Predictive Factors for Gram-negative Versus Gram-positive Bloodstream Infections in Children With Cancer.

BACKGROUND: Identifying potential predictive factors for the type of bacteremia (Gram-negative vs. Gram-positive) in children with cancer would be crucial for the timely selection of the appropriate empiric antibiotic treatment. MATERIALS AND METHODS: Demographic, clinical, and laboratory characteristics of children with cancer and a bacterial bloodstream infection (BSI) (February 1, 2011 to February 28, 2018) in a tertiary pediatric oncology department were retrospectively examined and were correlated with the type of isolated bacteria. RESULTS: Among 224 monomicrobial bacterial BSI episodes, Gram-negative and Gram-positive bacteria were isolated in 110 and 114 episodes, respectively. Gram-negative bacteria were isolated significantly more frequently in girls (Gram-negative/Gram-positive ratio 1.7:1) versus boys (Gram-negative/Gram-positive ratio 0.72:1), P=0.002, in patients with previous BSI episodes (1.4:1) versus those without (0.8:1), P=0.042, and in children with hematologic malignancy (1.3:1) versus those who suffered from solid tumors (0.52:1), P=0.003. Gram-negative BSI episodes were more frequently correlated with a lower count of leukocytes, P=0.009, neutrophils, P=0.009 and platelets, P=0.002, but with significantly higher C-reactive protein (CRP) levels, P=0.049. Female sex, hematologic malignancy, and higher CRP levels remained independent risk factors for Gram-negative BSI in the multivariate analysis. Among neutropenic patients, boys with solid tumors and a recent central venous catheter placement appear to be at increased risk for Gram-positive BSI in the multivariate analysis. CONCLUSIONS: Although Gram-negative and Gram-positive BSIs are close to balance in children with cancer, Gram-negative bacteria are more likely to be isolated in girls, children with hematologic malignancies and those with higher CRP level at admission. In contrast, neutropenic boys with solid tumors and a recently placed central venous catheter may be at increased risk for Gram-positive BSI indicating probably the need for initially adding antibiotics targeting Gram-positive bacteria.

Toxoplasma gondii: How fatal is it in pediatric allogeneic bone marrow transplantation setting?

Toxoplasmosis is a disease of the immunocompetent population. However, cases of toxoplasma infection associated with immunosuppression have been reported, especially the first months after transplantation. Limited data are available about toxoplasma infection, occurring even many months post-transplant in pediatric patients with nonmalignant and malignant diseases. We report the cases of three patients with early and late disseminated toxoplasmosis and review the literature.

A prospective study on the epidemiology and clinical significance of viral respiratory infections among pediatric oncology patients.

Respiratory infections in oncology are both common and potentially severe. However, there is still a gap in the literature, regarding the epidemiology of viral respiratory infections in children with cancer. We prospectively enrolled 224 patients, from September 2012 to August 2015. The cohort included children with hematologic or solid malignancies receiving chemotherapy, or undergoing hemopoietic stem cell transplantation, outpatients/inpatients exhibiting signs/symptoms of febrile/afebrile upper/lower respiratory infection. Viral infection was diagnosed by detection of ≥1 viruses from a sample at time of enrollment, using the CLART® PneumoVir kit (GENOMICA, Spain). Α detailed questionnaire including demographics and medical history was also completed. Samples were processed in batches, results were communicated as soon as they became available. Children recruited in whom no virus was detected composed the no virus detected group. Viral prevalence was 38.4% in children presenting with respiratory illness. A single virus was found in 30.4%, with RSV being the most frequent. Viral coinfections were detected in 8%. Children with viral infection were more likely to be febrile upon enrollment and to present with lower respiratory signs/symptoms. They had longer duration of illness and they were more likely to receive antibiotics/antifungals. Only 22% of children with influenza received oseltamivir. Mortality was low (2.7%), however, pediatric intensive care unit (PICU) admission and death were correlated with virus detection. In our study mortality was low and PICU admission was related to virus identification. Further research is needed to clarify whether antibiotics in virus-proven infection are of value and underline the importance of oseltamivir's timely administration in influenza.

