D Körholz

Universitätsklinikum Halle (Saale), Halle-on-the-Saale, Saxony-Anhalt, Germany

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Publications (151)482.77 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: Interim FDG-PET is used for treatment tailoring in lymphoma. Deauville response criteria consist of five ordinal categories based on visual comparison of residual tumor uptake to physiological reference uptakes. However, PET-response is a continuum and visual assessments can be distorted by optical illusions. With a novel semi-automatic quantification tool we eliminate optical illusions and extend the Deauville score to a continuous scale. SUVpeak of residual tumors and average uptake of the liver is measured with standardized volumes of interest. The qPET value is the quotient of these measurements. Deauville scores and qPET-values were determined in 898 pediatric Hodgkin's lymphoma patients after two OEPA chemotherapy cycles. Deauville categories translate to thresholds on the qPET scale: Categories 3, 4, 5 correspond to qPET values of 0.95, 1.3 and 2.0, respectively. The distribution of qPET values is unimodal with a peak representing metabolically normal responses and a tail of clearly abnormal outliers. In our patients, the peak is at qPET = 0.95 coinciding with the border between Deauville 2 and 3. qPET cut values of 1.3 or 2 (determined by fitting mixture models) select abnormal metabolic responses with high sensitivity, respectively, specificity. qPET methodology provides semi-automatic quantification for interim FDG-PET response in lymphoma extending ordinal Deauville scoring to a continuous scale. Deauville categories correspond to certain qPET cut values. Thresholds between normal and abnormal response can be derived from the qPET-distribution without need for follow-up data. In our patients, qPET < 1.3 excludes abnormal response with high sensitivity.
    European Journal of Nuclear Medicine 03/2014; · 4.53 Impact Factor
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    ABSTRACT: Sequencing of individual clones from a newly established cDNA library from the chemoresistant Hodgkin's lymphoma cell line L-1236 led to the isolation of a cDNA clone corresponding to a short sequence from chromosome 1. Reverse transcriptase-polymerase chain reaction indicated high expression of this sequence in Hodgkin's lymphoma derived cell lines but not in normal blood cells. Further characterization of this sequence and the surrounding genomic DNA revealed that this sequence is part of a human endogenous retrovirus locus. The sequence of this endogenous retrovirus is interrupted by a pseudogene of the dual specificity phosphatase 5 (DUSP5). Reverse transcriptase-polymerase chain reaction revealed high expression of this pseudogene (DUSP5P1) in HL cell lines but not in normal blood cells or Epstein-Barr virus-immortalized B cells. Cells from other tumor types (Burkitt's lymphoma, leukemia, neuroblastoma, Ewing sarcoma) also showed a higher DUSP5P1/DUSP5 ratio than normal cells. Furthermore, we observed that higher expression of DUSP5 in relation to DUSP5P1 correlated with the expression of the pro-apoptotic factor B cell leukemia/lymphoma 2-like 11 (BCL2L11) in peripheral blood cells and HL cells. Knock-down of DUSP5 in HL cells resulted in down-regulation of BCL2L11. Thus, the DUSP5/DUSP5P1 system could be responsible for regulation of BCL2L11 leading to inhibition of apoptosis in these tumor cells.
    PLoS ONE 01/2014; 9(2):e89577. · 3.73 Impact Factor
  • G Jorch, D Körholz, L Gortner
    Klinische Pädiatrie 12/2013; 225(7):377-8. · 1.90 Impact Factor
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    ABSTRACT: Cancer is linked to defects in immunosurveillance. Vaccination studies using dendritic cells (DC) try to re-establish immune responses toward tumor cells. Tumor-derived products such as interleukin-10 (IL-10) have inhibitory effects on DC function, and tumor-bearing hosts exhibit a lower number of DCs, suggesting inhibitory effects of tumor-derived factors on the recruitment of precursor cells. We generated DCs in the presence and absence of IL-10. DCs were then characterized by flow cytometry and cDNA microarray analysis. IL-10 interferes with differentiation of peripheral blood monocytes to DCs and induces cells with a distinct phenotype. Microarray analysis revealed that IL-10 exhibits inhibitory as well as stimulatory effects on the expression of several genes. Addition of IL-10 to the differentiation cocktail induces a sustained inhibitory effect on subsequent maturation stimuli. IL-10 inhibits DC function and redirects differentiation of DCs to cells with a different phenotype, thereby reducing the pool of potential DC precursors.
