| Autor(en) |
Titel |
Quelle |
Links |
| Haaf H, Kaatsch P, Keller B, Michaelis J |
Regionale Analysen der Krebsinzidenz bei kleinen Fallzahlen. |
Gesundheit und Umwelt 1992, 273 |
 |
| Haas R, Schmidt P, Göbel U, Harms D |
Therapy of testicular germ cell tumors. Current status of the MAHO studies. |
Klin Pädiatr 1993, 205: 225 |
|
| Haas R, Schmidt P, Göbel U, Harms D |
Treatment of malignant testicular tumors in childhood. |
Med Pediatr Oncol 1994, 23: 400 |
|
| Haas R, Schmidt P |
Testicular germ-cell tumors in childhood and adolescence. |
World J Urol 1995, 13: 203 |
 |
| Haas R, Schmidt P, Göbel U, Harms D |
Testicular germ cell tumors. Results of the GPO MAHO studies -82-88-92. |
Klin Pädiatr 1995, 207: 145 |
|
| Haas R, Schmidt P, Göbel U, Harms D |
Testicular germ cell tumors, an update. Results of the German cooperative studies 1982-1997. |
Klin Pädiatr 1999, 211: 300 |
|
| Haberle B, Hero B, Berthold F, von Schweinitz D |
Characteristics and outcome of thoracic neuroblastoma. |
Eur J Pediatr Surg 2002, 12: 145 |
|
| Haberle B, Bode U, von Schweinitz D |
Differentiated treatment protocols for high- and standard-risk hepatoblastoma--an interim report of the German Liver Tumor Study HB99. |
Klin Pädiatr 2003, 215: 159 |
|
| Hadrich D, Berthold F, Steckhan E, Bonisch H |
Synthesis and characterization of fluorescent ligands for the norepinephrine transporter. |
J Med Chem 1999, 42: 3101 |
|
| Haecker F, von Schweinitz D, Harms D, Buerger D, Graf N |
Partial nephrectomy for unilateral Wilms tumor. |
J Urol 2003, 170: 939 |
|
| Haeusler J, Ranft A, Boelling T, Gosheger G, Braun-Munzinger G, Vieth V, Burdach S, van den Berg H, Jürgens H, Dirksen U |
The value of local treatment in patients with primary, disseminated, multifocal Ewing sarcoma (PDMES). |
Cancer 2010, 116: 443 |
|
| Halperin EC, Friedman HS, Schold SC Jr, Fuchs HE, Oakes WJ, Hockenberger B, Burger PC |
Surgery, hyperfractionated craniospinal irradiation, and adjuvant chemotherapy in the management of supratentorial embryonal neuroepithelial neoplasms in children. [+] |
Surgical neurology 1993, 40: 278 |
|
| Supratentorial embryonal neuroepithelial tumors are undifferentiated neoplasms. We have used this term in preference to the controversial classification primitive neuroectodermal tumors (PNET). These lesions in children are malignant neoplasms which are usually fatal within 2 years of diagnosis in spite of therapy with surgery, radiotherapy, and chemotherapy. We have adopted an aggressive approach to the treatment of these tumors with surgical resection, hyperfractionated craniospinal irradiation of 30.6-43.9 Gy followed by a tumor boost to a total dose of 50-63.7 Gy, and adjuvant chemotherapy with cyclophosphamide, vincristine, and cis-platinum. We have treated five children, aged 4-18 years, with this approach. In contrast to the results reported in the literature, four children are alive without evidence of tumor from 4.3 to 8.0 years following diagnosis. One has suffered a tumor relapse at 2.3 years following diagnosis but remains alive. The basis of our therapeutic strategy for childhood supratentorial embryonal neuroepithelial tumors and the implications of our clinical results are discussed. |
| Hammerle K, Shayan P, Niemeyer CM, Flotho C |
Expression analysis of alpha-NAC and ANX2 in juvenile myelomonocytic leukemia using SMART polymerase chain reaction and. [+] |
Cancer genetics and cytogenetics 2003, 142: 149 |
|
| Juvenile myelomonocytic leukemia (JMML) is a malignant hematopoietic disease of early childhood with both myeloproliferative and myelodysplastic features. We had previously identified the genes for the alpha-chain of the nascent polypeptide-associated complex (NACA) and annexin II (ANX2) as potentially involved in the pathophysiology of JMML. Now we used SMART cDNA synthesis and subsequent |
| Hammer GP, Seidenbusch MC, Schneider K, Regulla DF, Zeeb H, Spix C, Blettner M |
A cohort study of childhood cancer incidence after postnatal diagnostic X-ray exposure. [+] |
Radiation research 2009, 171: 504 |
|
| Ionizing radiation is an established cause of cancer, yet little is known about the health effects of doses from diagnostic examinations in children. The risk of childhood cancer was studied in a cohort of 92.957 children who had been examined with diagnostic X rays in a large German hospital during 1976-2003. Radiation doses were reconstructed using the individual dose area product and other exposure parameters, together with conversion coefficients developed specifically for the medical devices and standards used at the radiology department. Newly diagnosed cancers occurring between 1980 and 2006 were determined through record linkage to the German Childhood Cancer Registry. The median radiation dose was 7 microSv. Eight-seven incident cases were found in the cohort: 33 leukemia, 13 lymphoma, 10 central nervous system tumors, and 31 other tumors. The standardized incidence ratio (SIR) for all cancers was 0.99 (95% CI: 0.79-1.22). No trend in the incidence of total cancer, leukemia or solid tumors with increasing radiation dose was observed in the SIR analysis or in the multivariate Poisson regression. Risk did not differ significantly in girls and boys. Overall, while no increase in cancer risk with diagnostic radiation was observed, the results are compatible with a broad range of risk estimates. |
| Hanenberg H, Batish SD, Pollok KE, Vieten L, Verlander PC, Leurs C, Cooper RJ, Göttsche K, Haneline L, Clapp DW, Lobitz S, Williams DA, Auerbach AD |
Phenotypic correction of primary Fanconi anemia T cells with retroviral vectors as a diagnostic tool. [+] |
Exp Hematol 2002, 30: 410 |
|
| The aim of this study was to develop a rapid laboratory procedure that is capable of subtyping Fanconi anemia (FA) complementation groups FA-A, FA-C, FA-G, and FA-nonACG patients from a small amount of peripheral blood. |
| Hanke CA, Roessler J, Stegmaier S, Koscielniak E, Niemeyer CM, Kontny U |
Alveolar rhabdomyosarcoma mimicking lymphoma with bone marrow involvement. |
European journal of pediatrics 2007, 166: 505 |
|
| Handgretinger R, Zugmaier G, Henze G, Kreyenberg H, Lang P, von Stackelberg A |
Complete remission after blinatumomab-induced donor T-cell activation in three pediatric patients with post-transplant relapsed acute lymphoblastic leukemia. |
Leukemia 2010 Oct 14; |
|
| Harisiadis L, Chang CH |
Medulloblastoma in children: a correlation between staging and results of treatment. |
Int J Radiat Oncol Biol Phys 1977 (9-10): 833 |
|
| Harbott J, Budde M, Creutzig U, Engel R, Fengler R, Rudolph B, Lampert F |
Prognostic meaning of chromosome aberrations in acute lymphocytic leukemia and acute nonlymphocytic leukemia patients of the BFM study group. |
Haematology and Blood Transfusion 1987, 30: 497 |
|
| Harbott J, Ritterbach J, Creutzig U, Riehm H, Lampert F |
Cytogenetic findings in acute leukemias of infants. |
Contrib Oncol 1990, 41: 50 |
|
| Harms D, Gortitz I, Lambrecht W, Kabisch H, Erttmann R, Janka-Schaub G |
Infectious risks of Broviac catheters in children with neoplastic diseases. |
Pediatr Infect Dis J 1992, 11: 1014 |
|
| Harbott J, Ritterbach J, Ludwig W, Bartram C, Reiter A, Lampert F |
Clinical significance of cytogenetic studies in childhood acute lymphoblastic leukemia. |
Recent Results Cancer Res 1993, 131: 123 |
|
| Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC, et al. |
A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. |
Blood 1994, 84: 1361-92. |
|
| Hartmann S, Schäper E, Lamprecht-Dinnesen A, Boos J |
Ototoxizität von Cisplatin im Kindesalter. |
Oto Rhino Laryng 1995, 222 |
|
| Harbott J, Reinisch-Becker I, Ritterbach J, Creutzig U, Ludwig W, Gutjahr P, Borkhardt A, Lampert F |
Karyotypic abnormalities in secondary leukemia of children. |
Haematology and Blood Transfusion 1996, 38: 24 |
|
| Harbott J, Viehmann S, Borkhardt A, Henze G, Lampert F |
Incidence of TEL/AML1 fusion gene analyzed consecutively in children with acute lymphoblastic leukemia in relapse. |
Blood 1997, 90: 4933 |
|
| Harms D, Jänig U, Göbel U |
Pathology of germ cell tumors. Report of the Kiel pediatric tumor registry (KPTR). |
Med Pediatr Oncol 1998, 31: 189 |
|
| Harms D, Leuschner I, Krams M, Pilgrim T, Treuner J |
Rhabdomyosarcoma and extraosseous Ewing's sarcoma. |
Verh Dtsch Ges Pathol 1998, 82: 83 |
|
| Harms D, Janka-Schaub G |
Co-operative study group for childhood acute lymphoblastic leukemia (COALL). |
Leukemia 2000, 14: 2234 |
|
| Hartmann O, Berthold F |
Treatment of advanced Neuroblastoma:the European Experience, in Brodeur G, M.; Sawada Y; Tsuchida Y; Voute,Pd (Hrsg.), Neuroblastoma. |
Elsevier 2000, 437 |
|
| Hartmann W, Waha A, Koch A, Goodyer C, Albrecht S, von Schweinitz D, Pietsch T |
p57(KIP2) is not mutated in hepatoblastoma but shows increased transcriptional activity in a comparative analysis of the three imprinted genes p57(KIP2), IGF2, and H19. |
Am J Pathol 2000, 157: 1393 |
|
| Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J |
Lymphoma classification--from controversy to consensus: the R. E.A. L. and WHO Classification of lymphoid neoplasms. |
Ann Oncol 2000, 11 Suppl 1: 3-10. Review. |
|
| Harms D, Göbel U, Spaar H, Graubner U, Jorch N, Gutjahr P, Janka-Schaub G |
Thioguanine offers no advantage over mercaptopurine in maintenance treatment of childhood ALL. |
Blood 2003, 102: 2736 |
|
| Hartmann W, Küchler J, Koch A, Friedrichs N, Waha A, Endl E, Czerwitzki J, Metzger D, Steiner S, Wurst P, Leuschner I, von Schweinitz D, Buettner R, Pietsch T |
Activation of phosphatidylinositol-3'-kinase/AKT signaling is essential in hepatoblastoma survival. [+] |
Clinical cancer research 2009, 15: 4538 |
|
| PURPOSE: Hepatoblastoma represents the most frequent malignant liver tumor in childhood. The phosphatidylinositol-3'-kinase (PI3K)/AKT pathway is crucial in downstream signaling of multiple receptor tyrosine kinases of pathogenic importance in hepatoblastoma. Increased PI3K/AKT signaling pathway activity and activating mutations of PIK3CA, encoding a PI3K catalytic subunit, have been reported in different childhood tumors. The current study was done to analyze the role of PI3K/AKT signaling in hepatoblastoma. EXPERIMENTAL DESIGN: Immunohistochemical stainings of (Ser473)-phosphorylated (p)-AKT protein, its targets p-(Ser9)-GSK-3beta and p-(Ser2448)-mTOR, as well as the cell cycle regulators Cyclin D1, p27(KIP1), and p21(CIP1) were done and the PIK3CA gene was screened for mutations. In vitro, two hepatoblastoma cell lines treated with the PI3K inhibitor LY294002 were analyzed for AKT and GSK-3beta phosphorylation, cell proliferation, and apoptosis. Additionally, simultaneous treatments of hepatoblastoma with LY294002 and cytotoxic drugs were carried out. RESULTS: Most tumors strongly expressed p-AKT, p-GSK-3beta, and p-mTOR; subgroups showed significant Cyclin D1, p27(KIP1), and p21(CIP1) expression. One hepatoblastoma carried an E545A mutation in the PIK3CA gene. In vitro, PI3K inhibition diminished hepatoblastoma cell growth being accompanied by reduced AKT and GSK-3beta phosphorylation. Flow cytometry and 4', 6-diamidino-2-phenylindole stainings showed that PI3K pathway inhibition leads to a substantial increase in apoptosis and a decrease in cellular proliferation linked to reduced Cyclin D1 and increased p27(KIP1) levels. Simultaneous treatment of hepatoblastoma cell lines with LY294002 and cytotoxic drugs resulted in positive interactions. CONCLUSIONS: Our findings imply that PI3K signaling plays an essential role in growth control of hepatoblastoma and might be successfully targeted in multimodal therapeutic strategies. |