BCL2L12 improves risk stratification and prediction of BFM-chemotherapy response in childhood acute lymphoblastic leukemia.

Background Risk-adjusted treatment has led to outstanding improvements of the remission and survival rates of childhood acute lymphoblastic leukemia (ALL). Nevertheless, overtreatment-related toxicity and resistance to therapy have not been fully prevented. In the present study, we evaluated for the first time the clinical impact of the apoptosis-related BCL2L12 gene in prognosis and risk stratification of BFM-treated childhood ALL. Methods Bone marrow specimens were obtained from childhood ALL patients upon disease diagnosis and the end-of-induction (EoI; day 33) of the BFM protocol, as well as from control children. Following total RNA extraction and reverse transcription, BCL2L12 expression levels were determined by qPCR. Patients' cytogenetics, immunophenotyping and minimal residual disease (MRD) evaluation were performed according to the international guidelines. Results BCL2L12 expression was significantly increased in childhood ALL and correlated with higher BCL2/BAX expression ratio and favorable disease markers. More importantly, BCL2L12 expression was associated with disease remission, while the reduced BCL2L12 expression was able to predict patients' poor response to BFM therapy, in terms of M2-M3 response and MRD≥0.1% on day 15. The survival analysis confirmed the significantly higher risk of the BFM-treated patients underexpressing BCL2L12 at disease diagnosis for early relapse and worse survival. Lastly, evaluation of BCL2L12 expression clearly strengthened the prognostic value of the established disease prognostic markers, leading to superior prediction of patients' outcome and improved specificity of BFM risk stratification. Conclusions The expression levels of the apoptosis-related BCL2L12 predict response to treatment and survival outcome of childhood ALL patients receiving BFM chemotherapy.

Voriconazole Antifungal Prophylaxis in Children With Malignancies: A Nationwide Study.

BACKGROUND: Antifungal prophylaxis (AFP) is recommended in at-risk hematology-oncology patients. We evaluated the safety of AFP with voriconazole (VRC) in pediatric hematology/oncology patients. MATERIALS AND METHODS: A retrospective study of VRC AFP in children with malignancies hospitalized in all 7 Greek pediatric hematology/oncology centers during 2008 to 2012 was conducted. Patients' demographics, outcome, and adverse event (AE) data were recorded. RESULTS: Four hundred twenty-nine VRC AFP courses in 249 patients (median age 6 y, 55% boys) were studied. The most common underlying diseases were acute lymphoblastic leukemia (51%), non Hodgkin lymphoma (8.6%), and acute myeloid leukemia (7.7%). The median number of VRC courses per patient was 1.7, whereas the median VRC dose was 7 mg/kg (range, 5 to 7 mg/kg) every 12 hours. During the last 2 weeks before AFP, 51% of the patients had received corticosteroids, 43% suffered from severe neutropenia, and 17.3% from mucositis. The median duration of VRC AFP was 17 days (range, 1 to 31 d). A single breakthrough fungemia due to Candida glabrata was recorded. Only 1 patient died due to the underlying disease. The most common AEs reported in 70/429 (16.3%) courses with ≥1 AE were elevated liver enzymes (50%), hypokalemia (24.3%), and ophthalmological disorders (14.3%). The median time of AE onset was 5 days (range, 1 to 21 d). Among 70 AEs reported, 38.5%, 48.4%, and 12.8% were of grade I, II, and III, respectively. CONCLUSIONS: VRC prophylaxis in pediatric hematology/oncology patients appears to be well tolerated.

Optic pathway glioma in children: 10 years of experience in a single institution.

