| Autor(en) |
Titel |
Quelle |
Links |
| Da Costa L, Tchernia G, Gascard P, Lo A, Meerpohl J, Niemeyer C, Chasis, JA, Fixler J, Mohandas, N |
Nucleolar localization of RPS19 protein in normal cells and mislocalization due to mutations in the nucleolar localization signals in 2 Diamond-Blackfan anemia patients: potential insights into pathophysiology. |
Blood 2003, 101: 5039-45. Epub 2003 Feb 13. |
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| Ribosomal protein S19 (RPS19) is frequently mutated in Diamond-Blackfan anemia (DBA), a rare congenital hypoplastic anemia. Recent studies have shown that RPS19 expression decreases during terminal erythroid differentiation. Currently no information is available on the subcellular localization of normal RPS19 and the potential effects of various RPS19 mutations on cellular localization. In the present study, using wild-type and mutant RPS19 cDNA, we explored the subcellular distribution of normal and mutant proteins in a fibroblast cell line (Cos-7 cells). RPS19 was detected primarily in the nucleus, and more specifically in the nucleoli, where RPS19 colocalized with the nucleolar protein nucleolin. Using various N-terminal and C-terminal deletion constructs, we identified 2 nucleolar localization signals (NoSs) in RPS19: the first comprising amino acids Met1 to Arg16 in the NH2-terminus and the second comprising Gly120 to Asn142 in the COOH-terminus. Importantly, 2 mutations identified in DBA patients, Val15Phe and Gly127Gln, each of which localized to 1 of the 2 NoS, failed to localize RPS19 to the nucleolus. In addition to their mislocalization, there was a dramatic decrease in the expression of the 2 mutant proteins compared to the wild type. This decrease in protein expression was specific for the mutant RPS19, since expression of other proteins was normal. The present findings enable us to document the nucleolar localization signals in RPS19 and help define the phenotypic consequences of some mutations in RPS19 in DBA. |
| Da Costa L, Leblanc T, Mohandas N |
Diamond-Blackfan anemia. |
Blood 2020, 136: 1262 |
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| Diamond-Blackfan anemia (DBA) was the first ribosomopathy described and is a constitutional inherited bone marrow failure syndrome. Erythroblastopenia is the major characteristic of the disease, which is a model for ribosomal diseases, related to a heterozygous allelic variation in 1 of the 20 ribosomal protein genes of either the small or large ribosomal subunit. The salient feature of classical DBA is a defect in ribosomal RNA maturation that generates nucleolar stress, leading to stabilization of p53 and activation of its targets, resulting in cell-cycle arrest and apoptosis. Although activation of p53 may not explain all aspects of DBA erythroid tropism, involvement of GATA1/HSP70 and globin/heme imbalance, with an excess of the toxic free heme leading to reactive oxygen species production, account for defective erythropoiesis in DBA. Despite significant progress in defining the molecular basis of DBA and increased understanding of the mechanistic basis for DBA pathophysiology, progress in developing new therapeutic options has been limited. However, recent advances in gene therapy, better outcomes with stem cell transplantation, and discoveries of putative new drugs through systematic drug screening using large chemical libraries provide hope for improvement. |
| Daecke W, Bielack S, Martini AK, Ewerbeck V, Jürgens H, Kotz R, Winkelmann W, Kabisch H, Kevric M, Bernd L |
Osteosarcoma of the hand and forearm: experience of the Cooperative Osteosarcoma Study Group. |
Annals of surgical oncology : the official journal of the Society of Surgical Oncology 2005, 12: 322 |
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| BACKGROUND: Osteosarcoma is extremely rare in the hand and forearm. Therefore, only limited data are available for planning treatment or predicting the outcome and prognosis of osteosarcoma in the peripheral upper extremity. METHODS: Epidemiological, clinical, and histopathologic data were analyzed in 39 patients with osteosarcoma of the forearm or hand who were enrolled in studies of the Cooperative German-Austrian-Swiss Osteosarcoma Study Group from 1977 to December 2000. In patients with high-grade osteosarcoma, the treatment entailed surgical resection in combination with chemotherapy, whereas patients with low-grade osteosarcoma underwent only surgery. RESULTS: The 5-year overall survival rate among the 33 patients with high-grade central osteosarcoma of the distal upper extremity was 86.2% +/- 6.4%. The 5-year event-free survival rate was 65.4% +/- 9.6%. Five of the eight patients with secondary metastases were in remission at the time of analysis. Four patients died of their disease, and two patients died of chemotherapy-related complications. The mean overall survival rate was 88.0% +/- 6.5% in patients treated by wide or radical tumor resection and was 75.0% +/- 21.7% in patients with nonwide margins of resection. Whether amputation or local resection was performed had no significant influence on the prognosis. All six patients whose osteosarcoma was not classified as high-grade central osteosarcoma were in remission at the time of analysis. CONCLUSIONS: The results demonstrate a remarkably high survival rate for patients with high-grade osteosarcoma of the hand and forearm and confirm that multiagent chemotherapy in combination with wide excision is a highly effective treatment for this malignant tumor. |
| Daecke W, Ahrens S, Jürgens H, Martini AK, Ewerbeck V, Kotz R, Winkelmann W, Bernd L |
Ewing's sarcoma and primitive neuroectodermal tumor of hand and forearm. Experience of the Cooperative Ewing's Sarcoma Study Group. |
Journal of cancer research and clinical oncology 2005, 131: 219 |
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| PURPOSE: Because Ewing's sarcoma (EWS) is extremely rare in the hand and forearm, only limited data are available for planning treatment or predicting prognosis. METHODS: Data of 33 patients with EWS of the forearm or hand who were enrolled in studies of the German Association for Paediatric Oncology/Haematology and the European Intergroup Cooperative Ewing's Sarcoma Study Group were analyzed. Patients received neoadjuvant multi-agent chemotherapy according to the valid protocol. Local treatment consisted of surgery (n=7), radiotherapy (n=7), or a combination of both (n=19). RESULTS: The 5/10-year overall survival rate was 84.1% (95% CI: 71.2-96.9)/74.1% (95% CI: 56.8-91.5), and both 5/10-year event-free survival rate were 71.3% (95% CI: 55.4-87.1). Only one of seven patients with secondary metastases was in remission at the time of analysis. One patient with local recurrence and another with primary metastases died. Altogether, eight of 33 patients died of their disease. The event-free survival rate was 80.6% in patients with good response to chemotherapy and 33.3% in patients with poor response. Surgery in combination with radiotherapy achieved a higher survival rate compared with radiotherapy or surgery alone. One out of two patients with non-wide margins of resection died of disease. CONCLUSIONS: The results demonstrate a remarkably high survival rate for patients with EWS of the hand and forearm. |
| Daldrup-Link H, Franzius C, Link T, Laukamp D, Sciuk J, Jürgens H, Schober O, Rummeny E |
Whole-body MR imaging for detection of bone metastases in children and young adults. |
AJR Am J Roentgenol 2001, 177: 229 |
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| Dale DC, Bolyard AA, Aprikyan A |
Cyclic neutropenia. |
Seminars in hematology 2002, 39: 89 |
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| Cyclic neutropenia is a rare hematologic disorder, characterized by repetitive episodes of fever, mouth ulcers, and infections attributable to recurrent severe neutropenia. Fluctuations in blood cells are due to oscillatory production of cells by the bone marrow. Recent genetic, molecular, and cellular studies have shown that autosomal-dominant cyclic neutropenia and sporadic cases of this disease are due to a mutation in the gene for neutrophil elastase (ELA2), located at 19p13.3. This enzyme is synthesized in neutrophil precursors early in the process of primary granule formation. It is currently presumed that the mutant neutrophil elastase functions aberrantly within the cells to accelerate apoptosis of the precursors, resulting in effective and oscillatory production. Cyclic neutropenia is effectively treated with granulocyte colony-stimulating factor (G-CSF), usually at doses of 1 to 5 microg/kg/d (median dose, 2.5 microg/kg/d). Long-term, daily, or alternate-day administration reduces fever, mouth ulcers, and other inflammatory events associated with this disorder. Leukemic transformation is not a recognized risk for cyclic neutropenia, with or without treatment with G-CSF. |
| Dall'Igna P, Bisogno G, Ferrari A, Treuner J, Carli M, Zanetti I, Guglielmi M, Cecchetto G |
Primary transcrotal excision for paratesticular rhabdomyosarcoma. |
Cancer 2003, 97: 1981 |
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| Dale DC, Cottle TE, Fier CJ, Bolyard AA, Bonilla MA, Boxer LA, Cham B, Freedman MH, Kannourakis G, Kinsey SE, Davis R, Scarlata D, Schwinzer B, Zeidler C, Welte K |
Severe chronic neutropenia: treatment and follow-up of patients in the Severe Chronic Neutropenia International Registry. |
American journal of hematology 2003, 72: 82 |
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| Severe chronic neutropenia (SCN) is defined as an absolute neutrophil (ANC) of less than 0.5 x 10(9)/L, lasting for months or years. Congenital, cyclic, and idiopathic neutropenia are principal categories of SCN. Since 1994, the Severe Chronic Neutropenia International Registry (SCNIR) has collected data to monitor the clinical course, treatments, and disease outcomes for SCN patients. This report summarizes data for 853 patients, almost all treated with daily or alternate-day recombinant human granulocyte colony-stimulating factor (G-CSF or Filgrastim). G-CSF treatment increased the ANC overall from 0.34 x 10(9)/L +/- 0.018 pre-treatment to 3.70 x 10(9)/L +/- 0.18 during the first year of treatment. For most patients, the responses were durable with patients remaining on the same dose of G-CSF for many years. Long-term hematological observations showed stable mean leukocyte and neutrophil counts and gradually increasing hemoglobin levels. Thrombocytopenia developed in 4% of patients. As of January 1, 2000, myelodysplasia (MDS) or acute myelogenous leukemia (AML) has occurred in 35 of 387 patients with congenital neutropenia with a cumulative risk of 13% after 8 years of G-CSF treatment. This event occurred without a predictable relationship to the duration or dose of G-CSF treatment. No patients with cyclic or idiopathic neutropenia developed MDS or AML. Other important adverse events included hepatomegaly, osteoporosis, vasculitis, glomerulonephritis, and deaths in 4 of 14 cases requiring splenectomy. Growth and development and the outcome of pregnancy appeared to be unaffected by G-CSF treatment. These data indicate that congenital, cyclic, and idiopathic neutropenia can be effectively treated with long-term G-CSF. The risk of leukemia, osteoporosis, other potentially adverse events, and pregnancy outcome need to be further evaluated with continuing long-term observations. |
| Dale DC, Bolyard AA, Schwinzer BG, Pracht G, Bonilla MA, Boxer L, Freedman MH, Donadieu J, Kannourakis G, Alter BP, Cham BP, Winkelstein J, Kinsey SE, Zeidler C, Welte K |
The Severe Chronic Neutropenia International Registry: 10-Year Follow-up Report. |
Supportive cancer therapy 2006 Jul 1; 3: 220 |
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| Background: The Severe Chronic Neutropenia International Registry (SCNIR) was organized 10 years ago to improve understanding and treatment of the group of rare hematologic disorders causing blood neutrophil counts to be < 500/muL for months or years. Patients and Methods: Patients now enrolled include those with severe congenital neutropenia (n = 526), cyclic neutropenia (n = 205), idiopathic neutropenia (n = 349), autoimmune neutropenia (n = 68), and other (n = 15). More than 90% (1053 of 1163) of patients in the SCNIR have been treated with granulocyte colony-stimulating factor (G-CSF), median dose 3.33 mug/kg per day. Results: Granulocyte colony-stimulating factor has reduced the occurrence of infection, hospitalization, and antibiotics and improved patients' quality of life. Most patients have noted few adverse effects with G-CSF treatment. Osteoporosis/osteopenia has been reported in 14% of all patients, and myelodysplastic syndrome and acute myelocytic leukemia have occurred in 57 patients, including severe congenital neutropenia (11.8%; 50 of 422), Shwachman-Diamond syndrome (8.1%; 3 of 37), and 4 others. The SCNIR is an important resource for studies on the genetic and molecular basis for the disorders causing chronic neutropenia. Conclusion: The findings of mutations in the gene for neutrophil elastase as causing cyclic and congenital neutropenia, the role of mutations in the gene for the G-CSF receptor in the evolution of severe congenital neutropenia to acute myelocytic leukemia, and the importance of apoptosis as the cellular mechanism for several diseases causing severe chronic neutropenia have come from studies on these patients. |
