Michael Paulussen

Universität Witten/Herdecke, Witten, North Rhine-Westphalia, Germany

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Publications (112)620.63 Total impact

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    ABSTRACT: Based on the randomised Euro-EWING99-R1 trial, vincristine, adriamycin, cyclophosphamide (VAC) may be able to replace vincristine, adriamycin, ifosfamide (VAI) in the treatment of standard-risk Ewing sarcoma. However some heterogeneity of treatment effect by gender was observed. The current exploratory study aimed at investigating the influence of gender on treatment efficacy and acute toxicity. Impact of gender on event-free survival (EFS), acute toxicity by course, switches between treatment arms and cumulative dose of alkylating agents was evaluated in multivariable models adjusted for age including terms to test for heterogeneity of treatment effect by gender. The analysis of the EFS was performed on the intention-to-treat population. EFS did not significantly differ between the 509 males and 347 females (p=0.33), but an interaction in terms of efficacy was suspected between treatment and gender (p=0.058): VAC was associated with poorer EFS than VAI in males, hazard ratio (HR) (VAC/VAI)=1.37 [95% confidence interval (CI), 0.98-1.90], contrasting with HR=0.81 [95%CI, 0.53-1.24] in females. Severe toxicity was more frequent in females, whatever the toxicity type. Thirty patients switched from VAI to VAC (9/251 males, 4%, and 21/174 females, 12%) mostly due to renal toxicity, and three from VAC to VAI (2/258 males, 0.8%, and 1/173 females, 0.6%). A reduction of alkylating agent cumulative dose >20% was more frequent in females (15% versus 9%, p=0.005), with no major difference between VAC and VAI (10% versus 13%, p=0.15). Differences of acute toxicity rate and cumulative doses of alkylating agents could not explain the marginal interaction observed in the Euro-EWING99-R1 trial data. Effects of gender-dependent polymorphism/activity of metabolic enzymes (e.g. known for CYP2B6) of ifosfamide versus cyclophosphamide should be explored. External data are required to further evaluate whether there is heterogeneity of alkylating agent effect by gender. NCT00987636 and EudraCT 2008-003658-13. Copyright © 2015 Elsevier Ltd. All rights reserved.
    European journal of cancer (Oxford, England: 1990) 08/2015; DOI:10.1016/j.ejca.2015.06.123 · 4.82 Impact Factor
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    ABSTRACT: Coenzyme Q10 (CoQ10) is synthesized in most human tissues, with high concentration in the skeletal muscle. CoQ10 functions in the mitochondrial respiratory chain and serves as a potent liphophilic antioxidant in membranes. CoQ10 deficiency impairs mitochondrial ATP synthesis and increases oxidative stress. It has been suggested that plasma CoQ10 status is not a robust proxy for the diagnosis of CoQ10 deficiency. We determined the concentration and redox-status of CoQ10 in plasma and muscle tissue from 140 healthy children (0.8-15.3 yrs) by HPLC with ED. There was no correlation between CoQ10 concentration or redox status between plasma and muscle tissue. Lipid-related CoQ10 plasma concentrations showed a negative correlation with age (Spearman's, p≤0.02), but there was no significant age-related correlation for muscle concentration. In muscle tissue we found a distinct shift in the redox status in favour of the oxidized proportion with increasing age (Spearman's, p≤0.00001). Reference values for muscle CoQ10 concentration (40.5±12.2 pmol/mg wet tissue) and CoQ10 redox status (46.8±6.8% oxidized within total) were established for healthy children. The age related redox shift in muscle tissue suggests changes in antioxidative defence during childhood. The reference values established here provide a necessary prerequisite for diagnosing early CoQ10 deficiency.Pediatric Research (2015); doi:10.1038/pr.2015.124.
    Pediatric Research 06/2015; DOI:10.1038/pr.2015.124 · 2.84 Impact Factor
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    ABSTRACT: Curative therapies for Ewing sarcoma have been developed within cooperative groups. Consecutive clinical trials have systematically assessed the impact and timing of local therapy and the activity of cytotoxic drugs and their combinations. They have led to an increase of long-term disease-free survival to around 70% in patients with localized disease. Translational research in ES remains an area in which interdisciplinary and international cooperation is essential for future progress. This article reviews current state-of-the art therapy, with a focus on trials performed in Europe, and summarizes novel strategies to further advance both the cure rates and quality of survival. © Georg Thieme Verlag KG Stuttgart · New York.