| Harrison CJ, Hills RK, Moorman AV, Grimwade DJ, Hann I, Webb DK, Wheatley K, de Graaf SS, van den Berg E, Burnett AK, Gibson BE |
Cytogenetics of childhood acute myeloid leukemia: United Kingdom Medical Research Council Treatment trials AML 10 and 12. [+] |
Journal of clinical oncology 2010, 28: 2674 |
|
| Karyotype is an independent indicator of prognosis in acute myeloid leukemia (AML) that is widely applied to risk-adapted therapy. Because AML is rare in children, the true prognostic significance of individual chromosomal abnormalities in this age group remains unclear. |
| Hasle H, Arico M, Basso G, Biondi A, Cantu Rajnoldi, Creutzig U, Fenu S, Fonatsch C, Haas O, Harbott J, Kardos G, Kerndrup G, Mann G, Niemeyer C, Ptoszkova H, Ritter J, Slater R, Stary J, Stollmann-Gibbels B, Testi A, van Wering E, Zimmermann M |
Myelodysplastic syndrome, juvenile myelomonocytic leukemia, and acute myeloid leukemia associated with complete or partial monosomy 7. European Working Group on MDS in Childhood (EWOG-MDS). |
Leukemia 1999, 13: 376 |
|
| Hasle H, Niemeyer C, Chessells J, Baumann I, Bennett J, Kerndrup G, Head D |
A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases. |
Leukemia 2003, 17: 277 |
|
| Hasle H, Niemeyer CM, Chessells JM, Baumann I, Bennett JM, Kerndrup G, Head DR |
A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases. [+] |
Leukemia 2003, 17: 277 |
|
| Myelodysplastic and myeloproliferative disorders are rare in childhood and there is no widely accepted system for their diagnosis and classification. We propose minimal diagnostic criteria and a simple classification scheme which, while based on accepted morphological features and conforming with the recent suggestions of the WHO, allows for the special problems of myelodysplastic diseases in children. The classification recognizes three major diagnostic groups: (1) juvenile myelomonocytic leukemia (JMML), previously named chronic myelomonocytic leukemia (CMML) or juvenile chronic myeloid leukemia (JCML); (2) myeloid leukemia of Down syndrome, a disease with distinct clinical and biological features, encompassing both MDS and AML occurring in Down syndrome; and (3) MDS occurring both de novo and as a complication of previous therapy or pre-existing bone marrow disorder (secondary MDS). The main subtypes of MDS are refractory cytopenia (RC) and refractory anemia with excess of blasts (RAEB). It is suggested retaining the subtype of RAEB-T with 20-30% blasts in the marrow until more data are available. Cytogenetics and serial assessments of the patients are essential adjuncts to morphology both in diagnosis and classification. |
| Hasle H, Baumann I, Bergstrasser E, Fenu S, Fischer A, Kardos G, Kerndrup G, Locatelli F, Rogge T, Schultz KR, Stary J, Trebo M, van den Heuvel-Eibrink MM, Harbott J, Nollke P, Niemeyer CM, European Working Group on childhood MDS |
The International Prognostic Scoring System (IPSS) for childhood myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukemia (JMML). [+] |
Leukemia 2004, 18: 2008 |
|
| The International Prognostic Scoring System (IPSS) for myelodysplastic syndrome (MDS) is based upon weighted data on bone marrow (BM) blast percentage, cytopenia, and cytogenetics, separating patients into four prognostic groups. We analyzed the value of the IPSS in 142 children with de novo MDS and 166 children with juvenile myelomonocytic leukemia (JMML) enrolled in retro- and prospective studies of the European Working Group on childhood MDS (EWOG-MDS). Survivals in MDS and JMML were analyzed separately. Among the criteria considered by the IPSS score, only BM blasts <5% and platelets >100 x 10(9)/l were significantly associated with a superior survival in MDS. In JMML, better survival was associated with platelets >40 x 10(9)/l, but not with any other IPSS factors including cytogenetics. In conclusion, the IPSS is of limited value in both pediatric MDS and JMML. The results reflect the differences between myelodysplastic and myeloproliferative diseases in children and adults. |
| Hasle H, Alonzo TA, Auvrignon A, Behar C, Chang M, Creutzig U, Fischer A, Forestier E, Fynn A, Haas OA, Harbott J, Harrison CJ, Heerema NA, van den Heuvel-Eibrink MM, Kaspers GJ, Locatelli F, Noellke P, Polychronopoulou S, Ravindranath Y, Razzouk B, Reinhardt D, Savva NN, Stark B, Suciu S, Tsukimoto I, Webb DK, Wojcik D, Woods WG, Zimmermann M, Niemeyer CM, Raimondi SC |
Monosomy 7 and deletion 7q in children and adolescents with acute myeloid leukemia: an international retrospective study. [+] |
Blood 2007, 109: 4641 |
|
| Monosomy 7 (-7) and deletion 7q \del(7q)] are rare in childhood acute myeloid leukemia (AML). We retrospectively collected data on 258 children with AML or refractory anemia with excess blasts in transformation (RAEB-T) and -7 or del(7q) with or without other cytogenetic aberrations \+/- other]. Karyotypes included -7 (n = 90), -7 other (n = 82), del(7q) (n = 21), and del(7q) other (n = 65). Complete remission (CR) was achieved in fewer patients with -7 +/- other compared with del(7q) +/- other (61% versus 89%, P < .001). Overall, the 5-year survival rate was 39% (SE, 3%). Survival was superior in del(7q) +/- other compared with -7 +/- other (51% versus 30%, P < .01). Cytogenetic aberrations considered favorable in AML \t(8;21)(q22;q22), inv(16)(p13q22), t(15;17)(q22;q21), t(9;11)(p22;q23)] (n = 24) were strongly associated with del(7q) and a higher 5-year survival rate compared with del(7q) without favorable cytogenetics (75% versus 46%, P = .03). Patients with -7 and inv(3),-5/del(5q), or + 21 had a 5-year survival rate of 5%. Stem cell transplantation analyzed as a time-dependent variable had no impact on overall survival. However, patients not achieving CR had a 31% survival rate after stem cell transplantation. Childhood AML with chromosome 7 aberrations represents a heterogeneous group of disorders with additional cytogenetic aberrations having a major prognostic impact which should be reflected in future risk-group stratification. |
| Hasselblatt M, Mühlisch J, Wrede B, Kallinger B, Jeibmann A, Peters O, Kutluk T, Wolff JE, Paulus W, Frühwald MC |
Aberrant MGMT (O6-methylguanine-DNA methyltransferase) promoter methylation in choroid plexus tumors. [+] |
J Neurooncol 2009, 91: 151 |
|
| Aberrant methylation of the MGMT (O6-methylguanine-DNA methyltransferase) DNA-repair gene is a predictive marker for the response to chemotherapy with alkylating agents (e.g., temozolomide) in malignant gliomas. Since temozolomide is considered for the treatment of choroid plexus tumors, MGMT promoter methylation status was retrospectively assessed in 36 choroid plexus tumors using methylation specific PCR, combined bisulfite restriction analysis (COBRA), and clone sequencing. By methylation specific PCR, all samples demonstrated a signal for MGMT methylation. COBRA confirmed >10% methylation of CpGs 17 and 31 in 58% of tumors. Clone sequencing of six cases methylated by COBRA confirmed aberrant methylation including a previously recognized enhancer element. In conclusion, MGMT promoter methylation is frequent in choroid plexus tumors and can be quantified using COBRA. Determination of MGMT promoter methylation status might be useful for the stratification of patients for alkylator-based treatments in future clinical trials. |
| Hasle H, Niemeyer CM |
Advances in the prognostication and management of advanced MDS in children. [+] |
Br J Haematol 2011, 154: 185 |
|
| Advanced myelodysplastic syndrome (MDS) in children includes refractory anaemia with excess blasts (RAEB) and RAEB in transformation (RAEB-T) according to the paediatric modification of the World Health Organization classification. Clinical features and cytogenetics are essential to make a diagnosis because blast count alone is insufficient to differentiate MDS from acute myeloid leukaemia (AML). Little is known about molecular genetics in paediatric MDS but hypermethylation seem to be frequent. Monosomy 7 is the most common cytogenetic aberration but prognostic neutral whereas those with structural complex karyotype have a very poor outcome. Haematopoietic stem cell transplantation (HSCT) is the treatment of choice and results in cure rates of around 60%. Intensive chemotherapy prior to HSCT provides no survival benefit for children with RAEB and RAEB-T and can generally not be recommended. Intensive chemotherapy before HSCT should be considered in patients with myelodysplasia-related-AML (MDR-AML). |
| Hasselblatt M, Gesk S, Oyen F, Rossi S, Viscardi E, Giangaspero F, Giannini C, Judkins AR, Frühwald MC, Obser T, Schneppenheim R, Siebert R, Paulus W |
Nonsense mutation and inactivation of SMARCA4 (BRG1) in an atypical teratoid/rhabdoid tumor showing retained SMARCB1 (INI1) expression. [+] |
The American journal of surgical pathology 2011, 35: 933 |
|
| Atypical teratoid/rhabdoid tumors (AT/RTs) are highly aggressive brain tumors of early childhood poorly responding to therapy. The majority of cases show inactivation of SMARCB1 (INI1, hSNF5, BAF47), a core member of the adenosine triphosphate (ATP)-dependent SWI/SNF chromatin-remodeling complex. We here report the case of a supratentorial AT/RT in a 9-month-old boy, which showed retained SMARCB1 staining on immunohistochemistry and lacked genetic alterations of SMARCB1. Instead, the tumor showed loss of protein expression of another SWI/SNF chromatin-remodeling complex member, the ATPase subunit SMARCA4 (BRG1) due to a homozygous SMARCA4 mutation [c.2032C>T (p.Q678X)]. Our findings highlight the role of SMARCA4 in the pathogenesis of SMARCB1-positive AT/RT and the usefulness of antibodies directed against SMARCA4 in this diagnostic setting. |
| Haupt R, Fears T, Heise A, Gadner H, Loiacono G, De Terlizzi M, Tucker M |
Risk of secondary leukemia after treatment with etoposide (VP-16) for Langerhans' cell histiocytosis in Italian and Austrian-German populations. |
Int J Cancer 1997, 71: 9 |
|
| Hawkins DS, Schuetze SM, Butrynski JE, Rajendran JG, Vernon CB, Conrad EU 3rd, Eary JF |
[18F]Fluorodeoxyglucose positron emission tomography predicts outcome for Ewing sarcoma family of tumors. |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2005, 23: 8828 |
|
