| Autor(en) |
Titel |
Quelle |
Links |
| Kaatsch P, Michaelis J |
Epidemiological data on childhood malignancies in the first year of life. |
Contrib Oncol 1990, 41: 1 |
 |
| Kaatsch P, Haaf G, Michaelis J |
Empfehlungen zur Vorgehensweise bei vermuteten regionalen Häufungen von Krebserkrankungen. |
Europäische Perspektiven der Medizinischen Informatik, Biometrie und Epidemiologie 1993, 33 |
|
| Kaatsch P, Haaf G, Michaelis J |
Childhood malignancies in Germany - methods and results of a nationwide registry. |
Eur J Cancer 1995, 31A: 993 |
 |
| Kaatsch P, Haaf G, Michaelis J |
Haben Krebserkrankungen im Kindesalter zugenommen? |
Monatsschrift Kinderheilkunde 1995, 143: 554 |
|
| Kaatsch P, Michaelis J |
Wie oft Kinder krank werden. |
Leben will ich jeden Tag 1995, 22 |
|
| Kaatsch P, Michaelis J |
Second neoplasms after malignant diseases in childhood. |
Klin Pädiatr 1995, 207: 158 |
|
| Kaatsch P, Michaelis J |
Second neoplasms after malignant diseases in childhood. |
Klin Pädiatr 1995, 207: 158 |
|
| Kaatsch P, Kaletsch U, Krummenauer F, Meinert R, Miesner A, Haaf G, Michaelis J |
Case control study on childhood leukemia in Lower Saxony, Germany. Basic considerations, methodology, and summary of results. |
Klin Pädiatr 1996, 208: 179 |
|
| Kaatsch P, Kaletsch U, Meinert R, Michaelis J |
An extended study on childhood malignancies in the vicinity of German nuclear power plants. |
Cancer Causes Control 1998, 9: 529 |
|
| Kaatsch P, Kaletsch U, Meinert R, Miesner A, Hoisl M, Schuz J, Michaelis J |
German case control study on childhood leukaemia--basic considerations, methodology and summary of the results. |
Klin Pädiatr 1998, 210: 185 |
|
| Kaatsch P |
Studien des Deutschen Kinderkrebsregisters zum Auftreten von Leukämien und anderen Krebserkrankungen bei Kindern. |
Forum Deutsche Krebsgesellschaft 1999, 300 |
|
| Kaatsch P, Rickert C, Kühl J, Schuz J, Michaelis J |
Population-based epidemiologic data on brain tumors in German children. |
Cancer 2001, 92: 3155 |
|
| Kaatsch P |
Das Deutsche Kinderkrebsregister zwei Jahrzehnte nach Beginn seiner Tätigkeit. |
Monatsschr Kinderheilkd 2002, 150: 966 |
|
| Kaatsch P, Klein G, Schulz B, Spix C |
Epidemiological data on secondary malignant neoplasms after childhood cancer in Germany [Abstract]. |
Med Ped Oncol 2002, 39: 254 |
|
| Kaatsch P, Schüz J |
Epidemiologische Studien zu politisch kontrovers diskutierten Themen und deren Kommunikation in die Öffentlichkeit - Empfehlungen zur Risikokommunikation. |
Informatik, Biometrie und Epidemiologie in Medizin und Biologie 2002, 83 |
|
| Kaatsch P, Spix C, Michaelis J |
German Childhood Cancer Registry - Annual Report 2000 (Jahresbericht 2000 des Deutschen Kinderkrebsregisters). |
|
|
| Kaaijk P, Kaspers G, van Wering E, Broekema G, Loonen A, Hahlen K, Schmiegelow K, Janka-Schaub G, Henze G, Creutzig U, Veerman A |
Cell proliferation is related to in vitro drug resistance in childhood acute leukaemia. |
Br J Cancer 2003, 88: 775 |
|
| Kaatsch P |
German Childhood Cancer Registry and its favorable setting. |
Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2004, 47: 437 |
|
| Kaatsch P, Blettner M |
Das Langzeit-follow-up in der deutschen pädiatrischen Onkologie als Grundlage für Studien mit Langzeitüberlebenden. |
Monatsschr Kinderheilkd 2004, 152 |
|
| Kaatsch P, Spix C |
German Childhood Cancer Registry - Annual Report 2003 (Jahresbericht 2003 des Deutschen Kinderkrebsregisters). |
|
|
| Kaatsch P, Spix C |
Jahresbericht 2004 des Deutschen Kinderkrebsregisters. |
Technischer Bericht, Universität Mainz 2005 |
|
| Kaatsch P, Blettner M, Spix C, Jürgens H |
Follow up of long-term survivors after childhood cancer in Germany. [+] |
Klinische Pädiatrie 2005, 217: 169 |
|
| BACKGROUND: In recent years, the long-term survival of childhood cancer patients has increased considerably. While this is desirable, more patients with late effects are to be expected and studies thereof become increasingly important. We will need to be able to stay in touch with as many former patients as possible in order to make a systematic and comprehensive long-term follow-up possible. PATIENTS: Childhood cancer patients under 15 years of age at diagnosis resident in Germany and registered at the German Childhood Cancer Registry (GCCR). METHODS: The GCCR has established a 3-phase procedure for follow-up. We developed principles for the long-term follow up of these patients. They are based on the many years of experience at the GCCR and were developed based on the long-standing collaboration between the therapy optimization studies (TOS) in the Society for Paediatric Oncology and Haematology (GPOH) and the GCCR. RESULTS: Currently 8 012 adult survivors diagnosed before 2000 are under observation at the GCCR and could be contacted for studies. About half of the children diagnosed in the 1980ies still in follow-up have been under observation more than 14 years. When asked to personally extend the originally parental consent to data storage at the GCCR and the TOS at about 16 years of age, about 85 % of the patients agree. CONCLUSIONS: Establishing an open-end, systematic long-term follow-up will provide a unique and broad basis for paediatric oncology in Germany to perform representative studies regarding long-term survival after childhood cancer in Germany in the long run. |
| Kaatsch P |
Deutsches Kinderkrebsregister - Eine international angesehene Datenquelle. |
Dtsch Arztebl 102: A1421-22, 2005 |
|
| Kaatsch P, Spix C, Schüz J |
Epidemiologie, Ätiologie, Prävention. |
In: Gadner H, Gaedicke G, Niemeyer C, Ritter J (Hrsg): Pädiatrische Hämatologie und Onkologie, S. 421-35 Springer Medizin Verlag Heidelberg. 2005 |
|
| Kaatsch P |
25 Jahre Deutsches Kinderkrebsregister: Langzeitfolgen rücken ins Blickfeld - Nehmen Krebserkrankungen bei Kindern zu? |
WIR-Informationsschrift von DLFH-Dachverband und Aktion für krebskranke Kinder e.V. (Bonn) 2005, 3 |
|
| Kaatsch P, Spix C |
German Childhood Cancer Registry - Annual Report 2005 (Jahresbericht 2005 des Deutschen Kinderkrebsregisters). |
Technischer Bericht, Universität Mainz 2006 |
|
| Kaatsch P, Spix C |
Registry - Annual Report 2006/07 (Jahresbericht 2006/07 des Deutschen Kinderkrebsregisters). |
Technischer Bericht, Universität Mainz |
|
| Kaatsch P, Spix C, Schulze-Rath R, Schmiedel S, Blettner M |
Leukaemia in young children living in the vicinity of German nuclear power plants. [+] |
International journal of cancer. Journal international du cancer 2008, 122: 721 |
|
| A case control study was conducted where cases were children younger than 5 years (diseased between 1980 and 2003) registered at the german childhood cancer registry (GCCR). Population-based matched controls (1:3) were selected from the corresponding registrar's office. Residential proximity to the nearest nuclear power plant was determined for each subject individually (with a precision of about 25 m). The report is focused on leukaemia and mainly on cases in the inner 5-km zone around the plants. The study includes 593 leukaemia cases and 1,766 matched controls. All leukaemia combined show a statistically significant trend for 1/distance with a positive regression coefficient of 1.75 [lower 95%-confidence limit (CL): 0.65]; for acute lymphoid leukaemia 1.63 (lower 95%-CL: 0.39), for acute nonlymphocytic leukaemia 1.99 (lower 95%-CL: -0.41). This indicates a negative trend for distance. Cases live closer to nuclear power plants than the randomly selected controls. A categorical analysis shows a statistically significant odds ratio of 2.19 (lower 95%-CL: 1.51) for residential proximity within 5 km compared to residence outside this area. This result is largely attributed to cases in previous studies of the GCCR (especially in the inner zone) as there is clearly some overlap between those studies. The result was not to be expected under current radiation-epidemiological knowledge. Considering that there is no evidence of relevant accidents and that possible confounders could not be identified, the observed positive distance trend remains unexplained. |
| Kaatsch P, Spix C |
Registry - Annual Report 2008 (Jahresbericht 2008 des Deutschen Kinderkrebsregisters). |
Technischer Bericht, Universität Mainz 2008 |
|
| Kaatsch P, Spix C, Jung I, Blettner M |
Childhood leukemia in the vicinity of nuclear power plants in Germany. [+] |
Deutsches Arzteblatt international 2008, 105: 725 |
|
| INTRODUCTION: The causes of leukemia are largely unclear. The question whether leukemia rates are increased near nuclear power plants is controversial. The German Childhood Cancer Registry has published an epidemiological case-control study on childhood cancer and nuclear power plants. METHOD: The study was based on the distance of children's residences from nuclear power plants and addressed the question whether children under age 5 with cancer live closer, on average, to nuclear power plants than randomly selected controls. Odds Ratios (OR) for distance categories and standardized incidence ratios (SIR) were calculated. RESULTS: An association was found between the nearness of residence to nuclear power plants and the risk of leukemia (593 cases, 1766 controls). Within the 5-km zone, the OR for the development of leukemia in children under 5 years of age was 2.19 compared to the rest of the region, and this elevation of the OR was statistically significant. The incidence of leukemia in the overall study region was the same as that in Germany as a whole (SIR=0.99; 95% confidence interval 0.92-1.07). DISCUSSION: Based on the available information about radiation emissions from German nuclear power plants, a direct relation to radiation seems implausible. Many factors may conceivably cause leukemia, possibly operating in combination, and these factors may be present to a greater extent in the vicinity of German nuclear power plants. |
| Kaatsch P, Reinisch I, Spix C, Berthold F, Janka-Schaub G, Mergenthaler A, Michaelis J, Blettner M |
Case-control study on the therapy of childhood cancer and the occurrence of second malignant neoplasms in Germany. [+] |
Cancer causes & control 2009, 20: 965 |
|
| We report on a nested case-control study with 328 cases with second malignant neoplasm (SMN) following childhood cancer and 639 matched controls based on the German Childhood Cancer Registry. In the adjusted overall analysis, the odds ratio (OR) for SMN following any radiotherapy or chemotherapy is 2.1 [95% confidence interval (CI): 1.8-3.3] and 1.8 (95% CI: 0.98-3.1), respectively. The strongest effect is seen for alkylating agents (OR=2.0, 95% CI: 1.2-3.3). The risk of SMN after leukemia is pronounced for antimetabolites (OR=17.2, 95% CI: 1.7-177) and asparaginase (OR=4.3, 95% CI: 1.7-11.0). Following solid tumors, the greatest effect is seen for platinum derivatives (OR=4.1, 95% CI: 1.7-10.1). For anthracyclines, a decreased risk is observed (OR=0.3, 95% CI: 0.1-0.6). Secondary solid tumors are mainly associated with radiotherapy (OR=4.5, 95% CI: 2.5-8.0), especially secondary carcinomas. Secondary acute myeloid leukemia and myelodysplastic syndrome are mainly associated with alkylating agents (OR=8.5, 95% CI: 0.97-74.8), asparaginase (OR=6.8, 95% CI: 2.3-20.6), and platinum derivatives (OR=4.5, 95% CI: 1.5-13.6). The observed risks are in many instances lower than the ones published in previous studies relating to earlier treatment eras of the primary diseases. These differences may be attributed to less toxic but still effective treatment regimes but also to differences in the length of follow-up. |
| Kaatsch P, Debling D, Blettner M, Spix C |
Second malignant neoplasms after childhood cancer in Germany--results from the long-term follow-up of the German Childhood Cancer Registry. |
Strahlentherapie und Onkologie 2009, 185 Suppl 2: 8 |
|
| Kaatsch P, Scheidemann-Wesp U, Schüz J |
Maternal use of antibiotics and cancer in the offspring: results of a case-control study in Germany. [+] |
Cancer causes & control 2010 |
|
| OBJECTIVE: As previous results were inconsistent, we assessed the association between maternal use of antibiotics during pregnancy or 3 months before conception and childhood cancer in the offspring in a large case-control study in Germany. METHODS: This population-based study on potential risk factors for childhood cancer was conducted by the German Childhood Cancer Registry (GCCR) and included a total of 1,867 registered cancer cases aged 0-14, diagnosed between October 1992 and September 1994. A total of 2,057 controls were randomly drawn from population registries, matched by age, gender, and region. Conditional logistic regression models for frequency-matched datasets were used to estimate odds ratios (OR) with 95% confidence intervals (95% CI). RESULTS: Positive statistically significant associations with self-reported maternal antibiotic use were observed for acute lymphoid leukemia (based on 59 mothers exposed to antibiotics, OR = 1.47; 95% CI: 1.06-2.04), acute myeloid leukemia (18 exposed, OR = 3.21; 95% CI: 1.83-5.62), and Burkitt lymphoma (three exposed, OR = 5.89; 95% CI: 1.47-23.69), but not other cancer types. CONCLUSIONS: The results provide some support for the hypothesis that maternal use of antibiotics increases the risk of cancer in the offspring. Although recall bias is a concern, it is unlikely that this fully explains the observed effect. Further, the observed associations might be related to the underlying infections. |
| Kaatsch P, Spix C |
Jahresbericht 2011. |
Deutsches Kinderkrebsregister, Universitätsmedizin der Johannes Gutenberg-Universität Mainz 2011 |
|
| Kager L, Heise A, Minkov M, Mobius D, Kotte W, Schulte-Overberg U, Henze G, Gadner H |
Occurrence of acute nonlymphoblastic leukemia in two girls after treatment of recurrent, disseminated Langerhans cell histiocytosis. |
Pediatr Hematol Oncol 1999, 16: 251 |
|
| Kager L, Zoubek A, Potschger U, Kastner U, Flege S, Kempf-Bielack B, Branscheid D, Kotz R, Salzer-Kuntschik M, Winkelmann W, Jundt G, Kabisch H, Reichardt P, Jürgens H, Gadner H, Bielack S |
Primary metastatic osteosarcoma. |
J Clin Oncol 2003, 21: 2011 |
|
| Kager L, Zoubek A, Dominkus M, Lang S, Bodmer N, Jundt G, Klingebiel T, Jürgens H, Gadner H, Bielack S, for the COSS Study Group |
Osteosarcoma in very young children: experience of the Cooperative Osteosarcoma Study Group. [+] |
Cancer 2010, |
|
| BACKGROUND:: This study was conducted to investigate presentation, treatment, and outcome in very young children with osteosarcoma. METHODS:: The authors retrospectively analyzed the data of 2706 consecutive COSS patients with newly diagnosed osteosarcoma and identified 28 (1.0%) patients aged younger than 5 years at diagnosis. Demographic, diagnostic, tumor, treatment-related variables, response, and survival data were analyzed. RESULTS:: Of the 28 preschoolers, 27 presented with high-grade central osteosarcoma of an extremity, and 1 had a secondary osteosarcoma of the orbit. This analysis focused on the 27 patients with extremity tumors. The size of the primary was large (>/=one-third of the involved bone) in 20 of 27 patients. Primary metastases were detected in 4 of 27 children. All patients received multiagent chemotherapy, and 11 of 18 analyzed tumors responded well (>90% necrosis) to neoadjuvant chemotherapy. Limb-sparing surgery was performed in 9 cases, ablative procedures were performed in 15, and, in 3 cases, no local surgery was performed. With a median follow-up of 4 years (6.2 years for survivors), 13 patients were alive. Four patients never achieved a complete remission, and 11 developed recurrences; 14 of these 15 patients died. Five-year overall and event-free survival probabilities were 51% (standard error of the mean [SE], 10%) and 48% (SE, 10%). Better survival was correlated with good response to chemotherapy and later time period of diagnosis. CONCLUSIONS:: Osteosarcoma is extremely rare in preschool children. These patients often have large tumors that may require mutilating resections. Prognosis is in the range of that reported for older patients. Cancer 2010. (c) 2010 American Cancer Society. |
| Kager L, Kempf-Bielack B, Bielack S |
Synchronous and metachronous lung metastases in high-grade osteosarcoma. |
Japanese journal of clinical oncology 2010, 40: 94 |
|
| Kager L, Pötschger U, Bielack S |
Review of mifamurtide in the treatment of patients with osteosarcoma. [+] |
Ther Clin Risk Manag 2010, 24; 6: 279 |
|
| Osteosarcoma is the most common primary malignant tumor of bone. The disease, however, is very rare with less than 2,000 expected patients at all age groups per year within the European Union and the United States of America. With multimodal therapy, which combines multiagent chemotherapy and complete resection of all macroscopically detectable tumors, about 60%-70% of patients with localized osteosarcoma can be cured. The prognosis, however, is still poor for patients with synchronous or metachronous metastatic or nonresectable primary disease, with reported 5-year event-free survival (EFS) rates of less than 30%. Overall, the EFS rate has been rather stable since the introduction of combination chemotherapy including doxorubicin, cisplatin, high-dose methotrexate with leukovorin rescue, and/or ifosfamide. Mifamurtide, a modulator of innate immunity, which activates macrophages and monocytes, which in turn release chemicals with potential tumoricidal effects, may help to control microscopic metastatic disease and has been safely given together with standard adjuvant chemotherapy to patients with high-grade osteosarcoma. Results of the recently published intergroup study 0133 trial from the Children's Cancer and Pediatric Oncology Groups suggest that mifamurtide is a medicine that deserves further investigation in this orphan disease. |
| Kager L, Zoubek A, Dominkus M, Lang S, Bodmer N, Jundt G, Klingebiel T, Jürgens H, Gadner H, Bielack S, COSS Study Group |
Osteosarcoma in very young children: experience of the Cooperative Osteosarcoma Study Group. [+] |
Cancer 2010, 116: 5316 |
|
| BACKGROUND:
This study was conducted to investigate presentation, treatment, and outcome in very young children with osteosarcoma.
METHODS:
The authors retrospectively analyzed the data of 2706 consecutive COSS patients with newly diagnosed osteosarcoma and identified 28 (1.0%) patients aged younger than 5 years at diagnosis. Demographic, diagnostic, tumor, treatment-related variables, response, and survival data were analyzed.
RESULTS:
Of the 28 preschoolers, 27 presented with high-grade central osteosarcoma of an extremity, and 1 had a secondary osteosarcoma of the orbit. This analysis focused on the 27 patients with extremity tumors. The size of the primary was large (≥one-third of the involved bone) in 20 of 27 patients. Primary metastases were detected in 4 of 27 children. All patients received multiagent chemotherapy, and 11 of 18 analyzed tumors responded well (>90% necrosis) to neoadjuvant chemotherapy. Limb-sparing surgery was performed in 9 cases, ablative procedures were performed in 15, and, in 3 cases, no local surgery was performed. With a median follow-up of 4 years (6.2 years for survivors), 13 patients were alive. Four patients never achieved a complete remission, and 11 developed recurrences; 14 of these 15 patients died. Five-year overall and event-free survival probabilities were 51% (standard error of the mean [SE], 10%) and 48% (SE, 10%). Better survival was correlated with good response to chemotherapy and later time period of diagnosis.
CONCLUSIONS:
Osteosarcoma is extremely rare in preschool children. These patients often have large tumors that may require mutilating resections. Prognosis is in the range of that reported for older patients. |
| Kahle W (Hrsg) |
Taschenatlas der Anatomie für Studium und Praxis: 3, Nervensystem und Sinnesorgane. |
Georg-Thieme-Verlag 6. überarbeitete Aufl. 1991 |
|
| Kaletsch U, Kaatsch P, Meinert R, Schuz J, Czarwinski R, Michaelis J |
Childhood cancer and residential radon exposure - results of a population-based case-control study in Lower Saxony (Germany). |
Radiat Environ Biophys 1999, 38: 211 |
|
| Kallage V, Müller J, Zimmermann M, Beck J, Ritter J, Creutzig U |
Prognosis, treatment completion, and complications in nonresponders in the study AML-BFM87. |
Klin Pädiatr 1999, 211: 250 |
|
| Kamps W, Bokkerink J, Hahlen K, Hermans J, Riehm H, Gadner H, Schrappe M, Slater R, Ruiter van, Smets L, de Vaan G, Weening R, van Weerden J, van Wering E, Berg den |
Intensive treatment of children with acute lymphoblastic leukemia according to ALL-BFM-86 without cranial radiotherapy. |
Blood 1999, 94: 1226 |
|
| Kappler R, von Schweinitz D |
A better way forward: targeting hedgehog signaling in liver cancer. [+] |
Frontiers in bioscience 2012, 4: 277 |
|
| Accumulated experimental evidence indicates that Hedgehog (Hh) signaling regulates cell proliferation and specification in a variety of organs during embryonic development. However, abnormal activation of this pathway in postnatal tissues has been linked to a large number of human cancers. With respect to the liver, it is known that Hh signaling not only influences bipotential precursor cells capable of pancreas and liver development, but is also implicated in the pathogenesis of liver tumors such as hepatoblastoma, hepatocellular and cholangiocellular carcinoma, if aberrantly activated. Blockade of Hh signaling by several specific inhibitors has been proven to successfully inhibit tumor growth of various Hh-associated cancers in vitro and in preclinical mouse models, and recent clinical data suggest that the implementation of novel anticancer therapeutics based on Hh interference into commonly accepted regimens are within reach. Thus, it is highly probable that Hh targeted therapies could be used for the treatment of Hh-dependent liver cancers in the future. |
| Karthaus M, Wolf H, Egerer G, Kämpfe D, Ritter J, Jürgens H |
Ceftriaxone in the treatment of solid tumor patients with febrile neutropenia. |
Onkologie, International Journal for Cancer Treatment and Therapy 1998, 21: 212 |
|
| Karawajew L, Ruppert V, Wuchter C, Kosser A, Schrappe M, Dorken B, Ludwig W |
Inhibition of in vitro spontaneous apoptosis by IL-7 correlates with bcl-2 up-regulation, cortical/mature immunophenotype, and better early cytoreduction of childhood T-cell acute lymphoblastic leukemia. |
Blood 2000, 96: 297 |
|
| Karajannis M, Hummel M, Oschlies I, Anagnostopoulos I, Zimmermann M, Stein H, Parwaresch R, Reiter A |
Epstein-Barr virus infection in Western European pediatric non-Hodgkin lymphomas. |
Blood 2003, 102 |
|
| Kardos G, Baumann I, Passmore S, Locatelli F, Hasle H, Schultz K, Stary J, Schmitt-Graeff A, Fischer A, Harbott J, Chessells J, Hann I, Fenu S, Rajnoldi A, Kerndrup G, van Wering E, Rogge T, Nollke P, Niemeyer C |
Refractory anemia in childhood. |
Blood 2003, 102: 1997 |
|
| Karachunskiy A, Herold R, von Stackelberg A, Miakova N, Timakow A, Mahortih T, Bajdun L, Maschan A, Fechina L, Shamardina A, Dudkin S, Lebedev V, Varfolomeeva S, Timofeeva V, Roumiantseva J, Chipsanova N, Rumjanzew A, Henze G |
Results of the first randomized multicentre trial on childhood acute lymphoblastic leukaemia in Russia. [+] |
Leukemia 2008, 22: 1144 |
|
| Until 1990, the survival of children with acute lymphoblastic leukaemia (ALL) in Russia was below 10%. To establish a protocol feasible under conditions there, ALL-MB 91 was designed to avoid prolonged bone marrow aplasia, thereby reducing needs for extensive supportive care, blood transfusions, long-lasting hospitalization and costs. High-dose therapies were avoided, anthracycline use was limited and CNS radiation therapy only foreseen in high-risk patients (about 30%). This was randomized against a modified BFM protocol. From 1995 to 2002, 834 patients of age up to 18 years were registered in 10 centres and 713 received after central randomization the allocated risk-stratified treatment. After a median follow-up of 7 years, the event-free survival (EFS) was 67+/-3% on ALL-MB 91 (N=358) vs 68+/-3% on ALL-BFM 90m (N=355). The overall survival (OS) was 71+/-3% vs 74+/-2%, respectively. Anaemia, thrombocytopenia, agranulocytosis >10 days and hospitalization (median 35 vs 68 days) were lower on ALL-MB 91 (P<0.01, N=197). While EFS and OS were similar with both protocols, ALL-MB 91 significantly incurred fewer toxicity and resource requirements and, therefore, has been increasingly used across Russia. |
| Karremann M, Butenhoff S, Rausche U, Pietsch T, Wolff JE, Kramm CM |
Pediatric giant cell glioblastoma: New insights into a rare tumor entity. [+] |
Neuro-oncology 2009, 11: 323 |
|
| Little is known about giant cell glioblastoma (GCG) in pediatric patients. The present study identified 18 pediatric patients with centrally reviewed GCG from the HIT-GBM database of the Gesellschaft für Paediatrische Onkologie und Haematologie in Germany, Austria, and Switzerland. Clinical and epidemiological data were compared with those of 178 pediatric patients with centrally reviewed glioblastoma multiforme (GBM) from the same database. In this unique series, median age, male preference, and median clinical history did not differ significantly between pediatric GCG and GBM patients. GCG showed a stronger predilection for cerebral hemispheres than did GBM, which may only partly explain the higher percentage of gross total tumor resections in GCG patients. Most surprising, the widely distributed hypothesis that GCG may imply a better prognosis than GBM could not be substantiated for our pediatric series. Future studies with larger patient numbers and molecular pathological analyses are still needed to corroborate the present findings and further elucidate the biology of GCG in children. |
| Karow A, Baumann I, Niemeyer CM |
Morphologic differential diagnosis of juvenile myelomonocytic leukemia--pitfalls apart from viral infection. |
Journal of pediatric hematology/oncology 2009, 31: 380 |
|
| Karremann M, Pietsch T, Janssen G, Kramm CM, Wolff JE |
Anaplastic ganglioglioma in children. [+] |
J Neurooncol 2009, 92: 157 |
|
| PURPOSE: Anaplastic gangliogliomas (AGG) are gangliogliomas with areas of pronounced hypercellularity, vascular proliferation, necrosis, and many mitotic figures. As very few pediatric patients have been studied, we analyzed the cases registered in the HIT-GBM database.
PATIENTS AND METHODS: Patient data were obtained from the German HIT-GBM database. Inclusion criteria were diagnosis of AGG proven by a central neuropathological review and patient age 0 to 17 years. Eight patients (five male and three female) were identified.
RESULTS: Patients' median age was 10 years. The median history of disease was 9 months (range, 1.0-43.0 months). Initial symptoms included signs of raised intracranial pressure, seizures, and, in the case of spinal cord tumor, bladder dysfunction. In five cases, AGGs were localized supratentorially with three patients having multiple lobes involved. The tumors affected the frontal (n = 3 cases), parietal (n = 2), temporal (n = 2), and occipital lobes (n = 1), as well as the brainstem (n = 1) and the spinal cord (n = 2). Gross total tumor resection was achieved in six patients. The estimated 5-year overall survival rate +/- standard error was 88 +/- 12%, and the event-free survival rate was 63 +/- 17%. While gender and tumor location did not affect survival rates, gross total tumor resection provided a better overall survival than non-total resection.
CONCLUSION: The prognosis of pediatric patients with AGG is good, especially for those who undergo gross total tumor resection. |
| Karremann M, Rausche U, Fleischhack G, Nathrath M, Pietsch T, Kramm CM, Wolff JE |
Clinical and epidemiological characteristics of pediatric gliosarcomas. [+] |
Journal of neuro-oncology 2010, 97: 257 |
|
| Gliosarcoma (GS) is a glioblastoma with a sarcomatous component that is presumed to be a metaplastic differentiation of glioma cells. We studied the clinical relevance of this histological glioblastoma subentity within the pediatric population. We obtained patient data from the German HIT-GBM database, which contains clinical data for more than 600 pediatric patients with centrally reviewed high-grade gliomas. By applying defined inclusion criteria (diagnosis of GS proven by central neuropathological review; patient age 0 to 21 years), four patients were identified. In addition, after a review of the English medical scientific literature, 19 additional cases were found. The relative frequency of GS in the German HIT-GBM database was only 1.9%. In the whole series of 23 pediatric GS patients, including previously reported cases, the male-to-female-ratio was 1.2:1. GS was found in all pediatric age groups with a median age of 11 years, but there was an unexpectedly high accumulation in infants (6 of 23 <3 years of age, 26%). GS showed a strong predilection of the cerebral hemispheres (22 out of 23 cases). Increased intracranial pressure was the leading symptom of a short clinical history with a median duration of 0.7 month. Interestingly, six patients (26%) were reported with a history of cranial radiotherapy prior to GS diagnosis. In 60% of the GS patients in our series, gross total resection was achieved. Median overall (OS) and event-free survivals (EFS) of the total cohort were 12.1 and 9.8 months, respectively. In conclusion, GS is a very rare tumor entity in children. Literature review suggests a relatively higher incidence in infants and in patients with a previous history of radiotherapy. |
| Kaspers G, Zwaan M, Creutzig U, Ritter J, Rottier M, Pieters R, Veerman A |
In vitro drug resistance in childhood acute myeloid leukemia. |
Haematology and Blood Transfusion 1997, 39: 491 |
|
| Kaspers GJ, Veerman AJ, Pieters R, Van Zantwijk CH, Smets LA, Van Wering ER, Van Der Does-Van Den Berg A |
In vitro cellular drug resistance and prognosis in newly diagnosed childhood acute lymphoblastic leukemia. |
Blood 1997, 90: 2723 |
|
| Kaspers G, Zwaan C, Veerman A, Rots M, Pieters R, Bucsky P, Domula M, Göbel U, Graf N, Havers W, Jorch N, Kabisch K, Spaar H, Ritter J, Creutzig U |
Cellular drug resistance in acute myeloid leukemia. |
Klin Pädiatr 1999, 211: 239 |
|
| Kaspers GJL, Zimmermann M, Reinhardt D et al. |
Improved outcome in pediatric Relapsed AML: results of a randomized trial on liposomal daunorubicin by the International BFM Study Group. |
J Clin Oncol, in press 2012 |
|
| Kaspers GJ, Zimmermann M, Reinhardt D, Gibson BE, Tamminga RY, Aleinikova O, Armendariz H, Dworzak M, Ha SY, Hasle H, Hovi L, Maschan A, Bertrand Y, Leverger GG, Razzouk BI, Rizzari C, Smisek P, Smith O, Stark B, Creutzig U |
Improved Outcome in Pediatric Relapsed Acute Myeloid Leukemia: Results of a Randomized Trial on Liposomal Daunorubicin by the International BFM Study Group. [+] |
J Clin Oncol 2013 Jan 14; [Epub ahead of print] |
|
| PURPOSEIn pediatric relapsed acute myeloid leukemia (AML), optimal reinduction therapy is unknown. Studies suggest that liposomal daunorubicin (DNX; DaunoXome; Galen, Craigavon, United Kingdom) is effective and less cardiotoxic, which is important in this setting. These considerations led to a randomized phase III study by the International Berlin-Frankfurt-Münster Study Group. PATIENTS AND METHODSPatients with relapsed or primary refractory non-French-American-British type M3 AML who were younger than 21 years of age were eligible. Patients were randomly assigned to fludarabine, cytarabine, and granulocyte colony-stimulating factor (FLAG) or to FLAG plus DNX in the first reinduction course. The primary end point was status of the bone marrow (BM) sampled shortly before the second course of chemotherapy (the day 28 BM). Data are presented according to intention-to-treat for all 394 randomly assigned patients (median follow-up, 4.0 years).ResultsThe complete remission (CR) rate was 64%, and the 4-year probability of survival (pOS) was 38% (SE, 3%). The day 28 BM status (available in 359 patients) was good (≤ 20% leukemic blasts) in 80% of patients randomly assigned to FLAG/DNX and 70% for patients randomly assigned to FLAG (P = .04). Concerning secondary end points, the CR rate was 69% with FLAG/DNX and 59% with FLAG (P = .07), but overall survival was similar. However, core-binding factor (CBF) AML treated with FLAG/DNX resulted in pOS of 82% versus 58% with FLAG (P = .04). Grade 3 to 4 toxicity was essentially similar in both groups. CONCLUSIONDNX added to FLAG improves early treatment response in pediatric relapsed AML. Overall long-term survival was similar, but CBF-AML showed an improved survival with FLAG/DNX. International collaboration proved feasible and resulted in the best outcome for pediatric relapsed AML reported thus far. |
| Kazanowska B, Reich A, Stegmaier S, Békássy AN, Leuschner I, Chybicka A, Koscielniak E |
Pax3-fkhr and pax7-fkhr fusion genes impact outcome of alveolar rhabdomyosarcoma in children. [+] |
Fetal and pediatric pathology 2007, 26: 17 |
|
| Rhabdomyosarcoma is a highly malignant embryonic tumor of childhood. Two specific translocations t(2;13)(q35;q14) and t(1;13)(p36;q14) have been identified in about 75-80% of ARMS cells. The aim of this multicenter study was to analyze the relationships between the identified fusion transcripts and survival including some selected clinical parameters. The extent of disease was graded according to clinical staging system with following distribution: 3 children with stage I, 4 with stage II, 23 with stage III, and 18 with stage IV spread disease having distant metastases. PAX3-FKHR fusion genes were detected in 28 and PAX7-FKHR fusion genes in 7 tumor biopsy specimens. Children with PAX3-FKHR fusion gene had often distant metastases at presentation (p = 0.03). PAX3-FKHR positive patients with locoregional disease had significantly poorer outcome compared with the ones with PAX7-FKHR positive tumors (p = 0.04). Although analyzed groups were small, significant differences in survival and clinical characteristics between PAX3-FKHR and PAX7-FKHR positive tumors were stated indicating their role in carcinogenesis. In addition, fusion gene analysis is a helpful tool in differential diagnosis of poorly differentiated soft tissue tumors. |
| Kebelmann-Betzing C, Körner G, Badiali L, Buchwald D, Möricke A, Korte A, Köchling J, Wu S, Kappelmeier D, Oettel K, Henze G, Seeger K |
Characterization of cytokine, growth factor receptor, costimulatory and adhesion molecule expression patterns of bone marrow blasts in relapsed childhood B cell precursor ALL. |
Cytokine 2001, 13: 39 |
|
| Kellie SJ |
Chemotherapy of central nervous system tumours in infants. [+] |
Childs Nerv Syst 1999, 592 |
|
| The development of curative strategies for infants and children with central nervous system tumours or acute lymphoblastic leukaemia involve similar clinical research principles. Both areas of paediatric oncology research focus on cancers with a broad range of sensitivity to chemotherapy and radiation therapy, together with concerns about the neurodevelopmental, neuroendocrine and growth outcomes of survivors. These considerations have influenced the design of curative- intent treatments, strategies for successfully eradicating leptomeningeal disease, and the importance of anatomic and functional identification of residual disease. Unlike the situation with childhood leukaemia, the emotional barriers of pessimism or even nihilism previously evident towards infants with brain tumours have only begun to crumble during the past decade. The challenge to improve both the quality and overall survival of infants with CNS tumours described in this chapter is ours to meet as we move into the new millennium. This paper examines the development of 'infant' approaches to the treatment of CNS tumours, including a discussion of epidemiology, the reasons for avoiding or delaying radiation therapy, and traces the chemotherapy hypotheses tested over the past two decades in the process of developing potentially curative therapy. The reasons for the disappointing rate of progress compared with that in childhood leukaemia, despite similar clinical research paradigms, are discussed, and potential opportunities are identified. |
| Kelly MJ, Pennarola BW, Rodday AM, Parsons SK, on behalf of the Journeys to Recovery Study, the HSCT-CHESS™ Study |
Health-related quality of life (HRQL) in children with sickle cell disease and thalassemia following hematopoietic stem cell transplant (HSCT). [+] |
Pediatric blood & cancer 2011 Dec 19; |
|
| BACKGROUND: Little is known regarding the health-related quality of life (HRQL) trajectory of children with sickle cell disease or thalassemia ( |
| Kempf-Bielack B, Bielack SS, Jürgens H, Branscheid D, Berdel WE, Exner GU, Göbel U, Helmke K, Jundt G, Kabisch H, Kevric M, Klingebiel T, Kotz R, Maas R, Schwarz R, Semik M, Treuner J, Zoubek A, Winkler K |
Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). [+] |
Journal of clinical oncology 2005, 23: 559 |
|
| PURPOSE: To evaluate the impact of patient, tumor, and treatment-related factors on outcome in unselected patients with recurrent osteosarcoma. PATIENTS AND METHODS: Five hundred seventy-six consecutive patients who had achieved a first complete surgical remission (CR) during combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group (COSS) protocols and then developed recurrent osteosarcoma were analyzed (median time from biopsy to relapse, 1.6 years; range, 0.1 to 14.3 years). There were 501 patients with metastases, 44 with local recurrences, and 31 with both. Metastases involved lungs (469 patients), bones (90 patients), and/or other sites (54 patients). RESULTS: After a median follow-up of 1.2 years for all patients and 4.2 years for survivors, actuarial overall survival (OS) rates at 2, 5, and 10 years were 0.38, 0.23, and 0.18, respectively. Five-year OS was 0.39 for 339 patients with and 0.00 for 229 patients without a second surgical CR (P < .0001). A long time to relapse, a solitary lesion, and, in the case of pulmonary metastases, unilateral disease and the absence of pleural disruption, were of positive prognostic value in uni- and multivariate analyses, as were a second surgical CR and the use of second-line chemotherapy. Radiotherapy was associated with moderately prolonged survival in patients without a second CR. The very limited prognostic differences associated with the use of second-line chemotherapy appeared to be more pronounced with polychemotherapy. CONCLUSION: Time to relapse and tumor burden correlate with postrelapse outcome in osteosarcoma. Complete surgery is an essential component of curative second-line therapy. Chemotherapy, particularly chemotherapy with more than one agent, may contribute to limited improvements in outcome. |
| Kersten W, Brade W |
[Treatment of bronchitis with cefaclor (Panoral) (author's transl)]. [+] |
MMW, Munchener medizinische Wochenschrift 1979 Feb 16; 121: 247 |
|
| 14 patients from the Allergy Unit of an outpatient clinic suffering from acute exacerbation of chronic bronchitis and 13 outpatients with acute bronchitis were treated with 250 mg cefaclor (Panoral) 3 times daily per os for 5 days. 59% of the organisms isolated from cefaclor-sensitive sputum at the time of prominent clinical symptoms were resistent to tetracycline, 53% of them were resistant to penicillin, and 37% were resistant to ampicillin. 12 out of the 14 patients with acute exacerbation of chronic bronchitis became asymptomatic, and no organisms could be detected in the sputum of 13 out of the same 14 patients two days after cessation of cefaclor treatment. In 12 out of the 13 patients with acute bronchitis, the acute clinical symptoms disappeared and in 11 out of the 13 patients the initial sputum organisms were two days after stopping cefaclor treatment. |
| Kern W, Büchner T, Wörmann B, Ritter J, Creutzig U, Hiddemann W |
Akute Leukämien; Prognostische Faktoren und Therapiestrategien. |
Internist 1999, 40: 983 |
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| Kersting C, Gebert C, Agelopoulos K, Schmidt H, van Diest PJ, Jürgens H, Winkelmann W, Kevric M, Gosheger G, Brandt B, Bielack S, Buerger H |
Epidermal growth factor receptor expression in high-grade osteosarcomas is associated with a good clinical outcome. [+] |
Clinical cancer research 2007, 13: 2998 |
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| PURPOSE: The expression of the epidermal growth factor receptor (EGFR) in osteosarcomas has repeatedly been described. With the introduction of anti-EGFR-targeted therapies in clinical practice, these findings regain increased attention. Experience with anti-EGFR-targeted therapies in other cancers has made clear that besides the expression status of EGFR, a detailed knowledge about gene mutations is of major predictive power. We therefore aimed to explore the EGFR expression and gene mutation status in high-grade osteosarcomas. EXPERIMENTAL DESIGN: We investigated tumor samples of osteosarcoma patients of all age groups by means of immunohistochemistry (n=111) and egfr fluorescence in situ hybridization (n=39). Sixty-three patients were treated according to the Cooperative Osteosarcoma Study Group protocols and complete clinical follow-up was available in these cases. RESULTS: Ninety-one of 111 (81%) of osteosarcomas revealed an expression of EGFR. EGFR expression showed a dose-response relation with improved event-free and overall survival. This was independent of the degree of tumor regression due to neoadjuvant chemotherapy. Nine of 39 (23%) osteosarcomas showed egfr amplifications by means of fluorescence in situ hybridization. All these cases expressed EGFR. When comparing EGFR expression between primary biopsy and resection specimen (n=19), viable residual tumor cells in resection specimens revealed a lower EGFR expression and a tendency toward membranous staining compared with the initial biopsy. CONCLUSIONS: In conclusion, expression and amplification of EGFR are frequently observed in high-grade osteosarcomas and are associated with improved prognosis in a dose-responsive way. This implies that low EGFR expression possibly predicts lack of response to conventional treatment in high-grade osteosarcomas and may warrant a more intensive therapeutic approach, although not based on EGFR targeting. |
| Khan J, Wei J, Ringner M, Saal L, Ladanyi M, Westermann F, Berthold F, Schwab M, Antonescu C, Peterson C, Meltzer P |
Classification and diagnostic prediction of cancers using gene expression profiling and artificial neural networks. |
Nat Med 2001, 7: 673 |
|
| Khalil MN, Erb N, Khalil PN, Escherich G, Janka-Schaub GE |
Interference free and simplyfied liquid chromatography-based determination of thiopurine S-methyltransferase activity in erythrocytes. [+] |
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 2005, 821: 105 |
|
| The determination of the thiopurine S-methyltransferase activity (TPMT; EC 2.1.1.67) has become an important issue during thiopurine therapy due to its known genetic polymorphism resulting in a wide range of TPMT activity. Therefore, the standard thiopurine drug regimen is associated with increased hematopoetic toxicity in patients with low or absent TPMT activity, whereas patients with high activity may be insufficiently treated. However, presently available methods are labour intensive and time consuming and tend towards too high or too low enzyme activity due to their methodological approach. The use of instable substrate solutions (6-MP or 6-TG), organic solvents like dimethyl sulfoxide and too high substrate and co-substrate saturation concentrations contribute to this phenomenon. We therefore, established an optimized and fast isocratic HPLC linked TPMT assay based on the enzymatic methylation of mercaptopurine or thioguanine in RBC lysates with S-adenosyl-l-methionine as methyl donor. Unspecific non-enzymatic methylation was not detectable. The recovery of 6-methyl-mercaptopurine was 97-102%, the intra- and interday variation between 1.0 and 5.0%, respectively. The assay dispenses with a time consuming extraction procedure with organic solvents, a heating step, and a gradient elution and is therefore, favourable for clinical routine application. The TPMT activity was measured in 62 untreated children with acute lymphoblastic leucemia at the time of diagnosis (activity = 34.0+/-10.6 nmol/g Hb/h, range: 11.5-55.4 nmol/g Hb/h) and in 12 adult healthy volunteers (62.8+/-7.7 nmol/g Hb/h, range: 48-82 nmol/g Hb/h) reflecting the wide measurable TPMT activity found in erythrocytes. |
| Kidas E, Möricke A, Beier R, Welte K, Schrappe M, Stanulla M, Grigull L |
Genetic polymorphisms of the lymphotoxin alpha gene are associated with increased risk for lethal infections during induction therapy for childhood acute leukemia: a case-control study. [+] |
International journal of hematology 2009, 89: 584 |
|
| Specific mutations of the TNF-alpha (TNF-alpha) and Lymphotoxin-alpha (LT-alpha) genes are correlated to the outcome of patients during serious infections. This study aimed at correlating these polymorphisms to lethal infections during childhood acute lymphoblastic leukemia (ALL). A matched case-control study of 34 patients who died due to infections during ALL treatment and 68 ALL patients without lethal infections was performed. Genomic DNA was isolated from blood smears and specific fragments including the polymorphic site of each gene were amplified. In the total study population, 23/102 (22.5%) of the children carried at least two variant alleles (high-producer haplotype). The variant genotypes were equally distributed between cases and controls [relative risk (RR) 1.17 (CI 0.33-2.22, P = 0.752)]. With regard to infective organisms, no statistically significant differences could be detected between the groups for bacterial infections [RR 1.59 (CI 0.56-4.50), P 0.379]. Patients with a LT-alpha (10.5 kb/5.5 kb; 5.5 kb/5.5 kb) haplotype, however, seemed to have a significant higher risk of attracting a lethal infection during induction/consolidation chemotherapy (RR 2.98, CI 0.98-9.01, P = 0.05). These results support a role of specific genetic polymorphisms on lethal infections during induction chemotherapy of ALL treatment. |
| Kircher B, Niederwieser D, Gächter A, Lindner B, Mitterschiffthaler A, Urban C, Greinix H, Peters C, Lätzer K, Gastl G, Nachbaur D |
T-cell precursor frequencies and long-term outcome following unrelated hematopoietic stem cell transplantation. [+] |
International journal of laboratory hematology 2008, 30: 499 |
|
| Functional assays measuring alloreactivity of donor cells are desired to detect either cryptic epitopes inducing graft-vs.-host disease (GvHD) after human leukocyte antigen (HLA)-identical hematopoietic stem cell transplantation (HSCT) or permissible HLA mismatches. However, their value in predicting GvHD and survival is still limited. We determined the cytotoxic and helper T-cell precursor (CTLp and HTLp) frequencies by limiting dilution analysis (LDA) in 40 unrelated recipient/donor combinations. The median observation period at the time of this writing was 4.44 years (range from 0.1 to 11.28). Better overall survival was observed in patients with rather low host-specific CTLp and HTLp frequencies, whereas a trend toward high CTLp frequencies was seen in patients with higher incidence of acute GvHD, especially in patients mismatched in HLA-C. CTLp and HTLp frequencies did not correlate with the incidence of chronic GvHD and relapse. In conclusion, we detected a trend toward better overall survival of patient/donor pairs with low CTLp and HTLp frequencies, however, recommend to use LDA as an additional tool for identifying the most suitable donor when more than one fully HLA-matched stem cell donor is available. |
| Kitao H, Takata M |
Fanconi anemia: a disorder defective in the DNA damage response. [+] |
Int J Hematol 2011, 93: 417 |
|
| Fanconi anemia (FA) is a cancer predisposition disorder characterized by progressive bone marrow failure, congenital developmental defects, chromosomal abnormalities, and cellular hypersensitivity to DNA interstrand crosslink (ICL) agents. So far mutations in 14 FANC genes were identified in FA or FA-like patients. These gene products constitute a common ubiquitin-phosphorylation network called the |
| Kivela T |
Trilateral retinoblastoma: a meta-analysis of hereditary retinoblastoma associated with primary ectopic intracranial retinoblastoma. [+] |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 1999, 17: 1829 |
|
| PURPOSE: To obtain refined knowledge regarding trilateral retinoblastoma (TRb), which is a syndrome that consists of hereditary retinoblastoma associated with an intracranial neuroblastic tumor. MATERIALS AND METHODS: Using a systematic literature review, we contacted authors to obtain missing information. Data from 106 children were used in a meta-analysis including frequency distributions and Kaplan-Meier survival curves. RESULTS: TRb showed no sex predilection. Median age at diagnosis of retinoblastoma was 5 months (range, 0 to 29 months); age at diagnosis was younger among 47 children (47%) with familial retinoblastoma compared with age at diagnosis among 52 children (53%) with sporadic retinoblastoma (2 v 6.5 months, P <.0001). TRb usually affected the second or third generation with retinoblastoma. Median time from retinoblastoma to TRb was 21 months (range, 6 months before to 141 months after); time to TRb was longer for 78 (77%) pineal tumors compared with 23 (23%) suprasellar tumors (32 v 6.5 months, P <.0001). The size (27 v 32 mm, P =.57) and prognosis (survival of 9 v 8 months, P =.91) of pineal and suprasellar tumors were similar. TRb was detected earlier (1 v 22 months, P =.0007) and the child survived longer if neuroimaging was routinely performed (16 v 8 months, P =.001), but age at death was similar (36 v 37 months, P =.98). Cumulative 5-year survival (which was likely to indicate cure) was 27% (v 0%) if screening was undertaken. All children whose TRb exceeded 15 mm in size died. CONCLUSION: The family history, age at diagnosis, and laterality of retinoblastoma in children with TRb resembled that of ordinary hereditary retinoblastoma. Suprasellar TRb were diagnosed earlier, and may arise earlier, than pineal TRb. Screening by neuroimaging could improve the cure rate if cases of TRb were detected when tumors were 15 mm or smaller in size. |
| Klamt B, Schulze M, Thate C, Mares J, Goetz P, Kodet R, Scheulen W, Weirich A, Graf N, Gessler M |
Allele loss in Wilms tumors of chromosome arms 11q, 16q, and 22q correlate with clinicopathological parameters. |
Genes Chromosomes Cancer 1998, 22: 287 |
|
| Kleinman GM, Hochberg FH, Richardson EP Jr |
Systemic metastases from medulloblastoma: report of two cases and review of the literature. [+] |
Cancer 1981 Nov 15; 48: 2296 |
|
| The clinical and pathologic data from two cases of medulloblastoma with systemic metastases, and 101 previously reported cases were evaluated to define better the clinical presentation and natural history. Patients ranged in age from six months to 48 years, with a mean of 13 years; two thirds of the patients were male. Ventricular shunts had been inserted in 20% of the patients. Systemic metastases occurred on an average of two years after the diagnosis of the primary tumor in patients without shunts, but only 1.3 years in patients with shunts. Fifty-nine percent of the patients were known to have experienced recurrence or spread of medulloblastoma within the central nervous system by the time systemic metastases appeared. Ninety percent showed radiologic evidence of bone metastases, of which 60% were osteoblastic. Bones most frequently involved were pelvis, femur and vertebrae; pain was the most common initial symptom. At autopsy, lymph node metastases were found in 65% and liver metastases were found in 28% of all cases in addition to bone metastases in 82%. Lung metastases occurred in 9% of the patients without shunts, compared with 30% of patients with shunts. The average survival was seven months after the appearance of systemic metastases for patients both with and without shunts. Approximately 5% of patients with medulloblastoma may be expected to develop systemic metastases. This development is associated with increased morbidity and a shortened life expectancy. |
| Klein G, Schulz B, Spix C, Kaatsch P |
Risikoabschätzung für Sekundärmalignome nach Krebs im Kindesalter. |
Monatsschr Kinderheilkd 2002, 150 : 564 |
|
| Klein G, Schulz B, Spix C, Kaatsch P |
Risikoabschätzung für sekundäre Malignome nach kindlicher Krebserkrankung – bevölkerungsbezogene Analysen des Deutschen Kinderkrebsregisters. |
Informatik, Biometrie und Epidemiologie in Medizin und Biologie 2002, 2: 109 |
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| Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, Cavenee WK |
The WHO classification of tumors of the nervous system. |
J Neuropathol Exp Neurol 2002, 61: 215 |
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| Kleideiter E, Schwab M, Friedrich U, Koscielniak E, Schafer B, Klotz U |
Telomerase activity in cell lines of pediatric soft tissue sarcomas. |
Pediatr Res 2003, 54: 718 |
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| Klein G, Michaelis J, Spix C, Wibbing R, Eggers G, Ritter J, Kaatsch P |
Second malignant neoplasms after treatment of childhood cancer. |
Eur J Cancer 2003, 39: 808 |
|
| Klein C, Welte K |
Genetic insights into congenital neutropenia. [+] |
Clinical reviews in allergy & immunology 2010, 38: 68 |
|
| Congenital neutropenia syndromes comprise a heterogeneous group of disorders leading to increased susceptibility to bacterial infections. Recent work has elucidated the molecular basis of several congenital neutropenia syndromes such as mutations in ELA2, HAX1, GF11, and WAS. In addition, a number of complex clinical syndromes associating congenital neutropenia have been recognized and elucidated on a genetic level, e.g. p14-deficiency or G6PC3-deficiency. The clinical and genetic findings of various neutropenia syndromes are being discussed. |
| Klingebiel T, Berthold F, Treuner J, Schwabe D, Fischer M, Feine U, Maul F, Waters W, Wehinger H, Niethammer D |
Metaiodobenzylguanidine (mIBG) in treatment of 47 patients with neuroblastoma. |
Med Pediatr Oncol 1991, 19: 84 |
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| Klingebiel T, Feine U, Treuner J, Reuland P, Handgretinger R, Niethammer D |
Treatment of neuroblastoma with [131I]metaiodobenzylguanidine. |
J Nucl Biol Med 1991, 35: 216 |
|
| Klingebiel T, Ritter J, Schellong G, Creutzig U, Riehm H, Henze G, Bender-Götze C, Dopfer R, Ebell W, Friedrich W, Haas R, Schmitz N, Stollmann B, Niethammer D |
Role and perspectives of BMT in AML. |
1991, 7: 66 |
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| Klingebiel T, Pertl U, Hess C, Jürgens H, Koscielniak E, Potter R, van Heek-Romanowski R, Rossi R, Schott C, Spaar H, Willnow U, Treuner J |
Treatment of children with relapsed soft tissue sarcoma. |
Med Pediatr Oncol 1998, 30: 269 |
|
| Klingebiel T |
Knochenmark- und Stammzelltransplantation, in Gutjahr P: Krebs bei Kindern und Jugendlichen. |
Deutscher Ärzte-Verlag Köln 5. Aufl. 2004, 83 |
|
| Klingebiel T, E Koscielniak Weichteilsarkome |
In: Kiess/Merckenschlager/Pfäffle/Siekmeyer:Therapie im Kindes-und Jugendalter. |
ISBN 3-437-23200-2, im Druck |
|
| Klingebiel T, Koscielniak E |
Weichteilsarkome, in: Rüben H (Hrsg.): Uroonkologie. |
Springer Verlag Heidelberg 4. Aufl. 2007, 657 |
|
| Klingebiel T, Koscielniak E |
Weichteilsarkome, in: Kiess W, Merkenschlager A, Pfäffle R, Siekmeyer W (Hrsg.): Therapie in der Kinder- und Jugendmedizin. |
Elsevier, Urban & Fischer, München Jena 1. Aufl. 2007, 820 |
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| Klingebiel T, Boos J, Beske F, Hallmen E, Int-Veen C, Dantonello T, Treuner J, Gadner H, Marky I, Kazanowska B, Koscielniak E |
Treatment of children with metastatic soft tissue sarcoma with oral maintenance compared to high dose chemotherapy: report of the HD CWS-96 trial. [+] |
Pediatric blood & cancer 2008, 50: 739 |
|
| PURPOSE: We prospectively studied the efficacy of high dose therapy (HDT) versus an oral maintenance treatment (OMT) in patients with stage IV soft tissue sarcoma (STS). PATIENTS AND METHODS: Both groups were pretreated with the CEVAIE combination consisting of carboplatin, etoposide, vincristine, actinomycin D, ifosfamide, and epirubicin. HDT consisted of a tandem cycle of thiotepa (600 mg/m(2)) plus cyclophosphamide (4,500 mg/m(2)) and melphalan (120 mg/m(2)) plus etoposide (1,800 mg/m(2)). This treatment was compared with OMT, consisting of four cycles trofosfamide (10 days 2 x 75 mg/m(2)/day) plus etoposide (10 days 2 x 25 mg/m(2)/day), and 4 cycles trofosfamide (10 days 2 x 75 mg/m(2)/day) plus idarubicin (10 days 4 x 5 mg/m(2)). Eligibility criteria were: diagnosis confirmed by reference pathology, primary stage IV, below 22 years of age, and having completed the study therapy. RESULTS: From 96 patients 45 were treated with HDT and 51 with OMT. The main risk parameters were equally distributed in both arms. After a median follow-up of 57.4 months, 11/45 (24.4%) patients in the HDT-arm and 26/51 (57.8%) patients in OMT-arm were alive. Kaplan-Meier analysis demonstrated an overall survival for the whole group of 0.27 (OMT group: 0.52, HDT group 0.27, log rank P = 0.03). The proportional hazard analysis for patients with rhabdomyosarcoma (RMS) or |
| Klingebiel, T |
Was Hoffnung kosten darf: Ist die Einlagerung von autologem Nabelschnurblut nötig und sinnvoll? |
Dtsch Arztebl 2009, 106: 829 |
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| Klingebiel T, Cornish J, Labopin M, Locatelli F, Darbyshire P, Handgretinger R, Balduzzi A, Owoc-Lempach J, Fagioli F, Or R, Peters C, Aversa F, Polge E, Dini G, Rocha V, Pediatric Diseases and Acute Leukemia Working Parties of the European Group for Blood and Marrow Transplantation (EBMT) |
Results and factors influencing outcome after fully haploidentical hematopoietic stem cell transplantation in children with very high-risk acute lymphoblastic leukemia: impact of center size: an analysis on behalf of the Acute Leukemia and Pediatric Disease Working Parties of the European Blood and Marrow Transplant group. [+] |
Blood 2010, 115: 3437 |
|
| T cell-depleted haploidentical hematopoietic stem cell transplantation (haploHSCT) is an option to treat children with very high-risk acute lymphoblastic leukemia (ALL) lacking an HLA-identical donor. We analyzed 127 children with ALL who underwent haploHSCT in first (n = 22), second (n = 48), or third (n = 32), complete remission or in relapse (n = 25). The 5-year leukemia-free survival (LFS) was 30%, 34%, 22%, and 0%, respectively. A risk-factor analysis was performed for patients who underwent transplantation in remission (n = 102). Five-year nonrelapse mortality (NRM), relapse incidence (RI), and LFS were 37%, 36%, and 27%, respectively. A trend of improved LFS rate and decreased RI was observed for children given a graft with higher number of CD34(+) cells (adjusted P = .09 and P = .07, respectively). In a multivariate analysis, haploHSCT performed in larger centers (performing > or = 231 allotransplantations in the studied period) was associated with improved LFS rate and decreased RI (adjusted P = .01 and P = .04, respectively), adjusting for different patient-, disease-, and transplant-related factors such as number of previous autotransplantations, cytomegalovirus serology status, type of T-cell depletion, and use of total body irradiation and antithymocyte globulin. In conclusion, higher CD34(+) cell dose and better patient selection may improve outcomes of children with ALL who undergo a haploHSCT. Transplant centers initiating programs on haploHSCT for children may collaborate with more experienced centers. |
| Klumper E, Pieters R, Kaspers G, Loonen A, Huismans D, VanZantwijk C, Hählen K, VanWering E, Henze G, Veerman A |
Cytostatic drug resistance in childhood relapsed acute lymphoblastic leukemia. |
Haematol Blood Transfus 1994, 36: 291 |
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| Klumper E, Pieters R, Kaspers G, Huismans D, Loonen A, Rottier M, van Wering E, van der Does-van den Berg A, Hählen K, Creutzig U, Veermann A |
In vitro chemosensitivity assessed with the MTT assay in childhood acute nonlymphoblastic leukemia. |
Leukemia 1995, 9: 1864 |
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| Klumper E, Pieters R, Veerman A, Huismans D, Loonen A, Hahlen K, Kaspers G, van Wering E, Hartmann R, Henze G |
In vitro cellular drug resistance in children with relapsed/refractory acute lymphoblastic leukemia. |
Blood 1995, 86: 3861 |
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| Klusmann JH, Creutzig U, Zimmermann M, Dworzak M, Jorch N, Langebrake C, Pekrun A, Macakova-Reinhardt K, Reinhardt D |
Treatment and prognostic impact of transient leukemia in neonates with Down's syndrome. [+] |
Blood 2008, 111: 2991 |
|
| Approximately 10% of the neonates with Down's syndrome (DS) exhibit a unique transient leukemia (TL). Though TL resolves spontaneously in the majority of cases, early death and development of myeloid leukemia (ML-DS) may occur. Prognostic factors as well as treatment indication are currently uncertain. To resolve that issue, we prospectively collected clinical, biological and treatment data of 146 patients with TL. 5-year overall survival (OS) and event free survival (EFS) were 85+/-3% and 63+/-4%, respectively. Multivariate analysis revealed a correlation between high white blood cell (WBC) count, ascites, preterm delivery, bleeding diatheses, failure of spontaneous remission and the occurrence of early death. Treatment with cytarabine (0.5-1.5 mg/kg) was administered to 28 patients with high WBC count, thrombocytopenia or liver dysfunction. The therapy had a beneficial effect on the outcome of those children with risk factors for early death (5-yr EFS 52+/-12% vs. 28+/-11% (no treatment); p=0.02). Multivariate analysis demonstrated its favorable prognostic impact. 29 TL patients (23%) subsequently developed ML-DS. ML-DS patients with a history of TL had a significantly better 5-yr EFS (93+/-5%) than those without documented TL (71+/-4%), primarily due to a lower relapse rate. A history of TL may therefore define a lower-risk ML-DS subgroup. This study was registered at www.ClinicalTrials.gov as #NCT 00111345. |
| Klusmann JH, Li Z, Böhmer K, Maroz A, Koch ML, Emmrich S, Godinho FJ, Orkin SH, Reinhardt D |
miR-125b-2 is a potential oncomiR on human chromosome 21 in megakaryoblastic leukemia. [+] |
Genes & development 2010, 24: 478 |
|
| Children with trisomy 21/Down syndrome (DS) are at high risk to develop acute megakaryoblastic leukemia (DS-AMKL) and the related transient leukemia (DS-TL). The factors on human chromosome 21 (Hsa21) that confer this predisposing effect, especially in synergy with consistently mutated transcription factor GATA1 (GATA1s), remain poorly understood. Here, we investigated the role of Hsa21-encoded miR-125b-2, a microRNA (miRNA) overexpressed in DS-AMKL/TL, in hematopoiesis and leukemogenesis. We identified a function of miR-125b-2 in increasing proliferation and self-renewal of human and mouse megakaryocytic progenitors (MPs) and megakaryocytic/erythroid progenitors (MEPs). miR-125b-2 overexpression did not affect megakaryocytic and erythroid differentiation, but severely perturbed myeloid differentiation. The proproliferative effect of miR-125b-2 on MEPs accentuated the Gata1s mutation, whereas growth of DS-AMKL/TL cells was impaired upon miR-125b repression, suggesting synergism during leukemic transformation in GATA1s-mutated DS-AMKL/TL. Integrative transcriptome analysis of hematopoietic cells upon modulation of miR-125b expression levels uncovered a set of miR-125b target genes, including DICER1 and ST18 as direct targets. Gene Set Enrichment Analysis revealed that this target gene set is down-regulated in DS-AMKL patients highly expressing miR-125b. Thus, we propose miR-125b-2 as a positive regulator of megakaryopoiesis and an oncomiR involved in the pathogenesis of trisomy 21-associated megakaryoblastic leukemia. |
| Klusmann JH, Reinhardt D, Zimmermann M, Kremens B, Vormoor J, Dworzak M, Creutzig U, Klingebiel T |
The role of matched sibling donor allogeneic stem cell transplantation in pediatric high-risk acute myeloid leukemia: results from the AML-BFM 98 study. [+] |
Haematologica 2012, 97: 21 |
|
| Background. The role of allogeneic stem cell transplantation in post-remission management of pediatric high-risk acute myeloid leukemia remains controversial. In the multi-center AML-BFM 98 study we prospectively evaluated the impact of allogeneic stem cell transplantation in children with high-risk acute myeloid leukemia in first complete remission. Design and Methods. HLA-typed high-risk acute myeloid leukemia patients, who achieved first complete remission (n=247), were included in this analysis. All patients received double induction and consolidation. Based on availability of matched-sibling donor, patients were allocated by genetic chance to allogeneic stem cell transplantation (n=61) or chemotherapy-only (i.e. intensification and maintenance therapy; n=181). The main analysis was done on an intention-to-treat basis according to this allocation. Results. Intention-to-treat analysis did not show a significantly different 5-year disease-free survival (49±6% vs. 45±4%, plog rank=0.44) and overall survival (68+/-6% vs. 57+/-4%, plog rank=0.17) between the matched-sibling donor and no-matched-sibling donor groups, whereas late adverse effects occurred more frequently after allogeneic stem cell transplantation (72.5% vs. 31.8%, pFischer<0.01). Those results were confirmed by as-treated analysis corrected for the time until transplantation (5-year overall survival: 72+/-8% vs.60+/-4%, pMantel-byar 0.21). Subgroup analysis demonstrated improved survival rates for patients with 11q23 aberrations allocated to allogeneic stem cell transplantation (5-year overall survival: 94+/-6% vs. 52+/-7%, plog-rank=0.01; n=18 vs. 49) in contrast to patients without 11q23 aberrations (5-year overall survival: 58+/-8% vs. 55+/-5%, plog-rank=0.66). Conclusions. Our analysis defined a genetic subgroup of the high-risk acute myeloid leukemia patients, which showed a benefit from allogeneic stem cell transplantation in the prospective multi-center AML-BFM 98 study. For the remainder of the pediatric high-risk acute myeloid leukemia patients, the prognosis could not be improved by allogeneic stem cell transplantation, which was, however, associated with a higher rate of late sequelae.This trial was registered at www.clinicaltrials.gov as #NCT00111345. |
| Kluge R, Körholz D |
[Role of FDG-PET in Staging and Therapy of Children with Hodgkin Lymphoma. [+] |
Klinische Padiatrie 2011, [Epub ahead of print] |
|
| 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. |
| Klusmann JH, Reinhardt D, Zimmermann M, Kremens B, Vormoor J, Dworzak M, Creutzig U, Klingebiel T |
The role of matched sibling donor allogeneic stem cell transplantation in pediatric high-risk acute myeloid leukemia: results from the AML-BFM 98 study. [+] |
Haematologica 2012, 97: 21 |
|
| The role of allogeneic stem cell transplantation in post-remission management of children with high-risk acute myeloid leukemia remains controversial. In the multi-center AML-BFM 98 study we prospectively evaluated the impact of allogeneic stem cell transplantation in children with high-risk acute myeloid leukemia in first complete remission. |
| Knowles DM |
Inmunodeficiency-associated lymphoproliferative disorders. |
Mod Pathol 1999, 12: 200 |
|
| Koch A, Dörr H, Beyer R, Erhardt J, Fahlbusch R, Dunst J, Beck J |
Wachstum und Wachstumsstörungen von Kindern nach Therapie eines Medulloblastoms. |
Monatsschr Kinderheilkd 1994, 142: 884 |
|
| Kochling J, Konig-Merediz S, Stripecke R, Buchwald D, Korte A, Von Einsiedel H, Sack F, Henze G, Seeger K, Wittig B, Schmidt M |
Protection of mice against Philadelphia chromosome-positive acute lymphoblastic leukemia by cell-based vaccination using nonviral, minimalistic expression vectors and immunomodulatory oligonucleotides. |
Clin Cancer Res 2003, 9: 3142 |
|
| Koch A, Weber N, Waha A, Hartmann W, Denkhaus D, Behrens J, Birchmeier W, von Schweinitz D, Pietsch T |
Mutations and elevated transcriptional activity of conductin (AXIN2) in hepatoblastomas. [+] |
The Journal of pathology 2004, 204: 546 |
|
| Hepatoblastoma (HB) is the most frequent malignant liver tumour of childhood. Most HBs develop sporadically but their incidence is highly elevated in patients with familial adenomatous polyposis coli (FAP). These patients carry germline mutations in the adenomatous polyposis coli (APC) tumour suppressor gene. APC forms a multi-protein complex involved in the WNT signalling pathway that controls the stability of beta-catenin, the central effector in this cascade. Whereas APC mutations are rare in sporadic HBs, a high frequency of beta-catenin mutations leading to overactivation of WNT signalling was previously found in these tumours. This pathway is negatively controlled by conductin (axin2), representing a further partner in this signalling complex. To investigate whether alterations in conductin may also be involved in the pathogenesis of sporadic HBs, 37 HBs and five HB cell lines were screened for mutations using single-strand conformation polymorphism (SSCP) analysis, reverse transcription-polymerase chain reaction (RT-PCR), and direct sequencing. In two cases, larger deletions (52 and 1624 bp) leading to frameshifts were found. In addition, one HB carried a somatic point mutation. Expression analysis by competitive RT-PCR in HBs revealed up-regulation of conductin mRNA compared with adjacent liver samples. This mRNA overexpression resulted in increased conductin protein levels demonstrated by western blot analysis. Tumours with activating beta-catenin mutations revealed higher levels of conductin mRNA transcripts. This finding indicates that conductin is a direct target gene of WNT signalling in HBs, as has been demonstrated in other tissues. In summary, conductin mutations may represent an alternative mechanism leading to activation of WNT signalling in HBs. The overexpression of conductin mRNA in HBs reflects activation of the WNT pathway because conductin represents a target gene of WNT signalling in liver tissue. |
| Koch A, Waha A, Hartmann W, Hrychyk A, Schuller U, Waha A, Wharton KA Jr, Fuchs SY, von Schweinitz D, Pietsch T |
Elevated expression of Wnt antagonists is a common event in hepatoblastomas. [+] |
Clinical cancer research 2005, 11: 4295 |
|
| Hepatoblastomas are the most frequent malignant liver tumors of childhood. A high frequency of activating beta-catenin mutations in hepatoblastomas indicates that the Wnt signaling pathway plays an important role in the development of this embryonic neoplasm. Stabilization of beta-catenin leads to an increased formation of nuclear beta-catenin-T-cell factor complexes and altered expression of Wnt-inducible target genes. In this study, we analyzed the mRNA expression levels of nine Wnt genes, including c-JUN, c-MYC, CYCLIN D1, FRA-1, NKD-1, ITF-2, MMP-7, uPAR, and beta-TRCP, by competitive reverse transcription-PCR. We analyzed 23 hepatoblastoma biopsies for which matching liver tissue was available, 6 hepatoblastoma cell lines, and 3 human fetal liver samples. beta-TRCP and NKD-1 were highly expressed in all hepatoblastoma samples, independent of the beta-catenin mutational status, in comparison with their nontumorous counterparts. beta-TRCP mRNA overexpression was associated with accumulation of intracytoplasmic and nuclear beta-TrCP protein. In human liver tumor cells without beta-catenin mutations, Nkd-1 inhibited the Wnt-3a-activated Tcf-responsive-luciferase reporter activity, whereas Nkd-1 in hepatoblastomas with beta-catenin mutations had no antagonistic effect. Our data emphasize the inhibitory effect of beta-TrCP and Nkd-1 on the Wnt signaling pathway in a manner analogous to Conductin (AXIN2) and Dkk-1, inhibitors shown previously to be up-regulated in hepatoblastomas. Our findings indicate that overexpression of the Wnt antagonists Nkd-1 and beta-TrCP reveals an activation of the Wnt signaling pathway as a common event in hepatoblastomas. We propose that Nkd-1 and beta-TrCP may be used as possible diagnostic markers for the activated Wnt signaling pathway in hepatoblastomas. |
| Körholz D, Wirtz I, Vosberg H, Rüther W, Jürgens H, Göbel U |
The role of bone scintigraphy in the follow-up of osteogenic sarcoma. |
Eur J Cancer 1996, 32A: 461 |
|
| Körholz D, Kluge R, Wickmann L, Hirsch W, Lüders H, Lotz I, Dannenberg C, Hasenclever D, Dörffel W, Sabri O |
Importance of F18-fluorodeoxy-D-2-glucose positron emission tomography (FDG-PET) for staging and therapy control of Hodgkin's lymphoma in childhood and adolescence - consequences for the GPOH-HD 2003 protocol. [+] |
Onkologie 2003, 26: 489 |
|
| The prognosis for children and adolescents with Hodgkin's lymphoma is excellent. However, many patients will show secondary malignancies 15-30 years after the initial diagnosis, which appears to be connected with the intensity of treatment during primary disease. In the GPOH-HD 95 trial, the indication for radiotherapy was limited to patients who did not show a complete remission after chemotherapy, as determined radiographically. In the future protocol, the indication for radiotherapy in patients with early-stage Hodgkin's lymphoma should be further refined by using FDG-PET for evaluating the response to chemotherapy. Furthermore, in patients at an advanced stage of the disease, it should be determined if sequential FDG-PET research during chemotherapy can separate patients into subgroups with an excellent or a poor prognosis. This article gives a review of the current literature on FDG-PET in patients with Hodgkin's lymphoma and outlines the consequences for future protocols. |
| Körholz D, Claviez A, Hasenclever D, Kluge R, Hirsch W, Kamprad F, Dörffel W, Wickmann L, Papsdorf K, Dieckmann K, Kahn T, Mauz-Korholz C, Dannenberg C, Potter R, Brosteanu O, Schellong G, Sabri O |
The concept of the GPOH-HD 2003 therapy study for pediatric Hodgkin's disease. |
Klin Pädiatr 2004, 216: 150 |
|
| Kohne E |
Diagnostik von Hämoglobinopathien. |
J Lab Med 2004, 28 , 400 |
|
| Kohne E, Kleihauer E |
Hämoglobinopathien - eine Langzeitstudie über vier Jahrzehnte. |
Dtsch Arztebl Int 2010, 107: 65 |
|
| Konemann S, Bolling T, Schuck A, Malath J, Kolkmeyer A, Horn K, Riesenbeck D, Hesselmann S, Diallo R, Vormoor J, Willich N |
Effect of radiation on Ewing tumour subpopulations characterized on a single-cell level. |
Int J Radiat Biol 2003, 79: 181 |
|
| Konemann S, Bolling T, Kolkmeyer A, Riesenbeck D, Hesselmann S, Vormoor J, Willich N, Schuck A |
Heterogeneity of radiation induced apoptosis in Ewing Tumor cell lines characterized on a single cell level. [+] |
Apoptosis 2005, 10: 177 |
|
| The objective of this study was to investigate heterogeneity of radiation induced apoptosis on a single cell level. Two Ewing tumor cell lines were characterized in vitro before and 24 and 72 h after radiation with 5 Gy by multiparametric flow cytometry. Annexin V, 7-AAD and fluorescence conjugated antibodies that were directed against HLA-ABC, CD11a and CD62L were used. Based on these markers radiation induced apoptosis was quantified, multiple apoptotic subpopulations were identified and a characteristic individual apoptotic profile was characterized. The characterization of HLA-ABC, CD11a and CD62L was informative to detect subpopulations of apoptotic cells. The observed heterogeneity and the identification of multiple apoptotic subpopulations reflect the complexity and diversity of biology of radiation induced cell death. This might be an indication for co-existing apoptotic pathways or it might represent sequential steps of the apoptotic cascade. |
| Kook H |
Fanconi anemia: current management. [+] |
Hematology 2005, 10 Suppl 1: 108 |
|
| Fanconi anemia (FA) is an autosomal recessive chromosomal instability disorder, characterized by congenital anomalies, defective hematopoiesis and a high risk of developing acute myeloid leukemia and certain solid tumors. All racial and ethnic groups are at risk, and at least 11 complementation groups have been identified and the genes defective in eight of these have been identified (FANCA, C, D2, E, F, G, L and BRCA2). FA-A is the most common complementation group, accounting for approximately 65% of all affected individuals. The gold-standard screening test for FA is based on the characteristic hypersensitivity of FA cells to the crosslinking agents, such as mitomicin C or diepoxybutane. Recent progress has been made in identifying the genes bearing pathogenetically relevant mutations, but slower progress has been made in defining the precise functions of the proteins in normal cells, in part because that the proteins are multifunctional. Molecular studies have established that a common pathway exist, both between the FA proteins and other proteins involved in DNA repair such as NBS1, ATM, BRCA1 and BRCA2. Stem cell transplantation (SCT) is the only option for establishing normal hematopoiesis. To reduce undue toxicities due to inherent hypersensitivity, nonmyeloablative conditioning for transplants has been advocated. This review summarizes the general clinical and hematologic features and the current management of FA. Fanconi anemia (FA) is the commonest type of inherited bone marrow failure syndrome with the birth incidence of around three per million. The inheritance pattern is autosomal recessive with the estimated heterozygote frequency being one in 300 in Europe and the US. |
| Kortmann R, Timmermann B, Becker G, Kühl J, Bamberg M |
Advances in treatment techniques and time/dose schedules in external radiation therapy of brain tumours in childhood. |
Klin Pädiatr 1998, 210: 220 |
|
| Kortmann R, Timmermann B, Kühl J, Willich N, Flentje M, Meisner C, Bamberg M |
HIT '91 (prospective, co-operative study for the treatment of malignant brain tumors in childhood). |
Strahlenther Onkol 1999, 175: 162 |
|
| Korte A, Köchling J, Badiali L, Eckert C, Andreae J, Geilen W, Kebelmann-Betzing C, Taube T, Wu S, Henze G, Seeger K |
Expression analysis and characterization of alternatively spliced transcripts of human IL-7R alpha chain encoding two truncated receptor proteins in relapsed childhood ALL. |
Cytokine 2000, 12: 1597 |
|
| Kortmann R, Klingebiel Th, Timmermann B, Kühl J, Müller S, Göbel U, Bamberg M |
Aktuelle radioonkologische Strategien bei der Behandlung von malignen Tumoren im Kindesalter. |
Onkologe 2000, 6: 854 |
|
| Kortmann R, Kühl J, Timmermann B, Mittler U, Urban C, Budach V, Richter E, Willich N, Flentje M, Berthold F, Slavc I, Wolff J, Meisner C, Wiestler O, Sörensen N, Warmuth-Metz M, Bamberg M |
Postoperative neoadjuvant chemotherapy before radiotherapy as compared to immediate radiotherapy followed by maintenance chemotherapy in the treatment of medulloblastoma in childhood. |
Int J Radiat Oncol Biol Phys 2000, 46: 269 |
|
| Kortmann R, Kühl J, Timmermann B, Calaminus G, Dieckmann K, Wurm R, Sörensen N, Urban C, Göbel U, Bamberg M |
Current and future strategies in interdisciplinary treatment of medulloblastomas, supratentorial PNET (primitive neuroectodermal tumors) and intracranial germ cell tumors in childhood. |
Strahlenther Onkol 2001, 177: 447 |
|
| Kortmann R, Timmermann B, Taylor R, Scarzello G, Plasswilm L, Paulsen F, Jeremic B, Gnekow A, Dieckmann K, Kay S, Bamberg M |
Current and future strategies in radiotherapy of childhood low-grade glioma of the brain. Part I |
Strahlenther Onkol 2003, 179: 509 |
|
| Kortmann R, Timmermann B, Taylor R, Scarzello G, Plasswilm L, Paulsen F, Jeremic B, Gnekow A, Dieckmann K, Kay S, Bamberg M |
Current and future strategies in radiotherapy of childhood low-grade glioma of the brain. Part II. |
Strahlenther Onkol 2003, 179: 585 |
|
| Kortmann RD, Timmermann B, Rutkowski S, Bamberg M |
Re: B. Beuthien-Baumann, et al. Differentiation between recurrent tumor and radiation necrosis in a child with anaplastic ependymoma after chemotherapy and radiation therapy. Strahlenther Onkol 2003;179:819-22. |
Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al]. 2004, 180: 245 |
|
| Korinthenberg R, Warmuth-Metz M, Rutkowski S |
Leitsymptome und Diagnostik der Hirntumoren im Kindes- und Jugendalter. |
Interdisziplinäre Leitlinie der Deutschen Krebsgesellschaft (Gemeinsame Leitlinie der Gesellschaft für Neuropädiatrie und der Gesellschaft für Pädiatrische Onkologie und Hämatologie 2007 |
|
| Korinthenberg R, Warmuth-Metz M, Rutkowski S, Weckesser M |
Leitsymptome und Diagnostik der Hirntumoren im Kindes- und Jugendalter. |
Interdisziplinäre Leitlinie der Deutschen Krebsgesellschaft (Gemeinsame Leitlinie der Gesellschaft für Neuropädiatrie und der Gesellschaft für Pädiatrische Onkologie und Hämatologie 2010 |
|
| Korshunov A, Witt H, Hielscher T, Benner A, Remke M, Ryzhova M, Milde T, Bender S, Wittmann A, Schöttler A, Kulozik AE, Witt O, von Deimling A, Lichter P, Pfister S |
Molecular staging of intracranial ependymoma in children and adults. [+] |
J Clin Oncol 2010, 28: 3182 |
|
| The biologic behavior of intracranial ependymoma is unpredictable on the basis of current staging approaches. We aimed at the identification of recurrent genetic aberrations in ependymoma and evaluated their prognostic significance to develop a molecular staging system that could complement current classification criteria. |
| Korinthenberg R, Neuburger D, Nikkhah G, Teske C, Schnabel K, Calaminus G |
Assessing Quality of Life in Long-Term Survivors after 125I Brachytherapy for Low-Grade Glioma in Childhood. [+] |
Neuropediatrics 2011, 42: 110 |
|
| Quality of life (QOL) is important for the survivors of malignancies. We investigated health-related QOL in 51 patients treated with iodine-125 (125I) brachytherapy for childhood low-grade gliomas. Instruments included a questionnaire on life situation, German versions of PEDQOL (8-18 years), EORTC QLQ-30 and head and neck module H&N-35 (>18 years), strength and difficulties questionnaire, "Fertigkeitsskala Münster Heidelberg", and an adapted Rankin score. The time lapsed since 125I-brachytherapy was 134 months (median, range: 29-293 months). 57% of the patients were over 18 years of age, 34% were 11-17 years old and 8% were younger. 14 had undergone other treatments after 125I brachytherapy. Over half of the >18 year olds reported residual problems; 68% were disabled, 38% to a severe degree. Many of the young adults still lived with their parents and 17% were jobless. 43% of the children/adolescents needed rehabilitative treatment, 20% visited special schools and 71% were disabled, 33% severely. The patients and their caregivers rated their QOL as not different from that of the normal population. However, many QOL dimensions correlated to the severity of disability. Comparison of QOL outcomes between different treatment measures would require a prospective study controlling for the most important factors of influence. |
| Kordes U, Flitsch J, Hagel C, Goebell E, Schwarz R, Herberhold T, von Bueren AO, Rutkowski S, Müller HL |
Ectopic craniopharyngioma. [+] |
Klin padiatr 2011, 223: 176 |
|
| Introduction
Ectopic extra-axial craniopharyngioma may be caused by surgical tumor seeding, demonstrating viability and metastatic potential of primary craniopharyngioma tumor cells. It is a rare but distinct post-operative complication of craniopharyngioma that is different from leptomeningeal progression of other low grade pediatric brain tumors such as pilocytic astrocytoma. We present clinical pathological data from a young boy who suffered a metastasis of his craniopharyngioma along the surgical route shortly after irradiation for progressive disease at the primary site. |
| Koscielniak E, Treuner J, Jürgens H, Winkler K, Bürger D, Herbst M, Ritter J, Niethammer D, Müller-Weihrich S, Bernhard G |
Treatment of soft tissue sarcomas in childhood and adolescence. |
Klinische Pädiatrie 1991, 203: 211 |
|
| Koscielniak E, Jürgens H, Winkler K, Bürger D, Herbst M, Keim M, Bernhard G, Treuner J |
Treatment of soft tissue sarcoma in childhood and adolescence. A report of the German Cooperative Soft Tissue Sarcoma Study. |
Cancer 1992, 70: 2557 |
|
| Koscielniak E, Rodary C, Flamant F, Carli M, Treuner J, Pinkerton C, Grotto P |
Metastatic soft tissue sarcoma in childhood. |
Med Pediatr Oncol 1992, 209 |
|
| Koscielniak E, Rodary C, Flamant F, Carli M, Treuner J, Pinkerton C, Grotto P |
Metastatic rhabdomyosarcoma and histologically similar tumors in childhood. |
Med Pediatr Oncol 1992, 20: 209 |
|
| Koscielniak E, Hammer S, Blank J |
Effects of rh-GM-GSF on hematopoietic recovery and infections complications in children with solid tumors after high-dose chemotherapy followed by ABMT. |
Br J Haematology 1994 |
|
| Koscielniak E, Herbst M, Niethammer D, Treuner J |
Improved local tumor control by early and risk-adjusted use of radiotherapy in primary non-resectable rhabdomyosarcomas. |
Klinische Pädiatrie 1994, 206: 269 |
|
| Koscielniak E, Klingebiel T, Peters C, Hermann J, Burdach S, Bender-Götze C, Müller-Weihrich S, Treuner J |
Do patients with metastatic and recurrent rhabdomyosarcoma benefit from high-dose therapy with hematopoietic rescue? |
Bone Marrow Transplant 1997, 19: 227 |
|
| Koscielniak E, Harms D, Henze G, Jürgens H, Gadner H, Herbst M, Klingebiel T, Schmidt B, Morgan M, Knietig R, Treuner J |
Results of treatment for soft tissue sarcoma in childhood and adolescence. |
J Clin Oncol 1999, 17: 3706 |
|
| Koscielniak E, Morgan M, Treuner J |
Soft tissue sarcoma in children. |
Paediatr Drugs 2002, 4: 21 |
|
| Koscielniak E, T Klingebiel, A Schuck, I Leuschner |
Weichteilsarkome im Kindesalter. Diagnostik und Therapie. |
Der Onkologe 2005 (electronic on line first article) |
|
| Koscielniak E, Treuner J |
Weichteilsarkome. |
Interdisziplinäre Leitlinie der Deutschen Krebsgesellschaft und Leitlinien und der Gesellschaft für Pädiatrische Onkologie und Hämatologie 2008 |
|
| Koscielniak E, Dantonello T, Klingebiel T |
Weichteiltumoren – Neue Projekte der CWS-Studiengruppe: das Register „SoTiSaR für Weichteilsarkome und –tumoren sowie die multizentrische Studie CWS-2007-HR zur Behandlung von Patienten mit lokalisierten rhabdomyosarkomartigen Weichteilsarkomen. |
Wir – die Zeitschrift der Deutschen Leukämie-Forschungshilfe e.V. und der Deutschen Kinderkrebsstiftung 3/2009 |
|
| Koscielniak E |
Weichteilsarkome. |
Leitlinie der Gesellschaft für Pädiatrische Onkologie und Hämatologie AWMF online 2011 |
|
| Kovnar E, Kun L, Burger P, et al. |
Patterns of dissemination and recurrence in childhood ependymoma: Preliminary results of Pediatric Oncology Group Protocol #8532. |
Ann Neurol 30: 457, 1991 |
|
| Kovnar EH |
Hyperfractionated irradiation for childhood ependymoma: early results of a phase III Pediatric Oncology Group study. |
VIIth Symposium Pediatric Neurooncology Abstract 31, Washington 1996 |
|
| Kraus J, Albrecht S, Wiestler O, von Schweinitz D, Pietsch T |
Loss of heterozygosity on chromosome 1 in human hepatoblastoma. |
Int J Cancer 1996, 67: 467 |
|
| Krams M, Hero B, Berthold F, Parwaresch R, Harms D, Rudolph P |
Proliferation marker KI-S5 discriminates between favorable and adverse prognosis in advanced stages of neuroblastoma with and without MYCN amplification. |
Cancer 2002, 94: 854 |
|
| Krams M, Hero B, Berthold F, Parwaresch R, Harms D, Rudolph P |
Full-length telomerase reverse transcriptase messenger RNA is an independent prognostic factor in neuroblastoma. |
Am J Pathol 2003, 162: 1019 |
|
| Krams M, Heidebrecht HJ, Hero B, Berthold F, Harms D, Parwaresch R, Rudolph P |
Repp86 expression and outcome in patients with neuroblastoma. [+] |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2003, 21: 1810 |
|
| PURPOSE: Given the well-known challenges of neuroblastoma prognosis, we investigated whether the expression of restrictedly expressed proliferation-associated protein of 86 kDa theoretical molecular mass (repp86), a proliferation-associated protein expressed in S, G2, and M phases of the cell cycle, correlates with the clinical outcome in patients with neuroblastoma. PATIENTS AND METHODS: 161 children with different stages of neuroblastoma were studied; the median follow-up time was 72.8 months. The patients were staged according to the International Neuroblastoma Staging System, and histologic grading of the tumors was performed according to the criteria of Hughes and those of the International Neuroblastoma Pathology Classification. The MYCN gene copy number was determined by Southern blot analysis or fluorescence in situ-hybridization, and repp86 expression was assessed immunohistochemically by means of monoclonal antibody Ki-S2 on paraffin sections from archival tumor samples. RESULTS: A repp86 labeling index (RI) of more than 10% positive tumor cells significantly predicted a shortened disease-free interval and an increased tumor mortality (both P <.0001). Moreover, the RI allowed the identification of patients with favorable and adverse prognosis in subsets defined by stage, grade, age, and MYCN status. In a multivariate analysis, the RI emerged as the most important predictor of event-free and disease-specific survival with hazard ratios of 11.7 and 10.5, respectively (both P <.0001). CONCLUSION: It seems that repp86 expression is closely associated with the biologic behavior of neuroblastoma. Assessment of the RI might, therefore, considerably refine prognostic models. |
| Kratz CP, Rogge T, Kopp M, Baumann I, Niemeyer CM |
Myelodysplastic features in an infant with cystic fibrosis presenting with anaemia, oedema and failure to thrive. |
European journal of pediatrics 2005, 164: 56 |
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| Kratz CP, Niemeyer CM, Castleberry RP, Cetin M, Bergstrasser E, Emanuel PD, Hasle H, Kardos G, Klein C, Kojima S, Stary J, Trebo M, Zecca M, Gelb BD, Tartaglia M, Loh ML |
The mutational spectrum of PTPN11 in juvenile myelomonocytic leukemia and Noonan syndrome/myeloproliferative disease. [+] |
Blood 2005, 106: 2183 |
|
| Germ line PTPN11 mutations cause 50% of cases of Noonan syndrome (NS). Somatic mutations in PTPN11 occur in 35% of patients with de novo, nonsyndromic juvenile myelomonocytic leukemia (JMML). Myeloproliferative disorders (MPDs), either transient or more fulminant forms, can also occur in infants with NS (NS/MPD). We identified PTPN11 mutations in blood or bone marrow specimens from 77 newly reported patients with JMML (n = 69) or NS/MPD (n = 8). Together with previous reports, we compared the spectrum of PTPN11 mutations in 3 groups: (1) patients with JMML (n = 107); (2) patients with NS/MPD (n = 19); and (3) patients with NS (n = 243). Glu76 was the most commonly affected residue in JMML (n = 45), with the Glu76Lys alteration (n = 29) being most frequent. Eight of 19 patients with NS/MPD carried the Thr73Ile substitution. These data suggest that there is a genotype/phenotype correlation in the spectrum of PTPN11 mutations found in patients with JMML, NS/MPD, and NS. This supports the need to characterize the spectrum of hematologic abnormalities in individuals with NS and to better define the impact of the PTPN11 lesion on the disease course in patients with NS/MPD and JMML. |
| Kramm CM, Wagner S, Van Gool S, Schmid H, Strater R, Gnekow A, Rutkowski S, Wolff JE |
Improved survival after gross total resection of malignant gliomas in pediatric patients from the HIT-GBM studies. |
Anticancer Res 2006, 26: 3773 |
|
| Kratz CP, Steinemann D, Niemeyer CM, Schlegelberger B, Koscielniak E, Kontny U, Zenker M |
Uniparental disomy at chromosome 11p15. 5 followed by HRAS mutations in embryonal rhabdomyosarcoma: lessons from Costello syndrome. [+] |
Human molecular genetics 2007, 16: 374 |
|
| Costello syndrome (CS; MIM 218040) is characterized by short stature, facial dysmorphism, cardiac defects and predisposition to embryonal rhabdomyosarcoma (CS/ERMS) and other neoplasias. CS is caused by germline mutations in the HRAS gene on chromosome 11p15.5, a region showing allelic imbalances in sporadic ERMS and CS/ERMS. The critical gene for ERMS development in this region is unknown. The association of CS and ERMS as well as previous reports illustrating that somatic HRAS mutations are found in a proportion of these tumors prompted us to clarify the significance and a possible correlation of HRAS mutations and genomic rearrangements at 11p15.5 in sporadic ERMS. We screened for somatic HRAS mutations and 11p15.5 imbalances in six sporadic ERMS samples. This analysis uncovered five ERMS samples with uniparental disomy (UPD) at the HRAS locus, two of which harbored HRAS mutations. By analyzing informative genetic variations in or at the HRAS gene locus, we show that one HRAS allele is entirely lost in specimens with UPD at 11p15.5. Notably, in both cases with UPD and HRAS mutations these mutations were heterozygous. Therefore, they must have succeeded the emergence of UPD. In contrast, HRAS germline mutations are the first step in CS/ERMS. Subsequent development of UPD at 11p15.5 may explain previous observations that CS/ERMS express mutant HRAS only. These data implicate that in sporadic ERMS, UPD at 11p15.5 is not driven by HRAS mutations and that imbalances at 11p15.5 and HRAS mutations represent independent but cooperating events during ERMS development. |
| Krappmann P, Paulides M, Stöhr W, Ittner E, Plattig B, Nickel P, Lackner H, Schrappe M, Janka G, Beck JD, Langer T |
Almost normal cognitive function in patients during therapy for childhood acute lymphoblastic leukemia without cranial irradiation according to ALL-BFM 95 and COALL 06-97 protocols: results of an Austrian-German multicenter longitudinal study and implications for follow-up. [+] |
Pediatric hematology and oncology 2007, 24: 101 |
|
| In a multicenter study the authors prospectively investigated neurocognitive function in childhood ALL patients. Sixty-six patients (mean age at diagnosis 7.9 +/- 3.6 years, 34 female), treated with repeated intrathecal and systemical methotrexate administrations without cranial irradiation, underwent psychometric testing for intelligence, concentration, and visual-motor integration postdiagnosis and after reinduction therapy. Although there was a statistically significant decline of intellectual function after reinduction therapy for younger patients and girls (IQ scores still within normative data range), there were no differences in visual-motor performance and concentration over the time of induction therapy. Thus, neurocognitive examination should focus on younger ALL patients and girls. |
| Kramm C, Wolff JEA |
Hochgradig maligne Gliome und Ponsgliome im Kindes- und Jugendalter. |
Interdisziplinäre Leitlinie der Deutschen Krebsgesellschaft und der Deutschen Gesellschaft für Pädiatrische Onkologie und Hämatologie 2008 |
|
| Kramm C, Rausche U, Butenhoff S, Kühnöl C, Kunze C, Kortmann R, Wolff J, van Gool S |
Hochmaligne Gliome im Kindes- und Jugendalter. |
Monatsschr Kinderheilkd 2008, 156: 1201 |
|
| Kramm C |
Die HIT-HGG-Studiengruppe - Beratung und Protokolle für alle Behandlungssituationen bei hochmalignen Gliomen im Kindes- und Jugendalter. |
WiR - die Zeitschrift der Deutschen Leukämie-Forschungshilfe e.V. und der Deutschen Kinderkrebsstiftung 1/2010 |
|
| Kramm CM, Butenhoff S, Rausche U, Warmuth-Metz M, Kortmann RD, Pietsch T, Gnekow A, Jorch N, Janssen G, Berthold F, Wolff JE |
Thalamic high-grade gliomas in children: a distinct clinical subset? [+] |
Neuro Oncol 2011, 13: 680 |
|
| Pediatric high-grade gliomas (HGGs) of the thalamic region account for up to 13% of pediatric HGGs and usually result in only anecdotal long-term survival. Because very little is known about these tumors, we aimed to further characterize them. In our series of 99 pediatric thalamic HGGs, there were no significant differences in survival between patients with tumors affecting the thalamus alone (including bithalamic lesions) and patients with tumors affecting the thalamus plus adjacent structures. Tumor resection (event-free survival/overall survival) and an early treatment response to radiotherapy/chemotherapy (event-free survival) had independent prognostic significance, as shown by Kaplan-Meier and multivariate Cox regression analyses. When we compared clinical characteristics and outcomes of pediatric thalamic HGG with those of pediatric (nonthalamic) supratentorial (n = 177) as well as pediatric pontine HGG (including diffuse intrinsic pontine gliomas; n = 234), we found that thalamic HGG shared more similarities with pontine than with supratentorial HGG, but overall, it appeared to represent a clinically distinct subgroup of pediatric HGG. The varying extent of tumor resection in the different tumor localizations may play some role in the observed clinical differences, as shown by multivariate Cox regression analyses, but the tumor site itself was also identified as an independent prognostic parameter. Thus, an additional location-specific effect on survival and/or tumor biology, despite different neurosurgical accessibility, has to be considered. Therefore, future investigations should try to further characterize the obviously site-specific heterogeneity of pediatric HGG on a molecular genetic basis. |
| Kremens B, Klingebiel T, Herrmann F, Bender-Gotze C, Burdach S, Ebell W, Friedrich W, Koscielniak E, Schmid H, Siegert W, |
High-dose consolidation with local radiation and bone marrow rescue in patients with advanced neuroblastoma. |
Med Pediatr Oncol 1994, 23: 470 |
|
| Kremens B, Gruhn B, Klingebiel T, Hasan C, Laws H, Koscielniak E, Hero B, Selle B, Niemeyer C, Finckenstein F, Schulz A, Wawer A, Zintl F, Graf N |
High-dose chemotherapy with autologous stem cell rescue in children with nephroblastoma. |
Bone Marrow Transplant 2002, 30: 893 |
|
| Kremens B, Hero B, Esser J, Weinel P, Filger-Brillinger J, Fleischhack G, Graf N, Gruttner H, Niemeyer C, Schulz A, Wickmann L, Berthold F |
Ocular symptoms in children treated with human-mouse chimeric anti-GD2 mAb ch14. 18 for neuroblastoma. |
Cancer Immunol Immunother 2002, 51: 107 |
|
| Kremens B, Gruhn B, Klingebiel T, Hasan C, Laws H, Koscielniak E, Hero B, Selle B, Niemeyer C, Finkenstein F, Schulz A, Wawer A, Zintl F, Graf N |
High-dose chemotherapy with autologous stem cell rescue in children with nephroblastoma. |
Bone Marrow Transplant 2003, 31 |
|
| Kremens B, Wieland R, Reinhard H, Neubert D, Beck JD, Klingebiel T, Bornfeld N, Havers W |
High-dose chemotherapy with autologous stem cell rescue in children with retinoblastoma. [+] |
Bone marrow transplantation 2003, 31: 281 |
|
| Children with metastatic retinoblastoma are considered to have a poor prognosis after conventional chemotherapy. We used high-dose chemotherapy (HDC) with peripheral hematopoietic stem cell transplantation in such patients in an attempt to improve their survival. Four patients with bone marrow metastases and one child with extraorbital disease were treated with HDC after achieving complete remission by enucleation and conventional chemotherapy. The child with extraorbital tumor was the only one to receive local irradiation. The conditioning regimen included thiotepa (900 mg/m(2)), etoposide (40 mg/kg) and carboplatin (1.5 g/m(2)) in four patients, and BCNU (300 mg/m(2)), cyclophosphamide (6.8 g/m(2)) and etoposide (1.6 g/m(2)) in one child. Hematologic recovery occurred without delay in all patients. The main toxicities were diarrhea, mucositis and infectious complications. No toxic deaths or any major late toxicities were observed. The child treated with the BCNU regimen developed a meningeal relapse 10 months after HDC, which was partially resected and treated with conventional chemotherapy, but not with radiotherapy. He is in complete remission (CR) 105 months off treatment. The other patients are in CCR for 107, 57, 9 and 8 months after HDC. HDC with thiotepa, etoposide and carboplatin may represent a curative option for children with extrabulbar or disseminated retinoblastoma responsive to chemotherapy. It may control occult CNS disease. The necessity to irradiate these children and the curative potential of this strategy for patients with bulky CNS disease remain to be determined. |
| Kreuter M, Bieker R, Bielack SS, Auras T, Buerger H, Gosheger G, Jürgens H, Berdel WE, Mesters RM |
Prognostic relevance of increased angiogenesis in osteosarcoma. [+] |
Clinical cancer research : an official journal of the American Association for Cancer Research 2004, 10: 8531 |
|
| PURPOSE: The purpose of this work was to evaluate the prognostic relevance of microvessel density (MVD) for response to chemotherapy and long-term outcome in osteosarcoma. EXPERIMENTAL DESIGN: Pretherapeutic tumor biopsies of 60 patients with high-grade central osteosarcoma, who were treated according to multimodal neoadjuvant protocols of the German-Austrian-Swiss Cooperative Osteosarcoma Study Group, were evaluated for intratumoral MVD. MVD was correlated with demographic and tumor-related variables, response, and survival. RESULTS: The median intratumoral MVD was 52 microvessels per 0.26-mm2 field area (interquartile range, 31-77 microvessels per 0.26-mm2 field area). At a median follow-up period of 3.5 years, patients with a high (>median) MVD had significantly higher 5- and 10-year overall survival rates (84%) than patients with low (< or =median) MVD (49%; P = 0.0029). Furthermore, increased relapse-free survival for patients with high MVD (P = 0.0064) was observed. In a subgroup analysis of 44 patients with primary high-grade central osteosarcoma of the extremities without primary metastases and good surgical remission, high MVD was associated with 5- and 10-year overall survival rates of 91% compared with 58% for low MVD (P = 0.034). Cox regression analysis revealed that MVD was an independent prognostic factor for survival. A good response to chemotherapy (histologic grading scale of Salzer-Kuntschik) correlated significantly with a high MVD (P = 0.006). CONCLUSIONS: Increased angiogenesis is a prognostic indicator for higher survival and response rates to chemotherapy in patients with osteosarcoma. Thus, measurement of MVD might be useful in decisions selecting patients for future neoadjuvant treatment. |
| Kreuter M, Paulussen M, Boeckeler J, Gerss J, Buerger H, Liebscher C, Kessler T, Jürgens H, Berdel WE, Mesters RM |
Clinical significance of Vascular Endothelial Growth Factor-A expression in Ewing's sarcoma. [+] |
European journal of cancer (Oxford, England : 1990) 2006, 42: 1904 |
|
| The aim of our study was to gain further insight into the role of angiogenesis in Ewing's sarcoma. To this end, expression of Vascular Endothelial Growth Factor-A (VEGF-A), its receptors VEGFR-1 and -2 and microvessel density (MVD) were evaluated by quantitative immunohistochemistry in pretherapeutic biopsies of 40 patients with Ewing's sarcoma treated within standardised neoadjuvant protocols. Median expression levels were 1.5 arbitrary units (AU) for VEGF-A, 8.2 AU for VEGFR-2 and median MVD was 96/0.26 mm(2). VEGFR-1 was expressed in 12.5% of the samples, only. Ten-year relapse free and overall survival rates were significantly higher for patients with high VEGF-A expression (60% versus 29%, p=0.0216 and 65% versus 25%, p=0.013, respectively). Multivariate Cox regression analysis revealed that VEGF-A expression was an independent prognostic factor for survival. In conclusion, these data suggest that the angiogenic mediator VEGF plays an important prognostic role in Ewing's sarcoma. |
| Krentz S, Hof J, Mendioroz A, Vaggopoulou R, Dörge P, Lottaz C, Engelmann JC, Groeneveld TW, Körner G, Seeger K, Hagemeier C, Henze G, Eckert C, von Stackelberg A, Kirschner-Schwabe R |
Prognostic value of genetic alterations in children with first bone marrow relapse of childhood B-cell precursor acute lymphoblastic leukemia. [+] |
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 2012, [Epub ahead of print] |
|
| Despite risk-adapted treatment, survival of children with relapse of acute lymphoblastic leukemia (ALL) remains poor compared with that of patients with initial diagnosis of ALL. Leukemia-associated genetic alterations may provide novel prognostic factors to refine present relapse treatment strategies. Therefore, we investigated the clinical relevance of 13 recurrent genetic alterations in 204 children treated uniformly for relapsed B-cell precursor ALL according to the ALL-REZ BFM 2002 protocol. The most common alterations were deletions of CDKN2A/2B, IKZF1, PAX5, ETV6, fusion of ETV6-RUNX1 and deletions and/or mutations of TP53. Multivariate analysis identified IKZF1 deletion and TP53 alteration as independent predictors of inferior outcome (P=0.002 and P=0.001). Next, we investigated how both alterations can improve the established risk stratification in relapsed ALL. Intermediate-risk relapse patients with low minimal residual disease are currently considered to have a good prognosis. In this group, deletion of IKZF1 and alteration of TP53 identify patients with significantly inferior outcome (P<0.001). In high-risk relapse patients, deletion of IKZF1 is strongly predictive of a second relapse after stem cell transplantation (P<0.001). We conclude that IKZF1 and TP53 represent relevant prognostic factors that should be considered in future risk assessment of children with relapsed ALL to indicate treatment intensification or intervention.Leukemia advance online publication, 3 July 2012; doi:10.1038/leu.2012.155. |
| Krieger D, Moericke A, Oschlies I, Zimmermann M, Schrappe M, Reiter A, Burkhardt B |
Frequency and clinical relevance of DNA microsatellite alterations of the CDKN2A/B, ATM and p53 gene loci: a comparison between pediatric precursor T-cell lymphoblastic lymphoma and T-cell lymphoblastic leukemia. [+] |
Haematologica 2010, 95: 158 |
|
| Although deletions of cell cycle regulatory gene loci have long been reported in various malignancies, little is known regarding their relevance in pediatric T-cell lymphoblastic lymphoma (T-LBL) and T-cell lymphoblastic leukemia (TALL). The current study focused on loss of heterozygosity (LOH) analyses of the CDKN2A/B (chromosome 9p), ATM (chromosome 11q) and p53 (chromosome 17p) gene loci. Frequencies of LOH were compared in 113 pediatric T-LBL and 125 T-ALL who were treated uniformly according to ALL-BFM strategies. Furthermore, LOH findings were correlated with clinical characteristics and tested for their prognostic relevance. LOH at 9p was detected in 47% of T-LBL and 51% of T-ALL, and was associated with male gender in both. In T-ALL, LOH at 9p was associated with favorable initial treatment response. A tendency for favorable event-free-survival was observed in LOH 9p positive T-LBL. The frequency of LOH at chromosomes 11q and 17p was 5% or less for both diseases. |
| Krümpelmann S, Tillmann B, Schulze-Westhoff P, Jürgens H, Boos J |
Comparison of oral vs. intravenous etoposide. |
Med Pediatr Oncol 1996, 27 |
|
| Kuçi S, Rettinger E, Voss B, Weber G, Stais M, Kreyenberg H, Willasch A, Kuçi Z, Koscielniak E, Klöss S, von Laer D, Klingebiel T, Bader P |
Efficient lysis of rhabdomyosarcoma cells by cytokine-induced killer cells: implications for adoptive immunotherapy after allogeneic stem cell transplantation. [+] |
Haematologica 95: 1579 |
|
| BACKGROUND: Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood and has a poor prognosis. Here we assessed the capability of ex vivo expanded cytokine-induced killer cells to lyse both alveolar and embryonic rhabdomyosarcoma cell lines and investigated the mechanisms involved.
DESIGN AND METHODS: Peripheral blood mononuclear cells from six healthy donors were used to generate and expand cytokine-induced killer cells. The phenotype and composition of these cells were determined by multiparameter flow cytometry, while their cytotoxic effect against rhabdomyosarcoma cells was evaluated by a europium release assay.
RESULTS: Cytokine-induced killer cells efficiently lysed cells from both rhabdomyosarcoma cell lines. Antibody-mediated masking of either NKG2D molecule on cytokine-induced killer cells or its ligands on rhabdomyosarcoma cells (major histocompatibility antigen related chain A and B and UL16 binding protein 2) diminished this effect by 50%, suggesting a major role for the NKG2D molecule in rhabdomyosarcoma cell killing. No effect was observed after blocking CD11a, CD3 or TCRalphabeta molecules on cytokine-induced killer cells or CD1d on rhabdomyosar-coma cells. Remarkably, cytokine-induced killer cells used tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to activate caspase-3, as the main caspase responsible for the execution of apoptosis. Accordingly, blocking TRAIL receptors on embryonic rhabdomyosarcoma cell lines significantly reduced the anti-tumor effect of cytokine-induced killer cells. About 50% of T cells within the cytokine-induced killer population had an effector memory phenotype, 20% had a naïve phenotype and approximately 30% of the cells had a central memory phenotype. In addition, cytokine-induced killer cells expressed low levels of activation-induced markers CD69 and CD137 and demonstrated a low alloreactive potential.
CONCLUSIONS: Our data suggest that cytokine-induced killer cells may be used as a novel adoptive immunotherapy for the treatment of patients with rhabdomyosarcoma after allogeneic stem cell transplantation. |
| Kühl J |
Chemotherapy of brain tumors in childhood. Review of the literature and pilot protocol. |
Klin Pädiatr 1988, 200: 214 |
|
| Kühl J, Rating D, Berthold F, Graf N, Maass E, Gnekow A, Weinl P, Göbel U, Havers W, Lakomek M, Gutjahr P, Urban Ch, Bamberg M, Bode U, Kaatsch P, Kleihues P, Niethammer D, Sörensen N |
Ergebnisse der multizentrischen Chemotherapiepilotstudie HIT '88/'89. |
Aktuelle Neuropädiatrie 1991 1992, 176 |
|
| Kühl J, Berthold M, Bode U, Bucsky P, Graf N, Gnekow A, Maass E, Bamberg M, Kaatsch P, Kleihues P, Rating D, Riehm H, Sörensen N |
Preradiation chemotherapy of children with poor-prognosis medulloblastoma:response rate and toxicity of the ifosfamide-containing multidrug regimen HIT 88/89. |
The Am J Pediatr Hematol Oncol 1993, 15: 67 |
|
| Kühl J |
Interdisziplinäre Behandlung von Medulloblastom und PNET. |
Klinische Onkologie 94/95 (Sonderband der Schweizer Rundschau für Medizin) 1994, 16 |
|
| Kühl J |
Ergebnisse der Pädiatrischen Neuro-Onkologie III, Berichte von der Tagung der Arbeitsgruppe für Hirntumoren im Kindesalter der Gesellschaft für Pädiatrische Onkologie und Hämatologie und der Gesellschaft für Neuropädiatrie am 13./14. Juni 1997 in Würzburg. |
GPOH 1997 |
|
| Kühl J |
Modern treatment strategies in medulloblastoma. |
Childs Nerv Syst 1998, 14: 2 |
|
| Kühl J, Muller H, Berthold F, Kortmann R, Deinlein F, Maass E, Graf N, Gnekow A, Scheurlen W, Göbel U, Wolff J, Bamberg M, Kaatsch P, Kleihues P, Rating D, Sörensen N, Wiestler O |
Preradiation chemotherapy of children and young adults with malignant brain tumors. |
Klin Pädiatr 1998, 210: 227 |
|
| Kühl J, Kortmann R, Pietsch T, Sörensen N, Warmuth-Metz M |
Medulloblastom. |
Hämatologie und Onkologie - ODIN-Kompendium Hannover 2000,Onkologisch-hämatologisches Daten- und Informationsnetz, Berlin: HOS-multimedica Health Online Service |
|
| Kühl J |
Therapie von Kindern mit einem Medulloblastom. |
WIR Informationsschrift der Aktion für krebskranke Kinder e.V. (Bonn) 2001, 4: 8 |
|
| Kühne T, Imbach P, Bolton-Maggs PH, Berchtold W, Blanchette V, Buchanan GR, Intercontinental Childhood ITP Study Group |
Newly diagnosed idiopathic thrombocytopenic purpura in childhood: an observational study. [+] |
Lancet 2001, 358: 2122 |
|
| Diagnosis and management of idiopathic thrombocytopenic purpura (ITP) have been based primarily on expert opinion and practice guidelines rather than on evidence. We have used a registry to prospectively survey the presenting features and the diagnostic evaluation and management practices used for children with ITP worldwide. |
| Kühl J, Korinthenberg R |
ZNS-Tumoren. In: Gadner H, Gaedicke G, Niemeyer CH, Ritter J (Hrsg.): Pädiatrische Hämatologie und Onkologie. |
Springer-Verlag 2006, 777 |
|
| Kulozik A |
Hemoglobin variants and the rarer hemoglobin disorders. |
In: Lilleyman JS, Hann IM, Blanchette VS (Hrsg.): Pediatric hematology, 2nd ed 1999, p. 231.256 |
|
| Kulozik, AE |
Hemoglobin variants and the rarer hemoglobin disorders. |
In: Pediatric Hematology, 3rd Edition,Robert J. Arceci (Editor), Ian M. Hann (Editor), Owen P. Smith (Editor), A. Victor Hoffbrand ( 2006 |
|
| Kulozik, AE |
Thalassämien. |
In: Gadner, H, Gaedicke, G, Niemeyer, C, Ritter, J (Hrsg.): Pädiatrische Hämatologie und Onkologie, Springer Medizin Verlag 2006 |
|
| Kulozik AE, Kunz J |
Anämiediagnostik im Kindesalter. [+] |
AWMF Leitlinien |
|
| Für eine rationale und rationelle Diagnostik sind Häufigkeit der Erkrankungen, Bedeutung einer raschen
Diagnosestellung und Vermeidung unnötiger Untersuchungen wesentliche Gesichtspunkte. Der abgebildete
Algorithmus soll in der klinischen Situation "Kind mit Anämie" helfen, die zugrunde liegende Störung systematisch
und schrittweise zu identifizieren und damit eine ungezielte und/oder teure Globaldiagnostik vermeiden. Es muss
jedoch betont werden, dass diese Leitlinie ausführlichere Informationsquellen nicht ersetzen will oder kann. |
| Kulozik E |
Hämoglobinopathien nehmen zu. |
Dtsch Arztebl Int 2010; 107: 63 |
|
| Kulozik AE, Kunz J |
Leitlinie der Gesellschaft für Pädiatrische Onkologie und Hämatologie. Anämiediagnostik im Kindesalter. |
AWMF online 2012 |
|
| Kun LE, Kovnar EH, Sanford RA |
Ependymomas in children. |
Pediatr Neurosci 1988, 14: 57-63. Review |
|
| Kuppers R, Klein U, Hansmann ML, Rajewsky K |
Cellular origin of human B-cell lymphomas. |
N Engl J Med 1999, 341: 1520 |
|
| Kurowski C, Berthold F |
Presence of classical multidrug resistance and P-glycoprotein expression in human neuroblastoma cells. |
Ann Oncol 1998, 9: 1009 |
|
| Kusch M, Labouvie H, Langer T, Winkler von Mohrenfels U, Topf R, Felder-Puig R, Beck J, Gadner H, Bode U |
Psychosoziale Folgen von Krebs im Kindes- und Jugendalter. |
Versorgungsmanagement in Theorie und Praxis 1999, 4: 1 |
|
| Kutler DI, Singh B, Satagopan J, Batish SD, Berwick M, Giampietro PF, Hanenberg H, Auerbach AD |
A 20-year perspective on the International Fanconi Anemia Registry (IFAR). [+] |
Blood 2003, 101: 1249 |
|
| Fanconi anemia (FA) is an autosomal recessive disorder characterized by cellular hypersensitivity to DNA cross-linking agents and cancer predisposition. Recent evidence for the interactions of ataxia-telangiectasia mutated protein ATM and breast cancer susceptibility proteins BRCA1 and BRCA2 (identified as FANCD1) with other known FA proteins suggests that FA proteins have a significant role in DNA repair/recombination and cell cycle control. The International Fanconi Anemia Registry (IFAR), a prospectively collected database of FA patients, allows us the unique opportunity to analyze the natural history of this rare, clinically heterogeneous disorder in a large number of patients. Of the 754 subjects in this study, 601 (80%) experienced the onset of bone marrow failure (BMF), and 173 (23%) had a total of 199 neoplasms. Of these neoplasms, 120 (60%) were hematologic and 79 (40%) were nonhematologic. The risk of developing BMF and hematologic and nonhematologic neoplasms increased with advancing age with a 90%, 33%, and 28% cumulative incidence, respectively, by 40 years of age. Univariate analysis revealed a significantly earlier onset of BMF and poorer survival for complementation group C compared with groups A and G; however, there was no significant difference in the time to hematologic or nonhematologic neoplasm development between these groups. Multivariate analysis of overall survival time shows that FANCC mutations (P =.007) and hematopoietic stem cell transplantation (P = <.0001) define a poor-risk subgroup. The results of this study of patients registered in the IFAR over a 20-year period provide information that will enable better prediction of outcome and aid clinicians with decisions regarding major therapeutic modalities. |
| Kühne T, Freedman J, Semple JW, Doyle J, Butchart S, Blanchette VS |
Platelet and immune responses to oral cyclic dexamethasone therapy in childhood chronic immune thrombocytopenic purpura. [+] |
The Journal of pediatrics 1997, 130: 17 |
|
| To examine the effectiveness of cyclic oral high-dose (HD) dexamethasone therapy in pediatric patients with chronic immune thrombocytopenic purpura (ITP), which has been reported to cause complete remission in adults with chronic ITP. |
| Köller U, Haas O, Ludwig W, Bartram C, Harbott J, Panzer-Grümayer R, Hansen-Hagge T, Ritter J, Creutzig U, Knapp W, Gadner H |
Phenotypic and genotypic heterogeneity in infant acute leukemia II. Acute non-lymphoblastic leukemia. |
Leukemia 1989, 3: 708 |
|
| 190 items found |
