Daniela Sperl

Amphotericin B transfer to CSF following intravenous administration of liposomal amphotericin B

OBJECTIVES Although amphotericin B (AmB) and its lipid formulations are used for the treatment of fungal infections of the CNS, the kinetics of AmB in the CSF after intravenous administration of liposomal amphotericin B (LAmB) are not well characterized. PATIENTS AND METHODS From 14 paediatric haemato-oncological patients (aged 0.4-19.5 years, median 7.6 years), we obtained 30 CSF samples by means of routine punctures (performed for intrathecal treatment of the underlying diseases) at different timepoints after the prophylactic intravenous infusion of LAmB (AmBisome, 3 mg/kg/day). Concurrent serum samples were obtained to calculate the transfer rates. An HPLC method was used for AmB detection. RESULTS CSF levels of AmB 1-100 h after the intravenous infusion of LAmB were between 10 and 120 ng/mL, except in one case with a level of 529 ng/mL. Concurrent serum levels were about 1000-fold higher, ranging between 3 and 75 μg/mL. CSF levels did not show a clear time-dependent concentration profile, but remained at a steady-state for longer than 48 h after infusion. The transfer rate ranged from 0.02% to 0.92% (median 0.13%) and correlated significantly (r=0.801, P<0.001) with increasing time after infusion. CONCLUSIONS After the intravenous administration of LAmB, AmB CSF levels were low, confirming published animal data. CSF levels remained at a steady-state level for longer than 48 h. As indicated by published post mortem data, higher levels in brain tissue, which would be necessary for the successful treatment of CNS infections, might be possible.

Age- and gender-related differences in teicoplanin levels in paediatric patients

OBJECTIVES Teicoplanin is a glycopeptide antibiotic active against Gram-positive bacteria, including methicillin-resistant staphylococci. While teicoplanin trough levels (TTLs) >10 mg/L are commonly considered appropriate, levels >20 mg/L are aimed for in the treatment of severe infections. Due to toxicity, it is recommended to avoid levels >60 mg/L. PATIENTS AND METHODS In our institution, the initial dosing schedule of teicoplanin (10-15 mg/kg every 12 h for three loading doses and every 24 h thereafter) is adapted according to TTLs analysed by a fluorescence polarization immunoassay on treatment days 2 to 4. Teicoplanin peak levels (TPLs) are analysed in selected cases 30 min after the end of infusion. In a retrospective analysis we evaluated 1357 TTLs and 333 TPLs from 410 treatment episodes from 2005 to 2011. RESULTS Initial TTLs were <10 mg/L in 14.1% and <20 mg/L in 72.6% of episodes. Toddlers had significantly lower TTLs, with a 2-fold and 2.5-fold increased risk of having levels <10 mg/L (24.6%) and <20 mg/L (82.6%), respectively. For the entire cohort, follow-up TTLs were less likely to be <10 mg/L and more likely to be >20 mg/L when compared with initial TTLs (P < 0.001, each). Adolescent girls had significantly higher initial TPLs (P = 0.001) and significantly higher follow-up TTLs (P = 0.016) than adolescent boys. In parallel, adolescent girls had initial TPLs >60 mg/L significantly more frequently (P = 0.012) and follow-up TTLs <10 mg/L significantly less frequently (P = 0.005). CONCLUSIONS More tailored dosing regimens with higher loading doses, especially for toddlers, should be considered. While further pharmacokinetic data in paediatric patients are pending, therapeutic drug monitoring is mandatory.

Use of NADA ear acupuncture in an adolescent patient with phantom limb pain after surgery for osteosarcoma

Your readers may be interested to hear of our experiences with ear acupuncture, as they may recall the recent letter by Tseng et al 1 describing scalp acupuncture in a 74-year-old patient suffering from phantom limb pain. We used National Acupuncture Detoxification Association (NADA) acupuncture in an adolescent girl suffering from phantom limb pain after hemipelvectomy for osteosarcoma. Positive effects were found on pain and personal well-being evaluated using the Measure Yourself Concerns and Wellbeing (MYCaW) questionnaire.2 Acupuncture is increasingly used as an adjunct therapy in oncology to treat pain and other symptoms such as nausea and vomiting. However, the evidence in paediatric oncology is scarce, and limited to studies describing a reduction in pain or vomiting.3 Contributing factors for the lack of evidence might be fear of needles4 or vulnerability of the patients. Ear acupuncture is used to treat a variety of disorders including both psychological and somatic diseases.5 ,6 Currently, more than 100 ear acupuncture points are known. The NADA protocol combines five ear acupuncture points ( Shenmen (point 55), Liver (point 97), Kidney (point 95), Lung (point 101) and Sympathetic point (point 51) on both ears) with a non-verbal patient approach and group therapy as a simple treatment concept to treat drug withdrawal.7 The NADA protocol has …

Unrelated CD3/CD19-Depleted Peripheral Stem Cell Transplantation for Hurler Syndrome

