Prompt administration of antibiotics is associated with improved outcomes in febrile neutropenia in children with cancer

Background

Time‐to‐antibiotic (TTA) administration is a widely used quality‐of‐care measure for children with cancer and febrile neutropenia (FN). We sought to determine whether TTA is associated with outcomes of FN.

Procedure

A single‐center, retrospective cohort study was conducted of 1,628 FN admissions from 653 patients from 2001 to 2009. Outcome variables included (1) an adverse event (AE) composite of in‐hospital mortality, pediatric intensive care unit (PICU) admission within 24 hours of presentation, and/or fluid resuscitation ≥40 ml/kg within 24 hours of presentation and (2) length of stay (LOS). TTA was measured as a continuous variable and in 60‐minute intervals. Mixed regression models were constructed to evaluate associations of TTA with the outcome variables after adjusting for relevant covariates including cancer diagnosis, degree of myelosuppression, and presence of bacteremia.

Results

The composite AE outcome occurred in 11.1% of admissions including 0.7% in‐hospital mortality, 4.7% PICU admission, and 10.1% fluid resuscitation. In univariate analysis, TTA was associated with the composite AE outcome (Odds Ratio [OR] 1.29, 95% CI 1.02–1.64) but not LOS. In multivariate analysis, after adjustment for relevant covariates, 60‐minute TTA intervals were associated with the composite AE outcome (61–120 minutes vs. ≤60 minutes, OR 1.81, 95% CI 1.01–3.26). Unexpectedly, admission from the emergency department (ED) was also independently associated with the composite AE outcome (ED vs. clinic, OR 3.15, 95% CI 1.95–5.09).

Conclusions

TTA and presentation to the ED are independently associated with poor outcomes of FN. Pediatr Blood Cancer 2013;60:1299–1306. © 2013 Wiley Periodicals, Inc.     

Omega-3 polyunsaturated essential fatty acids are associated with depression in adolescents with eating disorders and weight loss

Aim: To study the relationship between polyunsaturated fatty acids (PUFA) status and depression in adolescents with eating disorders (ED) and weight loss. Methods: Erythrocyte membranes from 217 adolescents (209 girls, eight boys) with ED were analysed for fatty acids (FA). ED and depression were diagnosed by clinical interviews and supported by self‐report instruments. Results: Adolescents with ED and depression did not differ from those with ED only in terms of age, BMI, weight loss and duration of disease. In their FA profile, depressed adolescents had lower proportions of eicosapentanoic acid (EPA) and docosahexanoic acid (DHA), the end products of the ω3 PUFA series. The ratio of long‐chain (>18 carbons) ω6/ω3 PUFA was therefore higher in depressed adolescents. Indices of desaturase activities did not differ between depressed and not depressed adolescents. Conclusion: Low ω3 status is related to depression in adolescents with ED. This cannot be explained by differences in weight (loss) and duration of disease, nor by differences in PUFA processing by desaturases. Data suggest a lower dietary intake of ω3 PUFA in those with depression. Further investigations should determine whether ω3 PUFA status improves by refeeding only or whether supplementation with PUFA is warranted.     

Essential fatty acid status in teenage girls with eating disorders and weight loss

Aim: To explore the relationship between essential fatty acids (FA) and weight changes in adolescent girls with eating disorders (ED). Methods: Blood samples were obtained from 220 girls with ED and 39 healthy controls. The girls with ED were 15.3 ± 1.5 years of age and weighed 49.8 ± 8.7 kg (BMI 18.3 ± 2.8 kg/m²) after a weight loss of 6.8 ± 6.4 kg. FA were analysed in plasma phospholipids (PPL) and erythrocyte membranes (ERY). Results: The proportions of saturated and monounsaturated FA were increased during weight loss, while linoleic acid (18:2ω6) was decreased. The proportions of eicosapentanoic acid (EPA) (20:5ω3) and docosahexanoic acid (DHA) (22:6ω3) in PPL and ERY did not differ from controls. The activity of stearoyl‐CoA‐desaturase was increased as evidenced by an increased product/precursor ratio and correlated with the rate of weight loss. The activities of delta‐6‐desaturase and delta‐5‐desaturase did not differ from controls. The rate of weight loss was inversely correlated with delta‐6‐desaturase and directly correlated with delta‐5‐desaturase. Conclusion: The FA profile indicates low‐fat intake, fat mobilization from stores and an increased conversion of essential FA at the delta‐5‐desaturase step during weight loss in adolescent girls with ED. Normal levels of EPA and DHA were maintained.     