Optic pathway glioma (OPG) is a rare brain tumor that occurs more commonly during early childhood and is frequently associated with neurofibromatosis type 1 (NF1). In this study, our aim was to describe the characteristics, management, and outcome of patients with OPG. We retrospectively analyzed the clinical charts of all children diagnosed with OPG at our institution from 2003 to 2013. Twenty children (11 boys and 9 girls, median age: 5 and 3/12 years; NF1: 15/20) were diagnosed with OPG. The diagnosis was based on magnetic resonance imaging (MRI) findings. A biopsy was useful in 3 patients. The main reason for seeking medical advice was decreased vision (7/20 patients), whereas in 10/20 patients, the diagnosis was established during the routine follow-up for their NF1. Fifteen patients demonstrated MRI findings of optic nerve involvement and/or chiasmal tumor, whereas in 5 children, postchiasmal structures were also involved. Sixteen patients (16/20) received carboplatin-based regimens, whereas 4/20 patients were only under close observation. Six patients showed deterioration of visual acuity and/or imaging findings at the end of treatment and/or during their follow-up. Three of them (3/6) underwent tumor resection, whereas 1 (1/6) received radiation treatment. None of our patients had total blindness from both eyes. Half of our patients were diagnosed during follow-up for their NF1, the incidence of which was high in our group. Our data suggest that chemotherapy helps in the preservation of vision in the majority of children.

Prayer and blessings focused for healing is the most popular complementary intervention in a paediatric oncology unit in Greece.

PURPOSE: Increasing numbers of children with cancer are using complementary and alternative medicine (CAM) therapies. Our aim was to estimate the rate of use, the beliefs of users and non-users and factors related with the use of CAM among Greek families. METHODS: A self-reported questionnaire was given to parents of 184 children with cancer. We assessed the rate of use, types of CAM therapies and factors potentially associated with the use of CAM. RESULTS: Based on the 110 questionnaires which were completed (59.8% of the families), 23 families (21%) had used at least one complementary treatment. The most common forms were: spiritual healing/prayer/blessings 18/23 (78%), art therapies 4, dietary supplements 3, massage 3, homeopathy 2, and herbals 2. The reasons given for use included: making the child stronger 17/23 (48%, hope of stopping the cancerous process 11/23 (49%), and coping with side effects 6/23 (26%). Among the reasons given by the parents for not using CAM therapies the most common (84%) was the effective conventional treatment and, therefore, there was no need for CAM use. Another 24% reported that were unaware of these "alternative" and "complementary" therapies and a further 7% had considered using them but finally they didn't. In bivariate analysis, the use of CAM was not associated either with age, sex, nationality, education or occupation of the parents at the time of the survey, or with diagnosis, mode of therapy or age of the child at diagnosis. CONCLUSIONS: The use of CAM therapies by Greek families for their children with cancer does not appear to be very popular, although the experiences of those who did use them were generally positive.

A novel karyotype in acute myeloid leukemia with basophilia.

Acute basophilic leukemia is a distinct entity of Acute Myeloid Leukemia (AML) with primary differentiation to basophils. Increased basophil count has been described in AML cases with translocation t(6;9)(p23;q34) or other chromosomal abnormalities. We describe a 15-year old female teenager with AML and excess peripheral blood and bone marrow basophils. Her white blood cell count at diagnosis was 15.4 G/L with 53% basophils and 17% blasts. The bone marrow cytogenetics analysis did not reveal any of the usual abnormalities. The karyotype showed two closely related leukemic clones: the first (16 metaphases), with a total of 48 chromosomes, had an extra chromosome 8 with deletion of the long arm and an additional 21 (48,XX, +del(8)(q24.2q24.3), t21[16]), while the second clone (2 metaphases), with a total of 47 chromosomes, did not contain the extra 21 chromosome (47, sl, -21[2]). In summary, in this case of AML-M2 with excess basophils, there is a novel chromosomal abnormality, not previously reported in this entity.

Differences between younger and older patients with childhood hodgkin lymphoma.