    Klinische Pädiatrie 05/2015; 227(3):108-115. DOI:10.1055/s-0035-1545263 · 1.90 Impact Factor
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    ABSTRACT: PURPOSE: Relative efficacy and toxicity of cyclophosphamide compared with ifosfamide are debatable. The Euro-EWING99-R1 trial asked whether cyclophosphamide may replace ifosfamide in combination with vincristine and dactinomycin (vincristine, dactinomycin, and cyclophosphamide [VAC] v vincristine, dactinomycin, and ifosfamide [VAI]) after an intensive induction chemotherapy containing vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) in standard-risk localized disease (NCT00020566). METHODS: Standard-risk Ewing sarcomas were localized tumors with either a good histologic response to chemotherapy (< 10% cells) or small tumors (< 200 mL) resected at diagnosis or receiving radiotherapy alone as local treatment. Patients entered the trial after six VIDE+1 VAI courses. Allocated treatment was either 7 VAC courses with 1.5 g/m2 of cyclophosphamide or seven VAI-courses with 6 g/m2 ifosfamide. The limit of noninferiority was set at -8.5% for the 3-year event-free survival rate (EFS), equivalent to 1.43 in terms of the hazard ratio of event (HRevent). RESULTS: This large international trial recruited 856 patients between February 2000 and March 2010 (n = 431 receiving VAC and n = 425 receiving VAI). With a median follow-up of 5.9 years, the 3-year EFSs were 75.4% and 78.2%, respectively, the 3-year EFS difference was -2.8% (91.4% CI, -7.8 to 2.2%), the HRevent was 1.12 (91.4% CI, 0.89 to 1.41), and the HRdeath was 1.09 (91.4% CI, 0.84 to 1.42; intention-to-treat). The HRevent was 1.22 (91.4% CI, 0.96 to 1.54) on the per-protocol population. Major treatment modifications were significantly less frequent in the VAC arm (< 1%) than in the VAI arm (7%), mainly resulting from toxicity. Patients experienced more frequent thrombocytopenia in the VAC arm (45% v 35%) but fewer grade 2 to 4 acute tubular toxicities (16% v 31%). CONCLUSION: Cyclophosphamide may be able to replace ifosfamide in consolidation treatment of standard-risk Ewing sarcoma. However, some uncertainty surrounding the noninferiority of VAC compared with VAI remains at this stage. The ongoing comparative evaluation of long-term renal and gonadal toxicity is crucial to decisions regarding future patients. ©American Society of Clinical Oncology.
    Journal of Clinical Oncology 06/2014; · 18.43 Impact Factor
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    ABSTRACT: Relative efficacy and toxicity of cyclophosphamide compared with ifosfamide are debatable. The Euro-EWING99-R1 trial asked whether cyclophosphamide may replace ifosfamide in combination with vincristine and dactinomycin (vincristine, dactinomycin, and cyclophosphamide [VAC] v vincristine, dactinomycin, and ifosfamide [VAI]) after an intensive induction chemotherapy containing vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) in standard-risk localized disease (NCT00020566).