    Anticancer research 11/2013; 33(11):4791-8. · 1.71 Impact Factor
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    ABSTRACT: In the last years the prevalence of multi-resistant pathogens (MRPs) has increased. Systemic infections remain important for neonatal morbidity and mortality.Neonates born between January 2011 and December 2012 and admitted to the neonatology before their tenth day of life were included into this retrospective analysis. Vancomycin-resistant Enterococci, Methicillin-resistant Staphylococcus aureus, Gram-negative bacilli with Extend Spectrum Beta Lactamase or AMP-C resistance were defined as multi-resistant pathogens (MRPs). MRP positive and negative patients were analyzed regarding clinical risk factors and the incidence of systemic infections.635 neonates were admitted during the analysis period. In 31 patients MRPs were detected. 2 patients developed MRP-associated infections. Both were discharged without long term health risks. Low gestational age and need for mechanical ventilation were risk factors for colonization with MRPs in the univariat analysis. The incidence density (per 1 000 patient days) for all MRE increased from 0.76 in 2011 to 3.51 in 2012. In contrast the sepsis rate remained stable (14.9% and 14.2%). 2 MRP colonization clusters were detected by routine microbiology swabs. Both could be controlled by appropriate hygienic measures.The prevalence of Gram-negative MRPs increased in neonates. Microbiological screening seems to be helpful for early detection of colonization and thus prevention of nosocomial infections with MRPs. Despite the increased attention towards the problems associated with multiresistant bacteria, there are still major efforts needed for prevention and early treatment of sepsis with non-resistant bacteria.
    Klinische Pädiatrie 10/2013; · 1.90 Impact Factor
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    ABSTRACT: Further survival improvements of adolescents and young adults (AYA) with cancer are clearly affected by biological characteristics of the malignancies and age-specific needs. Multidisciplinary teams drawing expertice from both pediatric and adult cancer teams as well as clinical trials are required to meet the age specific needs of AYA patients with cancer. In 2011, the first AYA unit was established at the University Hospital Halle (Saale), where patients with newly-diagnosed cancer aged 15-25 are treated interdisciplinary by pediatric and adult oncologists. The enrollment into pediatric or adult clinical trials is controlled by age 18. Over the last 2 years, 19 AYA with cancer have been treated at the unit; and, in turn patients and their relatives reflected a high satisfaction with the offered novel health care approach. In the scope of the future Comprehensive Cancer Center at the University Hospital Halle (Saale), a complete ward is planned for all admitted AYA up to 25 years with cancer. The patients will be treated by a tumor-specialized multidisciplinary team of adult or pediatric oncologists and oncological surgeons. Therefore, we intend to establish a special teaching curriculum for physicians, nurses and psychosocial health care staff. Rather than age, cancer biology of a malignancy, surveillance data of late side effects as well as the age-specific needs of AYA patients will be crucial for best treatment options.
    Klinische Pädiatrie 10/2013; · 1.90 Impact Factor
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    ABSTRACT: Since 2007, children and adolescents with Hodgkin lymphomas are treated in the Europe-wide EuroNet-PHL trials. A real time central review process for stratification of the patients enhances quality control and efficient therapy management. This process includes reading of all cross-sectional-images. Since reference evaluation is time critical, a fast, easy to handle and safe data transfer is important. In addition, immediate and constant access to all the data has to be guaranteed in case of queries and for regulatory reasons. To meet the mentioned requirements the EuroNet Paediatric Hodgkin Data Network (funded by the European Union - Project Number: 2007108) was established between 2008 and 2011. A respective tailored data protection plan was formulated. The aim of this article is to describe the networks' mode of operation and the advantages for multi-centre trials that include centralized image review.
    Klinische Pädiatrie 10/2013; · 1.90 Impact Factor
  • D Körholz, L Gortner, U Göbel
    Klinische Pädiatrie 07/2013; 225(4):191-192. · 1.90 Impact Factor
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    ABSTRACT: Microbiological screening (MS) is standard on neonatal intensive care units (NICU). Objectives are the collection of information regarding bacterial pathogens of the individual patient as well as of the NICU, especially of multidrug-resistant pathogens (MRE). The role of microbiological screening for preterm infants ≤32 weeks of gestational age has not been fully evaluated.For preterm infants ≤32 weeks of gestational age admitted during a 41-month period the results of microbiological screening during the first 2 weeks of life were analysed retrospectively. The results were associated with documented septic episodes.Bacteria were isolated in 215/972 of postnatal and 416/862 of later swabs. Detection of bacteria in the initial MS was associated with vaginal birth, low gestational age, low APGAR values at 5 and 10 min and mechanical ventilation. The proportion of patients with positive microbiological screening in subsequent swabs was not influenced by gestational age, birth weight, sex, mode of delivery and APGAR score. During the observation period 52 cases of sepsis (28 clinic, 24 microbiological) occurred. The sepsis rate was increased in patients with positive postnatal swabs, low gestational age, low birth weight, low 5 min APGAR score, male sex or need for mechanical ventilation.Microbiological screening provides an overview of the NICU-specific pathogens but is of limited value in the prediction of septicaemias in preterm infants ≤32 weeks gestational age.