From 1979 to 2006, 74 children with Hodgkin's lymphoma were treated at our center. Among them, 15 (14 boys and 1 girl) and 59 (33 boys and 26 girls) patients were younger and older than 8 years, respectively. Six (40%) children among younger patients and 26 (44%) among older patients had advanced stage disease. We detected 3 (20%) relapses among younger patients and 5 (8.5%) among the older patients. All of younger patients are alive whereas three of the older patients have died. Second malignancy developed in one and three children among younger and older patients, respectively. The only difference that was detected concerning the age was a male predominance among the younger patients.

Compliance with immunization against H1N1 influenza virus among children with cancer.

In this report, we describe the experience with immunization against pandemic influenza A H1N1 in children with cancer treated at a pediatric oncology department during the pandemic season (2009). According to the guidelines, vaccination of all children with cancer receiving chemotherapy as well as those who had completed treatment was scheduled. Among the 140 children who were eligible for immunization, 122 were immunized, achieving a compliance rate of 87% despite negative publicity and low vaccine uptake in the general population. The vaccine was tolerated and none of the vaccinated children developed influenza. It is concluded that high immunization rates can be achieved among pediatric oncology patients.

Childhood Acute Lymphoblastic Leukemia: Results of the Randomized Acute Lymphoblastic Leukemia Intercontinental-Berlin-Frankfurt-Münster 2009 Trial.

PURPOSE: The International Berlin-Frankfurt-Münster (BFM) study group conducted a study on pediatric acute lymphoblastic leukemia (ALL). Minimal residual disease (MRD) was assessed using flow cytometry (FCM), and the impact of early intensification and methotrexate (MTX) dose on survival was evaluated. PATIENTS AND METHODS: We included 6,187 patients younger than 19 years. MRD by FCM refined the risk group definition previously used in the ALL intercontinental-BFM 2002 study on the basis of age, WBC count, unfavorable genetic aberrations, and treatment response measured morphologically. Patients at intermediate risk (IR) and high risk (HR) were randomly assigned to protocol augmented protocol I phase B (IB) versus IB regimen. MTX doses of 2 versus 5 g/m2 every 2 weeks, four times, were evaluated in precursor B-cell-ALL (pcB-ALL) IR. RESULTS: The 5-year event-free survival (EFS ± SE) and overall survival (OS ± SE) rates were 75.2% ± 0.6% and 82.6% ± 0.5%, respectively. Their values in risk groups were standard risk (n = 624), 90.7% ± 1.4% and 94.7% ± 1.1%; IR (n = 4,111), 77.9% ± 0.7% and 85.7% ± 0.6%; and HR (n = 1,452), 60.8% ± 1.5% and 68.4% ± 1.4%, respectively. MRD by FCM was available in 82.6% of cases. The 5-year EFS rates in patients randomly assigned to protocol IB (n = 1,669) and augmented IB (n = 1,620) were 73.6% ± 1.2% and 72.8% ± 1.2%, respectively (P = .55), while those in patients receiving MTX doses of 2 g/m2 (n = 1,056) and MTX 5 g/m2 (n = 1,027) were 78.8% ± 1.4% and 78.9% ± 1.4%, respectively (P = .84). CONCLUSION: The MRDs were successfully assessed using FCM. An MTX dose of 2 g/m2 was effective in preventing relapse in non-HR pcB-ALL. Augmented IB showed no advantages over the standard IB.[Media: see text].

Acute megakaryoblastic leukemia with increased hematogones in children.