| Dale DC, Welte K |
Cyclic and chronic neutropenia. |
Cancer treatment and research 2011, 157: 97 |
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| Patients with severe chronic neutropenia have blood neutrophil level <0.5 × 10(9)/L, predisposing them to increased susceptibility to life-threatening bacterial infections. This chapter focuses on cyclic and congenital neutropenia, two very interesting and rare hematological conditions causing severe chronic neutropenia. Both disorders respond well to treatment with the myeloid growth factor, granulocyte colony-stimulating factor (G-CSF). This chapter describes the basic features of these diseases and addresses several current clinical issues regarding their diagnosis and management. Cyclic neutropenia is a rare, inherited autosomal dominant disorder due to mutations in the gene for neutrophil elastase (ELA-2 or ELANE). Usually these patients have regular oscillation of blood neutrophil counts with periods of severe neutropenia occurring every 21 days. During these periods, they have painful mouth ulcers, fevers, and bacterial infections. The most severe consequences are gangrene, bacteremia, and septic shock. Cyclic neutropenia patients respond well to treatment with granulocyte colony-stimulating factor (G-CSF) given by subcutaneous injections on a daily or alternate-day basis. Severe congenital neutropenia is also a rare hematological disease, but it is probably more common than cyclic neutropenia. Blood neutrophils are extremely low on a continuing basis; the levels may be <0.2 × 10(9)/L, and the risk of severe bacterial infections is even greater than in cyclic neutropenia. The majority of cases are due to autosomal dominant inheritance of mutations in the ELA-2 or ELANE gene. Less commonly, mutations in HAX-1, G6PC3, and other genes cause this disorder. Treatment with G-CSF is usually effective, but the dose of G-CSF required to normalize blood neutrophils varies greatly. Ten to thirty percent of severe congenital neutropenia patients evolve to develop acute myeloid leukemia, necessitating careful clinical monitoring. |
| Dale DC, Bolyard AA, Marrero T, Kelley ML, Makaryan V, Tran E, Leung J, Boxer LA, Kishnani PS, Austin S, Wanner C, Ferrecchia IA, Khalaf D, Maze D, Kurtzberg J, Zeidler C, Welte K, Weinstein DA |
Neutropenia in glycogen storage disease Ib: outcomes for patients treated with granulocyte colony-stimulating factor. |
Current opinion in hematology 2019, 26: 16 |
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| Glycogen storage disease Ib (GSD Ib) is characterized by hepatomegaly, hypoglycemia, neutropenia, enterocolitis and recurrent bacterial infections. It is attributable to mutations in G6PT1, the gene for the glucose-6-phosphate transporter responsible for transport of glucose into the endoplasmic reticulum. Neutropenia in GSD Ib is now frequently treated with granulocyte colony-stimulating factor (G-CSF). We formed a cooperative group to review outcomes of the long-term treatment of GSD Ib patients treated with G-CSF. |
| Dale DC, Bolyard AA, Steele LA, Zeidler C, Welte K, Severe Chronic Neutropenia International Registry |
Registries for study of nonmalignant hematological diseases: the example of the Severe Chronic Neutropenia International Registry. |
Current opinion in hematology 2020, 27: 18 |
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| Registries provide 'real world' perspectives on the natural history and outcomes for many clinical conditions. The purpose of this review is to identify registries for nonmalignant hematological disease and to describe the operation of a successful long-term registry for patients with severe chronic neutropenia. |
| Dame C, Sutor AH |
Primary and secondary thrombocytosis in childhood. |
British journal of haematology 2005, 129: 165 |
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| This review summarizes current data on the pathomechanisms and clinical aspects of primary and secondary thrombocytosis in childhood. Primary thrombocytosis is extremely rare in childhood, mostly diagnosed at the beginning of the second decade of life. As in adults, the criteria of the Polycythemia Vera Group are appropriate to diagnose primary thrombocytosis. The pathomechansims of non-familial forms are complex and include spontaneous formation of megakaryopoietic progenitors and increased sensitivity to thrombopoietin (Tpo). Familial forms can be caused by mutations in Tpo or Tpo receptor (c-mpl) genes. These mutations result in overexpression of Tpo, sustained intracellular signalling or disturbed regulation of circulating Tpo. Treatment of primary thrombocytosis is not recommended if platelet counts are <1500/nl and bleeding or thrombosis did not occur in patient's history. In severe cases, decision on treatment should weigh potential risks of treatment options (hydroxyurea, anagrelide) against expected benefits for preventing thrombosis or haemorrhage. Secondary thrombocytosis is frequent in children, in particular in the first decade of life. Hepatic Tpo production is stimulated in acute response reaction to a variety of disorders. Thrombosis prophylaxis is not required, even at platelet counts >1000/nl, except for cases with additional prothrombotic risk factors. |
| Damm-Welk C, Busch K, Burkhardt B, Schieferstein J, Viehmann S, Oschlies I, Klapper W, Zimmermann M, Harbott J, Reiter A, Woessmann W |
Prognostic significance of circulating tumor cells in bone marrow or peripheral blood as detected by qualitative and quantitative PCR in pediatric NPM-ALK-positive anaplastic large-cell lymphoma. |
Blood 2007, 110: 670 |
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| Dantonello TM, Int-Veen C, Leuschner I, Schuck A, Furtwaengler R, Claviez A, Schneider DT, Klingebiel T, Bielack SS, Koscielniak E |
Mesenchymal chondrosarcoma of soft tissues and bone in children, adolescents, and young adults : experiences of the CWS and COSS study groups. |
Cancer 2008, 112: 2424 |
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| BACKGROUND.: Mesenchymal chondrosarcoma (MCS) is a rare tumor with a strong tendency toward late recurrences leading to reported 10-year survival rates below 50%. The recommended treatment is resection with wide margins; the effectiveness of chemo- and radiotherapy remain poorly defined. As reports about MCS in young patients are scarce, treatment and outcomes of children/adolescents/young adults in the CWS and COSS studies were investigated. METHODS.: Since 1977, 15 of >7000 CWS and COSS patients |
| Dantonello TM, Int-Veen C, Winkler P, Leuschner I, Schuck A, Schmidt BF, Lochbuehler H, Kirsch S, Hallmen E, Veit-Friedrich I, Bielack SS, Niggli F, Kazanowska B, Ladenstein R, Wiebe T, Klingebiel T, Treuner J, Koscielniak E |
Initial patient characteristics can predict pattern and risk of relapse in localized rhabdomyosarcoma. |
Journal of clinical oncology 2008, 26: 406 |
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| PURPOSE: Evaluation of primary tumor-, treatment-, and patient-related factors predicting relapse pattern, risk, and survival after relapse with the aim to design a risk-adapted, tumor-directed surveillance program for patients with localized rhabdomyosarcoma (RMS). PATIENTS AND METHODS: One thousand one hundred sixty-four patients with nonmetastatic RMS achieved complete remission at the end of multimodal therapy in the consecutive trials of the Cooperative Weichteilsarkom Studiengruppe (CWS)-81, CWS-86, CWS-91, and CWS-96 between 1980 and 2002 (median follow-up, 5 years). Three hundred thirty-seven of these individuals developed either locoregional, metastatic, or combined relapses. Predictive factors for relapse, its pattern, and postrelapse survival were analyzed. RESULTS: Age, histology, tumor size, tumor site, postsurgical stage, and omission of radiotherapy were identified as factors associated with an increased relapse risk in multivariate analyses. Relapse rates did not differ among the CWS trials. Median time to relapse was 1.43 years from first diagnosis (range, 0.13 to 13.5 years). There were 217 locoregional, 72 metastatic, and 48 combined recurrences. Only two patients developed metastases more than 4 years after diagnosis, and both had combined recurrences. Five-year postrelapse survival was 24%. Patient subsets with consistent relapse pattern, risk, and postrelapse survival rates were identified on the basis of histologic subtype and tumor size. CONCLUSION: Initial patient and tumor characteristics predict pattern and risk of relapse and also correlate with postrelapse survival probabilities. In localized RMS, tumor-directed follow-up should focus on the primary site. Screening for metastatic relapse may not be necessary more than 4 years after diagnosis. The identification of subgroups with distinctive pattern and risk of relapse may be used to develop risk-adapted, tumor-directed guidance for detection of recurrent disease in localized RMS. |
| Dantonello TM, Int-Veen C, Harms D, Leuschner I, Schmidt BF, Herbst M, Jürgens H, Scheel-Walter HG, Bielack SS, Klingebiel T, Dickerhoff R, Kirsch S, Brecht I, Schmelzle R, Greulich M, Gadner H, Greiner J, Marky I, Treuner J, Koscielniak E |
Cooperative trial CWS-91 for localized soft tissue sarcoma in children, adolescents, and young adults. |
Journal of clinical oncology 2009, 27: 1446 |
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| Dantonello TM, Winkler P, Boelling T, Friedel G, Schmid I, Mattke AC, Ljungman G, Bielack SS, Klingebiel T, Koscielniak E, on behalf of the CWS Study Group |
Embryonal rhabdomyosarcoma with metastases confined to the lungs: Report from the CWS Study Group. |
Pediatr Blood Cancer 2010, [Epub ahead of print] |
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| BACKGROUND: Embryonal rhabdomyosarcoma [RME] is the most common pediatric soft tissue sarcoma. Whereas the prognosis of localized rhabdomyosarcoma has improved, it remains poor for metastatic disease.
METHODS: We analyzed RME-patients with isolated pulmonary metastases [PRME] treated in four consecutive CWS-trials. Treatment included multiagent chemotherapy and local treatment of the primary tumor. Therapy of lung metastases after induction chemotherapy depended on response and individual decisions.
RESULTS: Twenty-nine patients <21 years had PRME. Their median age was six years, the median follow-up nine years. Twenty-eight children had their primary tumor located in an unfavorable site and 22 of the primaries were >5 cm. In addition to conventional chemotherapy, seven patients received high-dose treatment and eight patients oral metronomic chemotherapy. The lung metastases were in remission after induction chemotherapy in 22 individuals. 19 patients received no local treatment of metastases; 3 patients had pulmonary metastasectomy and lung radiation was administered to 9 individuals. In total, 24/29 patients achieved a complete remission [CR]. Actuarial 5-year event-free and overall survival for all patients was 37.9 ± 18% and 48.7 ± 18%, respectively; it was 45.8 ± 20% and 58.3 ± 20% for the 24 patients who achieved a CR. Local treatment of metastases had no impact on the failure pattern. Younger age, good response, achievement of CR and maintenance-treatment were favorable prognostic factors in univariate analysis.
CONCLUSIONS: Children with PRME have a fair prognosis. Local treatment of metastases did not improve outcome in our sample. Metronomic treatment may be an attractive option for PREM-patients. [correction made here after initial online publication]. |
| Dantonello TM, Winkler P, Boelling T, Friedel G, Schmid I, Mattke AC, Ljungman G, Bielack SS, Klingebiel T, Koscielniak E, CWS Study Group |
Embryonal rhabdomyosarcoma with metastases confined to the lungs: report from the CWS Study Group. |
Pediatr Blood Cancer 2011, 56: 725 |
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| BACKGROUND:
Embryonal rhabdomyosarcoma [RME] is the most common pediatric soft tissue sarcoma. Whereas the prognosis of localized rhabdomyosarcoma has improved, it remains poor for metastatic disease.
METHODS:
We analyzed RME-patients with isolated pulmonary metastases [PRME] treated in four consecutive CWS-trials. Treatment included multiagent chemotherapy and local treatment of the primary tumor. Therapy of lung metastases after induction chemotherapy depended on response and individual decisions.