For patients with mucopolysaccharidosis type IH (MPS1-H; Hurler syndrome), early allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice. One boy and one girl aged 20.5 and 22 months, respectively, with MPS1-H received a conditioning regimen consisting of thiotepa, fludarabine, treosulfan, and ATG. Grafts were peripheral blood stem cells from unrelated donors (10/12 and 11/11 matched), that were manipulated by CD3/CD19 depletion and contained 20.3 and 28.2 × 106 CD34+ cells/kg body weight, respectively. Both patients achieved stable hematopoietic engraftment and stable donor chimerism. Neither acute or chronic graft-versus-host disease (GVHD) nor other severe transplant-related complications occurred. At a follow-up of 48 and 37 months, both patients are alive and well with normal levels of α-L-iduronidase and have made major neurodevelopmental progress. Treosulfan-based conditioning offers the advantage of reduced toxicity; the use of unrelated CD3/CD19-depleted peripheral stem cell grafts allows transfusion of high CD34+ cell numbers together with a “tailored” number of CD3+ cells as well as engraftment facilitating cells in order to achieve rapid hematopoietic engraftment while reducing the risk of graft rejection and GVHD. This regimen might be an additional option when unrelated donor HSCT is considered for a patient with MPS1-H.

Low penetration of caspofungin into cerebrospinal fluid following intravenous administration of standard doses

The kinetics of caspofungin (CAS) in cerebrospinal fluid (CSF) following intravenous (i.v.) administration has been studied exclusively in animal models. Human data are missing so far. In this study, 13 CSF samples were obtained at different time points following i.v. infusion of CAS in ten paediatric haemato-/oncological patients (age range 1.0-14.2 years, median 8.6 years) without signs of central nervous system (CNS) infection (n = 10 samples) or with infectious meningitis (n = 3 samples). Serum samples were obtained concurrently. Liquid chromatography-tandem mass spectrometry was used for CAS quantification. Whilst CAS serum levels were in the expected range, varying between 0.6 and 20.3 µg/mL (median 7.0 µg/mL), 11 of 13 CSF levels were below the limit of detection of 0.084 µg/mL at 3.0-48.0 h (median 23.3 h) following i.v. infusion. Only two (of three) levels in patients with bacterial meningitis were above the limit of detection (0.3 µg/mL and 0.09 µg/mL, respectively). These results indicate the low capacity of CAS to penetrate into the CNS even in inflamed meninges. Monotherapy with standard doses of CAS appears not to be suitable for treatment of fungal CNS infections.

Neuroblastoma causes alterations of the intestinal microbiome, gut hormones, inflammatory cytokines, and bile acid composition.

To assess the effect of neuroblastoma (NB) on the intestinal microbiome, metabolism, and inflammatory parameters in a murine model.

Osteomyelitis of the Patella in a 10-Year-Old Girl: A Case Report and Review of the Literature

The incidence of osteomyelitis constantly declines. While the disease most commonly affects the long bones, involvement of the patella is rarely seen. Due to this rarity and the variable clinical presentation, diagnosis is often delayed. The present case report describes a 10-year-old female patient with a delayed diagnosis of patella osteomyelitis. The diagnostic procedures and the treatment regimen are described. Additionally, a detailed literature review of the available publications reporting osteomyelitis of the patella in children is presented.

Enterovirus infections in pediatric hematologic/oncologic patients

Enteroviruses (EV) are a large group of Picornaviruses associated with respiratory, gastrointestinal, and neurologic symptoms in the immunocompetent host. Little is known about the epidemiologic and clinical impact in pediatric hematologic/oncologic patients.

Life-threatening sinusoidal obstruction syndrome after high-dose chemotherapy linked to compound heterozygous mutations in ABCB11

To the Editor: Sinusoidal obstruction syndrome (SOS, formerly known as veno-occlusive disease) is a severe complication of chemotherapy including cyclophosphamide, busulphan, dactinomycin, radiationcontaining treatment regimens for solid tumors, and conditioning regimen in the context of hematopoietic stem cell transplantation (HSCT). SOS results from damage to the hepatic endothelial cells and hepatocellular necrosis, and it manifests with hepatomegaly, ascites, weight gain, and jaundice.1,2 The treatment and prophylaxis of SOS in children after HSCT includes defibrotide,3 promoting endothelial integrity, and regulating coagulation.2,4 Its genetic basis is poorly understood. The membrane-associated protein bile salt export pump (BSEP) is needed to transport cholate conjugates from hepatocytes to the bile. Mutations in theBSEP-encoding gene,ATP-binding cassette, subfamily Bmember 11 (ABCB11), are associated with benign recurrent intrahepatic

Congenital Infantile Fibrosarcoma Causing Intestinal Perforation in a Newborn

Congenital infantile fibrosarcoma (CIF) is a rare malignant mesenchymal tumor and only 14 cases have been reported with gastrointestinal manifestation. We report about a female newborn delivered per emergency cesarean section at 34 weeks of gestation. Postnatally, she rapidly developed an acute abdomen and sonographic evidence of intestinal perforation requiring laparotomy on the first day of life. A perforated 2 × 3 cm sized spherical tumorous structure of the jejunum was identified. Due to unknown histopathology at this point and unclear resectional margins, she received a temporary ileostomy, which was closed two months later. Histopathology revealed a congenital intestinal fibrosarcoma without the characteristic ETV6-NTRK3 fusion transcript. In conclusion, this rare tumor must be considered as differential diagnosis of intestinal perforations in newborns.