| Hedborg F, Franklin G, Norrman J, Grimelius L, Wassberg E, Hero B, Schilling F, Berthold F, Harms D, Sandstedt B |
Evidence of chromaffin oxygen sensing in neuroblastoma. |
Med Pediatr Oncol 2001, 36: 149 |
|
| Hedborg F, Ulleras E, Grimelius L, Wassberg E, Maxwell P, Hero B, Berthold F, Schilling F, Harms D, Sandstedt B, Franklin G |
Evidence for hypoxia-induced neuronal-to-chromaffin metaplasia in neuroblastoma. |
FASEB J 2003, 17: 598 |
|
| Heerema N, Harbott J, Galimberti S, Camitta B, Gaynon P, Janka-Schaub G, Kamps W, Basso G, Pui C, Schrappe M, Auclerc M, Carroll A, Conter V, Harrison C, Pullen J, Raimondi S, Richards S, Riehm H, Sather H, Shuster J, Silverman L, Valsecchi M, Arico M |
Secondary cytogenetic aberrations in childhood Philadelphia chromosome positive acute lymphoblastic leukemia are nonrandom and may be associated with outcome. |
Leukemia 2004, 18: 693 |
|
| Heinsohn S, Scholz R, Weber B, Wittenstein B, Werner M, Delling G, Kempf-Bielack B, Setlak P, Bielack S, Kabisch H |
SV40 sequences in human osteosarcoma of German origin. |
Anticancer Res 2000, 20: 4539 |
|
| Heimpel H |
Congenital dyserythropoietic anemias: epidemiology, clinical significance, and progress in understanding their pathogenesis. [+] |
Annals of hematology 2004, 83: 613 |
|
| The congenital dyserythropoietic anemias (CDAs) comprise a group of rare hereditary disorders of erythropoiesis, characterized by ineffective erythropoiesis as the predominant mechanism of anemia and by distinct morphological abnormalities of the majority of erythroblasts in the bone marrow. The classification in three types as proposed in 1968 is still valid, but there is genetic heterogeneity within each type, and there are additional variants of unknown genetic basis. CDA II is the most frequent, and the nonfamilial type of CDA III the rarest group. The genes of CDA II and CDA III were mapped to chromosome 20 and 15, respectively, and the gene of CDA I on 15q was recently cloned. Therapeutic decision making requires definition of the type, an estimate of individual severity, and presence of or risk for complications. Therapeutic measures include interferon-alpha for CDA I, splenectomy for CDA II, and iron depletion for all individuals at risk for secondary hemochromatosis. |
| Heimpel H, Iolascon, A |
Congenical dyserythropoietic anemias. |
In: Beaument C, Beris, Ph, Beuzard, Y, Brugnara, C editors, ESH Handbook on Disorders of Erythropoiesis, Erythrocytes and Iron Metabolism 2009, 2nd edition, p178 |
|
| Hellenbrecht A |
Kinderwunsch und Hormonhaushalt. |
WIR 2005, 1 |
|
| Hempel L, Kremens B, Weirich A, Graf N, Zintl F, Ludwig R |
High dose consolidation with autologous stem cell rescue (ASCR) for nephroblastoma initially treated according to the SIOP 9/GPOH trial and study. |
Klin Pädiatr 1996, 208: 186 |
|
| Hempel G, Reinhardt D, Creutzig U, Boos J |
Population pharmacokinetics of liposomal daunorubicin in children. |
Br J Clin Pharmacol 2003, 56: 370 |
|
| Hempel L, Sauerbrey A, Zintl F, Weirich A, Lemmer A, Graf N |
Successful management of a child with clear cell sarcoma of the kidney (CCSK) and multifocal bone metastases at diagnosis. |
Med Pediatr Oncol 2003, 41: 97 |
|
| Hempel G, Müller HJ, Lanvers-Kaminsky C, Würthwein G, Hoppe A, Boos J |
A population pharmacokinetic model for pegylated-asparaginase in children. [+] |
British journal of haematology 2010, 148: 119 |
|
| We analysed 1221 serum activity measurements in 168 children from the Berlin-Frankfürt-Münster acute lymphoblastic leukaemia studies, ALL-BFM (Berlin-Frankfürt-Münster) 95 and ALL-BFM REZ, in order to develop a pharmacokinetic model describing the activity-time course of pegylated (PEG)-asparaginase for all dose levels. Patients received 500, 750, 1000 or 2500 U/m(2) PEG-asparaginase on up to nine occasions. Serum samples were analysed for asparaginase activity and data analysis was done using nonlinear mixed effects modelling (NONMEM Vers. VI, Globomax, Hanouet, MD, USA). Different linear and nonlinear models were tested. The best model applicable to all dosing groups was a one-compartmental model with clearance (Cl) increasing with time according to the formula: Cl=Cl(i) *e((0.0793 *t)) where Cl(i) = initial clearance and t = time after dose. The parameters found were: volume of distribution (V) 1.02 +/- 26% l/m(2), Cl(i) 59.9 +/- 59% ml/d per m(2) (mean +/- interindividual variability). Interoccasion variability was substantial with 0.183 l/m(2) for V and 44.7 ml/d per m(2) for Cl, respectively. A subgroup of the patients showed a high clearance, probably due to the development of inactivating antibodies. This is the first model able to predict the activity-time course of PEG-asparaginase at different dosing levels and can therefore be used for developing new dosing regimens. |
| Henter JI, Elinder G, Ost A |
Diagnostic guidelines for hemophagocytic lymphohistiocytosis. The FHL Study Group of the Histiocyte Society. |
Seminars in oncology 1991, 18: 29 |
|
| Henze G, Fengler R, Hartmann R |
Chemotherapy for relapsed childhood acute lymphoblastic leukemia. |
Haematol Blood Transfus 1994, 36: 374 |
|
| Henze G, Hartmann R, Fengler R |
Salvage therapy of childhood ALL. |
Haematol Blood Transfus 1995, 223 |
|
| Henze G Agthe AG, Neuendank A, Hartmann R, Dörffel W, Brühmüller S, Klumper E, Pieters R, Veerman AJ |
Tailored therapy for relapsed or refractory childhood acute lymphoblastic leukaemia. |
Leukemia 1995, 9 : 538 |
|
| Henze G |
Autologe Knochenmarktransplantation versus Chemotherapie bei Kindern mit akuter lymphoblastischer Leukämie in zweiter Remission. |
Deutsches Ärzteblatt 1996, 93: 935 |
|
| Henter J, Arico M, Egeler R, Elinder G, Favara B, Filipovich A, Gadner H, Imashuku S, Janka-Schaub G, Komp D, Ladisch S, Webb D |
HLH-94: a treatment protocol for hemophagocytic lymphohistiocytosis. HLH study Group of the Histiocyte Society. |
Med Pediatr Oncol 1997, 28: 342 |
|
| Henze G |
Chemotherapy for relapsed childhood acute lymphoblastic leukemia. |
Int J Pediatr Hematol Oncol 1998, 5: 199 |
|
| Henze G, Borgmann A, Stackelberg A, Baumgarten E, Uchanska-Ziegler B, Ziegler A, Wittig B |
Immunotherapy of acute lymphoblastic leukemia by vaccination with autologoues leukemic cells transfected with a cDNA expression plasmid coding for an allogeneic HLA class I antigen combined with interleukin-2 treatment. |
J Mol Med 1998, 76: 215 |
|
| Hense H, Ahrens S, Paulussen M, Lehnert M, Jürgens H |
Factors associated with tumor volume and primary metastases in Ewing tumors. |
Ann Oncol 1999, 10: 1073 |
|
| Hense H, Ahrens S, Paulussen M, Lehnert M, Jürgens H |
Descriptive epidemiology of Ewing's tumor--analysis of German patients from (EI)CESS 1980-1997. |
Klin Pädiatr 1999, 211: 271 |
|
| Henze G |
Leukämien. |
In:Gutjahr, P , Krebs bei Kindern und Jugendlichen Deutscher Ärzte-Verlag, Köln, 4 Auflage 1999, 240 |
|
| Henze G, Herold R, Creutzig U |
Kompetenznetz Pädiatrische Onkologie und Hämatologie nach der ersten Förderperiode - zukünftige Pläne. |
Monatsschrift für Kinderheilkunde 2002, 150 |
|
| Henter JI, Samuelsson-Horne A, Aricò M, Egeler RM, Elinder G, Filipovich AH, Gadner H, Imashuku S, Komp D, Ladisch S, Webb D, Janka G, Histocyte Society |
Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. [+] |
Blood 2002, 100: 2367 |
|
| Hemophagocytic lymphohistiocytosis (HLH) comprises familial (primary) hemophagocytic lymphohistiocytosis (FHL) and secondary HLH (SHLH), both clinically characterized by fever, hepatosplenomegaly, and cytopenia. FHL, an autosomal recessive disease invariably fatal when untreated, is associated with defective triggering of apoptosis and reduced cytotoxic activity, resulting in a widespread accumulation of T lymphocytes and activated macrophages. In 1994 the Histiocyte Society initiated a prospective international collaborative therapeutic study (HLH-94), aiming at improved survival. It combined chemotherapy and immunotherapy (etoposide, corticosteroids, cyclosporin A, and, in selected patients, intrathecal methotrexate), followed by bone marrow transplantation (BMT) in persistent, recurring, and/or familial disease. Between July 1, 1994, and June 30, 1998, 113 eligible patients aged no more than 15 years from 21 countries started HLH-94. All had either an affected sibling (n = 25) and/or fulfilled the Histiocyte Society diagnostic criteria. At a median follow-up of 3.1 years, the estimated 3-year probability of survival overall was 55% (95% confidence interval +/- 9%), and in the familial cases, 51% (+/- 20%). Twenty enrolled children were alive and off therapy for more than 12 months without BMT. For patients who received transplants (n = 65), died prior to BMT (n = 25), or were still on therapy (n = 3), the 3-year survival was 45% (+/- 10%). The 3-year probability of survival after BMT was 62% (+/- 12%). HLH-94 is very effective, allowing BMT in most patients. Survival of children with HLH has been greatly improved. |
| Henze G |
Kryokonservierung von Nabelschnurstammzellen bei Neugeborenen zur eventuellen späteren Eigennutzung. |
Die Mitteilungen von GPOH und KPOH 2003, 1: 7 |
|
| Henze G |
Leukämien, in Gutjahr P: Krebs bei Kindern und Jugendlichen. |
Deutscher Ärzte-Verlag Köln 5. Aufl. 2004, 293 |
|
| Henze G |
20 Jahre Studien zur Behandlung von Kindern mit Rezidiv einer akuten lymphoblastischen Leukämie (ALL-REZ BFM). |
WIR Informationsschrift der Aktion für krebskranke Kinder e.V. (Bonn) 2004, 3: 13 |
|
| Henze G |
Maligne Non-Hodgkin-Lymphome, in Gutjahr P: Krebs bei Kindern und Jugendlichen. |
Deutscher Ärzte-Verlag Köln 5. Aufl. 2004, 328 |
|
| Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G |
HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. [+] |
Pediatric blood & cancer 2007, 48: 124 |
|
| In HLH-94, the first prospective international treatment study for hemophagocytic lymphohistiocytosis (HLH), diagnosis was based on five criteria (fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, and hemophagocytosis). In HLH-2004 three additional criteria are introduced; low/absent NK-cell-activity, hyperferritinemia, and high-soluble interleukin-2-receptor levels. Altogether five of these eight criteria must be fulfilled, unless family history or molecular diagnosis is consistent with HLH. HLH-2004 chemo-immunotherapy includes etoposide, dexamethasone, cyclosporine A upfront and, in selected patients, intrathecal therapy with methotrexate and corticosteroids. Subsequent hematopoietic stem cell transplantation (HSCT) is recommended for patients with familial disease or molecular diagnosis, and patients with severe and persistent, or reactivated, disease. In order to hopefully further improve diagnosis, therapy and biological understanding, participation in HLH studies is encouraged. |
| Hennes E, Zahn S, Lopes LF, Schönberger S, Leuschner I, Göbel U, Calaminus G, Schneider DT |
Molecular genetic analysis of bilateral ovarian germ cell tumors. [+] |
Klinische Padiatrie 2012, 224: 359 |
|