    Zeitschrift für Geburtshilfe und Neonatologie 04/2013; 217(2):56-60. · 0.56 Impact Factor
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    ABSTRACT: In adult cancer patients the negative predictive value of elevated CRP levels has been described for several malignancies. Only few studies have analyzed the prognostic role of CRP in children and adolescents with classical HL. In these studies elevated CRP levels correlate with the presence of classical risk factors and adverse outcome.The prognostic role of CRP for patients with classical HL admitted to the GPOH-HD-2002 study was analyzed retrospectively.CRP levels were documented for 369 of 573 patients. Significant (p<0.05) increased median CRP levels were found in the presence of B-Symptoms (25.7 vs. 5.1 mg/l), extranodal involvement (21.5 vs. 7.5 mg/l), elevated erythrocyte sedimentation rate (ESR, 13.0 vs. 1.0 mg/l) and stage III/IV disease (15.5 vs. 5.3 mg/l). 83.9% of patients with elevated and 45.8% of patients with normal CRP had an ESR >30 mm/h.Elevated CRP levels were associated with classical risk factors of HL. CRP and ESR may reflect different biological processes. CRP was prognostic within early stage TG-1 patients treated with reduced treatment, but not within advanced stage TG-2+3.
    Klinische Pädiatrie 10/2012; · 1.90 Impact Factor
  • Klinische Pädiatrie 10/2012; 224(6):335-8. · 1.90 Impact Factor
  • Klinische Pädiatrie 07/2012; 224(4):230-2. · 1.90 Impact Factor
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    ABSTRACT: Methotrexate (MTX) is commonly administered in high doses for treatment of childhood acute lymphoblastic leukemia (ALL). The aim of this analysis was to study the influence of 2 common MTHFR polymorphisms (MTHFR 677C>T and 1298 A>C) on MTX toxicity in children with ALL.Retrospective analysis of 129 MTX courses in 34 pediatric patients with ALL.677C>T variants (CT or TT) were found in 19 (14 heterozygous, 5 homozygous) and 1298A>C variants (AC or CC) in 20 (16 heterozygous, 4 homozygous) patients. The MTHFR 677C>T wild type was associated with an increased frequency of grade III and IV leukopenia (60% vs. 31%, p<0.05) compared to the variants. The rate of severe infections (21% vs. 0%, p<0.05) and grade III-IV anemia (26% vs. 5%, p<0.05) was increased in carriers of the MTHFR 677C>T wild type compared to patients with the TT variant. Grade III-IV anemia was more frequent in patients with the MTHFR 1298A>C CC variant compared to the wild type (56% vs. 21%, p<0.05). The differences were not significant in a patient-based analysis.MTX related toxicity might be influenced by the MTHFR 677C>T or the MTHFR 1298A>C polymorphisms. Differences in MTX toxicity are only partially explainable by these 2 polymorphisms.
    Klinische Pädiatrie 04/2012; 224(3):156-9. · 1.90 Impact Factor
  • R Kluge, D Körholz
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    ABSTRACT: The paediatric Hodgkin lymphoma treatment optimisation concepts aim at reduction of treatment intensity with preservation of the high cure rates. A negative interim FDG-PET result after 2 cycles of chemotherapy is associated with a good prognosis. In the current EuroNet-PHL-C1 study radiotherapy is being omitted, if interim PET becomes negative. In addition to the early interim PET after 2 cycles of chemotherapy, all patients undergo an initial PET investigation which is part of the staging processs and plays an essential role for the interpretation of the interim PET. Skeletal involvement can be detected by a typical FDG-PET uptake pattern with high sensitivity and specifity. Therefore, in the forthcoming EuroNet-PHL-C2 study bone marrow biopsy and bone scintigraphy will no longer be part of the staging algorithm.
