Carola Hasan

Procalcitonin in paediatric cancer patients: its diagnostic relevance is superior to that of C-reactive protein, interleukin 6, interleukin 8, soluble interleukin 2 receptor and soluble tumour necrosis factor receptor II.

Sensitive parameters of inflammation are rare in neutropenic cancer patients. In this study, procalcitonin (PCT), C‐reactive protein (CRP), interleukin 6 (IL‐6), IL‐8, the soluble IL‐2 receptor (sIL‐2R) and the soluble tumour necrosis factor receptor II (sTNFRII) were evaluated for their diagnostic relevance in febrile episodes of cancer patients. Plasma or serum levels of these parameters were determined in neutropenic children with febrile episodes (n = 122) classified according to both the kind of infection [60 cases of fever of unknown origin (FUO), 28 cases of localized infection, 13 cases of pneumonia, 20 cases of bacteraemia, one case of fungaemia] and the World Health Organization (WHO) score of chemotherapy‐induced mucositis. At baseline and during the febrile episodes, the highest levels of all parameters were observed in cases of gram‐negative bacteraemia. However, in FUO and localized infections, low or only slightly elevated median levels of all parameters were documented. The degree of chemotherapy‐induced mucositis did not influence the value of any parameter. In comparison with the other inflammatory parameters, PCT (optimum cut‐off level 0·5 μg/l) was a more sensitive and more specific parameter in the diagnosis of high‐risk (gram‐negative bacteraemia) and low‐risk (FUO) episodes, as well as in the sequential assessment of all febrile neutropenic episodes.

Surveillance for Nosocomial and Central Line-Related Infections Among Pediatric Hematology-Oncology Patients

OBJECTIVE To determine the incidence of all nosocomial infections (NIs) in pediatric hematology-oncology patients, as well as central venous access device (CVAD)-associated infections acquired during home care. DESIGN Prospective surveillance study. SETTING The Pediatric Hematology and Oncology Department at the University Hospital Bonn. PATIENTS All patients admitted from January through October 1998 (surveillance period). METHODS Standardized surveillance system based on the Centers for Disease Control and Preventions National Nosocomial Infections Surveillance System. RESULTS A total of 143 patients were hospitalized for 3,701 days (776 admissions) during the surveillance period. Of the 40 NIs detected, 26 were CVAD-related, with 21 bloodstream infections (BSIs) and 5 local infections. Four were Clostridium difficile-associated diarrheal illnesses, 3 were pneumonias, and 7 were other infections. The incidence of NIs was 10.8 per 1,000 patient-days (5.2 NIs/100 admissions). The overall CVAD-related BSI rate was 7.4 per 1,000 utilization days, without a significant difference between implanted infusion ports and tunneled catheters. In addition, 7 CVAD-related infections occurred during home care. All 8 BSIs associated with tunneled catheters and 13 (76%) of the 17 BSIs associated with ports were acquired nosocomially. For inpatients and outpatients combined, the exit sites of tunneled catheters were more likely to become locally infected than were the needle entry sites of ports (relative risk, 8.0; P=.007). In 30 (75%) of the 40 NIs, the affected patients had severe neutropenia (<500/mm3) at the time of infection. CONCLUSIONS Most NIs in the pediatric hematology-oncology patients were associated with CVAD devices. Although many infections in this high-risk population may not be preventable through infection control measures, the careful evaluation of specific infection rates permits the identification of risk factors that may be targeted by infection control programs. Prospective surveillance for NIs on pediatric oncology units is an indispensable tool for this internal quality control.