| Ovarian germ cell tumors (oGCTs) are rare and highly heterogeneous with regard to their clinical and histologic appearance. The risk of tumor development is higher in children with aberrant sexual differentiation. Development of gonadoblastomas is seen in young women with 46,XY gonadal dysgenesis. At least 50 % of gonadoblastomas may develop into malignant oGCTs, mostly dysgerminomas. In this study, we evaluated bilateral oGCTs in clinically inapparent patients for sex chromosomal aberrations. |
| Hero B, Holschneider A, Berthold F |
Risk and benefits of surgical interventions in localized neuroblastoma--experiences from cooperative studies in Germany. |
Langenbecks Arch Chir Suppl Kongressbd 1996, 113: 1062 |
|
| Hertzberg H, Langer T |
Probleme der Chemotherapie im Kindesalter. |
mta 1996, 796 |
|
| Hero B, Kremens B, Klingebiel T, Bender-Gotze C, Burdach S, Schrappe M, Berthold F |
Does megatherapy contribute to survival in metastatic neuroblastoma? |
Klin Pädiatr 1997, 209: 196 |
|
| Hertzberg H, Huk W, Überall M, Langer T, Meier W, Dopfer R, Skalej M, Lackner H, Bode U, Janssen G, Zintl F, Beck J |
CNS late effects after ALL therapy in childhood. Part I |
Med Pediatr Oncol 1997, 28: 387 |
|
| Herold R, Creutzig U, Henze G |
Kompetenznetz Pädiatrische Onkologie und Hämatologie. |
humboldt spektrum 1999, 4: 4 |
|
| Herold R, Creutzig U, Henze G |
Kompetenznetz Pädiatrische Onkologie und Hämatologie. |
InFoOnkologie 1999, 5: 292 |
|
| Hero B, Berthold F |
Neuroblastoma. |
Leitlinien Kinderheilkunde und Jugendmedizin, D Reinhardt (Hrsg ), Urban & Fischer 2000, 1 |
|
| Hero B, Simon T, Horz S, Berthold F |
Metastatic neuroblastoma in infancy. |
Med Pediatr Oncol 2000, 35: 683 |
|
| Hero B, Hunneman D, Gahr M, Berthold F |
Evaluation of catecholamine metabolites, mIBG scan, and bone marrow cytology as response markers in stage 4 neuroblastoma. |
Med Pediatr Oncol 2001, 36: 220 |
|
| Herold R, Henze G, Creutzig U |
Kompetenznetz Pädiatrische Onkologie und Hämatologie. |
Lebendige Wissenschaft - Medizin 2001,alpha Verlag Lampertheim |
|
| Herold Ralf, Creutzig Ursula, Pommerening Klaus |
Use of an internet based knowledge Server for the Medical Research Network Pediatric Oncology and Hematology. |
Onkologie 2001, 24: 169 |
|
| Hertzberg H, Kremens B, Velten I, Beck JD, Greil J |
Recurrent disseminated retinoblastoma in a 7-year-old girl treated successfully by high-dose chemotherapy and CD34-selected autologous peripheral blood stem cell transplantation. [+] |
Bone marrow transplantation 2001, 27: 653 |
|
| A localized retinoblastoma of the left eye in a 7-year-old girl, was treated by enucleation. She received no additional therapy. Four months later, metastases of retinoblastoma in the lymph nodes, bone and bone marrow were diagnosed. Relapse chemotherapy consisting of three courses of vincristine, cyclophosphamide, etoposide and carboplatin led to a second complete remission. Subsequent high-dose chemotherapy with thiotepa, etoposide and carboplatin and autologous stem cell transplantation with CD34-selected stem cells were successful, with no adverse effects. No radiotherapy was given and the girl remains in continuous second remission with a follow-up of more than 4 years. |
| Hero B, Berthold F |
Neuroblastom. |
Monatschr Kinderheilkd 2002, 150: 775 |
|
| Hero B, Graf N, Simon T, Weirich A, Troger J, Berthold F |
Neuroblastoma preoperatively treated as nephroblastoma. |
Klin Pädiatr 2002, 214: 157 |
|
| Herold R, Berthold F |
Erfahrungen und praktische Regeln beim Kodieren von Diagnosen und Prozeduren in der Pädiatrischen Onkologie und Hämatologie [Abstract]. |
Monatsschrift für Kinderheilkunde 2002, 150 |
|
| Herold R, Grieámeier B, Tallen G, Henze G |
Nicht mehr krank, doch gesund noch lange nicht - Zur Situation von krebskranken Kindern und Jugendlichen. |
Forum Public Health 2002, 10: 13 |
|
| Herold R, Stibenz D, Hartmann R, Henze G, Bührer C |
Soluble l-selectin (sCD62L) in relapsed childhood acute lymphoblastic leukaemia. |
Br J Haematol 2002, 119: 677 |
|
| Herold R, Tallen G, Creutzig U |
Neuer Informationsserver im Internet für Betroffene, Fachleute und Laien der Pädiatrischen Onkologie und Hämatologie. |
Monatsschrift für Kinderheilkunde 2002, 150 |
|
| Herold R, Zimmermann M |
Konzepte und Perspektiven der elektronischen Unterstützung für die Medizinische Dokumentation in der Pädiatrischen Onkologie und Hämatologie [Abstract]. |
Monatsschrift für Kinderheilkunde 2002, 150 |
|
| Herold R, Von Stackelberg A, Hartmann R, Eisenreich B, Henze G |
Acute lymphoblastic leukemia-relapse study of the Berlin-Frankfurt-Münster Group (ALL-REZ BFM) experience. |
J Clin Oncol 2004, 22: 569 |
|
| Hero B, Berthold F |
Neuroblastoma. |
In: D. Reinhard (Hrsg.), Leitlinien Kinderheilkunde und Jugendmedizin Urban & Fischer, 2005, L5 1 |
|
| Hering A, Michel S, Ernst G, Claussen U, Kloetzer Ch, Parlowsky T, Bucsky P, Loncarevic IF |
Characteristic chromosomal imbalances in pediatric pheochromocytoma. |
Genes Chromosomes and Cancer (accepted paper) |
|
| Hero B, Berthold F |
Neuroblastome. |
Interdisziplinäre Leitlinie der Deutschen Krebsgesellschaft und der Deutschen Gesellschaft für Pädiatrische Onkologie und Hämatologie 2005 |
|
| Herold R, Reiche R, Creutzig U, Henze G |
[Assessment of staffing and infrastructures of paediatric oncology and haematology centres in Germany]. [+] |
Klinische Padiatrie 2007, 219: 380 |
|
| BACKGROUND AND METHODS: At the end of 2003, the Competence Network Paediatric Oncology and Haematology conducted a survey of paediatric oncology centres in Germany as one of its measures to support and advance the collaboration of paediatric oncology centres and trials in science and health care. There was a lack of key figures to describe their combined position in the health care system. The survey aimed to quantify existing structures in terms of personnel, facilities, and patients as well as to collect preliminary information on patterns of care and on quality assurance. Starting with the largest patient numbers, 53 German centres were included, which cared for at least 10 patients under the age of 15 years with a newly diagnosed malignant disease per year. MAIN RESULTS: 49 (92%) centres contributed to the survey. 40 centres cared for a total of 1712 patients under the age of 15 years with a first occurrence of a malignant disease, which corresponds to 83% of all such patients registered in the German Childhood Cancer Registry in 2003. The total number of patients cared for in these centers, which also includes those with a relapse and the above 15-year olds, exceeds the Registry numbers by about 50%. The survey's outcome on staffing revealed about two work positions per bed (in-patient or day-clinic). A significant part of this personnel is financed by third-party funds. On average, the centres responding to the survey were equipped with 7 physician, 21 nursing and 4,4 psychologist, social worker, medical documentarist, and secretariat posts to care for a mean of 54 patients or 18 in-patient beds. Including those working positions financed by third-party funds, the majority of centres scored staffing as good or excellent. Yet, one out of ten centres scored the staffing of one or more occupational groups as poor. CONCLUSIONS: The survey provided for the first time a national assessment of the variable levels of staffing and facilities in the most relevant German paediatric oncology centres. The data indicate that the relationship between several key figures such as the Registry patient subset's numbers and in-patient bed numbers, for example, is weak, whereas physician post numbers, for example, correlate reasonably well with actual patient numbers. Further data include the variety of special health care offered and preliminary provisions for quality assurance per centre. According to a comparison with a seminal publication on needs in German paediatric oncology health care published in 1991 and with a needs survey of the UK National Institute for Health and Clinical Excellence (NICE), there seems to be an insufficient response to the needs, which is undermined by the centres survey responses. In view of the DRG reimbursement system being introduced throughout German health care, future surveys should also focus on key figures related to the DRG system such as case numbers, but such data should be merged with patient data in order to maintain a perspective on the course of health care provision to children and young adults with cancer. |
| Hero B, Simon T, Spitz R, Ernestus K, Gnekow AK, Scheel-Walter HG, Schwabe D, Schilling FH, Benz-Bohm G, Berthold F |
Localized infant neuroblastomas often show spontaneous regression: results of the prospective trials NB95-S and NB97. [+] |
Journal of clinical oncology 2008, 26: 1504 |
|
| PURPOSE: The excellent prognosis of localized neuroblastoma in infants, the overdiagnosis observed in neuroblastoma screening studies, and several case reports of regression of localized neuroblastoma prompted us to initiate a prospective cooperative trial on observation of localized neuroblastoma without cytotoxic treatment. PATIENTS AND METHODS: For infants with localized neuroblastoma without MYCN amplification, chemotherapy was scheduled only in cases with threatening symptoms; otherwise, the tumor was either resected or observed by ultrasound and magnetic resonance imaging (MRI). RESULTS: Of 340 eligible participants, 190 underwent resection, 57 were treated with chemotherapy, and 93 were observed with gross residual tumor. Of those 93 patients with unresected tumors, spontaneous regression was seen in 44, local progression in 28, progression to stage 4S in seven, and progression to stage 4 in four. Time to regression was quite variable, with first signs of regression noted 1 to 18 months after diagnosis and in 15 of 44 patients even after the first year of life. So far, complete regression was observed in 17 of 44 patients 4 to 20 months after diagnosis. Known clinical risk factors were not able to differentiate between patients with regression and regional or metastatic progression. Overall survival (OS; 3-year OS, 0.99 +/- 0.01) and metastases-free survival (rate at 3 years, 0.94 +/- 0.03) for patients with unresected tumors was excellent and was not different from patients treated with surgery or chemotherapy. CONCLUSION: Spontaneous regression is regularly seen in infants with localized neuroblastoma and is not limited to the first year of life. A wait-and-see strategy is justified in those patients. |
| Hernáiz Driever P, von Hornstein S, Pietsch T, Kortmann R, Warmuth-Metz M, Emser A, Gnekow AK |
Natural history and management of low-grade glioma in NF-1 children. [+] |
Journal of neuro-oncology 2010, |
|
| Pediatric neurofibromatosis type 1 (NF-1) patients are prone to developing low-grade glioma (LGG). The HIT-LGG study 1996 aimed to observe the natural history of pediatric LGG and to postpone irradiation in younger children by using carboplatinum and vincristine in case non-surgical treatment was required. A total of 109 of 1,044 (10.4%) protocol patients had a genetic NF-1 trait [57 female patients; median age 5.1 years (range 1-15.4 years)]. Eighty-three patients (76%) suffered from an optic pathway tumor. Neuroimaging only allowed diagnosis in 67 patients. Histology revealed pilocytic astrocytoma WHO grade I in 38 of 42 biopsied patients. Sixty-five (60%) patients received non-surgical treatment, either chemotherapy (n = 55) or irradiation (n = 10). The overall survival rate of 96% after a median observation time of 5.25 years contrasts with an event free survival rate (EFS) of 0.24 at 5 years. Progressive LGG were observed even in children older than 11 years. Chiasmatic/postchiasmatic localization was a univariate risk factor for progressive disease. In the chemotherapy group, we observed a 5-year progression-free survival (PFS) rate of 0.73. Similarly, the PFS rate in the irradiation group was 0.78. Multivariate analysis revealed surgical intervention and localization within the optic pathway as factors that increased the risk of tumor progression. In this large prospective multinational study, LGG in NF-1 patients did progress in 75% of patients. Chemotherapy yielded acceptable PFS. The biological factors determining progression remain poorly understood. |
| Hero B, Papenheim H, Schuster U |
Neuroblastom – Informationen für Eltern. |
Fördergesellschaft Kinderkrebs-Neuroblastom-Forschung e.V., Baden 2011 |
|
| Hero B, Berthold F |
Neuroblastom. |
Leitlinie der Gesellschaft für Pädiatrische Onkologie und Hämatologie AWMF online 2011 |
|
| van den Heuvel-Eibrink MM, van Tinteren H, Rehorst H, Coulombe A, Patte C, de Camargo B, de Kraker J, Leuschner I, Lugtenberg R, Pritchard-Jones K, Sandstedt B, Spreafico F, Graf N, Vujanic GM |
Malignant rhabdoid tumours of the kidney (MRTKs), registered on recent SIOP protocols from 1993 to 2005: A report of the SIOP renal tumour study group. [+] |
Pediatr Blood Cancer 2010 [Epub ahead of print] |
|
| BACKGROUND: Survival data of malignant rhabdoid tumour of the kidney (MRTK) registered in SIOP trials, advocating preoperative chemotherapy, are not available. Aim To evaluate characteristics, response and survival of MRTK patients registered in recent SIOP protocols.
METHODS: An evaluation of all MRTK patients treated from 1993 to 2005 (SIOP trials 93-01 and 2001) was performed. Data were obtained from study specific case record forms and entered centrally in a database.
RESULTS: Hundred and seven patients were identified (57 male), with a median age at diagnosis of 13 months (interquartile range 6-27 months), and a median follow-up time of 60 months. Left and right kidneys were equally affected. Tumour stage distribution was stage I (6%), stage II (22%), stage III (43%), stage IV (22%) and stage V (3%). Stage IV patients included 17 with pulmonary metastasis (8 lung-only) and 12 with multiple organ metastases (bone, brain and liver). Primary surgery was the upfront treatment approach in 22/107 patients (21%), by which 19 patients reached a complete remission (CR). Median difference in tumour volume before and after preoperative chemotherapy was 69 ml (interquartile range: 4.5-158.0, P < 0.0001), indicating marked chemosensitivity. The 5-year event-free survival (EFS) of the total group was 22% (95% CI: 15-33) and overall survival 26% (95% CI: 18-37). Most events (86%) occurred within the first 2 years after diagnosis. Younger age at diagnosis was an important adverse prognostic factors for survival. In contrast, tumour volume at diagnosis, nor volume reduction was associated with outcome.
CONCLUSION: MRTK has a poor outcome especially in young and advanced-stage disease patients. Neither tumour volume at diagnosis, nor pre-operative chemosensitivity are prognostic factors for survival. Pediatr Blood Cancer © 2010 Wiley-Liss, Inc. |
| Hiddemann W, Ritter J, Wormann B, Budde M, Creutzig U, Schellong G, Buchner T, Riehm H |
DNA aneuploidy in children with acute leukemia. |
Klin Pädiatr 1985, 197: 215 |
|
| Hiddemann W, Harbott J, Ludwig W, Ritter J, Nehmer A, Reiter A, Kolkmeyer A, Laing T, Riehm H |
DNA aneuploidy in childhood acute lymphoblastic leukemia. |
Recent Results Cancer Res 1993, 131: 113 |
|
| Hillmann A, Ozaki T, Rübe C, Hoffmann C, Schuck A, Blasius S, Haas A, Jürgens H, Winkelmann W |
Surgical complications after preoperative irradiation of Ewing's sarcoma. |
J Cancer Res Clin Oncol 1997, 123: 57 |
|
| Hing S, Lu Y, Summersgill B, King-Underwood L, Nicholson J, Grundy P, Grundy R, Gessler M, Shipley J, Pritchard-Jones K |
Gain of 1q is associated with adverse outcome in favorable histology Wilms' tumors. |
Am J Pathol 2001, 158: 393 |
|
| Hirsch JF, Sainte Rose C, Pierre-Kahn A, Pfister A, Hoppe-Hirsch E |
Benign astrocytic and oligodendrocytic tumors of the cerebral hemispheres in children. |
J Neurosurg 1989, 70: 568 |
|
| Hitzler JK, Cheung J, Li Y, Scherer SW, Zipursky A |
GATA1 mutations in transient leukemia and acute megakaryoblastic leukemia of Down syndrome. [+] |
Blood 2003 Jun 1; 101: 4301 |
|
| Children with constitutional trisomy 21 (Down syndrome) have an approximately 500-fold increased risk of developing acute megakaryoblastic leukemia (AMKL), a form of acute myeloid leukemia. Unique to newborn infants with Down syndrome is a transient leukemia (TL), also referred to as transient myeloproliferative syndrome, that undergoes spontaneous remission in the majority of cases but in approximately 20% is followed by AMKL later in life. Recently mutations of the gene encoding the hematopoietic transcription factor GATA1 were shown to be specific for AMKL of Down syndrome. Here, we demonstrate that GATA1 mutations are present in blasts of TL and show the identical GATA1 mutation in sequential samples collected from a patient during TL and subsequent AMKL. These findings suggest a model of malignant transformation in Down syndrome AMKL in which GATA1 mutations are an early event and AMKL arises from latent TL clones following initial apparent remission. |
| Hoene V, Fischer M, Ivanova A, Wallach T, Berthold F, Dame C |
GATA factors in human neuroblastoma: distinctive expression patterns in clinical subtypes. [+] |
British journal of cancer 2009, 101: 1481 |
|
| BACKGROUND: The aim of this study is to elucidate the expression patterns of GATA transcription factors in neuroblastoma and the developing sympathetic nervous system (SNS). METHODS: GATA-2, -3 and -4 and their cofactor friend-of-GATA (FOG)-2 were investigated in primary neuroblastoma by immunohistochemistry, real-time RT-PCR (n=73) and microarray analysis (n=251). In addition, GATA-2, -3 and FOG-2 expression was determined by northern-blot hybridisation. In the developing murine SNS, Gata-4 and Fog-2 were examined by immunohistochemistry. RESULTS: Although Gata-2, -3 and Fog-2 are expressed in the developing nervous system, Gata-4 was not detected. In contrast, protein expression of all factors was observed in human neuroblastoma. Northern-blot hybridisation and real-time RT-PCR suggested specific expression patterns of the four genes in primary neuroblastoma, but did not show unequivocal results. In the large cohort examined by microarrays, a significant association of GATA-2, -3 and FOG-2 expression with low-risk features was observed, whereas GATA-4 mRNA levels correlated with MYCN-amplification. CONCLUSION: The transcription factors GATA-2 and -3, which are essential for normal SNS development, and their cofactor FOG-2 are downregulated in aggressive but not in favourable neuroblastoma. In contrast, upregulation of GATA-4 appears to be a common feature of this malignancy and might contribute to neuroblastoma pathogenesis. |
| Hoffmann C, Jabar S, Ahrens S, Rödl R, Rübe C, Winkelmann W, Dunst J, Jürgens H |
Prognosis in Ewing sarcoma patients with initial pathological fractures of the primary tumor site. |
Klin Pädiatr 1995, 207: 151 |
|
| Hoffmann C, Ahrens S, Dunst J, Hillmann A, Winkelmann W, Craft A, Göbel U, Rübe C, Voute P, Harms D, Jürgens H |
Pelvic Ewing sarcoma. A retrospective analysis of 241 cases. |
Cancer 1999, 85: 869 |
|
| Hoffmann C, Gosheger G, Gebert C, Jürgens H, Winkelmann, N |
Functional results and quality of life after treatment of pelvic sarcomas involving the acetabulum. [+] |
J Bone Joint Surg Am 88A; 3/2006, 575 |
|
| Background: Limb salvage after resection of a pelvic sarcoma that involves the acetabulum represents a surgical challenge. The ideal method of reconstruction after acetabular resection remains a subject of controversy, and the outcome in terms of the impact of therapy is still unknown. The purpose of this study was to determine the impact of surgery on health-related quality of life and function after acetabular resection. Methods: Eighty-one patients with a pelvic sarcoma underwent acetabular resection at a single institution. Functional evaluation and quality-of-life examination were performed in forty-five patients, and these patients comprised the study group. Quality of life was assessed with use of the European Organization for Research and Treatment of Cancer core quality-of-life questionnaire. Function was assessed with use of the Musculoskeletal Tumor Society system. Results: The median age of the patients was 30.4 years at the time of the acetabular resection and 35.7 years at the time of follow-up. The median time interval from the index operation to the latest follow-up was sixty-nine months. At the latest follow-up evaluation, the mean functional status score was 14.5 points of a maximum of 30 points. In a comparison of endoprosthetic replacement and hip transposition following resection, significantly better functional results (p = 0.017) and a lower number of complications were found in patients who had a hip transposition. Quality-of-life assessment results were also better in patients with a hip transposition, especially in role functioning (p = 0.043). Conclusions: On the basis of the low complication rate and the good functional and quality-of-life results, hip transposition after acetabular resection seems to be the optimal technique for treating patients with a pelvic sarcoma involving the acetabulum. |
| von Hoff K, Hinkes B, Gerber NU, Deinlein F, Mittler U, Urban C, Benesch M, Warmuth-Metz M, Soerensen N, Zwiener I, Goette H, Schlegel PG, Pietsch T, Kortmann RD, Kuehl J, Rutkowski S |
Long-term outcome and clinical prognostic factors in children with medulloblastoma treated in the prospective randomised multicentre trial HIT'91. [+] |
European journal of cancer (Oxford, England : 1990) 2009, 45: 1209 |
|