RESULTS:
Twenty-nine patients <21 years had PRME. Their median age was six years, the median follow-up nine years. Twenty-eight children had their primary tumor located in an unfavorable site and 22 of the primaries were >5 cm. In addition to conventional chemotherapy, seven patients received high-dose treatment and eight patients oral metronomic chemotherapy. The lung metastases were in remission after induction chemotherapy in 22 individuals. 19 patients received no local treatment of metastases; 3 patients had pulmonary metastasectomy and lung radiation was administered to 9 individuals. In total, 24/29 patients achieved a complete remission [CR]. Actuarial 5-year event-free and overall survival for all patients was 37.9 ± 18% and 48.7 ± 18%, respectively; it was 45.8 ± 20% and 58.3 ± 20% for the 24 patients who achieved a CR. Local treatment of metastases had no impact on the failure pattern. Younger age, good response, achievement of CR and maintenance-treatment were favorable prognostic factors in univariate analysis.
CONCLUSIONS:
Children with PRME have a fair prognosis. Local treatment of metastases did not improve outcome in our sample. Metronomic treatment may be an attractive option for PREM-patients. |
| Dantonello TM, Leuschner I, Vokuhl C, Gfroerer S, Schuck A, Kube S, Nathrath M, Bernbeck B, Kaatsch P, Pal N, Ljungman G, Bielack SS, Klingebiel T, Koscielniak E, on behalf of CWS |
Malignant ectomesenchymoma in children and adolescents: Report from the Cooperative Weichteilsarkom Studiengruppe (CWS). |
Pediatric blood & cancer 2012, [Epub ahead of print] |
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| BACKGROUND: Malignant ectomesenchymoma (MEM) is a soft tissue tumor with heterologous rhabdomyoblastic components believed to arise from pluripotent migratory neural crest cells. To date merely 50 cases have been published and the knowledge about the course of disease and optimal treatment is limited. METHODS: Six patients with MEM were registered 1996-2009. The diagnosis was confirmed according to current criteria. Their treatment and outcome was analyzed. RESULTS: The median age of the three females and three males was 0.6 years (range, 0.2-13.5). The mesenchymal component in all tumors was rhabdomyosarcoma (RMS), the neural component ganglioneuroblastoma/neuroblastoma (n = 5) and peripheral primitive neuroectodermal tumor in one case. Five patients presented with localized, one with metastatic disease. All but one patient received multiagent chemotherapy during their initial treatment. The tumors of 4/5 patients with localized MEM were at least grossly resected at best surgery; the patient without gross resection was additionally irradiated. Three of four evaluable tumors responded well to induction chemotherapy. All patients achieved a first complete remission (CR), but three recurrences (two local, one systemic) occurred. The individual with metastatic MEM did not survive, but all five patients with localized MEM are currently alive in CR with a median follow-up of 5 years (range: 2.1-13.7). CONCLUSIONS: Risk-factors and outcome of MEM appear to be comparable with other highly malignant pediatric soft tissue sarcoma when a multimodal treatment strategy including chemotherapy and adequate local treatment is pursued. We propose that treatment of patients with MEM be done according to pediatric protocols similar to other rhabdomyosarcoma-like soft tissue sarcoma. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc. |
| Dantonello TM, Int-Veen C, Schuck A, Seitz G, Leuschner I, Nathrath M, Schlegel PG, Kontny U, Behnisch W, Veit-Friedrich I, Kube S, Hallmen E, Kazanowska B, Ladenstein R, Paulussen M, Ljungman G, Bielack SS, Klingebiel T, Koscielniak E, on behalf of the Cooperative Weichteilsarkom Studiengruppe (CWS) |
Survival following disease recurrence of primary localized alveolar rhabdomyosarcoma. |
Pediatr Blood Cancer 2013, 60: 1267 |
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| BACKGROUND: Recurrences in primary localized alveolar rhabdomyosarcoma (RMA) are common. Post-relapse survival is poor. We evaluated prognostic factors including relapse treatment in patients with recurrent RMA. METHODS: Relapses occurred in 115/235 patients with nonmetastatic RMA treated in four consecutive CWS-trials after achievement of a complete remission. Sufficient information about post-relapse treatment and outcome could be obtained in 99 patients and was retrospectively analyzed. RESULTS: Nine of 99 patients received no salvage therapy and died after a median of 2 months. The remaining 90 patients received multimodal relapse treatment including mandatory chemotherapy. Recurrences were grossly resected in 39 patients; 57 patients received radiation. At a median follow-up from relapse of 8 years, 20 patients were alive and disease-free (5-year post-relapse survival [PROS] 21.3 ± 8). All surviving patients apart from a single individual had an isolated, circumscribed recurrence. Sixteen of 20 survivors were treated with adequate local relapse therapy (ALRT, i.e., either complete resection or gross resection + radiation). Survival in the subgroup of 27 individuals with circumscribed recurrences and ALRT was significantly better (PROS 53.7 ± 19) compared with disseminated recurrences and/or tumors treated without ALRT. Absence of primary lymph node involvement, circumscribed relapses, ALRT, and achievement of a second CR were identified as independent favorable risk factors. CONCLUSION: Post-relapse survival for primary localized RMA is generally poor. However, certain patient groups differed significantly in their likelihood of survival and 50% of patients with circumscribed relapses treated with ALRT survived. These findings may form the basis for an evidence-based risk-stratification for recurrent disease including relapse treatment. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc. |
| Dantonello TM, Leuschner I, Vokuhl C, Gfroerer S, Schuck A, Kube S, Nathrath M, Bernbeck B, Kaatsch P, Pal N, Ljungman G, Bielack SS, Klingebiel T, Koscielniak E, CWS |
Malignant ectomesenchymoma in children and adolescents: report from the Cooperative Weichteilsarkom Studiengruppe (CWS). |
Pediatric blood & cancer 2013, 60: 224 |
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| Malignant ectomesenchymoma (MEM) is a soft tissue tumor with heterologous rhabdomyoblastic components believed to arise from pluripotent migratory neural crest cells. To date merely 50 cases have been published and the knowledge about the course of disease and optimal treatment is limited. |
| Dantonello TM, Lochbühler H, Schuck A, Kube S, Godzinski J, Sköldenberg E, Ljungman G, Kosztyla D, Veit-Friedrich I, Hallmen E, Feuchtgruber S, Wessalowski R, Franke M, Bielack SS, Klingebiel T, Koscielniak E |
Challenges in the Local Treatment of Large Abdominal Embryonal Rhabdomyosarcoma. |
Annals of surgical oncology 2014, Epub ahead of print |
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| Embryonal rhabdomyosarcoma is the most common pediatric soft tissue sarcoma. The best local treatment in large, nonmetastatic primary unresected nongenitourinary embryonal rhabdomyosarcoma of the abdomen (LARME) is however unclear. |
| Dantonello TM, Stark M, Timmermann B, Fuchs J, Selle B, Linderkamp C, Handgretinger R, Hagen R, Feuchtgruber S, Kube S, Kosztyla D, Kazanowska B, Ladenstein R, Niggli F, Ljungman G, Bielack SS, Klingebiel T, Koscielniak E, Cooperative Weichteilsarkom Studiengruppe [CWS] |
Tumour volume reduction after neoadjuvant chemotherapy impacts outcome in localised embryonal rhabdomyosarcoma. |
Pediatric blood & cancer 2015, 62: 16 |
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| Response (tumour volume reduction) to induction chemotherapy has been used to stratify secondary local and systemic treatment of Intergroup Rhabdomyosarcoma Study Group III (IRSG-III) embryonal rhabdomyosarcoma (RME) in consecutive CWS-trials. To evaluate its actual impact we studied response-related treatment and outcomes. |
| Danaee A, Inusa B, Howard J, Robinson S |
Hyperhemolysis in Patients With Hemoglobinopathies: A Single-Center Experience and Review of the Literature. |
Transfusion medicine reviews 2015, 29: 220 |
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| Hyperhemolysis is a severe and potentially life-threatening complication of transfusion described in numerous case reports and gaining recognition since 2009 via the UK Serious Hazards of Transfusion scheme. Although it is predominantly seen in patients with sickle cell disease, there are several reports of this complication in patients with other hemoglobinopathies as well as patients with a range of other hematologic diagnoses who have blood transfusions as part of their management. Our understanding of the underlying pathophysiology of this subtype of delayed transfusion reaction has increased over the last few years; however, there are still questions, which remain unanswered. In our center alone, we have encountered 9 cases in the last 5 years both in the adult and pediatric population. Here we discuss our experience in the diagnosis and management of this complication, and review other cases reported in the literature and the various existing theories behind the pathophysiology of this process. We also discuss the role of genotyping and using DNA technology to aid selection of the most appropriate blood for this patient group. With an increased awareness of hyperhemolysis, it would be advantageous to finally develop international registries to determine the true incidence of hyperhemolysis, better understand the pathophysiology, identify markers to predict which patients are at risk, and inform management guidelines. |
| Dastugue N, Payen C, Lafage-Pochitaloff M et al. |
Prognostic significance of karyotype in de novo adult acute myeloid leukemia. The BGMT group. |
Leukemia 1995, 9: 1491 |
|
| Daubenbuechel AM, Hoffmann A, Eveslage M, Azyurt J, Lohle K, Reichel J, Thiel CM, Martens H, Geenen V, Mueller HL |
Oxytocin in survivors of childhood-onset craniopharyngioma. |
Endocrine 2016, 54: 524 |
|
| Quality of survival of childhood-onset craniopharyngioma patients is frequently impaired by hypothalamic involvement or surgical lesions sequelae such as obesity and neuropsychological deficits. Oxytocin, a peptide hormone produced in the hypothalamus and secreted by posterior pituitary gland, plays a major role in regulation of behavior and body composition. In a cross-sectional study, oxytocin saliva concentrations were analyzed in 34 long-term craniopharyngioma survivors with and without hypothalamic involvement or treatment-related damage, recruited in the German Childhood Craniopharyngioma Registry, and in 73 healthy controls, attending the Craniopharyngioma Support Group Meeting 2014. Oxytocin was measured in saliva of craniopharyngioma patients and controls before and after standardized breakfast and associations with gender, body mass index, hypothalamic involvement, diabetes insipidus, and irradiation were analyzed. Patients with preoperative hypothalamic involvement showed similar oxytocin levels compared to patients without hypothalamic involvement and controls. However, patients with surgical hypothalamic lesions grade 1 (anterior hypothalamic area) presented with lower levels (pâÂÂ=âÂÂ0.017) of oxytocin under fasting condition compared to patients with surgical lesion of posterior hypothalamic areas (grade 2) and patients without hypothalamic lesions (grade 0). Craniopharyngioma patients' changes in oxytocin levels before and after breakfast correlated (pâÂÂ=âÂÂ0.02) with their body mass index. Craniopharyngioma patients continue to secrete oxytocin, especially when anterior hypothalamic areas are not involved or damaged, but oxytocin shows less variation due to nutrition. Oxytocin supplementation should be explored as a therapeutic option in craniopharyngioma patients with hypothalamic obesity and/or behavioral pathologies due to lesions of specific anterior hypothalamic areas. Clinical trial number: KRANIOPHARYNGEOM 2000/2007(NCT00258453; NCT01272622). |
| Daubenbüchel AM, Ãzyurt J, Boekhoff S, Warmuth-Metz M, Eveslage M, Müller HL |
Eating behaviour and oxytocin in patients with childhood-onset craniopharyngioma and different grades of hypothalamic involvement. |
Pediatric obesity 2019, 14:e12527 |
|
| Patients with childhood-onset craniopharyngioma (CP) often suffer from tumour or treatment-related hypothalamic lesions (HL). These lesions may alter production of oxytocin, which plays a major role in the regulation of eating behaviour and body composition. |
| Davies SM, Radloff GA, DeFor TE, Levran O, Batish SD, Hanenberg H, Auerbach AD |
GST genotype may modify clinical phenotype in patients with Fanconi anaemia. |
Br J Haematol 2005, 131: 118 |
|
| In the search for genetic modifiers of the Fanconi anaemia (FA) phenotype, we examined the role of polymorphism in three glutathione s-transferase genes (GSTT1, GSTM1 and GSTP1) in 356 FA patients enrolled in the International Fanconi Anaemia Registry (IFAR). Cellular sensitivity to 1,2:3,4 diepoxybutane was significantly increased in GSTT1 deleted compared with GSTT1 positive cases (median chromosomal breaks 11.1 vs. 8.3, P < 0.01) but there was no effect on clinical manifestations of FA. GSTM1 genotype significantly influenced time to bone marrow failure in complementation group FA-C, (median age 3.0 years vs. 7.0 years, P < 0.01). GSTP1 genotype did not influence FA phenotype. |
| Davies JM, Lewis MP, Wimperis J, Rafi I, Ladhani S, Bolton-Maggs PH, British Committee for Standards in Haematology |
Review of guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen: prepared on behalf of the British Committee for Standards in Haematology by a working party of the Haemato-Oncology task force. |
British journal of haematology 2011, 155: 308 |
|
| Davis BA, Allard S, Qureshi A, Porter JB, Pancham S, Win N, Cho G, Ryan K, British Committee for Standards in Haematology |
Guidelines on red cell transfusion in sickle cell disease. Part I: principles and laboratory aspects. |
British journal of haematology 2017, 176: 179 |
|
| Dávila Fajardo R, Oldenburger E, Rübe C, López-Yurda M, Pritchard-Jones K, Bergeron C, Graf N, van Grotel M, van Tinteren H, Saunders D, van den Heuvel-Eibrink MM, Janssens GO, Oldenburger F |
Evaluation of boost irradiation in patients with intermediate-risk stage III Wilms tumour with positive lymph nodes only: Results from the SIOP-WT-2001 Registry. |
Pediatric blood & cancer 2018, 65:e27085 |
|
| OBJECTIVE: To evaluate the value of radiotherapy boost omission in patients with intermediate-risk, stage III Wilms tumours (WT) with positive lymph nodes (LN).