    Klinische Pädiatrie 11/2011; 223(6):315-9. · 1.90 Impact Factor
  • Klinische Pädiatrie 11/2011; 223(6):311-4. · 1.90 Impact Factor
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    ABSTRACT: A 16,5 year old female adolescent was diagnosed with nodular lymphocyte-predominant Hodgkin lymphoma (nLPHL), presenting bilateral inguinal and right iliac lymphadenopathy accompanied by B-symptoms. The patient was due to treatment according to the German Interim Guidelines of HD 2002-Pilot Study with 2x OPPA (vincristine, adriamycine, prednisone, procarbacine) and 2x COPP (cyclophosphamide, vincristine, prednisone, procarbazine) and radiotherapy. After 2x OPPA the patient presented a severe episode of a presumably prednisone-induced acute psychosis with need for psychiatric treatment and change of therapy regimen. She was successfully treated with a chimeric monoclonal anti-CD20 antibody (rituximab) and subsequent radiotherapy.
    Klinische Pädiatrie 11/2011; 223(6):370-1. · 1.90 Impact Factor
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    ABSTRACT: Children with chromosomal instability syndromes have an increased risk of developing lymphoma and leukaemia. The treatment of these malignancies is hampered by therapy-associated toxicity and infectious complications. This retrospective analysis evaluated the therapy outcome of 38 children with Ataxia teleangiectasia or Nijmegen-breakage syndrome with acute lymphoblastic leukaemia (ALL, n = 9), Non-Hodgkin lymphoma (NHL, n = 28) and Hodgkin lymphoma (HL, n = 1). All patients with NHL or ALL were treated in accordance to Berlin-Frankfurt-Münster (BFM)- or Co-operative study group for childhood ALL (CoALL)-oriented chemotherapy schedules. 22 patients received significantly reduced-intensity chemotherapy. After a median follow-up of 3·7 years the 10-year overall survival was 58%. Dosage-reduction of chemotherapeutic drugs seemed to have no disadvantages and reduced toxic side effects. On the other hand, reduced-intensity chemotherapy did not prevent second malignancies, which occurred in ten patients with a 10-year incidence of 25%. After individual treatment approaches three of these patients with second malignancies were in complete clinical remission for more than 5 years. We conclude that BFM- or CoALL-oriented chemotherapy is effective and can be administered in children with AT or NBS. Moreover, we show that even second lymphoid malignancies can successfully be treated in these patients.
    British Journal of Haematology 09/2011; 155(4):468-76. · 4.94 Impact Factor
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    ABSTRACT: Currently, a routine bone marrow biopsy (BMB) is performed to detect bone marrow (BM) involvement in pediatric Hodgkin's lymphoma (HL) stage greater than IIA. [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) is increasingly used for the initial staging of HL. The value of using FDG-PET to detect BM involvement has not been sufficiently defined. We compared the results of BMBs and FDG-PET for the diagnosis of BM involvement in a large pediatric group with HL. The initial staging of 175 pediatric patients with newly diagnosed classical HL stage greater than IIA was determined by using BMB, FDG-PET, chest computed tomography (CT), and magnetic resonance imaging (MRI) or CT of the neck, abdomen, and pelvis. Staging images were prospectively evaluated by a central review board. Skeletal regions that were suggestive of BM involvement by either method were re-evaluated by using different imaging modalities. In suspicious cases, bone scintigraphy was performed. If follow-up FDG-PET scans were available, the remission of skeletal lesions during treatment was evaluated. BMB results were positive in seven of 175 patients and were identified by FDG-PET. FDG-PET scans showed BM involvement in 45 patients. In addition, the lesions of 32 of these 45 patients had a typical multifocal pattern. In 38 of 39 follow-up positron emission tomography scans, most of the skeletal lesions disappeared after chemotherapy. There was no patient with skeletal findings suggestive of BM involvement by MRI or CT with a negative FDG-PET. FDG-PET is a sensitive and specific method for the detection of BM involvement in pediatric HL. The sensitivity of a BMB appears compromised by the focal pattern of BM involvement. Thus, FDG-PET may safely be substituted for a BMB in routine staging procedures.