| PURPOSE: To analyse long-term outcome and clinical prognostic factors in medulloblastoma. METHODS: We analysed 280 patients with medulloblastoma (3-18 years) included from 1991 to 1997 in the randomised multicentre trial HIT'91 comparing pre-('sandwich') and postradiation ('maintenance') chemotherapy (median follow-up of survivors for 10 years). RESULTS: In 187 patients with complete staging, overall survival (OS) was higher after maintenance compared to sandwich treatment for M0 (10-year OS 91% and 62%, p=0.001) and M1 patients (10-year OS 70% and 34%, p=0.020). In M2/3 disease, 10-year OS was 42% and 45%. Incomplete staging, metastases, younger age and sandwich chemotherapy were independent adverse risk factors. Twelve percent of all relapses (13 of 107) occurred after more than five years, and 12 patients had secondary neoplasms. CONCLUSIONS: After maintenance therapy, long-term survival was excellent in fully assessable patients with localised medulloblastoma, and favourable for M1 patients. Patients should be followed longer for late relapses and secondary tumours. |
| von Hoff K, Hartmann W, von Bueren AO, Gerber NU, Grotzer MA, Pietsch T, Rutkowski S |
Large cell/anaplastic medulloblastoma: outcome according to myc status, histopathological, and clinical risk factors. [+] |
Pediatric blood & cancer 2010, 54: 369 |
|
| PURPOSE: To evaluate the prognostic impact of large cell/anaplastic (LC/A) histology together with molecular and clinical risk factors in childhood medulloblastoma. METHODS: Three consecutive prospective medulloblastoma trials were screened for patients with the histological diagnosis of LC/A medulloblastoma. Tumors were considered as LC/A if they displayed areas of severe cytological anaplasia or a significant or predominant large cell component. Histology was centrally confirmed. Genomic DNA amplification of c-myc and n-myc, and mRNA expression of c-myc and trkC were analyzed. RESULTS: Twenty-eight patients with LC/A medulloblastoma with a median age of 6.1 years (1.4-16.5 years) and a median follow-up of 4.5 years were identified (5% of all medulloblastoma). Four-year event-free (EFS) and overall survival (OS) were 58% and 67%. Young age and metastases (n = 13, 4-year EFS 31% vs. 82% in 15 children >4 years and without metastases, P = 0.001), large cell histology (n = 9, 4-year EFS 22% vs. 75%, P = 0.005) and c-myc amplification (n = 9, 4-year EFS 22% vs. 89%, P < 0.0001) were negative prognostic factors. C-myc amplification was highly correlated with young age (P < 0.001), metastases (P = 0.002) and large cell histology (P = 0.007). Outcome of 12 patients with severely anaplastic tumors without these risk factors was not impaired (4-year EFS 86%). CONCLUSION: In a subgroup of patients without clinical and molecular risk factors outcome was favorable despite severely anaplastic histology. In contrast, c-myc amplification and large-cell histology were associated with an inferior outcome. Intensified treatment strategies should be considered for children with LC/A medulloblastoma and these characteristics. |
| Hof J, Krentz S, van Schewick C, Körner G, Shalapour S, Rhein P, Karawajew L, Ludwig WD, Seeger K, Henze G, von Stackelberg A, Hagemeier C, Eckert C, Kirschner-Schwabe R |
Mutations and Deletions of the TP53 Gene Predict Nonresponse to Treatment and Poor Outcome in First Relapse of Childhood Acute Lymphoblastic Leukemia. [+] |
J Clin Oncol 2011, [Epub ahead of print] |
|
| PURPOSE In the clinical management of children with relapsed acute lymphoblastic leukemia (ALL), treatment resistance remains a major challenge. Alterations of the TP53 gene are frequently associated with resistance to chemotherapy, but their significance in relapsed childhood ALL has remained controversial because of small studies. PATIENTS AND METHODS Therefore, we systematically studied 265 first-relapse patients enrolled in the German Acute Lymphoblastic Leukemia Relapse Berlin-Frankfurt-Münster 2002 (ALL-REZ BFM 2002) trial for sequence and copy number alterations of the TP53 gene by using direct sequencing and multiplex ligation-dependent probe amplification. Results We observed copy number and sequence alterations of TP53 in 12.4% (27 of 218) of patients with B-cell precursor ALL and 6.4% (three of 47) of patients with T-cell ALL relapse. Backtracking to initial ALL in 23 matched samples revealed that 54% of all TP53 alterations were gained at relapse. Within B-cell precursor ALL, TP53 alterations were consistently associated with nonresponse to chemotherapy (P < .001) and poor event-free survival (P < .001) and overall survival rates (P = .002). TP53 alterations also had a significant impact on survival within intermediate-risk (S2) and high-risk (S3/S4) relapse patients (P = .007 and P = .019, respectively). This prognostic significance of TP53 alterations was confirmed in multivariate analysis. Besides their clinical impact, TP53 alterations were associated with a higher fraction of leukemic cells in S/G(2)-M phase of the cell cycle at relapse diagnosis. CONCLUSION Alterations of the TP53 gene are of particular importance in the relapse stage of childhood ALL, in which they independently predict high risk of treatment failure in a significant number of patients. Therefore, they will aid in future risk assessment of children with ALL relapse. |
| von Hoff K, Hinkes B, Dannenmann-Stern E, von Bueren AO, Warmuth-Metz M, Soerensen N, Emser A, Zwiener I, Schlegel PG, Kuehl J, Frühwald MC, Kortmann RD, Pietsch T, Rutkowski S |
Frequency, risk-factors and survival of children with atypical teratoid rhabdoid tumors (AT/RT) of the CNS diagnosed between 1988 and 2004, and registered to the German HIT database. [+] |
Pediatric blood & cancer 2011, 1; 57: 978 |
|
| To analyze the frequency, prognostic factors, and outcome of children with atypical teratoid/rhabdoid tumors (AT/RT), a rare and highly malignant embryonal brain tumor. |
| Hohmann C, Borgmann A, Keil T |
Re: Induced abortions in Danish cancer survivors: a population-based cohort study. |
J Natl Cancer Inst 2011, 20; 103: 698 |
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| Hohmann C, Borgmann-Staudt A, Rendtorff R, Reinmuth S, Holzhausen S, Willich SN, Henze G, Goldbeck L, Keil T |
Patient counselling on the risk of infertility and its impact on childhood cancer survivors: results from a national survey. [+] |
Journal of psychosocial oncology 2011, 29: 274 |
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| Fertility can be impaired by radiation and chemotherapy among childhood cancer survivors. Therefore, timely and adequate patient counselling about the risk of infertility and preservation methods is needed. The primary study objective was to assess remembered counselling among childhood cancer survivors. As a second objective, the impact of lacking patient counselling on offspring-related attitudes and behaviour was examined. Counselling regarding the late effects of gonadotoxicity that could be recalled by patients was assessed using a questionnaire sent by the German Childhood Cancer Registry. The questionnaire was answered by 2754 adult childhood cancer survivors (53.1% female, mean = 25.7 years). The proportion of patients who could not remember patient counselling about the late effects of chemo-/radiotherapy on fertility decreased significantly over time. In 1980 to 1984 67%, in 2000 to 2004 50% of the patients reported no memories of counselling (p < .001). Counselled patients feared significantly less that their children may have an increased cancer risk (4.4% vs. 6.7%, p = .03). They were also more likely to undergo fertility testing than patients who could not recall counselling (odds ratio = 2.91, 95% confidence interval [2.12, 3.99]). Patients reported an increased memory of patient counselling over the past 25 years. Still, a 50% rate of recalled counselling shows an ongoing need for adequate and especially sustainable counselling of paediatric cancer patients about infertility and other long-term adverse treatment effects. Those who reported a lack of counselling had offspring-related fears more frequently, which stopped them from having children. |
| Holter W, Ressmann G, Grois N, Lehner M, Parolini O, Gadner H |
Normal monocyte-derived dendritic cell function in patients with Langerhans-cell-histiocytosis. [+] |
Medical and pediatric oncology 2002, 39: 181 |
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| BACKGROUND: Langerhans cell histiocytosis (LCH) is a histiocytic disease, characterized by the lesional accumulation of dendritic Langerhans cells together with T cells and eosinophils. The cause of this disease is unknown. Langerhans cells are bone marrow-derived dendritic cells (DCs), which can develop from CD34(+) hematopoietic progenitor cells as well as from monocytes. PROCEDURE: To test whether LCH patients have a general functional defect present in cells of their DC lineage, we generated immature DCs by culturing monocytes from nine patients with single- or multisystem LCH with GM-CSF and IL-4, and analyzed their phenotype and function before and after an in vitro maturation stimulus. Immature DCs were analyzed for their phenotype and cytokine production, DCs matured in response to TNF-alpha plus PGE(2) were analyzed for their phenotype, their stimulatory capacity in MLR, cell aggregation, and activation-induced apoptosis. RESULTS: In summary, no difference was found between both immature as well as mature DCs generated from patients and controls regarding the expression of CD1a, CD80, CD86, MHC class I, and MCH class II antigens. Similarly, no difference was found regarding IL-10, -12, and TNF-alpha production, as well as regarding cell aggregation and apoptosis in response to external stimuli. CONCLUSIONS: The absence of gross functional abnormalities in DCs generated from monocytes from patients with LCH makes the existence of a severe functional defect affecting all cells of the DC lineage in these patients unlikely. |
| Holleman A, Den Boer M, Kazemier K, Janka-Schaub G, Pieters R |
Resistance to different classes of drugs is associated with impaired apoptosis in childhood acute lymphoblastic leukemia. |
Blood 2003, 102: 4541 |
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| Holleman A, Cheok MH, den Boer ML, Yang W, Veerman AJ, Kazemier KM, Pei D, Cheng C, Pui CH, Relling MV, Janka-Schaub GE, Pieters R, Evans WE |
Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment. [+] |
The New England journal of medicine 2004, 351: 533 |