METHODS AND MATERIALS: All patients with intermediate-risk, stage III (LN positive) WT consecutively registered in the SIOP-WT-2001 study were included in this analysis. Endpoints were 5-year event-free survival (EFS), loco-regional control (LRC) and overall survival (OS).
RESULTS: Between June 2001 and May 2015, 2,569 patients with stage I to III WT after preoperative chemotherapy were registered in the SIOP-WT-2001 study. Five hundred and twenty-three (20%) had stage III disease, of which 113 patients had stage III due to positive LN only. Of those, 101 (89%) received radiotherapy, 36 of which (36%) received, apart from flank irradiation, a boost dose to the LN positive area. Four patients (4%) did not receive any adjuvant radiotherapy. In eight patients information on radiotherapy was not available. With a median follow-up of 71 months, no difference in 5-year EFS (84% vs. 83%, P = 0.77) and LRC (96% vs. 97%, P = 0.91) was observed between patients receiving a radiotherapy boost and those without boost, respectively. Five-year OS, including salvage therapy, was excellent (boost vs. no boost: 97% vs. 95%, P = 0.58).
CONCLUSIONS: Outcome data demonstrate that omission of the radiotherapy boost to the loco-regional positive lymph nodes in patients with intermediate-risk, stage III WT who receive preoperative chemotherapy and postoperative flank irradiation (14.4 Gy) can be considered a safe approach for future SIOP protocols.
© 2018 Wiley Periodicals, Inc. |
| Dávila Fajardo R, Furtwängler R, van Grotel M, van Tinteren H, Pasqualini C, Pritchard-Jones K, Al-Saadi R, de Camargo B, Ramírez Villar GL, Graf N, Muracciole X, Melchior P, Saunders D, Rübe C, van den Heuvel-Eibrink MM, Janssens GO, Verschuur AC |
Outcome of Stage IV Completely Necrotic Wilms Tumour and Local Stage III Treated According to the SIOP 2001 Protocol. |
Cancers 2021, 13 |
|
| Wilms tumour (WT) patients with a localised completely necrotic nephroblastoma after preoperative chemotherapy are a favourable outcome group. Since the introduction of the SIOP 2001 protocol, the SIOP- Renal Tumour Study Group (SIOP-RTSG) has omitted radiotherapy for such patients with low-risk, local stage III in an attempt to reduce treatment burden. However, for metastatic patients with local stage III, completely necrotic WT, the recommendations led to ambiguous use. The purpose of this descriptive study is to demonstrate the outcomes of patients with metastatic, completely necrotic and local stage III WT in relation to the application of radiotherapy or not. |
| Daw S, Hasenclever D, Mascarin M, Fernández-Teijeiro A, Balwierz W, Beishuizen A, Burnelli R, Cepelova M, Claviez A, Dieckmann K, Landman-Parker J, Kluge R, Körholz D, Mauz-Körholz C, Wallace WH, Leblanc T |
Risk and Response Adapted Treatment Guidelines for Managing First Relapsed and Refractory Classical Hodgkin Lymphoma in Children and Young People. Recommendations from the EuroNet Pediatric Hodgkin Lymphoma Group. |
HemaSphere 2020, 4:e329 |
|
| The objective of this guideline is to aid clinicians in making individual salvage treatment plans for pediatric and adolescent patients with first relapse or refractory (R/R) classical Hodgkin lymphoma (cHL). While salvage with standard dose chemotherapy followed by high dose chemotherapy and autologous stem cell transplant is often considered the standard of care in adult practice, pediatric practice adopts a more individualized risk stratified and response adapted approach to salvage treatment with greater use of non-transplant salvage. Here, we present on behalf of the EuroNet Pediatric Hodgkin Lymphoma group, evidence and consensus-based guidelines for standardized diagnostic, prognostic and response procedures to allocate children and adolescents with R/R cHL to stratified salvage treatments. |
| de Haas T, Zwaan C, Wondergem M, Pieters R, Kaspers G, Loonen A, Rottier M, Wünsche R, Creutzig U, Bartl S, Hählen K, Broxterman H, Ossenkoppele G, Veerman A |
In-vitro cellular drug resistance in acute non-lymphoblastic leukemia. |
Haematology and Blood Transfusion 2001, 40: 244 |
|
| Debling D, Spix C, Blettner M, Michaelis J, Kaatsch P |
The cohort of long-term survivors at the German childhood cancer registry. |
Klinische Padiatrie 2008, 220: 371 |
|
| BACKGROUND: With the increasing number of long-term survivors among patients diagnosed with cancer during childhood, questions concerning late effects have become a major research topic. To ascertain late effects, it is necessary to contact former patients. An essential requirement for such studies is a long-term surveillance (LTS) of former childhood cancer patients in their adolescence and their adulthood. The paper describes the role of the German Childhood Cancer Registry (GCCR) in LTS. A cohort of long-term survivors has been built up over the years. The characteristics of this LTS cohort and strategies for further improvement of LTS will be presented. PATIENTS AND METHODS: Since 1980 the GCCR systematically ascertains all malignant neoplasms and benign brain tumours in children under the age of 15 years at diagnosis. Participants are followed up actively by the treating hospitals and the clinical study groups in the first years after diagnosis, and by the GCCR thereafter. Late effects are accessed within the Scientific Society for Paediatric Oncology and Haematology (GPOH) of different groups with different focal points. Those groups are the GCCR (secondary malignant neoplasms), LESS (late effects after chemotherapy), RiSK (late effects after radiotherapy), and the working group on quality of life (quality of life and data on life circumstances). Additionally, the GCCR provides logistics for contacting patients during LTS. The LTS is supported by a recent basic publication ( |
| den Boer ML, Cario G, Moorman AV, Boer JM, de Groot-Kruseman HA, Fiocco M, Escherich G, Imamura T, Yeoh A, Sutton R, Dalla-Pozza L, Kiyokawa N, Schrappe M, Roberts KG, Mullighan CG, Hunger SP, Vora A, Attarbaschi A, Zaliova M, Elitzur S, Cazzaniga G, Biondi A, Loh ML, Pieters R, Ponte di Legno Childhood ALL Working Group |
Outcomes of paediatric patients with B-cell acute lymphocytic leukaemia with ABL-class fusion in the pre-tyrosine-kinase inhibitor era: a multicentre, retrospective, cohort study. |
The Lancet. Haematology 2021, 8:e55-e66 |
|
| ABL-class fusion genes other than BCR-ABL1 have been identified in approximately 3% of children with newly diagnosed acute lymphocytic leukaemia, and studies suggest that leukaemic cells carrying ABL-class fusions can be targeted successfully by tyrosine-kinase inhibitors. We aimed to establish the baseline characteristics and outcomes of paediatric patients with ABL-class fusion B-cell acute lymphocytic leukaemia in the pre-tyrosine-kinase inhibitor era. |
| Dedeken L, Lê PQ, Azzi N, Brachet C, Heijmans C, Huybrechts S, Devalck C, Ngalula M, Ferster A |
Haematopoietic stem cell transplantation for severe sickle cell disease in childhood: a single centre experience of 50 patients. |
British journal of haematology 2014,Epub ahead of print |
|
| Despite improvements in medical management, sickle cell disease (SCD) remains associated with severe morbidity and decreased survival. Allogeneic haematopoietic stem cell transplantation (HSCT) remains the only curative approach. We report the outcome of 50 consecutive children with severe SCD that received HSCT in our unit between November 1988 and April 2013. The stem cell source was bone marrow (n = 39), cord blood (n = 3), bone marrow and cord blood (n = 7) and peripheral blood stem cells (n = 1). All patients had ≥1 severe manifestation: 37 presented with recurrent vaso-occlusive crises/acute chest syndrome, 27 cerebral vasculopathy and 1 nephropathy. The conditioning regimen consisted of busulfan + cyclophosphamide (BuCy) before November 1991 and BuCy + rabbit antithymocyte globulin after that date. Since 1995, all patients have been treated with hydroxycarbamide (HC) prior to transplantation for a median duration of 2·7 years. Median age at transplantation and median follow-up was 8·3 and 7·7 years, respectively. Acute graft-versus-host disease (GVHD) and chronic GVHD were observed in 11 and 10 patients, respectively. An excellent outcome was achieved, with 8-year overall survival and event-free survival (EFS) rates of 94·1% and 85·6%, respectively. Since HC introduction, no graft failure occurred and EFS reached 97·4%. Prior treatment with HC may have contributed to successful engraftment. |
| De Franceschi L, Mura P, Schweiger V, Vencato E, Quaglia FM, Delmonte L, Evangelista M, Polati E, Olivieri O, Finco G |
Fentanyl Buccal Tablet: A New Breakthrough Pain Medication in Early Management of Severe Vaso-Occlusive Crisis in Sickle Cell Disease. |
Pain practice 2015, Epub ahead of print |
|
| Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder. The principal clinical manifestations of SCD are the chronic hemolytic anemia and the acute vaso-occlusive crisis (VOCs), which are mainly characterized by ischemic/reperfusion tissue injury. Pain is the main symptom of VOCs, and its management is still a challenge for hematologists, requiring a multidisciplinary approach. |
| Deutsche Gesellschaft für Radioonkologie |
S2 Leitlinie Supportive Maßnahmen in der Radioonkologie. |
AWMF 2015 |
|
| de Kraker J, Graf N, van Tinteren H, Pein F, Sandstedt B, Godzinski J, Tournade MF, SIOP |
Reduction of postoperative chemotherapy in children with stage I intermediate-risk and anaplastic Wilms' tumour (SIOP 93-01 trial): a randomised controlled trial. |
Lancet 2004, 364: 1229 |
|
| BACKGROUND: Present treatment for Wilms' tumour is very successful. Now, efforts are aimed at reducing toxicity and burden of treatment by shortening schedules without loss of effectiveness. The objective of this randomised trial was to assess whether postoperative chemotherapy for patients with stage I intermediate-risk and anaplastic Wilms' tumour could be shortened to only 4 weeks from the standard 18 weeks, while maintaining equivalent event-free survival. METHODS: Between June, 1993, and June, 2000, 410 patients were randomly assigned after four doses of vincristine plus one course of dactinomycin postoperatively either to stop further adjuvant chemotherapy (no further chemotherapy group, n=200), or to receive a further two courses of the same chemotherapy (standard group, n=210). Previous treatment consisted of chemotherapy before nephrectomy of four doses of vincristine and two courses of dactinomycin followed by surgical resection of the tumour. Eligible patients were at least 6 months old and had stage I tumours with either intermediate-risk histology or anaplasia. The primary endpoint of this equivalence trial was 2-year event-free survival. Both per-protocol and intention-to-treat analyses were done. FINDINGS: By 2 years, 18 recurrences were reported in the standard group, and 22 in the no further chemotherapy group. Event-free survival was 91.4% (95% CI 87.5-95.2) for the no further chemotherapy group and 88.8% (84.3-93.2) for the standard group (difference=2.6%, upper 97.5% confidence limit 8.4%). The null hypothesis, that experimental treatment is less effective than standard treatment, could be rejected (p=0.008). CONCLUSIONS: Shortening duration of chemotherapy could reduce acute and late side-effects and inconvenience for patient and parents while maintaining effectiveness, and could be beneficial in terms of health costs. |
| Delling G, Amling M, Posl M, Ritzel H, Maas R, Winkler K, Heise U, Werner M |
Periosteal osteosarcoma. Histologic characteristics, preparation technique, growth pattern and differential diagnosis. |
Pathologe 1996, 17: 86 |
|
| Le Deley MC, Reiter A, Williams D, Delsol G, Oschlies I, McCarthy K, Zimmermann M, Brugières L, European Intergroup for Childhood Non-Hodgkin Lymphoma |
Prognostic factors in childhood anaplastic large cell lymphoma: results of a large European intergroup study. |
Blood 2008, 111: 1560 |
|
| Le Deley MC, Rosolen A, Williams DM, Horibe K, Wrobel G, Attarbaschi A, Zsiros J, Uyttebroeck A, Marky IM, Lamant L, Woessmann W, Pillon M, Hobson R, Mauguen A, Reiter A, Brugières L |
Vinblastine in children and adolescents with high-risk anaplastic large-cell lymphoma: results of the randomized ALCL99-vinblastine trial. |
J Clin Oncol 2010 1; 28: 3987 |
|
| PURPOSE: The impact of adding vinblastine to a 4-month chemotherapy regimen, based on the Non-Hodgkin's Lymphoma Berlin-Frankfurt-Münster 90 protocol, in childhood high-risk anaplastic large-cell lymphoma (ALCL) was assessed.
PATIENTS AND METHODS: Children and adolescents with high-risk ALCL, defined by mediastinal, lung, liver, spleen, or skin involvement, were eligible for the trial. After a prephase and one chemotherapy course, patients were randomly assigned to receive either five further chemotherapy courses without vinblastine or the same regimen with one vinblastine injection (6 mg/m(2)) during each course followed by weekly vinblastine to complete a total of 1 year of treatment. The primary end point was event-free survival (EFS), analyzed on the intent-to-treat population.
RESULTS: Between November 1999 and June 2006, 110 patients were randomly assigned to receive vinblastine, and 107 were randomly assigned not to receive vinblastine. Median follow-up was 4.8 years. Patients in the vinblastine arm had a significantly reduced risk of events during the first year (hazard ratio [HR] = 0.31; 95% CI, 0.15 to 0.67; P = .002) followed by an increased risk thereafter (HR = 4.98; 95% CI, 1.65 to 15.0; P = .003). Consequently, EFS at 1 year differed significantly (91% in the vinblastine group v 74% in the no-vinblastine group), with no difference at 2 years (73% and 70%, respectively). Overall EFS curves did not differ significantly (HR = 0.91; 95% CI, 0.55 to 1.5; P = .71). Thirty-one percent of weekly doses of vinblastine were reduced as a result of hematologic toxicity, although vinblastine was discontinued for toxicity in only three patients.
CONCLUSION: Adding vinblastine during induction and as maintenance for a total treatment duration of 1 year significantly delayed the occurrence of relapses but did not reduce the risk of failure. |
| Den Boer M, Pieters R, Kazemier K, Klumper E, Janka-Schaub G, Henze G, Veerman A |
Daunorubicin uptake and retention in childhood acute lymphoblastic leukemia. |
Drug resistance in leukemia and lymphoma 1996, 375 |
|
| Den Boer M, Pieters R, Kazemier K, Janka-Schaub G, Henze G, Veerman A |
The modulating effect of PSC 833, cyclosporin A, verapamil and genistein on in vitro cytotoxicity and intracellular content of daunorubicin in childhood acute lymphoblastic leukemia. |
Leukemia 1998, 12: 912 |
|
| Den Boer M, Pieters R, Kazemier K, Rottier M, Zwaan C, Kaspers G, Janka-Schaub G, Henze G, Creutzig U, Scheper R, Veerman A |
Relationship between major vault protein/lung resistance protein, multidrug resistance-associated protein, P-glycoprotein expression, and drug resistance in childhood leukemia. |
Blood 1998, 91: 2092 |
|
| Den Boer M, Kapaun P, Pieters R, Kazemier K, Janka-Schaub G, Veerman A |
Myeloid antigen co-expression in childhood acute lymphoblastic leukaemia. |
Br J Haematol 1999, 105: 876 |
|
| Den Boer M, Pieters R, Kazemier K, Janka-Schaub G, Henze G, Creutzig U, Kaspers G, Kearns P, Hall A, Pearson A, Veerman A |
Different expression of glutathione S-transferase alpha, mu and pi in childhood acute lymphoblastic and myeloid leukaemia. |
Br J Haematol 1999, 104: 321 |
|
| Den Boer M, Harms D, Pieters R, Kazemier K, Göbel U, Körholz D, Graubner U, Haas R, Jorch N, Spaar H, Kaspers G, Kamps W, Berg van, van Wering E, Veerman A, Janka-Schaub G |
Patient stratification based on prednisolone-vincristine-asparaginase resistance profiles in children with acute lymphoblastic leukemia. |
J Clin Oncol 2003, 21: 3262 |
|
| Denzer C |
Endokrinologische Nachsorge nach onkologischen Erkrankungen im Kindes- und Jugendalter - Evidenzbasierte Leitlinie (S3) der Deutschen Gesellschaft für Kinderendokrinologie und -diabetologie e. V. (DGKED), der Gesellschaft für Pädiatrische Onkologie und Hämatologie e. V. (GPOH) und der beteiligten medizinisch-wissenschaftlichen Fachgesellschaften. |
AWMF online 2014 |
|
| Depuydt P, Boeva V, Hocking TD, Cannoodt R, Ambros IM, Ambros PF, Asgharzadeh S, Attiyeh EF, Combaret V, Defferrari R, Fischer M, Hero B, Hogarty MD, Irwin MS, Koster J, Kreissman S, Ladenstein R, Lapouble E, Laureys G, London WB, Mazzocco K, Nakagawara A, Noguera R, Ohira M, Park JR, Pötschger U, Theissen J, Tonini GP, Valteau-Couanet D, Varesio L, Versteeg R, Speleman F, Maris JM, Schleiermacher G, De Preter K |
Genomic Amplifications and Distal 6q Loss: Novel Markers for Poor Survival in High-risk Neuroblastoma Patients. |
Journal of the National Cancer Institute 2018 Oct 1; 110: 1084 |
|
| Neuroblastoma is characterized by substantial clinical heterogeneity. Despite intensive treatment, the survival rates of high-risk neuroblastoma patients are still disappointingly low. Somatic chromosomal copy number aberrations have been shown to be associated with patient outcome, particularly in low- and intermediate-risk neuroblastoma patients. To improve outcome prediction in high-risk neuroblastoma, we aimed to design a prognostic classification method based on copy number aberrations. |
| Desch AK, Hartung K, Botzen A, Brobeil A, Rummel M, Kurch L, Georgi T, Jox T, Bielack S, Burdach S, Classen CF, Claviez A, Debatin KM, Ebinger M, Eggert A, Faber J, Flotho C, Frühwald M, Graf N, Jorch N, Kontny U, Kramm C, Kulozik A, Kühr J, Sykora KW, Metzler M, Müller HL, Nathrath M, Nüßlein T, Paulussen M, Pekrun A, Reinhardt D, Reinhard H, Rössig C, Sauerbrey A, Schlegel PG, Schneider DT, Scheurlen W, Schweigerer L, Simon T, Suttorp M, Vorwerk P, Schmitz R, Kluge R, Mauz-Körholz C, Körholz D, Gattenlöhner S, Bräuninger A |
Genotyping circulating tumor DNA of pediatric Hodgkin lymphoma. |
Leukemia 2020, 34: 151 |
|
| We used hybrid capture-targeted next-generation sequencing of circulating cell-free DNA (ccfDNA) of pediatric Hodgkin lymphoma (PHL) patients to determine pathogenic mechanisms and assess the clinical utility of this method. Hodgkin-Reed/Sternberg (HRS) cell-derived single nucleotide variants, insertions/deletions, translocations and VH-DH-JH rearrangements were detected in pretherapy ccfDNA of 72 of 96 patients. Number of variants per patient ranged from 1 to 21 with allele frequencies from 0.6 to 42%. Nine translocation breakpoints were detected. Genes involved in JAK/STAT, NFkB and PI3K signaling and antigen presentation were most frequently affected. SOCS1 variants, mainly deletions, were found in most circulating tumor (ct) DNAs, and seven of the nine translocation breakpoints involved SOCS1. Analysis of VH-DH-JH rearrangements revealed an origin of PHL HRS cells from partially selected germinal center B cells. Amounts of pretherapy ctDNA were correlated with metabolic tumor volumes. Furthermore, in all ccfDNA samples of 43 patients with early response assessment quantitative qPET < 3, indicative of a favorable clinical course, ctDNA was not detectable. In contrast, in five of six patients with qPET > 3, indicative of an unfavorable clinical course, ctDNA remained detectable. ccfDNA analysis of PHL is thus a suitable approach to determine pathogenic mechanisms and monitor therapy response. |
| deVeber G, Andrew M, Adams C, Bjornson B, Booth F, Buckley DJ, Camfield CS, David M, Humphreys P, Langevin P, MacDonald EA, Gillett J, Meaney B, Shevell M, Sinclair DB, Yager J, Canadian Pediatric Ischemic Stroke Study Group |
Cerebral sinovenous thrombosis in children. |
The New England journal of medicine 2001 Aug 9; 345: 417 |
|
| deVeber G, Andrew M, Adams C, Bjornson B, Booth F, Buckley DJ, Camfield CS, David M, Humphreys P, Langevin P, MacDonald EA, Gillett J, Meaney B, Shevell M, Sinclair DB, Yager J, Canadian Pediatric Ischemic Stroke Study Group |
Cerebral sinovenous thrombosis in children. |
The New England journal of medicine 2001, 345: 417 |
|
| BACKGROUND: Cerebral sinovenous thrombosis in children is a serious disorder, and information is needed about its prevention and treatment.
METHODS: The Canadian Pediatric Ischemic Stroke Registry was initiated in 1992 at the 16 pediatric tertiary care centers in Canada. Children (newborn to 18 years of age) with symptoms and radiographic confirmation of sinovenous thrombosis were included.
RESULTS: During the first six years of the registry, 160 consecutive children with sinovenous thrombosis were enrolled, and the incidence of the disorder was 0.67 cases per 100,000 children per year. Neonates were most commonly affected. Fifty-eight percent of the children had seizures, 76 percent had diffuse neurologic signs, and 42 percent had focal neurologic signs. Risk factors included head and neck disorders (in 29 percent), acute systemic illnesses (in 54 percent), chronic systemic diseases (in 36 percent), and prothrombotic states (in 41 percent). Venous infarcts occurred in 41 percent of the children. Fifty-three percent of the children received antithrombotic agents. Neurologic deficits were present in 38 percent of the children, and 8 percent died; half the deaths were due to sinovenous thrombosis. Predictors of adverse neurologic outcomes were seizures at presentation and venous infarcts.
CONCLUSIONS: Sinovenous thrombosis in children affects primarily neonates and results in neurologic impairment or death in approximately half the cases. The occurrence of venous infarcts or seizures portends a poor outcome |
| Deutsche Gesellschaft für Angiologie - Gesellschaft für Gefäßmedizin eV |
S2k-Leitlinie Diagnostik und Therapie der Venenthrombose und der Lungenembolie. |
AWMF-Register Nr. 065-002 2015 |
|
| Deutsche Gesellschaft für Palliativmedizin |
Definitionen der Deutschen Gesellschaft für Palliativmedizin. |
|
|
| Dhom G, Kaatsch P, Kolles H, Michaelis J, Niemeyer A, Seitz G, Ziegler H |
Erkrankungshäufigkeit und Überlebenschancen bei Krebs. Ergebnisse des Saarländischen Krebsregisters und des bundesweiten Registers für bösartige Erkrankungen im Kindesalter. |
Schriftenreihe des Bundesministeriums für Gesundheit 1991, 2 |
|
| Dickerhoff R, Weirich A, Harms D, Schmidt D |
Successful therapy of local recurrence of congenital mesoblastic nephroma. |
Klin Pädiatr 1995, 207: 48 |
|
| Dickerhoff R, Von Rücker A, Kohne, E |
Sichelzellerkrankungen in Deutschland. |
Dt Arztebl 1998, 95, 1675 |
|
| Dickerhoff R, von Rücker A |
The clinical course of immune thrombocytopenic purpura in children who did not receive intravenous immunoglobulins or sustained prednisone treatment. |
J Pediatr 2000, 137: 629 |
|
| Objective: To demonstrate the result of watchful waiting without specific therapy in unselected children with acute immune thrombocytopenic purpura (ITP). Study design: Between May 1992 and October 1999, 55 consecutive children (aged 2 months to 16 years; 28 boys and 27 girls) with acute ITP did not receive intravenously administered immune globulin G (IVIG) or sustained prednisone treatment. Patients with extensive mucosal bleeding were given prednisone, 2 mg/kg/d, for 3 days. Results: In 37 of 55 patients the initial platelet count was <10,000/μL. Ten of these patients had active mucosal bleeding. Five additional patients with bleeding had platelet counts between 10,000 and 20,000/μL. Four patients were given a 3-day course of prednisone. Chronic ITP occurred in 7 (13%) of the patients; 29 patients achieved remission within 6 weeks, and 19 patients, between 6 weeks and 6 months. No life-threatening bleeding occurred, and no patient died. Conclusion: Most children with severe thrombocytopenia do not have active mucosal bleeding. This management approach, which did not administer specific therapy, avoided side effects, reduced cost, and was effective. |
| Dickerhoff R |
[Splenic sequestration in patients with sickle cell disease. ]. |
Klinische Padiatrie 2002 Mar-Apr; 214: 70 |
|
| Splenic sequestration is a potentially life threatening event that is characteristic for sickle cell disease. For reasons unknown a fraction of or even the entire blood volume is trapped in the splenic sinuses within a few hours and thus is no longer available for circulation. The result is splenomegaly, hypovolemia, anemia and extreme reticulocytosis. If the sequestered blood volume is very large the patient goes into fatal hypovolemic shock unless transfused instantly. If the sequestered volume is small there is a chance of spontaneous resolution. The etiology of splenic sequestration is not known. Children with homozygous sickle cell disease (HbSS) are at risk until age 6 years while individuals with compound heterozygous disease (HbSbetaThal, HbSC, HbSD) may develop splenic sequestration even in adulthood. Parents of infants and toddlers with sickle cell disease need to learn how to palpate the spleen in order to detect splenomegaly as early as possible and take the child to the hospital. Splenic sequestration with a drop in hemoglobin of more than 3 g/dl below the patient's usual hemoglobin level is a clear indication for splenectomy regardless of the patient's age as splenic sequestration tends to recur. |
| Dickerhoff R |
[Splenic sequestration in patients with sickle cell disease. ]. |
Klinische Padiatrie 2002, 214: 70 |
|
| Splenic sequestration is a potentially life threatening event that is characteristic for sickle cell disease. For reasons unknown a fraction of or even the entire blood volume is trapped in the splenic sinuses within a few hours and thus is no longer available for circulation. The result is splenomegaly, hypovolemia, anemia and extreme reticulocytosis. If the sequestered blood volume is very large the patient goes into fatal hypovolemic shock unless transfused instantly. If the sequestered volume is small there is a chance of spontaneous resolution. The etiology of splenic sequestration is not known. Children with homozygous sickle cell disease (HbSS) are at risk until age 6 years while individuals with compound heterozygous disease (HbSbetaThal, HbSC, HbSD) may develop splenic sequestration even in adulthood. Parents of infants and toddlers with sickle cell disease need to learn how to palpate the spleen in order to detect splenomegaly as early as possible and take the child to the hospital. Splenic sequestration with a drop in hemoglobin of more than 3 g/dl below the patient's usual hemoglobin level is a clear indication for splenectomy regardless of the patient's age as splenic sequestration tends to recur. |
| Dickerhoff R, Kulozik AE |
Sichelzelllkrankheit. |
In: Gadner H, Gaedicke G, Niemeyer C, Ritter J, editors: Pädiatrische Hämatologie und Onkologie Springer Verlag, 2006, 179 |
|
| Dickerhoff R |
Sichelzellkrankheit. |
Leitlinien zur Diagnostik und Therapie in der Pädiatrischen Onkologie und Hämatologie AWMF online 2010 |
|
| Dickerhoff R, Eberl W |
Leitlinie „Immunthrombozytopenie (ITP) im Kindes- und Jugendalter“ |
AWMF-Leitlinien |
|
| Dieckmann K, Potter R, Wagner W, Prott F, Hornig-Franz I, Rath B, Schellong G |
Up-front centralized data review and individualized treatment proposals in a multicenter pediatric Hodgkin's disease trial with 71 participating hospitals. |
Radiother Oncol 2002, 62: 191 |
|
| Dieckvoss B, Stanulla M, Schrappe M, Beier R, Zimmermann M, Welte K, Reiter A |
Polymorphisms within glutathione S-transferase genes in pediatric non-Hodgkin's lymphoma. |
haematologica 2002, 87: 709 |
|
| Dietzsch S, Placzek F, Pietschmann K, von Bueren AO, Matuschek C, Glück A, Guckenberger M, Budach V, Welzel J, Pöttgen C, Schmidberger H, Heinzelmann F, Paulsen F, Escudero MP, Schwarz R, Hornung D, Martini C, Grosu AL, Stueben G, Jablonska K, Dunst J, Stranzl-Lawatsch H, Dieckmann K, Timmermann B, Pietsch T, Warmuth-Metz M, Bison B, Kwiecien R, Benesch M, Gerber NU, Grotzer MA, Pfister SM, Clifford SC, von Hoff K, Klagges S, Rutkowski S, Kortmann RD, Mynarek M |
Evaluation of Prognostic Factors and Role of Participation in a Randomized Trial or a Prospective Registry in Pediatric and Adolescent Nonmetastatic Medulloblastoma - A Report From the HIT 2000 Trial. |
Advances in radiation oncology 2020, 5: 1158 |
|
| We aimed to compare treatment results in and outside of a randomized trial and to confirm factors influencing outcome in a large retrospective cohort of nonmetastatic medulloblastoma treated in Austria, Switzerland and Germany. |
| Dietzsch S, Braesigk A, Seidel C, Remmele J, Kitzing R, Schlender T, Mynarek M, Geismar D, Jablonska K, Schwarz R, Pazos M, Walser M, Frick S, Gurtner K, Matuschek C, Harrabi SB, Glück A, Lewitzki V, Dieckmann K, Benesch M, Gerber NU, Rutkowski S, Timmermann B, Kortmann RD |
Pretreatment central quality control for craniospinal irradiation in non-metastatic medulloblastoma : First experiences of the German radiotherapy quality control panel in the SIOP PNET5 MB trial. |
Strahlentherapie und Onkologie 2021, 197: 674 |
|
| Several studies have demonstrated the negative impact of radiotherapy protocol deviations on tumor control in medulloblastoma. In the SIOP PNET5 MB trial, a pretreatment radiotherapy quality control (RT-QC) program was introduced. A first analysis for patients enrolled in Germany, Switzerland and Austria with focus on types of deviations in the initial plan proposals and review criteria for modern radiation technologies was performed. |
| Diller L |
Clinical practice. Adult primary care after childhood acute lymphoblastic leukemia. |
N Engl J Med 2011; 365 : 1417 |
|
| Dini G, Locatelli F, Peters C, Wachowiak J, EBMT Paediatric Diseases |
Proceedings of the 6th Meeting of the EBMT Paediatric Diseases Working Party and 1st Meeting of the EBMT Paediatric Nurses. Introduction. |
Bone marrow transplantation 2008, 42 Suppl 2:S1 |
|
| DiNofia AM, Maude SL |
Chimeric Antigen Receptor T-Cell Therapy Clinical Results in Pediatric and Young Adult B-ALL. |
HemaSphere 2019, 3:e279 |
|
| Chimeric antigen receptor (CAR)-modified T-cell therapy has revolutionized the care of patients with relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL). Results from clinical trials across multiple institutions report remarkable remission rates with CD19-directed CAR-modified T-cell therapy. These remissions are also proving to be durable in many patients with a relapse-free survival (RFS) of approximately 50% to 60% at 1 year across several trials and institutions in this population that has been historically very difficult to treat. In addition, new products are being developed to enhance upon the original CAR T-cell products, which include a humanized CAR, allogeneic CARs, and both CD22 and biallelic CD19 and CD22 constructs. Toxicity after CAR-modified T-cell therapy is characterized by cytokine release syndrome (CRS) and neurotoxicity in the acute post-infusion period and B-cell aplasia as a long-term consequence of treatment. This review will summarize the published data thus far on the use of CAR-modified T-cell therapy in pediatric B-ALL and outline the various CAR products now being developed for this population. Delivery of this therapy and the decision to pursue hematopoietic stem cell transplant (HSCT) after treatment will be discussed. |
| Dirksen U, Poremba C, Schuck A |
Knochentumoren des Kindes-und Jugendalters. |
Der Onkologe 2005, 10: 1034 |
|
| Dirksen U, Jürgens H |
Ewing-Sarkome und PNET des Kindes- und Jugendalters. |
Interdisziplinäre Leitlinie der Deutschen Krebsgesellschaft und der Gesellschaft für Pädiatrische Onkologie und Hämatologie AWMF online |
|
| Dirksen U, Jürgens H |
Approaching Ewing sarcoma. |
Future Oncol 2010, 6: 1155 |
|
| Although Ewing sarcoma represents a rare malignancy of childhood and adolescence, it has attracted the attention of an increasing number of excellent researchers. With a tumor-specific EWS-ETS translocation coding for a transcription factor, which obviously profoundly modifies the intracellular signaling network, this rare malignancy opens insights in pathological gene and protein regulation. Despite decades of basic and translational research, clinical improvement has not yet been modulated by novel targeted therapies, but is produced by well-designed multimodal treatments. By using these multimodal treatment approaches, which always include chemotherapy and local treatment, the prognosis has been improved by up to 70%. For more than 10 years, the survival curves have plateaued at a relatively high level. However, a 30% relapse rate is still unacceptably high, considering that the prognosis after relapse is fatal for most patients. Therefore, novel treatment approaches are urgently required. This article provides an overview of the Ewing sarcoma research of the past few years; while not claiming to be complete, it offers a view on putative strategies with translational potential. |
| Dirksen U, Jürgens H |
Ewing-Sarkome des Kindes- und Jugendalters. |
S1-Leitlinie der Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH) AWMF online 2014 |
|
| Dirksen U, Jürgens H |
Ewing-Sarkom. |
in: Niemeyer C, Eggert A (Hrsg.): Pädiatrische Hämatologie und Onkologie, Springer-Verlag GmbH Deutschland, 2. vollständig überarbeitete Auflage 2018, 497 |
|
| Dirksen U, Brennan B, Le Deley MC, Cozic N, van den Berg H, Bhadri V, Brichard B, Claude L, Craft A, Amler S, Gaspar N, Gelderblom H, Goldsby R, Gorlick R, Grier HE, Guinbretiere JM, Hauser P, Hjorth L, Janeway K, Jürgens H, Judson I, Krailo M, Kruseova J, Kuehne T, Ladenstein R, Lervat C, Lessnick SL, Lewis I, Linassier C, Marec-Berard P, Marina N, Morland B, Pacquement H, Paulussen M, Randall RL, Ranft A, Le Teuff G, Wheatley K, Whelan J, Womer R, Oberlin O, Hawkins DS, Euro-EWING 99 and Ewing 2008 Investigators |
High-Dose Chemotherapy Compared With Standard Chemotherapy and Lung Radiation in Ewing Sarcoma With Pulmonary Metastases: Results of the European Ewing Tumour Working Initiative of National Groups, 99 Trial and EWING 2008. |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2019, 37: 3192 |
|
| The R2Pulm trial was conducted to evaluate the effect of busulfan-melphalan high-dose chemotherapy with autologous stem-cell rescue (BuMel) without whole-lung irradiation (WLI) on event-free survival (main end point) and overall survival, compared with standard chemotherapy with WLI in Ewing sarcoma (ES) presenting with pulmonary and/or pleural metastases. |
| Dirksen U, Brennan B, Le Deley MC, Cozic N, van den Berg H, Bhadri V, Brichard B, Claude L, Craft A, Amler S, Gaspar N, Gelderblom H, Goldsby R, Gorlick R, Grier HE, Guinbretiere JM, Hauser P, Hjorth L, Janeway K, Jürgens H, Judson I, Krailo M, Kruseova J, Kuehne T, Ladenstein R, Lervat C, Lessnick SL, Lewis I, Linassier C, Marec-Berard P, Marina N, Morland B, Pacquement H, Paulussen M, Randall RL, Ranft A, Le Teuff G, Wheatley K, Whelan J, Womer R, Oberlin O, Hawkins DS, Euro-EWING 99 and Ewing 2008 Investigators |
High-Dose Chemotherapy Compared With Standard Chemotherapy and Lung Radiation in Ewing Sarcoma With Pulmonary Metastases: Results of the European Ewing Tumour Working Initiative of National Groups, 99 Trial and EWING 2008. |
Journal of clinical oncology 2019,JCO1900915 |
|
| The R2Pulm trial was conducted to evaluate the effect of busulfan-melphalan high-dose chemotherapy with autologous stem-cell rescue (BuMel) without whole-lung irradiation (WLI) on event-free survival (main end point) and overall survival, compared with standard chemotherapy with WLI in Ewing sarcoma (ES) presenting with pulmonary and/or pleural metastases. |
| Zöllner SK, Amatruda JF, Bauer S, Collaud S, de Álava E, DuBois SG, Hardes J, Hartmann W, Kovar H, Metzler M, Shulman DS, Streitbürger A, Timmermann B, Toretsky JA, Uhlenbruch Y, Vieth V, Grünewald TGP, Dirksen U |
Ewing Sarcoma-Diagnosis, Treatment, Clinical Challenges and Future Perspectives. |
Journal of clinical medicine 2021, 10 |
|
| Ewing sarcoma, a highly aggressive bone and soft-tissue cancer, is considered a prime example of the paradigms of a translocation-positive sarcoma: a genetically rather simple disease with a specific and neomorphic-potential therapeutic target, whose oncogenic role was irrefutably defined decades ago. This is a disease that by definition has micrometastatic disease at diagnosis and a dismal prognosis for patients with macrometastatic or recurrent disease. International collaborations have defined the current standard of care in prospective studies, delivering multiple cycles of systemic therapy combined with local treatment; both are associated with significant morbidity that may result in strong psychological and physical burden for survivors. Nevertheless, the combination of non-directed chemotherapeutics and ever-evolving local modalities nowadays achieve a realistic chance of cure for the majority of patients with Ewing sarcoma. In this review, we focus on the current standard of diagnosis and treatment while attempting to answer some of the most pressing questions in clinical practice. In addition, this review provides scientific answers to clinical phenomena and occasionally defines the resulting translational studies needed to overcome the hurdle of treatment-associated morbidities and, most importantly, non-survival. |
| Distelmaier F, Calaminus G, Harms D, Sträter R, Kordes U, Fleischhack G, Göbel U, Schneider DT |
Ovarian small cell carcinoma of the hypercalcemic type in children and adolescents: a prognostically unfavorable but curable disease. |
Cancer 2006, 107: 2298 |
|
| BACKGROUND: Ovarian small cell carcinoma of the hypercalcemic type is a rare neoplasm that is associated with a poor prognosis. The objective of the current study was to investigate the clinicopathologic features of this tumor and to develop preliminary diagnostic and therapeutic guidelines. METHODS: Between 1994 and 2005, 11 girls (ages 9-22 years) who were registered on the German Maligne Keimzelltumoren studies and the Kiel Pediatric Tumor Registry were analyzed. Prior to histopathologic review, 8 patients had been misdiagnosed with either germ cell tumor or juvenile granulosa cell tumor. RESULTS: According to the International Federation of Gynecologic Oncology, 4 patients had Stage IA disease, 3 patients had Stage IC disease, and 4 patients had Stage III disease. After resection, 4 patients were followed without additional therapy, and all 4 patients developed recurrent disease after 3 to 11 months. Seven patients received adjuvant chemotherapy during first-line treatment. One patient with Stage III disease received additional regional deep hyperthermia. During first-line treatment, high-dose chemotherapy was received by 4 patients who achieved a complete response (CR) after conventional chemotherapy. All 4 of those patients remained in CR for 7 to 73 months, whereas the other 3 patients developed recurrent disease. Salvage treatment after recurrence or tumor progression consisted of surgery and chemotherapy. One patient received high-dose chemotherapy in 2nd CR and remained in 2nd CR. In total, 5 patients remained alive with no evidence of disease. CONCLUSIONS: Patients with ovarian small cell carcinoma of the hypercalcemic type require multiagent chemotherapy during first-line treatment. High-dose chemotherapy may be used to consolidate the therapeutic success. |
| Dittrich R, Kliesch S, Schüring A |
Fertilitätserhalt bei onkologischen Erkrankungen - Leitlinienprogramm der Deutschen, Österreichischen und Schweizerischen Gesellschaften für Gynäkologie und Geburtshilfe (DGGG, OEGGG, SGGG). |
AWMFonline S2k-Leitlinie 015/082, 2017 |
|
| Dittner-Moormann S, Reschke M, Abbink FCH, Aerts I, Atalay HT, Fedorovna Bobrova N, Biewald E, Brecht IB, Caspi S, Cassoux N, Castela G, Diarra Y, Duncan C, Ebinger M, Garcia Aldana D, Hadjistilianou D, Kepák T, Klett A, Kiratli H, Maka E, Opocher E, Pawinska-Wasikowska K, Rascon J, Russo I, Rutynowska-Pronicka O, Sábado Álvarez C, Pacheco SSR, Svojgr K, Timmermann B, Vishnevskia-Dai V, Eggert A, Ritter-Sovinz P, Bechrakis NE, Jenkinson H, Moll A, Munier FL, Popovic MB, Chantada G, Doz F, Ketteler P |
Adjuvant therapy of histopathological risk factors of retinoblastoma in Europe: A survey by the European Retinoblastoma Group (EURbG). |
Pediatric blood & cancer 2021, 68:e28963 |
|
| Advanced intraocular retinoblastoma can be cured by enucleation, but spread of retinoblastoma cells beyond the natural limits of the eye is related to a high mortality. Adjuvant therapy after enucleation has been shown to prevent metastasis in children with risk factors for extraocular retinoblastoma. However, histological criteria and adjuvant treatment regimens vary and there is no unifying consensus on the optimal choice of treatment. |
| Deutsche Kinderkrebsstiftung |
Viele offene Fragen - Studie stellt erhöhtes Leukämierisiko für Kinder in AKW-Nähe fest. |
WIR - Die Zeitschrift der Deutschen Kinderkrebsstiftung und der Deutschen Leukämie-Forschungshilfe e.V 1/08 |
|
| Dockhorn-Dworniczak B, Schäfer K, Dantcheva R, Blasius S, van, Burdach S, Winkelmann W, Jürgens H, Böcker W |
Molecular genetic detection of t(11;22)(q24;12) translocation in Ewing sarcoma and malignant peripheral neuroectodermal tumors. |
Pathologe 1994, 15: 103 |
|
| Dockhorn-Dworniczak B, Schäfer K, Dantcheva R, Blasius S, Böcker W, Jürgens H, Winkelmann W, Burdach S |
Prognostic features of Ewing's sarcoma on plain radiograph and computed tomography scan after initial treatment [letter; comment]. |
Cancer 1994, 74: 988 |
|
| Dockhorn-Dworniczak B, Schäfer K, Dantcheva R, Blasius S, Winkelmann W, Strehl S, Burdach S, van Valen F, Jürgens H, Böcker W |
Diagnostic value of the molecular genetic detection of the t(11;22) translocation in Ewing's tumours. |
Virchows Arch 1994, 425: 107 |
|
| Dockhorn-Dworniczak B, Schafer K, Blasius S, Christiansen H, Koscielniak E, Ritter J, Winkelmann W, Jürgens H, Bocker W |
Assessment of molecular genetic detection of chromosome translocations in the differential diagnosis of pediatric sarcomas. |
Klinische Pädiatrie 1997, 209: 156 |
|
| Dördelmann M, Reiter A, Borkhardt A, Ludwig W, Gotz N, Viehmann S, Gadner H, Riehm H, Schrappe M |
Prednisone response is the strongest predictor of treatment outcome in infant acute lymphoblastic leukemia. |
Blood 1999, 94: 1209 |
|
| Dörffel W |
Morbus Hodgkin. |
Leitlinien Kinderheilkunde und Jugendmedizin der Deutschen Gesellschaft für Kinderheilkunde und Jugendmedizin / Kompendium Onkologie 1999, 65 |
|
| Dörffel W, Lüders H, Rühl U, Albrecht M, Marciniak H, Parwaresch R, Pötter R, Schellong G, Schwarze E, Wickmann L |
Preliminary results of the multicenter trial GPOH-HD 95 for the treatment of Hodgkin's disease in children and adolescents. |
Klin Pädiatr 2003, 215: 139 |
|
| Dörffel W, Schellong G |
Morbus Hodgkin. |
in: Gadner H, Gaedicke G, Niemeyer CH, Ritter J: Pädiatrische Hämatologie und Onkologie Springer-Verlag, 2006, 752 |
|
| Dörffel W, Riepenhausen M, Ludwig W-D, Schellong G |
Langzeitfolgen nach Therapie eines Hodgkin-Lymphoms bei Kindern und Jugendlichen. |
Journal Onkologie 09, 449-456 2010 |
|
| Dörffel W, Riepenhausen M, Lüders H, Brämswig J, Wickmann L, Schellong G |
Langzeitfolgen nach Behandlung eines Hodgkin-Lymphoms im Kindes- und Jugendalter. |
Wir - Die Zeitschrift der Deutschen Leukämie-Forschungshilfe e.V. und der Deutschen Kinderkrebsstiftung 2011, 4: 24 |
|
| Dörffel W, Rühl U, Lüders H, Claviez A, Albrecht M, Bökkerink J, Holte H, Karlen J, Mann G, Marciniak H, Niggli F, Schmiegelow K, Schwarze EW, Pötter R, Wickmann L, Schellong G |
Treatment of children and adolescents with Hodgkin lymphoma without radiotherapy for patients in complete remission after chemotherapy: final results of the multinational trial GPOH-HD95. |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2013, 31: 1562 |
|
| PURPOSE To minimize the risk of late effects in pediatric Hodgkin lymphoma (HL) by omitting radiotherapy (RT) in patients in complete remission (CR) after chemotherapy and reducing the standard radiation dose to 20 Gy in patients in incomplete remission. |
| Dörffel W, Riepenhausen M, Lüders H, Brämswig J, Schellong, G |
Sekundäre maligne Neoplasien nach Therapie eines Hodgkin-Lymphoms im Kindes- und Jugendalter: Eine Kohortenstudie mit mehr als 30 Jahren Nachbeobachtung. |
Dtsch Arztebl Int 2015; 112: 320 |
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| Dolman KM, Revesz T, Niemeyer CM, van Wering ER, de Saint Basile G, Canninga M, Bierings MB, Wulffraat NM |
Myelodysplastic features in Griscelli syndrome. |
Journal of pediatric hematology/oncology : official journal of the American Society of Pediatric Hematology/Oncology 2004, 26: 275 |
|
| Dome JS, Graf N, Geller JI, Fernandez CV, Mullen EA, Spreafico F, Van den Heuvel-Eibrink M, Pritchard-Jones K |
Advances in Wilms Tumor Treatment and Biology: Progress Through International Collaboration. |
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2015 Sep 20; 33: 2999 |
|
| Clinical trials in Wilms tumor (WT) have resulted in overall survival rates of greater than 90%. This achievement is especially remarkable because improvements in disease-specific survival have occurred concurrently with a reduction of therapy for large patient subgroups. However, the outcomes for certain patient subgroups, including those with unfavorable histologic and molecular features, bilateral disease, and recurrent disease, remain well below the benchmark survival rate of 90%. Therapy for WT has been advanced in part by an increasingly complex risk-stratification system based on patient age; tumor stage, histology, and volume; response to chemotherapy; and loss of heterozygosity at chromosomes 1p and 16q. A consequence of this system has been the apportionment of patients into such small subgroups that only collaboration between large international WT study groups will support clinical trials that are sufficiently powered to answer challenging questions that move the field forward. This article gives an overview of the Children's Oncology Group and International Society of Pediatric Oncology approaches to WT and focuses on four subgroups (stage IV, initially inoperable, bilateral, and relapsed WT) for which international collaboration is pressing. In addition, biologic insights resulting from collaborative laboratory research are discussed. A coordinated expansion of international collaboration in both clinical trials and laboratory science will provide real opportunity to improve the treatment and outcomes for children with renal tumors on a global level.