    Journal of Clinical Oncology 08/2011; 29(26):3523-8. · 18.04 Impact Factor
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    ABSTRACT: The improving prognosis of children with cancer has partially been attributed to the increasing importance of pediatric intensive care units (PICU). We analyze whether outcome of these patients on a PICU improved during the last decade and which factors may influence the outcome in our hospital. The charts of all oncology patients admitted to the PICU between 1998 and 2009 have been reviewed retrospectively. The survival of patients admitted for life threatening complications has been correlated with basic data, organ failure and the PRISM score. The results of 2 consecutive treatment periods (1998-2003 and 2004-2009) were compared. 644 admissions of 226 patients were recorded. 79 admissions were performed because of potentially life threatening complications (Group A), 236 for monitoring (B) and 329 admissions for interventions (C). 62% of Group A patients and all Group B and C patients were discharged alive. Poor outcome was associated with admission >28 days after initial diagnosis, PRISM >10, organ failure >2 organs, sepsis, allogeneic stem cell transplantation, need for mechanical ventilation or for catecholamines. The PICU survival rate of Group A patients admitted between 2004 and 2009 (78%) was higher than in the period between 1998 and 2003 (48%). PICU provides essential services to support the pediatric oncology ward. Although children with cancer may have had benefit from advances in pediatric intensive care over the past decade, specific scoring systems for early identification of children with cancer needing PICU treatment are required. These systems might further improve PICU outcome in critical ill pediatric cancer patients.
    Klinische Pädiatrie 05/2011; 223(3):142-6. · 1.90 Impact Factor
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    ABSTRACT: Vincristine, etoposide, prednisone, and doxorubicin (OEPA)-cyclophosphamide, vincristine, prednisone, and dacarbazine (COPDAC) is derived from standard vincristine, procarbazine, prednisone, and doxorubicin (OPPA)-cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) chemotherapy by replacing procarbazine with etoposide and dacarbazine for a potentially less gonadotoxic regimen for boys with Hodgkin's lymphoma (HL). Five hundred seventy-three pediatric patients with classical HL were enrolled onto the German Society of Pediatric Oncology and Hematology-Hodgkin's Disease (GPOH-HD) -2002 study between November 2002 and December 2005. Boys received two courses of OEPA and girls received two courses of OPPA for induction. Treatment group (TG) -2 (intermediate stages) and TG-3 (advanced stages) patients received further two or four cycles COPP (girls) or COPDAC (boys), respectively. After chemotherapy all patients received involved-field irradiation with 19.8 Gy, except for patients with early-stage disease (TG-1) in complete remission. Five hundred seventy-three patients (287 males and 286 females) were less than 18 years old and fulfilled all inclusion criteria; 195 patients (34.0%) were allocated to TG-1, 139 (24.3%) were allocated to TG-2, and 239 (41.7%) were allocated to TG-3. Toxicity of OEPA-COPDAC was tolerable overall. Hematotoxicity was more pronounced with OEPA than OPPA, whereas it was less pronounced with COPDAC compared with COPP. The median observation time was 58.6 months. Overall survival and event-free survival (EFS) rates (+/- SE) at 5 years were 97.4% +/- 0.7% and 89.0% +/- 1.4%, respectively. In TG-1, overall EFS was 92.0% +/- 2.0%. EFS of patients without irradiation (93.2% +/- 3.3%) was similar to that of irradiated patients (91.7% +/- 2.5%), confirming results of the previous GPOH-HD-95 study. In TG-2+3, EFS did not significantly differ between boys and girls (90.2% +/- 2.3 v 84.7% +/- 2.7, respectively; P = .12). In TG-2+3, results in boys and girls are superimposable. OPPA-COPP and OEPA-COPDAC seem to be exchangeable regimens in intermediate- and advanced-stage classical HL in pediatric patients.
    Journal of Clinical Oncology 08/2010; 28(23):3680-6. · 18.04 Impact Factor

Publication Stats

1k Citations
482.77 Total Impact Points

Institutions

  • 2011–2013
    • Universitätsklinikum Halle (Saale)
      Halle-on-the-Saale, Saxony-Anhalt, Germany
  • 2008–2013
    • Martin Luther University of Halle-Wittenberg
      • Poliklinik für Kinder- und Jugendmedizin
      Halle, Saxony-Anhalt, Germany
  • 1987–2009
    • Heinrich-Heine-Universität Düsseldorf
      • • Kinderklinik
      • • Klinik für Hämatologie, Onkologie und Klinische Immunologie
      Düsseldorf, North Rhine-Westphalia, Germany
  • 2000–2005
    • University of Leipzig
      Leipzig, Saxony, Germany
  • 1996
    • Universitätsklinikum Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany