during 195 periods at risk of IA. Proven IA was diagnosed in seven periods, all with positive GM test results (true positives, 4%), and possible IA was diagnosed in 15 periods, all with negative GM test results (false negatives, 8%). The test result was positive with negative microbiological, histological and clinical features in three periods (false positives, 1%), and in 170 periods it was negative with negative microbiological, histological and clinical features (true negatives, 87%). The sensitivity was 0.32 and the specificity was 0.98; the positive predictive value was 0.70 and the negative predictive value was 0.92. The efficiency of the test was 0.91, the positive likelihood ratio was 18.3, and the negative likelihood ratio was 1.4. The probability of missing an IA because of a negative test result was 0.03. Test performance proved to be better during at-risk periods following chemotherapy than in periods following allogeneic HSCT. The GM assay is useful for identifying periods of IA in children undergoing aggressive chemotherapy or allogeneic HSCT.

Incidence of bacteremias and invasive mycoses in children with acute non-lymphoblastic leukemia: results from a multi-center Italian study.

Data on the epidemiology of bacteremias and invasive fungal diseases (IFD) in children with acute myeloid leukemia (AML) are scarce.

Re‐immunisation schedule in leukaemic children after intensive chemotherapy: a possible strategy

Abstract:  The aim of this retrospective study was to test the residual humoral immunity to compulsory vaccines after the end of chemotherapy for acute lymphoblastic leukaemia in a cohort of 70 Italian children. All the patients, who had been immunised according to the Italian schedule prior to the disease, were tested for antibody levels against tetanus and hepatitis B at a median of 10 months after the end of therapy. Median age at diagnosis of leukaemia was 48 months, and median age at vaccine titration was 84 months. The protective level of antibodies for tetanus and hepatitis B was shown in 83% and 81% of patients, respectively; the remaining 17% and 19% were not protected against the two pathogens. Double negativity was observed in only four of 62 (6%) patients in the cohort. These data were comparable with published data regarding healthy children of the same age and from the same geographical areas. Therefore, given the direct and indirect costs of performing laboratory tests, as well as the cost of revaccination, our proposal is to continue the vaccination schedule according to the childs age without any titration screening 6 months after the end of therapy. Larger studies are needed to confirm these observations.

Diagnostic potential of hepcidin testing in pediatrics

Hepcidin, a peptide hormone released by hepatocytes into circulation is the main regulator of dietary iron absorption and cellular iron release. Although commercial tests are available, assay harmonization for hepcidin has not been yet reached, making reference intervals and consequent clinical decisions still elusive for each assay and specific population. The aim of this study is to set up hepcidin measurement in pediatric age and to investigate its potential usefulness in the diagnosis and management of iron disorders in children.

Recommendations on hematopoietic stem cell transplantation for inherited bone marrow failure syndromes.

Allogeneic hematopoietic stem cell transplantation (HSCT) offers the potential to cure patients with an inherited bone marrow failure syndrome (IBMFS). However, the procedure involves the risk of treatment-related mortality and may be associated with significant early and late morbidity. For these reasons, the benefits should be carefully weighed against the risks. IBMFS are rare, whereas case reports and small series in the literature illustrate highly heterogeneous practices in terms of indications for HSCT, timing, stem cell source and conditioning regimens. A consensus meeting was therefore held in Vienna in September 2012 on behalf of the European Group for Blood and Marrow Transplantation to discuss HSCT in the setting of IBMFS. This report summarizes the recommendations from this expert panel, including indications for HSCT, timing, stem cell source and conditioning regimen.