We describe 2 patients, a 4-month-old male and a 17-month-old female, with de novo acute megakaryoblastic leukemia with increased number of hematogones at diagnosis. Both children were admitted in the hospital with thrombocytopenia. The bone marrow smears in the first child revealed the presence of 60% cells with morphologic features consistent with acute megakaryoblastic leukemia. In the other, the initial bone marrow aspirate was dry tap but on the following aspirate 10% cells with lymphoblastic morphology could be seen. The bone marrow flow cytometry showed the presence of hematogones-38% in the first case and 20% in the second-with absence of blasts. Repeated bone marrow aspirates, trephines, and immunophenotypic as well as molecular studies, confirmed the diagnosis of M7. Both children were treated according to the Berlin-Frankfurt-Munster 2004 protocol.

Successful bone marrow transplantation in a pediatric patient with chronic myeloid leukemia from a HLA-identical sibling selected by preimplantation HLA testing.

We report successful bone marrow transplantation in an 11-year-old male with chronic myeloid leukemia from his HLA-identical sibling selected by preimplantation HLA testing. Because collection of cord blood failed, the transplantation was performed when the donor reached the age of 19 months, and sufficient bone marrow could be harvested safely. The patient was BCR/ABL negative at the time of transplantation after complete molecular response to imatinib. Currently, 16 months post-transplantation he is well and in complete molecular remission. This report describes preimplantation HLA-genotyping to deliver a matched sibling donor for successful transplantation of a malignant disorder.

Optimal care for the child with cancer: A summary statement from the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology.

Since its foundation in 1991, the SIOP Working Committee on Psychosocial Issues in Paediatric Oncology1 has developed and published 12 sets of Guidelines for health-care professionals treating children with cancer and their families. Those elements considered essential in the process of cure and care of children with cancer are summarized in this document as a formal statement, developed at the 2007 SIOP annual meeting in Mumbai. Elaboration of the concepts with detailed strategies for practice can be found in the referenced guidelines [1-12] and in a companion publication [13]. This article is a summary of what practitioners considered critical elements in the optimal care of the child with cancer, with the goal of stimulating a broader application of these elements throughout the SIOP membership.

Quality of life of adolescent and young adult survivors of childhood cancer.

The purpose of this study was to assess the quality of life of Greek survivors of childhood cancer by addressing the physical, psychological, spiritual, and social dimensions of their functioning. The SF-36 Health Survey and the Quality of Life Questionnaire, which was designed for this study, were used. Survivors' scores on most subscales of SF-36 were similar to those of controls, despite some difficulties in their daily activities. They perceived self as more susceptible to health problems, but also more mature and grounded. Generally, they seem to adapt well and focus on the positive aspects of their cancer experience, which enhances the meaning and quality of their life.

Longitudinal assessment of immunological status and rate of immune recovery following treatment in children with ALL.

BACKGROUND: We prospectively evaluated the immunological status, immune recovery and risk of infection in pediatric ALL patients treated on the BFM 95 protocol. PROCEDURE: Humoral and cellular immunity were evaluated in 72 children with ALL at the end of intensive therapy and values were compared to those at the completion of therapy and 6-monthly. Parameters investigated included lymphocyte subpopulation by flow cytometry, immunoglobulin levels by nephelometry, antibody titers to previous immunizations and delayed hypersensitivity with skin testing. Immune responses were correlated to duration of therapy, CNS radiotherapy, age and sex. RESULTS: Humoral immunity was severely depressed by the end of intensive therapy with low immunoglobulin levels and CD19, improved after therapy cessation. Cellular immune responses were normal at the end of intensive treatment but declined significantly by the end of therapy and both CD4 and CD8 remained low at later evaluation points whereas CD4/CD8 ratio was increasing. Duration of therapy and CNS radiotherapy did not affect the rate of immune recovery whereas female had higher CD19, CD45RO, and IgM and children >7 years had higher CD19 and lower CD16 and CD3DR. Among immunized children, 86.7% maintained protective antibodies to MMR and 63% to polio. Despite impairment of immunity, infections outside the neutropenic periods were common viral illnesses. CONCLUSION: Humoral immunity was depressed in children with ALL at the end of intensive therapy but began to recover after cessation of therapy. In contrast, cellular immunity declined significantly by the end of therapy and remained abnormal for at least 1 year post-therapy.