Acupuncture against chemotherapy-induced nausea and vomiting in pediatric oncology

GoalsIn this multicenter crossover study, our aim was to evaluate the efficacy and acceptance of acupuncture as a supportive antiemetic approach during highly emetogenic chemotherapy in pediatric oncology.Patients and methodsEleven children receiving several courses of highly emetogenic chemotherapy for treatment of solid tumors were included. Randomization allocated patients to start chemotherapy either with antiemetic medication plus acupuncture or antiemetic medication alone. During all study courses, patients continued to receive their programmed and additional antiemetic medication as needed. Acupuncture was given at day 1 of chemotherapy and at subsequent days on patient’s demand. The amount of baseline and additional antiemetic medication during chemotherapy was documented. Patients maintained a daily diary of vomiting episodes and completed an evaluated nausea score at the end of every course. Their body weight was taken before and after a chemotherapy course.Main resultsTwenty-two courses with or without acupuncture were compared. The benefits of acupuncture in adolescents with respect to the reduction of additional antiemetic medication were observed. Acupuncture enabled patients to experience higher levels of alertness during chemotherapy and reduced nausea and vomiting. Except for needle pain, no side effects were noted. Patient’s acceptance of acupuncture was high.ConclusionOur data indicate that acupuncture might reduce antiemetic medication and episodes of vomiting in pediatric oncology.

Piperacillin, beta-lactam inhibitor plus gentamicin as empirical therapy of a sequential regimen in febrile neutropenia of pediatric cancer patients

Abstract. The beta-lactam/beta-lactamase inhibitor combinations are a good choice for empirical antimicrobial therapy in febrile neutropenic patients, because their antibacterial spectra include both gram-negative and gram-positive pathogens. This trial was initiated to assess the efficacy and safety of piperacillin with the beta-lactam inhibitors sulbactam (PSG group) or tazobactam (PTG group) and gentamicin as initial therapy in febrile neutropenia of pediatric patients. In a prospective study, 239 episodes of fever and neutropenia were analyzed for the clinical and microbiological response dependent on infection etiology and treatment group: 66.5% of episodes were classified as fever of unknown origin (FUO) and 33.5%, as microbiologically or clinically documented infections; 19.2% of all episodes were due to bacteremia, predominantly caused by gram-positive organisms (69.6%). The response to the initial therapy was 55.2% overall and 65.4% in episodes of FUO with a significant higher success rate in the PSG group than in the PTG group (70.1% vs. 52.4%, P=0.039), and 35.0% in documented infections. In episodes with documented infection longer duration of fever and antimicrobial therapy was recorded than for FUO episodes. Four patients died of causes related to infection. Fever relapse occurred in 26 episodes (11.1%), predominantly in patients who were still neutropenic. Toxic side effects were minimal. The initial therapy of piperacillin with sulbactam or tazobactam in combination with gentamicin is well tolerated, and its efficacy is comparable to that of other combination therapies or of monotherapy with beta-lactam antibiotics in pediatric neutropenic cancer patients.

Pancreatic toxicity after liposomal amphotericin B

Summary.  Though liposomal amphotericin B has been available in Germany since 1992, efficacy and safety of this formulation of amphotericin B are still not well‐documented in children. As far as gastrointestinal side‐effects are concerned, an elevated alkaline phosphatase and elevated transaminases have been reported. In our department, liposomal amphotericin B had been used since 1994 to treat patients with proven or suspected fungal infections in a daily dose of 1–3 mg kg−1. Additionally, patients with high‐dose chemotherapy and autologous stem cell support received liposomal amphotericin B prophylactically in a dose of 1 mg kg−1 three times per week. We performed a retrospective analysis of all 31 patients who had received liposomal amphotericin B by 1999. In five patients, an isolated transient elevation of the serum lipase level during, or shortly after, the therapy with liposomal amphotericin B was detected. Three of these patients showed clinical signs of pancreatitis, with one patient displaying slightly elevated transaminases. So far, elevated levels of serum lipase have not been described as a possible side‐effect of a liposomal amphotericin B therapy. The pathogenesis of this elevation is unclear. As possible reasons, an enzyme induction due to fat overload or a toxic damage of the pancreatic tissue by the liposomes or amphotericin B itself are discussed.