    Journal of Clinical Oncology 06/2014; 32(23). DOI:10.1200/JCO.2013.54.4833 · 18.43 Impact Factor
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    ABSTRACT: BACKGROUND: Recurrences in primary localized alveolar rhabdomyosarcoma (RMA) are common. Post-relapse survival is poor. We evaluated prognostic factors including relapse treatment in patients with recurrent RMA. METHODS: Relapses occurred in 115/235 patients with nonmetastatic RMA treated in four consecutive CWS-trials after achievement of a complete remission. Sufficient information about post-relapse treatment and outcome could be obtained in 99 patients and was retrospectively analyzed. RESULTS: Nine of 99 patients received no salvage therapy and died after a median of 2 months. The remaining 90 patients received multimodal relapse treatment including mandatory chemotherapy. Recurrences were grossly resected in 39 patients; 57 patients received radiation. At a median follow-up from relapse of 8 years, 20 patients were alive and disease-free (5-year post-relapse survival [PROS] 21.3 ± 8). All surviving patients apart from a single individual had an isolated, circumscribed recurrence. Sixteen of 20 survivors were treated with adequate local relapse therapy (ALRT, i.e., either complete resection or gross resection + radiation). Survival in the subgroup of 27 individuals with circumscribed recurrences and ALRT was significantly better (PROS 53.7 ± 19) compared with disseminated recurrences and/or tumors treated without ALRT. Absence of primary lymph node involvement, circumscribed relapses, ALRT, and achievement of a second CR were identified as independent favorable risk factors. CONCLUSION: Post-relapse survival for primary localized RMA is generally poor. However, certain patient groups differed significantly in their likelihood of survival and 50% of patients with circumscribed relapses treated with ALRT survived. These findings may form the basis for an evidence-based risk-stratification for recurrent disease including relapse treatment. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 08/2013; 60(8). DOI:10.1002/pbc.24488 · 2.56 Impact Factor
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    ABSTRACT: Background: The randomized Euro-EWING99-R1 trial assessed noninferiority of cyclophosphamide- vs ifosfamide-based consolidation regimens (VAC vs VAI) in SR localized ES patients. Overall, efficacy of VAC was deemed acceptable compared to VAI, with hazard ratio of event HR = 1.12 [0.89 - 1.41]. Based on its gender-stratified randomization, influence of gender on efficacy and acute toxicity were additionally explored. Methods: Impact of gender on EFS, acute toxicity by course, switches between treatment arms, and cumulative dose of alkylating agents was evaluated in multivariable models, including terms to test for heterogeneity of treatment effect by gender. Analysis was performed on the intention to treat population. Results: 856 patients (509 males, 347 females) were recruited between 2000 and 2010: 425 VAI and 431 VAC. EFS did not significantly differ between genders (p=0.33), but a marginal interaction was seen between treatment and gender (p=0.083): VAC was associated with poorer EFS in males than VAI, HR(VAC/VAI) = 1.34 [0.96 - 1.86], whereas, in females, VAC was slightly better than VAI, HR = 0.83 [0.54 - 1.28]. Similarly, males had a worse EFS than females with VAC, HR(M/F) = 1.42 [0.97 – 2.08], whereas results by gender were very similar with VAI, HR = 0.91 [0.62 – 1.33]. Severe hematological toxicity was more frequent with VAC than VAI whereas tubular renal impairment was more frequent with VAI. Severe toxicity was more frequent in females than in males, whatever the toxicity type, with no significant interaction between treatment and gender effect. 30 patients switched from VAI to VAC (21 F, 9 M) mostly due to renal toxicity, and 3 from VAC to VAI (1 F, 2 M). A reduction of alkylating agent cumulative dose >20% was more frequent in females (15% vs 9%, p=0.01), with no major difference between VAI and VAC (13% vs 10%, p=0.21). Conclusions: The marginal interaction between gender and type of alkylating agent on EFS has to be validated on external data. Differences of acute toxicity rate and compliance are not sufficient explanation. Effects of gender-dependant polymorphism/activity of metabolic enzymes (e.g. known for CYP2B6) of ifosfamide vs cyclophosphamide should be explored. Clinical trial information: NCT00020566.