Pegfilgrastim in children with severe congenital neutropenia

Two pediatric patients affected by severe congenital neutropenia (SCN) were treated with 100 mcg/L/dose every 9–12 days within a pilot study (Observatory of the Italian Ministry of Health, Eudract Code 2005‐003096‐20) on the use of pegfilgrastim in patients with chronic neutropenia. Both children increased their absolute neutrophil count, reduced their infectious load, and improved their quality of life. Serum concentrations of G‐CSF observed in pegfilgrastim mirrored those seen in filgrastim. These data suggest that pegfilgrastim may be beneficial in SCN patients with an exposure of hematopoietic cells to G‐CSF similar to that on filgrastim. Pediatr Blood Cancer 2010;54:465–467. © 2009 Wiley‐Liss, Inc.     

Long-term remission of children with relapsed and secondary anaplastic large cell non-Hodgkin lymphoma (ALCL) following treatment with pulsed dexamethasone and low dose etoposide

Anaplastic large cell lymphoma (ALCL) accounts for approximately 15% of childhood NHL. Relapsed ALCL represents a formidable challenge because outcome is poor despite the use of high-dose chemotherapy regimens. We report two patients with relapsed T-type and 0-type ALCL who achieved long-term 3rd and 4th remissions with 4-weekly oral dexamethasone (DEX) and etoposide pulses for 2 years. This regimen also induced and maintained remission in a third patient with Nijmegen breakage syndrome (NBS) with secondary T-type ALCL. These patients demonstrate that low-intensity oral chemotherapy can induce long-term remissions and offer a curative perspective in refractory, relapsed and secondary ALCL.     

Outcome of children with B cell lymphoma in Venezuela with the LMB-89 protocol

BACKGROUND: We analyzed the results of the LMB-89 protocol performed in seven centers in Venezuela in 96 children having B-cell non-Hodgkin lymphoma treated from 1995 to 2002. PROCEDURE: Mean age was 7.1 years with 71 (74%) been male. Eighty-two patients (85%) had diffuse small cell lymphoma Burkitt and Burkitt-like, and 14 (15%) had diffuse large B-cell lymphoma. Initial disease sites included the abdomen in 67%, peripheral nodes in 8%, and mediastinal in 4%. Treatment was directed to risk groups as described for LMB-89 protocol. Group A: seven patients (7%), group B: 80 patients (83%), and group C: nine patients (9%). RESULTS: Mean follow-up was 35 +/- 31 months. Complete remission (CR) occurred in 70 patients (73%); four patients (6%) had relapse during the first year and ten patients (10%) had progressive disease. Overall survival (OS) and event free survival (EFS) were 85 and 80% at 1 year, and 82 and 75% at 2 years, respectively. The EFS by therapeutic groups at 3 years was A: 100%; B: 76%, and C: 56%. Toxicity: neutropenia in 75%, thrombocytopenia in 63%, febrile neutropenia in 39%. Viral infections: hepatitis B in 20%, hepatitis C in 2%, and Herpes zoster in 3%. Tumor lysis syndrome (TLS) occurred in 9% during induction phase with a high mortality of 44% (urate-oxidase was available only at the end of the study). CONCLUSIONS: The high mortality rate during induction phase prohibited a better EFS. Prophylactic use of xantine-oxidase may improve future results. The high incidence of hepatitis B requires a vaccination program.     

The reliability of the disabled children's quality-of-life questionnaire in Swedish children with diabetes

Aim: To determine the reliability of the disabled children’s quality‐of‐life measure (DISABKIDS) chronic generic questionnaire and diabetes module in children. The questionnaire is being evaluated for repeated routine health‐related quality‐of‐life (HrQoL) assessment and in association with the Swedish national paediatric diabetes registry (Swediabkids), which is a tool for regular clinical use. Methods: Children and parents completed the questionnaire during a routine visit to the diabetes clinic. In total, 120 families completed the test and retest. Split‐half reliability correlation and intraclass correlation (ICC) coefficients were calculated. Bland & Altman plots were calculated on the generic HRQoL domain. Results: Both child and parent versions showed good internal consistency. Test–retest ICC coefficients for the generic HrQoL module were 0.913 for the children and 0.820 for the parent version. All generic domains independently showed good reliability. The diabetes module had a score of 0.855 for children and 0.823 for parents. Split‐half correlation for generic and diabetes modules was 0.930 and 0.848 for children, 0.953 and 0.903 for parents. Bland and Altman plots showed substantial agreement between the two administrations for both children and parents. Conclusion: The DISABKIDS questionnaire is a reliable instrument for the repeated measurements of HrQoL in children with diabetes.     

Successful treatment of a child with late-onset T-cell post-transplant lymphoproliferative disorder/lymphoma

We report a novel regimen for refractory post-transplant T-cell lymphoma (PTL). Our patient presented with non-Epstein-Barr virus (EBV) related, T-cell post-transplant lymphoproliferative disease (PTLD) 3.5 years after liver transplantation. Initially diagnosed as polyclonal PTLD, the disease progressed to a monoclonal, T-cell PTL that was refractory to several chemotherapy regimens but responded to a regimen consisting of fludarabine, cyclophosphamide, cytarabine, and alemtuzumab. Consolidation therapy included high-dose chemotherapy, autologous hematopoietic stem cell rescue, and radiation therapy. She remains in remission 2.5 years later. T-cell PTL is a rare disease with a poor prognosis; this regimen provides a novel, potentially curative approach for its treatment.     

Reduced iNOS expression in adenoids from children with otitis media with effusion

Granath A, Norrby‐Teglund A, Uddman R, Cardell L‐O. Reduced iNOS expression in adenoids from children with otitis media with effusion.
Pediatr Allergy Immunol 2010: 21: 1151–1156.
© 2010 John Wiley & Sons A/S Nitric oxide (NO) is a key mediator in the local immune response of human airways. Inducible NO‐synthases (iNOS), and endothelial NO‐synthases (eNOS) are two enzymes known to regulate its production. The role of NO in middle ear disease is not fully known. Previous studies suggest that NO might have a dual role, both promoting and suppressing middle ear inflammation. The aim of the present study was to compare the eNOS and iNOS expression in adenoids obtained from children with otitis media with effusion (OME) with the expression seen in adenoids derived from children without middle ear disease. In addition, the expression of IL‐1β and TNF‐α were analyzed, because of their role in the iNOS‐induction pathway. The iNOS and eNOS expression were analyzed with real‐time PCR in 8 OME and 11 control adenoids. The corresponding proteins were demonstrated by immunohistochemical staining of adenoid tissue. A Luminex^® assay was performed to analyze IL‐1β and TNF‐α in nasopharyngeal secretion in 10 OME and 8 controls, and immunohistochemistry was performed on adenoid tissue and imprints from the adenoid surface. Children with OME exhibited lower levels of iNOS than controls without middle ear disease. No such difference was seen for eNOS. The corresponding proteins were found mainly in conjunction with surface epithelium. No significant changes were seen among the cytokines tested. The present results indicate that local induction of iNOS in adenoids might be of importance for preventing development of OME.     

Castleman disease in a child with short stature

We report a 14‐year‐old boy with Castleman disease in this article. He complained of short stature, and his body height was 133.8 cm (<3rd percentile; z score ?4.5). There was marked delay in the appearance of secondary sexual characteristics. He was found to have a remittent fever and a lower mid‐abdominal tumor. Blood test revealed microcytic hypochromic anemia, thrombocytosis, polyclonal hypergammaglobulinemia, hyperfibrinogenemia, and elevated erythrocyte sedimentation rate. The serum IL‐6 and C‐reactive protein levels were increased. The mass was found to be mixed hyaline vascular and plasma cell type of Castleman disease through a pathological examination. Lymph nodes affected by Castleman disease cause overproduction of IL‐6. It decreases IGF‐1, IGFBP‐3 and serum testosterone levels. As a result of tumorectomy, his short stature and delay in the development of secondary sexual characteristics were improved.     

High-grade brain tumors in siblings with biallelic MSH6 mutations

Biallelic germline mutations of Constitutional mismatch repair-deficiency syndrome (CMMR-D) genes, MLH1, MSH2, MSH6, and PMS2 are characterized by increased risk of childhood malignancy. We report a case with CMMR-D caused by novel homozygous MSH6 mutations leading to gliomatosis cerebri and T-ALL in an 11-year-old female and glioblastoma multiforme in her 10-year-old brother, both with rapid progression of the diseases. A literature review on brain tumors in CMMR-D families shows that they are treatment-resistant and lead to early death. Identification of patients with CMMR-D is critical, and specific cancer screening programs with early surgery are recommended.     