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| BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) is curable with chemotherapy in approximately 80 percent of patients. However, the cause of treatment failure in the remaining 20 percent of patients is largely unknown. METHODS: We tested leukemia cells from 173 children for sensitivity in vitro to prednisolone, vincristine, asparaginase, and daunorubicin. The cells were then subjected to an assessment of gene expression with the use of 14,500 probe sets to identify differentially expressed genes in drug-sensitive and drug-resistant ALL. Gene-expression patterns that differed according to sensitivity or resistance to the four drugs were compared with treatment outcome in the original 173 patients and an independent cohort of 98 children treated with the same drugs at another institution. RESULTS: We identified sets of differentially expressed genes in B-lineage ALL that were sensitive or resistant to prednisolone (33 genes), vincristine (40 genes), asparaginase (35 genes), or daunorubicin (20 genes). A combined gene-expression score of resistance to the four drugs, as compared with sensitivity to the four, was significantly and independently related to treatment outcome in a multivariate analysis (hazard ratio for relapse, 3.0; P=0.027). Results were confirmed in an independent population of patients treated with the same medications (hazard ratio for relapse, 11.85; P=0.019). Of the 124 genes identified, 121 have not previously been associated with resistance to the four drugs we tested. CONCLUSIONS: Differential expression of a relatively small number of genes is associated with drug resistance and treatment outcome in childhood ALL. |
| Holleman A, den Boer ML, Kazemier KM, Beverloo HB, von Bergh AR, Janka-Schaub GE, Pieters R |
Decreased PARP and procaspase-2 protein levels are associated with cellular drug resistance in childhood acute lymphoblastic leukemia. [+] |
Blood 2005, 106: 1817 |
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| Drug resistance in childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) is associated with impaired ability to induce apoptosis. To elucidate causes of apoptotic defects, we studied the protein expression of Apaf-1, procaspases-2, -3, -6, -7, -8, -10, and poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) in cells from children with acute lymphoblastic leukemia (ALL; n = 43) and acute myeloid leukemia (AML; n = 10). PARP expression was present in all B-lineage samples, but absent in 4 of 15 T-lineage ALL samples and 3 of 10 AML cases, which was not caused by genomic deletions. PARP expression was a median 7-fold lower in T-lineage ALL (P < .001) and 10-fold lower in AML (P < .001) compared with B-lineage ALL. PARP expression was 4-fold lower in prednisolone, vincristine and L-asparaginase (PVA)-resistant compared with PVA-sensitive ALL patients (P < .001). Procaspase-2 expression was 3-fold lower in T-lineage ALL (P = .022) and AML (P = .014) compared with B-lineage ALL. In addition, procaspase-2 expression was 2-fold lower in PVA-resistant compared to PVA-sensitive ALL patients (P = .042). No relation between apoptotic protease-activating factor 1 (Apaf-1), procaspases-3, -6, -7, -8, -10, and drug resistance was found. In conclusion, low baseline expression of PARP and procaspase-2 is related to cellular drug resistance in childhood acute lymphoblastic leukemia. |
| Hollink IH, Zwaan CM, Zimmermann M, Arentsen-Peters TC, Pieters R, Cloos J, Kaspers GJ, de Graaf SS, Harbott J, Creutzig U, Reinhardt D, van den Heuvel-Eibrink MM, Thiede C |
Favorable prognostic impact of NPM1 gene mutations in childhood acute myeloid leukemia, with emphasis on cytogenetically normal AML. [+] |
Leukemia 2009, 23: 262 |
|
| Nucleophosmin (NPM1) mutations occur frequently in adult cytogenetically normal acute myeloid leukemia (CN-AML) and confer favorable outcome. We investigated the frequency and prognostic significance of NPM1 mutations in childhood AML (n=298), specifically focusing on the CN-AML subgroup (n=100). Mutations were found in 8.4%, and clustered significantly in the CN-AML subgroup (22%). No mutations were found in patients below the age of 3 years; in CN-AML, there was an increasing incidence above this age. In the overall group, NPM1 mutations conferred an independent favorable prognostic impact on event-free survival (5-year pEFS 66 vs 39%; P=0.02), which did not translate into a significantly better overall survival (5-year pOS 68 vs 56%; P=0.30). However, when the favorable cytogenetic subgroups [inv(16) and t(8;21)] were excluded from the NPM1 wild-type group, the difference in pOS was borderline statistically significant (68 vs 45%; P=0.07). In the CN-AML cohort, NPM1 mutations were an independent prognostic factor on pEFS (80 vs 39%; P=0.01), and pOS (85 vs 60%; P=0.06), which was not influenced by FLT3/ITD. However, in NPM1 wild-type CN-AML, FLT3/ITD-positive patients had a significantly worse outcome (pEFS 48 vs 18%; P<0.001). We conclude that NPM1 mutations confer a favorable prognosis in childhood AML and in CN-AML in particular. |
| Holzhauer S, Goldenberg NA, Junker R, Heller C, Stoll M, Manner D, Mesters R, Krümpel A, Stach M, Nowak-Göttl U |
Inherited thrombophilia in children with venous thromboembolism and the familial risk of thromboembolism: an observational study. [+] |
Blood 2012, Epub ahead of print |
|
| Screening for inherited thrombophilia (IT) is controversial, individuals at high risk for venous thromboembolism (VTE) who benefit from screening need to be identified. We tested 533 first and second degree relatives of 206 pediatric VTE patients for IT (antithrombin, protein C, protein S, factor V G1691A, factor II G20210A) and determined the incidence of symptomatic VTE relative to their IT status. The risk for VTE was significantly increased among family members with, versus without, IT (Hazard Ratio [HR] 7.6, 95% CI, 4.00-14.45]; P<0.001) and highest among carriers of antithrombin, protein C, or protein S deficiency (HR 25.7, 95% CI12.2-54.2]; P<0.001). Annual incidences of VTE were 2.82% (95% confidence interval [95%CI], 1.63-4.80%) among family members found to be carriers of antithrombin, protein C, or protein S deficiency, 0.42% (0.12-0.53%) for factor II G202010A, 0.25% (0.12-0.53%) for factor V G1691A, and 0.10% (0.06-0.17%) in relatives with no IT. Given the high absolute risk of VTE in relatives with protein C, protein S and antithrombin deficiency we suggest screening for these forms of hereditary thrombophilia in children with VTE and their relatives. Interventional studies are required to assess if thromboembolism can be prevented in this high risk population. |
| Hongo T, Yajima S, Sakurai M, Horikoshi Y, Hanada R |
In vitro drug sensitivity testing can predict induction failure and early relapse of childhood acute lymphoblastic leukemia. |
Blood 1997, 89: 2959−2965 |
|
| Horwitz M, Benson KF, Person RE, Aprikyan AG, Dale DC |
Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis. [+] |
Nature genetics 1999, 23: 433 |
|
| Human cyclic haematopoiesis (cyclic neutropenia, MIM 162800) is an autosomal dominant disease in which blood-cell production from the bone marrow oscillates with 21-day periodicity. Circulating neutrophils vary between almost normal numbers and zero. During intervals of neutropenia, affected individuals are at risk for opportunistic infection. Monocytes, platelets, lymphocytes and reticulocytes also cycle with the same frequency. Here we use a genome-wide screen and positional cloning to map the locus to chromosome 19p13.3. We identified 7 different single-base substitutions in the gene (ELA2) encoding neutrophil elastase (EC 3. 4.21.37, also known as leukocyte elastase, elastase 2 and medullasin), a serine protease of neutrophil and monocyte granules, on unique haplotypes in 13 of 13 families as well as a new mutation in a sporadic case. Neutrophil elastase (a 240-aa mature protein predominantly found in neutrophil granules) is the target for protease inhibition by alpha1-antitrypsin, and its unopposed release destroys tissue at sites of inflammation. We hypothesize that a perturbed interaction between neutrophil elastase and serpins or other substrates may regulate mechanisms governing the clock-like timing of haematopoiesis. |
| von Hornstein S, Kortmann RD, Pietsch T, Emser A, Warmuth-Metz M, Soerensen N, Straeter R, Graf N, Thieme B, Gnekow AK |
Impact of chemotherapy on disseminated low-grade glioma in children and adolescents: report from the HIT-LGG 1996 trial. [+] |
Pediatric blood & cancer 2011 Jul 1; 56: 1046 |
|
| We describe demographic data of disseminated childhood low-grade glioma (DLGG) prospectively recruited in the HIT-LGG 1996 study and evaluate the impact of primary chemotherapy (CT) on the outcome of these tumors, which have previously only been described in small and retrospective series. |
| Zur, Hoser G, Reiter A, Welte K, Sykora K |
Application of long PCR to detect t(8;14)(q24;q32) translocations in childhood Burkitt's lymphoma and B-ALL. |
Ann Oncol 1997, 8 Suppl 1: 31-5: 31 |
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| Hotfilder M, Lanvers C, Jürgens H, Boos J, Vormoor J |
c-KIT-expressing Ewing tumour cells are insensitive to imatinib mesylate (STI571). |
Cancer Chemother Pharmacol 2002, 50: 167 |
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| Hotfilder M, Sondermann P, Senss A, van Valen F, Jürgens H, Vormoor J |
PI3K/AKT is involved in mediating survival signals that rescue Ewing tumour cells from fibroblast growth factor 2-induced cell death. [+] |
British journal of cancer 2005, 92: 705 |
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| While in vitro studies had shown that fibroblast growth factor 2 (FGF2) can induce cell death in Ewing tumours, it remained unclear how Ewing tumour cells survive in vivo within a FGF2-rich microenvironment. Serum- and integrin-mediated survival signals were, therefore, studied in adherent monolayer and anchorage-independent colony cell cultures. In a panel of Ewing tumour cell lines, either adhesion to collagen or exposure to serum alone only had a minor protective effect against FGF2. However, both combined led to complete resistance to 5 ng ml(-1) FGF2 in three of four FGF2-sensitive cell lines (RD-ES, RM-82 and WE-68), and to an increased survival as compared to other culture conditions in TC-71 cells. Inhibition studies with LY294002 demonstrated that the serum signal is mediated via the phosphoinositide 3-OH kinase/AKT pathway. Thus, Ewing tumour cells escape FGF2-induced cell death by modulating FGF2 signalling. The tumour microenvironment provides the necessary survival signals by integrin-mediated adhesion and soluble serum factor(s). These survival signals warrant further investigation as a potential resistance mechanism to other apoptosis-inducing agents in vivo. |
| Houston SK, Murray TG, Wolfe SQ, Fernandes CE |
Current update on retinoblastoma. |
International ophthalmology clinics 2011, 51: 77 |
|
| Howe GR, Burch JD, Chiarelli AM, Risch HA, Choi BC |
An exploratory case-control study of brain tumors in children. |
Cancer Res 1989, 49: 4349 |
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| Hsu JL, Glaser SL |
Epstein-Barr virus-associated malignancies: epidemiologic patterns and etiologic implications. |
Crit Rev Oncol Hematol 2000, 34: 27 |
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| Hubner S, Cazzaniga G, Flohr T, van der, Konrad M, Potschger U, Basso G, Schrappe M, van Dongen J, Bartram C, Biondi A, Panzer-Grumayer E |
High incidence and unique features of antigen receptor gene rearrangements in TEL-AML1-positive leukemias. |