    Journal of Clinical Oncology 06/2013; 31(suppl):10031. · 18.43 Impact Factor
  • Petra Niklowitz · Frank Döring · Michael Paulussen · Thomas Menke
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    ABSTRACT: Swine tissues were used as surrogates for human tissues with coenzyme Q10 (CoQ10) as the primary endogenous quinoid to establish a reliable method for the analysis of total CoQ10 concentration and redox status using the reduced and oxidized forms of CoQ9 as internal standards. Specimens of frozen swine tissues were disrupted by bead milling using 2-propanol as the homogenization medium supplemented with the internal standards. After hexane extraction, CoQ10 was analyzed via high-performance liquid chromatography with electrochemical detection. The method is linear (12–60 mg fresh muscle tissue/sample), sensitive (∼200 pmol CoQ10/sample), and reproducible (coefficients of variation of 6.0 and 3.2% for total CoQ10 and 2.4 and 3.2% for the redox status of within-day and day-to-day precision, respectively), with analytic recoveries for ubiquinone-10, ubihydroquinone-10, and total Q10 of 91, 104, and 94%, respectively. The concentration and redox status were stable for at least 3 months at −84 °C. The total CoQ10 concentrations (pmol/mg fresh tissue) in swine tissues were as follows: lung (17.4 ± 1.42), skeletal muscle (26.7 ± 2.57), brain (40.7 ± 4.02), liver (62.1 ± 31.0), kidney (111.7 ± 37.08), and heart muscle (149.1 ± 36.78). Significant tissue-specific variations were also found for the redox status (% oxidation of total): swine liver (∼28), lung (∼36), kidney (∼37), heart muscle (∼57), skeletal muscle (∼61), and brain (∼67).
    Analytical Biochemistry 06/2013; 437(1):88–94. DOI:10.1016/j.ab.2013.02.015 · 2.22 Impact Factor
  • Michael Paulussen · Uta Dirksen · Heribert Juergens · Andreas Ranft
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    ABSTRACT: Background: 25% of Ewing sarcoma (ES) patients are 15-20 years of age; their outcome is worse than in children. The impact of the type (paediatric versus non-paediatric) and experience (patients per year) of the treating institution on outcome is unclear. Patients and Methods: 725 patients aged 15-20 years, treated on consecutive GPOH ES-trials (CESS-81, CESS-86, EICESS-92, EURO-EWING99), were analysed regarding event-free survival (EFS) in relation to type and experience of institution (“small”: <1 patient/year). 498 patients (68.7%) presented with localized disease (R1), 93 patients (12.8%) had pulmonary metastases (R2pulm), 134 patients (18.5%) had extra-pulmonary metastases (R3). Median follow-up was 3.85 years (range 0.20-28.63). Results: In the early trials (EI-)CESS-81-86-92, patients 15-20 years fared better when treated in paediatric (3y-EFS 0.54, SE=.03) rather than in other institutions (3y-EFS 0.43, SE=.05, p=.010; n=384). In the EURO-EWING99 trial, no effect of the type of institution (3y-EFS 0.57 vs. 0.61; p=.536; n=341) was found. In the early trials, outcome was worse in small institutions, but this effect disappeared in the recent EURO-EWING99 trial: “Small” institutions demonstrated improvements in patient outcome in EURO-EWING99 compared to previous trials (3y-EFS 0.63 versus 0.46; p=.003), whereas larger institutions did not (3y-EFS 0.56 versus 0.52; p=.607). In multivariate analyses, the interactions observed in the univariate analyses between period of treatment (EICESS81-92 vs. EURO-EWING99) and type of institution, or experience of institution, remained significant even when corrected for known confounders (p<.05). Conclusions: In CESS-81/CESS-86/EICESS92, patients aged 15-20 years fared better in paediatric and in more experienced institutions. Both effects were no more observed in the recent EURO-EWING99 trial. Outcome in smaller institutions has improved over time. As non-paediatric institutions in our trials tended to be “small”, we speculate that this also accounts for the improved outcome in non-paediatric institutions in recent years.