Acute lymphoblastic leukemia in a girl with Wilson's disease

Wilson's disease (WD) is an autosomal recessive defect in cellular copper transportation. Although acute lymphoblastic leukemia (ALL) is the most common form of childhood malignancy, only two cases of ALL associated with WD have been reported to date. One patient died of relapse and infection, and the other died of neutropenic sepsis during the treatment. We here describe the case of a 10‐year‐old girl with WD and ALL. Adverse events of chemotherapy, including liver toxicity and severe myelosuppression, necessitated adjustments in the chemotherapy doses. After completion of the treatment, the patient has remained in remission from ALL without progression of liver damage for 2 years. Severe treatment‐related toxicity should be considered in chemotherapy for patients with WD.     

The relationship of serum vitamin D with pre‐eclampsia in the Iranian women

Vitamin D deficiency may be a risk factor for negative outcome in pregnancy, such as pre‐term labour, low birthweight, intrauterine growth retardation and gestational diabetes. This study aimed to evaluate the relationship between vitamin D and pre‐eclampsia. This was a case–control study of 59 pre‐eclamptic women and 59 healthy pregnant women selected in two hospitals in Ahvaz, Iran. Women with term singleton pregnancy, nulliparous and of reproductive age were selected. Venous blood samples (2 mL) were taken and the level of 25‐dihydroxy vitamin D (25‐OH‐D) was measured. If the levels of 25‐OH‐D were less than 10 ng mL^?1, between 10 ng mL^?1 and 29 ng mL^?1 and more than 30 ng mL^?1, they were considered as indicating deficient, insufficient and normal 25‐OH‐D concentrations, respectively. The independent t‐test, Mann–Whitney U‐test, chi‐square and logistic regression were used for analysing the data. Vitamin D deficiency was significantly higher in the pre‐eclampsia group [odds ratio (OR) = 24.04, confidence interval (CI) = 2.10–274.8, P = 0.01]. Older women (30–35 years) were more likely to develop pre‐eclampsia compared with the control group (OR = 10.36, CI = 2.18–49.09, P = 0.003). The results showed that women with body mass index (BMI) <20 were more likely to develop pre‐eclampsia. The ages between 20 years and 30 years and normal BMI were not the risk factors for pre‐eclampsia. Vitamin D deficiency has a statistically significant relationship with pre‐eclampsia. It seems that the serum vitamin D levels are low in Iranian women because of their particular lifestyle and they may need more than 400 IU day^?1 vitamin D supplement during pregnancy.     

Successful treatment of doxorubicin and cisplatin resistant hepatoblastoma in a child with Beckwith-Wiedemann syndrome with high dose acetaminophen and N-acetylcysteine rescue

High dose acetaminophen (HDAC) with N-acetylcysteine (NAC) has been effective in adults with advanced malignancies. We report HDAC with NAC in a child with progressive hepatoblastoma, confirmed at biopsy of an unresectable hepatic mass. Alpha-fetoprotein (AFP) increased despite four courses of doxorubicin and one course of cisplatin, 5-flurouracil, and vincristine. Following HDAC with NAC, AFP markedly decreased. A continued response without toxicity was observed during four subsequent courses of HDAC with NAC and cisplatin. The residual necrotic tumor was resected. The child is now over 8 years disease free. HDAC and NAC are effective and well tolerated for progressive hepatoblastoma.     

Acute rejection associated with donor-specific anti-MICA antibody in a highly sensitized pediatric renal transplant recipient

Allograft rejection in HLA identical transplant recipients and in patients without detectable donor-specific anti-HLA antibodies has lead to the identification of non-HLA antigens as targets of the alloimmune response. MICA antigen has been recognized as an important non-HLA target in renal transplantation. Recent studies have shown that anti-MICA antibodies are associated with acute renal allograft rejection and failure. Current cross match procedures using donor lymphocytes fail to detect MICA antibodies. Transplant candidates are not routinely tested for pre-sensitization to MICA antigens nor are transplant donors typed for MICA alleles. Optimal classification and treatment of acute rejection associated with MICA antibody remains unknown. In this case report, we are the first to describe the clinical course and treatment of donor-specific MICA antibody associated with both Banff type II A ACR and AMR in a highly sensitized pediatric renal re-transplant recipient. This case also emphasizes the importance of pre-transplant screening for donor-specific MICA antibody especially in highly sensitized renal transplant patients.