Leukemia 2004, 18: 84 |
|
| Hubeek I, Peters GJ, Broekhuizen AJ, Talianidis I, Sigmond J, Gibson BE, Creutzig U, Giaccone G, Kaspers GJ |
Immunocytochemical detection of deoxycytidine kinase in haematological malignancies and solid tumours. [+] |
Journal of clinical pathology 2005, 58: 695 |
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| BACKGROUND: Deoxycytidine kinase (dCK) is responsible for the activation of several clinically important deoxynucleoside analogues used for the treatment of haematological and solid malignancies. AIM: To measure dCK expression in tumour cells from different origins. METHOD: A rabbit antihuman dCK antibody was used for the immunocytochemical detection of dCK expression in three leukaemic cell lines (HL60, U937, and CCRF-CEM) and 97 patient samples (paediatric acute myeloid leukaemia (AML) and lymphoid leukaemia (ALL), retinoblastoma, paediatric brain tumours, and adult non-small cell lung cancer (NSCLC)). RESULTS: CCRF-CEM, U937, and HL60 cells stained positively for dCK and the degree of expression correlated with dCK activity. dCK expression varied between tumour types and between individual patients within one tumour type. dCK was located predominantly in the cytoplasm. The staining intensity was scored as negative (0), low (1+), intermediate (2+), or high (3+). Expression of dCK was high in AML blasts. In contrast, brain tumour samples expressed low amounts of dCK. dCK staining ranged from low (1+) to high (3+) in ALL blasts, retinoblastoma, and NSCLC tissue samples. Staining was consistent (interobserver variability, 88%; kappa = 0.83) and specific. Western blotting detected the dCK protein appropriately at 30 kDa, without additional bands. CONCLUSIONS: Immunocytochemistry is an effective and reliable method for determining the expression of dCK in patient samples and requires little tumour material. This method enables large scale screening of dCK expression in tumour samples. |
| Hubertus J, Boxberger N, Redlich A, von Schweinitz D, Vorwerk P |
Surgical aspects in the treatment of adrenocortical carcinomas in children: data of the GPOH-MET 97 trial. [+] |
Klinische Padiatrie 2012, 224: 143 |
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| Adrenocortical carcinomas (ACCs) are a rare entity, with an incidence of 1.5 per million population per year. The prognosis of ACC is poor. Complete surgical resection is essential for a curative approach and significantly determines overall prognosis. Tumor resection is sophisticated and complicated by the vulnerability of the tumor and its invasive growth. Chemotherapy and Mitotane are additional therapeutic approaches that are combined with surgery in an interdisciplinary strategy. In this study, 59 patients between 2 months and 18 years of age with histologically verified ACC were analyzed retrospectively with respect to oncosurgical aspects. Patients were registered in the GPOH-MET 97 trial of the Society of Pediatric Oncology and Haematology. Preoperative management, factors influencing surgical severity, and operative complications were assessed.The gender ratio was 1:2 (m:f). A total of 58 patients showed increased hormonal activity and associated clinical signs of hormonal excess. Tumor volume was ≥ 300 mL in 25 patients. These patients showed an increased rate of operative complications and a poorer overall survival (OS) rate (p<0.01). A total of 14 patients showed metastatic spread, particularly to the lungs and lymph nodes. Biopsy of the tumor was performed in 12 patients. Tumor rupture occurred in 11 patients. Preoperative biopsy and/or experienced tumor rupture were associated with poorer OS rate. R2 resection only was achievable in 5 patients, and surgery was not feasible in 3 patients.In conclusion, since most of the pediatric ACC are hormone active and can be diagnosed clinically, the need of a tumor biopsy has to be discussed critically. Thorough pre- and perioperative management is essential for oncosurgical success. |
| Hudson MM, Poquette CA, Lee J, Greenwald CA, Shah A, Luo X, Thompson EI, Wilimas JA, Kun LE, Crist WM |
Increased mortality after successful treatment for Hodgkin's disease. |
J Clin Oncol 1998, 16: 3592 |
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| Hughes M, Marsden HB, Palmer MK |
Histologic patterns of neuroblastoma related to prognosis and clinical staging. |
Cancer 1974, 34: 1706 |
|
| Hug K, Grize L, Seidler A, Kaatsch P, Schüz J |
Parental occupational exposure to extremely low frequency magnetic fields and childhood cancer: a German case-control study. [+] |
American journal of epidemiology 2010, 171: 27 |
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| Extremely low frequency magnetic fields (ELF-MFs) have been classified as possibly carcinogenic to humans by the International Agency for Research on Cancer. The authors investigated, in a population-based case-control study in Germany, if children whose parents were exposed preconceptionally at work to ELF-MFs had an increased risk of developing cancer. Cases aged 0-14 years were ascertained from the German Childhood Cancer Registry. Controls were selected from local resident registration offices. The parental occupational history was recorded in questionnaires and telephone interviews, and preconceptional magnetic field exposure was estimated according to a job-exposure matrix. The analysis included 2,382 controls and 2,049 cases (846 children with acute leukemia, 159 children with non-Hodgkin's lymphoma, 444 children with central nervous system tumors, and 600 children with other solid tumors). Frequency-matched conditional logistic regression models revealed no increased cancer risks in children whose fathers were occupationally exposed to magnetic fields above 0.2 microT. Additionally, there was no evidence for a risk increase at magnetic field levels exceeding 1 microT. Based on much smaller numbers, maternal occupational exposure was also not related to increased cancer risks. In this large case-control study, the risk of childhood cancer was not linked to preconceptional parental ELF-MF exposure. |
| Humpl T |
Neuroblastome, in: Gutjahr P (Hrsg.): Krebs bei Kindern und Jugendlichen. |
Deutscher Ärzte-Verlag Köln 5. Aufl. 2004, 347 |
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| Hunold A, Weddeling N, Paulussen M, Ranft A, Liebscher C, Jürgens H |
Topotecan and cyclophosphamide in patients with refractory or relapsed Ewing tumors. |
Pediatric blood & cancer 2006, 47: 795 |
|
| Hundsdoerfer P, Dietrich I, Schmelz K, Eckert C, Henze G |
XIAP expression is post-transcriptionally upregulated in childhood ALL and is associated with glucocorticoid response in T-cell ALL. [+] |
Pediatric blood & cancer 2010, 55: 260 |
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| BACKGROUND: Resistance to glucocorticoid induced apoptosis is one of the major risk factors for relapse and poor outcome in childhood acute lymphoblastic leukemia (ALL). Overexpression of X-linked inhibitor of apoptosis protein (XIAP) has been shown to be associated with chemotherapy resistance in several malignancies. PROCEDURE: XIAP protein and mRNA expression were determined in leukemic blasts of 51 childhood ALL patients and normal bone marrow mononuclear cells. XIAP expression was correlated with glucocorticoid response and outcome. RESULTS: XIAP protein but not mRNA expression was found to be highly increased in childhood ALL compared to control bone marrow mononuclear cells (MNC) (median: 3.5 vs. 0.14 ng/10(5) MNC, P < 0.0001) indicating a post-transcriptional regulation of XIAP expression. In patients with T-cell ALL, poor prednisone response was associated with increased XIAP expression (median: 2.8 in good vs. 5.8 in poor responders; P = 0.005). Similarly, T-cell ALL patients suffering adverse events showed higher initial XIAP levels than patients in continuous complete remission (CCR) (median: 2.7 in patients in CCR vs. 5.6 in patients suffering adverse events; P = 0.007). XIAP inhibition using the low-molecular-weight SMAC mimetic LBW242 resulted in a significant increase of prednisone-induced apoptosis in vitro. CONCLUSION: In childhood ALL compared to control bone marrow, the expression of the apoptosis inhibitor XIAP is highly increased by post-transcriptional regulation. The association with poor in vivo glucocorticoid response and outcome in T-cell ALL suggests XIAP inhibition as a promising novel approach for the treatment of resistant ALL. |
| Hupp M, Falkenstein F, Bison B, Mirow C, Krauß J, Gnekow A, Solymosi L, Warmuth-Metz M |
Infarction following chiasmatic low grade glioma resection. [+] |
Child's nervous system 2011,Epub ahead of print |
|
| INTRODUCTION: The current SIOP (International Society for Paediatric Oncology)-LGG (low grade glioma) study protocol allows chiasmatic tumours identified as LGG on the basis of neuroradiological characteristics to be treated without histological verification. As some tumours do not respond well to treatment, the search for molecular tissue markers will gain importance for future studies. Anecdotal observations of infarctions after surgery for chiasmatic tumours during central reviewing initiated this study. MATERIALS AND METHODS: In 84 patients, histology was obtained during 102 interventions in the years 1992-2009 by 33 biopsies, 67 partial/subtotal and 2 total resections. Median age at the time of operation was 5 years (mean 5 years 11 months). We could identify 17 infarctions following partial resection of chiasmatic LGG. Biopsies were not complicated by infarction. Children developing infarction were considerably younger (median 3 years; mean 4 years 5 months) than the patients without infarction (median 5 years 4 months; mean 6 years 2 months). A total of 51 patients with cerebellar LGG (median 7 years; mean 7 years 4 months) served as a control group, with 65 surgical procedures (2 biopsies, 22 partial/subtotal resections and 41 total resections) performed in the years 2004-2009. Only one total resection (1.5%) in this group was followed by infarction. CONCLUSION: Partial/subtotal resections of chiasmatic LGG in our study population bear a considerable risk for infarction especially in young children. As there is currently no evidence for a better outcome after tumour resection, we suggest that the sampling of tumour tissue should be performed via biopsies whenever possible. |
| Häberle H |
Stationäre familienorientierte Nachsorge, in Schwarz R, Zettl S: Praxis der psychosozialen Onkologie. |
Verlag für Medizin Fischer 1993 |
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| Häberle H, Schwarz R, Mathes L |
Familienorientierte Betreuung bei krebskranken Kindern und Jugendlichen. |
Prax Kinderpsych 1997, 46: 406 |
|
| Häberle B, Hero B, Berthold F, von Schweinitz D |
Characteristics and outcome of thoracic neuroblastoma. |
Eur J Pediatr Surg 2002, 12: 145 |
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