    Pediatric Blood & Cancer 12/2012; 59(6):1046. · 2.56 Impact Factor
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    ABSTRACT: Ewing Sarcoma (ES) of the hand or foot is a rare clinical condition. Due to the critical site, it is of major importance to choose an optimal procedure for local control in terms of outcome and function. Local therapeutic options for these patients range from: surgery (OP), surgery followed by radiotherapy (OP & RT), or radiotherapy (RT) alone.Data from 80 patients with ES of the hand or foot were analyzed. All patients received chemotherapy according to the protocols of the Cooperative Ewing Sarcoma Study Group (CESS) from 1991 to 2009 (EICESS-92 and EURO-E.W.I.N.G.99). Local therapy consisted of: OP in 39%, OP & RT in 44%, and RT in 12%. In 5% of the patients no local therapy (noL) was performed. Primary endpoint of our study was the event-free-survival (EFS).The 3-year overall EFS was 62% (95%CI 0.50-0.72). Patients with localized disease had a significantly better outcome with an EFS of 77% (95%CI 0.63-0.86), compared to patients with primary disseminated disease with an EFS of 30% (95%CI 0.14-0.49; p<0.001). In comparing local treatment modalities, no significant difference was observed. The 3-year EFS for OP was 61% (95% CI 0.40-0.76), for OP & RT 66% (95%CI 0.47-0.79) and for RT only 70% (95%CI 0.32-0.89) (p=0.253). Patients who did not receive local treatment had an unfavourable prognosis (3-year EFS=0.25; 95%CI 0.01-0.67; p=0.024). A multivariate analysis which included local treatment modality and known prognosticators, showed that primary dissemination was the only significant prognostic factor.Ewing sarcoma of the hand or foot is associated with a favourable outcome. Our data analysed a limited group of patients and thus did not provide a clear indication for a preferred local treatment modality.
    Klinische Pädiatrie 10/2012; 224(6):348-352. DOI:10.1055/s-0032-1327607 · 1.90 Impact Factor
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    ABSTRACT: Adoptive immunotherapy with allogeneic purified natural killer (NK) cell products might exert graft-versus-tumor alloreactivity with little risk of GVHD. In a prospective phase II study in two centers, we administered purified NK cell products to high-risk patients treated with haploidentical T-cell-depleted SCT. Sixteen patients received a total of 29 NK cell infusions on days +3, +40 and +100 after transplantation. Median doses (and ranges) of infused NK- and T-cells per product were 1.21 (0.3-3.8) × 10(7)/kg and 0.03 (0.004-0.72) × 10(5)/kg, respectively. With a median follow-up of 5.8 years 4/16 patients are alive. Cause of death was relapse in five, GVHD in three, graft failure in three, and transplant related neurotoxicity in one patient. Four patients developed acute GVHDgrade II, all receiving a total of 0.5 × 10(5) T cells/kg. Compared with historical controls, NK cell infusions had no apparent effect on the rates of graft failure or relapse. Adoptive transfer of allogeneic NK cells is safe and feasible, but further studies are needed to determine the optimal dose and timing of NK cell therapy. Moreover, NK cell activation/expansion may be required to attain clinical benefit, while careful consideration must be given to the number of T cells infused.Bone Marrow Transplantation advance online publication, 3 September 2012; doi:10.1038/bmt.2012.162.
    Bone marrow transplantation 09/2012; 48(3). DOI:10.1038/bmt.2012.162 · 3.47 Impact Factor
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    ABSTRACT: The antioxidant status of coenzyme Q10 (CoQ10) was investigated in plasma, erythrocytes, and platelets of juvenile patients with anorexia nervosa. Blood for analysis of the CoQ10 status was taken from 16 juvenile patients suffering from anorexia nervosa (restricting form) at the time point of admission to the hospital and at discharge after about 12 weeks. Plasma and blood cells isolated by a density gradient were stored at -84 °C until analysis. CoQ10 concentration and redox status were measured by high pressure liquid chromatography with electrochemical detection and internal standardization. The improvement of physical health during the hospital refeeding process was followed up by the body mass index (BMI). The antioxidant status of plasma CoQ10 in juvenile patients suffering from anorexia nervosa indicated no abnormalities in comparison to healthy controls. However, the decreased concentration of CoQ10 observed in platelets at the time point of hospital admission may represent mitochondrial CoQ10 depletion. This initial deficit improved during the hospital refeeding process. The platelet CoQ10 concentration showed a positive correlation to the BMI of the patients.