Complications of Hickman-Broviac catheters in children with malignancies.

The aim of this study was to explore the complications related to Hickman-Broviac central venous catheters (Hickman-Broviac CVCs) in children with cancer, their incidence, and possible associations of complications and premature removal of CVCs with a number of risk factors. During the study period (1 Jan 2000-31 Dec 2003), 223 CVCs were inserted in 198 children (117 boys, 81 girls) at a mean age of 5.73 years (95% CI 5.19-6.27, SE 0.275). In total, 76 (38.4%) children suffered from solid tumors and 122 (61.6%) from leukemia. The mean follow-up after CVC insertion was 232.5 days (95% CI 214.9-250.2, SE 8.94) for a total of 51,839 catheter-days. A complication occurred in 20.8% of them and in 9.6% the complication led to the removal of the catheter. The most frequent complications were infection (63.9%), obstruction (26.2%), accidental failure (8.2%), and rupture (1.6%). An overall incidence of 1.17 (0.38 and 0.79 for mechanical complication and infection, respectively) per 1000 catheter days for the development of a complication was recorded. Additionally, the study revealed more nonelective removals in cases of leukemia compared to those of solid tumors. Systemic use of CVC does not appear to increase significantly the number of complications, and thus CVC remains an effective and safe tool for the management of childhood malignancies.

Immune response to influenza vaccination in children with cancer.

The aim of this study was to evaluate the ability of influenza immunization to evoke a protective immune response among children with cancer. We evaluated 75 children with cancer who received influenza vaccination. Hemagglutination Inhibition Antibody titers were determined before and after vaccination. The protective rates after vaccination were 79% for H1N1, 75% for H3N2 and 59% for influenza B virus whereas the seroconversion rates were 54%, 44% and 43% respectively. The differences pre- and post-vaccination were significant regardless the method which was used: seroprotection changes, seroconversion and geometric mean titers analyses. Variables such as the pre-vaccination antibody titers, the time when the responses were measured after the vaccination, the age and the type of malignancy as well as the absolute lymphocyte count were found to be correlated with the immune response but the findings were different for each vaccine subunit. In conclusion, influenza vaccination provides protection in a remarkable proportion of pediatric cancer patients whereas this protection is more obvious against H1N1 and H3N2 compared to influenza B. The immune response after vaccination is significant and seems to be influenced by a variety of factors.

Successful combination of antifungal agents and surgical resection for pulmonary aspergillosis in a child with Hodgkin disease: review of the literature.

The authors report on a 14-year-old adolescent boy suffering of Hodgkin disease in remission, who developed autoimmune anemia and thrombopenia. He was treated with high-dose steroids and he developed serious invasive lung aspergillosis, which was treated with antifungal agents and surgical intervention. Children suffering from cancer are prone to develop systemic fungal infections secondary to the severe immunosuppression caused by the disease itself and the antineoplastic therapy. Intravenous antifungal medications and, when feasible, surgery are used for treatment of pulmonary aspergillosis. Factors related to better outcome are early diagnosis, remission of underlying disease, aggressive antifungal therapy, and recovery from neutropenia.

Negative gallium-67 citrate and positive positron emission tomography/computed tomography spleen scans, in Hodgkin's stage IV lymphoma.

An 18-year-old male patient with Hodgkin's lymphoma stage IVB (HL-IVB), is presented. On a follow-up examination a splenic ultrasound scan showed the presence of multiple intense nodules. The gallium-67 citrate, single photon emission tomography scan was negative, while positron emission tomography/computerized tomography (PET/CT) scan with fluoro-18-fluordeoxyglucose was strongly positive. Massive infiltration of the spleen by HL-IVB tissue was confirmed by pathology after splenectomy. Two successive PET/CT studies for follow-up purposes three and twelve months after completion of chemotherapy, were normal.