ACUTE LIVER DISEASE AND APLASTIC ANEMIA ASSOCIATED WITH THE PERSISTENCE OF B19 DNA IN LIVER AND BONE MARROW

We observed a 12-year-old boy with acute hepatitis and associated aplastic anemia (AA), where parvovirus B19 genome was repeatedly detected in liver and bone marrow biopsies, but not in blood samples. We conclude that: (1) B19 infection may be underdiagnosed as the causative agent responsible for acute hepatitis and associated AA if no organ-specific diagnostic tests are applied; (2) B19 deoxyribonucleic acid (DNA) can persist in the liver; (3) during the acute phase of hepatitis, extramedullary hematopoiesis may be involved in the susceptibility for hepatic B19 infection.

The role of complete surgical resection in stage IV neuroblastoma

The purpose of this study was to examine the outcome of attempted radical surgical resection in patients with stage IV neuroblastoma. Between 1989 and 2003, 20 (median age 2.4 years, range 0.5–8.7 years) children with stage IV neuroblastoma were treated at the Department of Pediatrics. Surgery was performed in 7 consecutive children (6 male and 1 female) between July 1997 and February 2002 at the Department of Urology in Bonn. Mean age at diagnosis was 57 months (21–104 months). Mean age at the time of surgery was 54 months (8–390 months). Follow-up was available for all patients (100%) and mean follow-up after the operation was 32.5 months (4–56 months). Primary localization of the tumor was retroperitoneal in all cases; 4 out of 7 patients (57%) also had additional adrenal, 3 out of 7 (42%) paraganglion and 1 out of 7 (14%) thoracic primaries. Bone marrow and lymph node metastases were found in all patients (100%). Surgery led to complete tumor resection in 6 out of 7 patients (85%). Surgical approach was abdominal (chevron incision) in 6 out of 7 (85%) of the patients, in one patient the approach was thoraco-abdominal. After induction chemotherapy and delayed surgery, 6 out of 7 (86%) patients showed a complete remission (CR) and the mean CR lasted for about 27.7 months (range 3.1–55.4 months). At the last time of follow-up 5 out of 7 (71%) patients were alive, 2 had died due to recurrent disease. Mean time to recurrent disease was 24 and 51 months, respectively. Mean overall survival time since diagnosis was 38.3 months (11–64 months) and mean event-free survival was 34.5 months (11–60.3 months). The final outcome, overall survival and event-free survival time was influenced by metastatic or local relapse. Tumor resection is beneficial but the value of surgery can only be judged when we are able to control metastatic disease in stage IV neuroblastoma. The final outcome may rely on the extent of complete surgical resection, but is also related to treatment of metastases. A longer follow-up period is indicated to detect long term outcome.

Cyanotic Raynaud's phenomenon with conventional but not with liposomal amphotericin B: three case reports

Summary. Despite its common adverse effects intravenous (i.v.) amphotericin B is an indispensable antifungal drug in childhood oncology. We report here on three cases of painful cyanotic Raynauds phenomenon after i.v. administration or inhalation of amphotericin B. A liposomal i.v. preparation of amphotericin B was well tolerated by the infants. Spasms of peripheral vessels mediated by thromboxane A2 could be responsible for the Raynauds phenomenon. Hence, inhibitors of prostaglandin synthesis are suggested for therapy.

Treatment of Relapsed AML of Childhood with Daunoxome-FLAG (Liposomal Daunorubicin, Fludarabine, High-Dose Cytarabine and G-CSF)

Following years of successful treatment of children with refractory or relapsed acute myelogenous leukemia (AML) with the Idarubicin (IDA)-FLAG regimen in this study a combination therapy of liposomal daunorubicin (DaunoXome), fludarabine, cytarabine and G-CSF (DNX-FLAG) was emphasized on the assumption that the liposomal anthracyc-line would have lower cardiotoxicity than the non-liposomal one. This pilot trial was designed to explore the potential feasibility and efficacy of this reinduction therapy prior to BMT/PBSCT.