    BioFactors 01/2012; 38(1):53-8. DOI:10.1002/biof.193 · 3.00 Impact Factor
  • Pediatric Blood & Cancer 11/2011; 57(5):710-710. · 2.56 Impact Factor
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    ABSTRACT: The prognosis in patients with relapsed Ewing sarcoma is unfavorable. Our investigation identifies factors predicting for the outcome following relapse. We analyzed type of relapse, time to relapse and overall survival after relapse (OSr) in 714 patients with first recurrence. All patients had been treated within the Cooperative Ewing Sarcoma Studies (CESS) 81 or 86, or the European Intergroup CESS (EICESS 92). OSr time was calculated from diagnosis of first relapse to last follow-up or death. Median follow-up time from diagnosis of primary disease was 2.2 years (mean = 4.0; range: 0.2-24.9). Relapse sites were local in 15%, combined local and systemic in 12%, and systemic in 73%. Among patients with a localized primary tumor, 20% relapsed locally, while 12% showed combined and 68% systemic relapse. When the primary disease was disseminated, 82% developed systemic, 13% combined, and 5% local relapse. Five-year OSr was 0.13 (SE = 0.01). Outcome following local relapse, with a 5-year survival rate of 0.24 (P < 0.001), was superior to outcome after systemic or combined recurrence. Five-year OSr was 0.07 (SE = 0.01) in patients who relapsed 0-2 years after the diagnosis of primary disease, as compared to a 5-year OSr of 0.29 (SE = 0.03) when relapse occurred later. 5-year OSr in Ewing sarcoma is poor (<0.2). Prognostically favorable factors are: late onset (>2 years) and strictly localized relapse.
    Pediatric Blood & Cancer 10/2011; 57(4):549-53. DOI:10.1002/pbc.23040 · 2.56 Impact Factor
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    ABSTRACT: Background: Anthracyclines and alkylating agents are the main effective drugs known for ES. Ifosfamide and cyclophosphamide are widely used, have different toxicity profiles and unknown relative efficiency. The Euro-EWING.99-R1 trial compared, in SR localized ES, two consolidation regimens combining either ifosfamide or cyclophosphamide with vincristine and D-actinomycin (VAI vs VAC) given after an intense induction CT containing vincristine, ifosfamide, doxorubicin and etoposide (VIDE) (NCT00020566 ). Methods: SR tumors were localized ES with either a good histological response to VIDE chemo (<10% cells), or small tumors (< 200 ml) resected at diagnosis or receiving radiotherapy alone as local treatment. Pts entered the trial after 6 VIDE + 1 VAI courses. Allocated treatment was either 7 VAI courses with ifo = 6 g/m²/course or 7 VAC courses with cyclo = 1.5 g/m²/course. Randomization was stratified by gender, age, local treatment and data center. It was a non-inferiority trial comparing VAC to VAI with a limit of non-inferiority set at -8.5% for 3-y event-free survival rate (EFS). Overall, 806 pts were required to achieve 80%-power with 1-sided alpha = 5%. 91.4%-confidence intervals (CI) are given for this final analysis performed after 3 interim analyses. Results: 856 pts were recruited between 02/2000 and 08/2010 in 202 European pediatric and adult oncology centers in 11 countries: 424 VAI and 432 VAC. With a median FU of 4.6 y, the main results were: 3-y EFS = 77.1 and 76.0% respectively, 3-y EFS difference = -1.1% (-6.3; +4.2), hazard ratio (HR) of event = 1.06 (0.83; 1.36), HR of death = 1.05 (0.78; 1.41) (intention to treat). Results were stable on the per protocol population. Major modifications of CT were significantly more frequent in the VAI arm (13%) than in the VAC arm (6%) due to toxicity but also to an inferior compliance. We observed more thrombocytopenia in the VAC arm but more grade 2-4 acute tubular renal toxicity in the VAI arm (31 vs 16%). Conclusions: Cyclophosphamide and ifosfamide have a similar efficacy in consolidation treatment of standard risk Ewing sarcoma. Late effects studies are on-going to compare renal and gonadal toxicity of both arms.
    Journal of Clinical Oncology 06/2011; 29(15_suppl):9517. · 18.43 Impact Factor
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    ABSTRACT: To prospectively assess the incidence rates and characteristics of central venous line associated bloodstream infections (CLABSI) in one institution. All patients with indwelling central venous catheters (CVC) between 1 April 2008 and 31 March 2009 were enrolled. The medical records of patients were reviewed and information on relevant characteristics entered into a standardised questionnaire. Central laboratory records were regularly checked for positive blood cultures in study patients. There were 209 CVC for a total of 14752 CVC days in 152 patients (88 males, 58%) including neonates and patients with surgical conditions and haemato-oncological and other underlying diseases. Median age at CVC insertion was 3 months (IQR 0-56 months). Fourteen CLABSI occurred in 13 patients. Overall CLABSI incidence (per 1000 CVC days) was 0.95 (9.71 for silastic percutaneous CVC, 7.65 for other CVC, 1.97 for Broviac, 0.18 for Port-a-cath). CVC remained in place for ≤ 14 days in 109 (52%) instances, 15-90 days in 45 (22%) instances and > 90 days in 55 (26%) instances. The incidence of CLABSI in these three categories was 3.36, 4.36 and 0.47, respectively. Predominating cultured organisms were coagulase-negative staphylococci (N=3), S. aureus (N=3), and Enterococcus spp. (N=3). CLABSI incidence varied by type of catheter and type of patient, with the highest risk in neonates (with silastic percutaneous CVC) and by far the lowest risk for Port-a-cath CVC. Prophylactic measures to reduce CLABSI should be tailored to individual types of catheters and patient characteristics.
    Archives of Disease in Childhood 06/2011; 96(9):827-31. DOI:10.1136/adc.2010.208595 · 2.91 Impact Factor
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    ABSTRACT: INTRODUCTION: Odontogenic myxomas are benign but locally invasive tumours originating from primordial mesenchymal tooth forming tissues which do not metastasise. We present a series of two paediatric and two adult cases and focus on differences in diagnostic and therapeutic approaches between children and adults based on our own experience and a critical review of the literature.
    Journal of cranio-maxillo-facial surgery: official publication of the European Association for Cranio-Maxillo-Facial Surgery 05/2011; 40(3):271-6. DOI:10.1016/j.jcms.2011.04.009 · 2.60 Impact Factor
  • Heribert Juergens · Uta Dirksen · Michael Paulussen · Andreas Ranft
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    ABSTRACT: Purpose: Around 3-5% of patients with Ewing sarcoma will eventually following multimodal treatment with chemotherapy, radiotherapy and/or surgery present with a secondary malignancy. It is not however well documented how many patients are being diagnosed with Ewing sarcoma as secondary malignancy. Method: The GPOH (German Society of Pediatric Hematology and Oncology) database of two consecutive and nationwide Ewing sarcoma trials was reviewed for Ewing sarcoma as secondary malignancy. This included 2422 patients entered into and treated according to the EICESS92 and EURO-E.W.I.N.G.99 protocols from 1991-2009. The type of the primary malignancy, the interval from diagnosis the first malignancy to the diagnosis of Ewing sarcoma and the event-free-survival (EFS) were analyzed. Results: 26 cases of Ewing sarcomas as a secondary malignancy were identified. The most common primary malignancies were acute lymphoblastic leukemia (6) and lymphomas (4). The other diagnoses (16) included osteosarcoma (2), retinoblastoma (2) and other rare malignancies. Median time from diagnosis of the first malignancy to the diagnosis of Ewing sarcoma was 7.5 years (1-29). The median age at diagnosis was 16.5 years (6.7-59.8). 61% of patients presented with localized Ewing sarcoma, 39% with metastatic disease. 3yEFS was 0.77 (SE=0.12) for patients with localized, and 0.11 (SE=0.10) for patients with metastatic disease. Conclusion: Approximately 1% of Ewing sarcoma cases are diagnosed as a secondary malignancy. The outcome appears comparable to the outcome of patients with primary Ewing sarcoma.
    Pediatric Blood & Cancer 11/2010; 55(5):879-879. · 2.56 Impact Factor
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    ABSTRACT: To improve the poor prognosis of patients with primary disseminated multifocal Ewing sarcomas (PDMES) with a dose-intense treatment concept. From 1999 to 2005, 281 patients with PDMES were enrolled onto the Euro-EWING 99 R3 study. Median age was 16.2 years (range, 0.4 to 49 years). Recommended treatment consisted of six cycles of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE), one cycle of vincristine, dactinomycin, and ifosfamide (VAI), local treatment (surgery and/or radiotherapy), and high-dose busulfan-melphalan followed by autologous stem-cell transplantation (HDT/SCT). After a median follow-up of 3.8 years, event-free survival (EFS) and overall survival (OS) at 3 years for all 281 patients were 27% +/- 3% and 34% +/- 4% respectively. Six VIDE cycles were completed by 250 patients (89%); 169 patients (60%) received HDT/SCT. The estimated 3-year EFS from the start of HDT/SCT was 45% for 46 children younger than 14 years. Cox regression analyses demonstrated increased risk at diagnosis for patients older than 14 years (hazard ratio [HR] = 1.6), a primary tumor volume more than 200 mL (HR = 1.8), more than one bone metastatic site (HR = 2.0), bone marrow metastases (HR = 1.6), and additional lung metastases (HR = 1.5). An up-front risk score based on these HR factors identified three groups with EFS rates of 50% for score <or= 3 (82 patients), 25% for score more than 3 to less than 5 (102 patients), and 10% for score >or= 5 (70 patients; P < .0001). PDMES patients may survive with intensive multimodal therapy. Age, tumor volume, and extent of metastatic spread are relevant risk factors. A score based on these factors may facilitate risk-adapted treatment approaches.
    Journal of Clinical Oncology 07/2010; 28(20):3284-91. DOI:10.1200/JCO.2009.22.9864 · 18.43 Impact Factor
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    ABSTRACT: We describe a heterozygosity for a new missense mutation on the alpha1-globin gene of an 18-year-old woman of Portuguese ancestry with severe hypochromic anemia and iron deficiency. Hemoglobin (Hb) analysis by high performance liquid chromatography (HPLC) found a prominent peak constituting about 12% of total Hb. Sequencing of the globin genes of the index patient found the mutation alpha14(A12)Trp-->Leu (alpha1), HBA1:c.44G<T. We identified the same mutation in blood and DNA of the mother, which provides evidence that the variant is stable and does not have direct pathophysiological or hematological consequences.
    Hemoglobin 06/2010; 34(3):327-31. DOI:10.3109/03630269.2010.483960 · 0.96 Impact Factor

Publication Stats

3k Citations
620.63 Total Impact Points


  • 2011–2015
    • Universität Witten/Herdecke
      • Chair of Pediatrics
      Witten, North Rhine-Westphalia, Germany
  • 2013
    • Universität Basel
      Bâle, Basel-City, Switzerland
  • 2012
    • Universitätsspital Basel
      • Klinik für Infektiologie & Spitalhygiene
      Bâle, Basel-City, Switzerland
  • 1999–2011
    • University Children's Hospital Basel
      Bâle, Basel-City, Switzerland
    • Otto-von-Guericke-Universität Magdeburg
      Magdeburg, Saxony-Anhalt, Germany
    • University of Pennsylvania
      • Department of Pathology and Laboratory Medicine
      Filadelfia, Pennsylvania, United States
  • 2010
    • Newcastle University
      Newcastle-on-Tyne, England, United Kingdom
  • 1995–2006
    • University of Münster
      • • Department of Medicine, Hematology and Oncology
      • • Gerhard-Domagk-Institute of Pathology
      Muenster, North Rhine-Westphalia, Germany
  • 2000–2005
    • Universitätsklinikum Münster
      Muenster, North Rhine-Westphalia, Germany
  • 2004
    • Michiana Hematology Oncology
      Индиана, Pennsylvania, United States
  • 2003
    • Gesellschaft für Pädiatrische Onkologie und Hämatologie
      Muenster, North Rhine-Westphalia, Germany
  • 1997–1998
    • Martin Luther University of Halle-Wittenberg
      Halle-on-the-Saale, Saxony-Anhalt, Germany
  • 1994
    • Friedrich-Alexander Universität Erlangen-Nürnberg
      Erlangen, Bavaria, Germany
  • 1993
    • Universitätsklinikum Erlangen
      Erlangen, Bavaria, Germany
    • Heinrich-Heine-Universität Düsseldorf
      • Kinderklinik
      Düsseldorf, North Rhine-Westphalia, Germany