© 2015 by American Society of Clinical Oncology. |
| Donahue B, Scott CB, Nelson JS, Rotman M, Murray KJ, Nelson DF, Banker FL, Earle JD, Fischbach JA, Asbell SO, Gaspar LE, Markoe AM, Curran W |
Influence of an oligodendroglial component on the survival of patients with anaplastic astrocytomas: a report of Radiation Therapy Oncology Group 83-02. |
Int J Radiat Oncol Biol Phys 1997, 38: 911 |
|
| van Dongen JJ, Seriu T, Panzer-Grümayer ER, Biondi A, Pongers-Willemse MJ, Corral L, Stolz F, Schrappe M, Masera G, Kamps WA, Gadner H, van Wering ER, Ludwig WD, Basso G, de Bruijn MA, Cazzaniga G, Hettinger K, van der Does-van den Berg A, Hop WC, Riehm H, Bartram CR |
Prognostic value of minimal residual disease in acute lymphoblastic leukaemia in childhood. |
Lancet 1998, 352: 1731 |
|
| BACKGROUND: Sensitive techniques for detection of minimal residual disease (MRD) at degrees of one leukaemic cell per 10(3)-10(6) cells (10(-3)-10(-6)) during follow-up of children with acute lymphoblastic leukaemia (ALL) can provide insight into the effectiveness of cytotoxic treatment. However, it is not yet clear how information on MRD can be applied to treatment protocols. METHODS: We monitored 240 patients with childhood ALL who were treated according to national protocols of the International BFM Study Group. 60 patients relapsed and the patients in continuous complete remission (CCR) had a median event-free follow-up of 48 months. Bone-marrow samples were collected at up to nine time points during and after treatment. Standardised PCR analysis of patient-specific immunoglobulin and T-cell receptor gene rearrangements and TAL1 deletions were used as targets for semiquantitative estimation of MRD. Amount of MRD was classed as 10(-2) or more, 10(-3), and 10(-4) or less. FINDINGS: MRD negativity at the various follow-up times was associated with low relapse rates (3-15% at 3 years), but five-fold to ten-fold higher relapse rates (39-86% at 3 years) were found in MRD-positive patients. The distinct degrees of MRD appeared to have independent prognostic value (p [trend]<0.001) at all separate time points, especially at the first two time points (at the end of induction treatment and before consolidation treatment). At these two time points a high degree of MRD (> or = 10(-2)) was associated with a three-fold higher relapse rate when compared with patients with a low degree of MRD (< or = 10(-4)). At later time points (including the end of treatment) even a low degree of MRD was associated with a poor outcome. Positivity in patients in CCR after treatment was rare (< 1%). With the combined MRD information from the first two follow-up time points, it was possible to recognise three different risk groups--55 (43%) were in a low-risk group and had a 3-year relapse rate of only 2% (95% CI 0.05-12%); 19 (15%) were in a high-risk group and had a relapse rate of 75% (55-95%); and 55 (43%) were in an intermediate-risk group and had a 3-year relapse rate of 23% (13-36%). INTERPRETATION: Our collaborative MRD study shows that monitoring patients with childhood ALL at consecutive time points gives clinically relevant insight into the effectiveness of treatment. Combined information on MRD from the first 3 months of treatment distinguishes patients with good prognoses from those with poor prognoses, and this helps in decisions whether and how to modify treatment. |
| Donaldson S, Hudson M, Oberlin O, Brämswig J, Schellong G |
Pediatric Hodgkin's Disease. |
|
|
| Dopfer R |
Familienorientierte hämatoonkologische Rehabilitation. |
FORUM 2013 28: 96 |
|
| Dotsch J, Christiansen H, Hanze J, Lampert F, Rascher W |
Plasma neuropeptide Y of children with neuroblastoma in relation to stage, age and prognosis, and tissue neuropeptide Y |
Regul Pept 1998, 75-76: 185 |
|
| Dotsch J, Harmjanz A, Christiansen H, Hanze J, Lampert F, Rascher W |
Gene expression of neuronal nitric oxide synthase and adrenomedullin in human neuroblastoma using real-time PCR. |
Int J Cancer 2000, 88: 172 |
|
| Cines DB, Levine LD |
Thrombocytopenia in pregnancy. |
Hematology. American Society of Hematology 2017, 2017, 144 |
|
| hrombocytopenia develops in 5% to 10% of women during pregnancy or in the immediate postpartum period. A low platelet count is often an incidental feature, but it might also provide a biomarker of a coexisting systemic or gestational disorder and a potential reason for a maternal intervention or treatment that might pose harm to the fetus. This chapter reflects our approach to these issues with an emphasis on advances made over the past 5 to 10 years in understanding and managing the more common causes of thrombocytopenia in pregnancy. Recent trends in the management of immune thrombocytopenia translate into more women contemplating pregnancy while on treatment with thrombopoietin receptor agonists, rituximab, or mycophenylate, which pose known or unknown risks to the fetus. New criteria to diagnose preeclampsia, judicious reliance on measurement of ADAMTS13 to make management decisions in suspected thrombotic thrombocytopenic purpura, new evidence supporting the efficacy and safety of anticomplement therapy for atypical hemolytic uremic syndrome during pregnancy, and implications of thrombotic microangiopathies for subsequent pregnancies are evolving rapidly. The goals of the chapter are to help the hematology consultant work through the differential diagnosis of thrombocytopenia in pregnancy based on trimester of presentation, severity of thrombocytopenia, and coincident clinical and laboratory manifestations, and to provide guidance for dealing with some of the more common and difficult diagnostic and management decisions. |
| Dowling MM, Noetzel MJ, Rodeghier MJ, Quinn CT, Hirtz DG, Ichord RN, Kwiatkowski JL, Roach ES, Kirkham FJ, Casella JF, Debaun MR |
Headache and Migraine in Children with Sickle Cell Disease Are Associated with Lower Hemoglobin and Higher Pain Event Rates But Not Silent Cerebral Infarction. |
The Journal of pediatrics 2014, E-pub ahead of print |
|
| To identify risk factors for headache and migraine in children with sickle cell disease and test the hypothesis that either or both are independently associated with silent cerebral infarcts. |
| Draper GJ, Sanders BM, Kingston JE |
Second primary neoplasms in patients with retinoblastoma. |
British journal of cancer 1986, 53: 661 |
|
| In a series of 882 retinoblastoma patients, 384 known to have the genetic form of the disease and 498 others, 30 patients developed second primary neoplasms. The spectrum of these second neoplasms is discussed in relation to the forms of treatment used for the retinoblastoma. Cumulative incidence rates of second tumours in the whole series are 2.0% at 12 years after diagnosis and 4.2% after 18 years. For patients with the genetic form of retinoblastoma the cumulative incidence rate after 18 years is 8.4% for all second neoplasms and 6.0% for osteosarcomas alone. The inherent risk among survivors from genetic retinoblastoma of developing an osteosarcoma, excluding all possible effects of treatment, is estimated to be 2.2% after 18 years. Within the field of radiation treatment the cumulative incidence rate for all second neoplasms after 18 years is 6.6% and for osteosarcomas alone 3.7%. There is some evidence that patients with genetic retinoblastoma are particularly sensitive to the carcinogenic effects of radiation. The results also suggest that the use of cyclophosphamide may increase the risk of second primary neoplasms in patients with genetic retinoblastoma. The incidence rates of second primary neoplasms in retinoblastoma survivors reported here are lower than those quoted for previously published series. Evidence from this and other papers strongly suggests an association between retinoblastoma and malignant melanoma. |
| Driessen EM, de Lorenzo P, Campbell M, Felice M, Ferster A, Hann I, Vora A, Hovi L, Escherich G, Li CK, Mann G, Leblanc T, Locatelli F, Biondi A, Rubnitz J, Schrappe M, Silverman L, Stary J, Suppiah R, Szczepanski T, Valsecchi M, Pieters R |
Outcome of relapsed infant acute lymphoblastic leukemia treated on the interfant-99 protocol. |
Leukemia 2015, Epub ahead of print |
|
| Driessen EM, de Lorenzo P, Campbell M, Felice M, Ferster A, Hann I, Vora A, Hovi L, Escherich G, Li CK, Mann G, Leblanc T, Locatelli F, Biondi A, Rubnitz J, Schrappe M, Silverman L, Stary J, Suppiah R, Szczepanski T, Valsecchi M, Pieters R |
Outcome of relapsed infant acute lymphoblastic leukemia treated on the interfant-99 protocol. |
Leukemia 2016, 30: 1184 |
|
| Driss F, Hequet O |
Red blood cell exchange techniques and methods. |
Transfus apher sci 2019, 58: 132 |
|
| Red blood cell exchange (RBCX) has become a standard therapy to remove abnormal red blood cells (RBC) in patients with sickle cell disease (SCD). In the last few decades, RBCX techniques have gradually improved, allowing sickle RBCs to be removed with greater precision and enabling specific hematological targets to be set. Improved knowledge of the techniques as well as the clinical and biological targets has led to optimization of the procedures. The aim of this review is to summarize the current technique, methods, targets and schedules of RBCX and to consider the outstanding issues that require additional investigation. |
| Dror Y, Zipursky A, Blanchette VS |
Essential thrombocythemia in children. |
Journal of pediatric hematology/oncology 1999, 21: 356 |
|
| The objective of this study was to evaluate the clinical course, laboratory findings, and outcomes of children with essential thrombocythemia (ET). |
| Daw S, Hasenclever D, Mascarin M, Fernández-Teijeiro A, Balwierz W, Beishuizen A, Burnelli R, Cepelova M, Claviez A, Dieckmann K, Landman-Parker J, Kluge R, Körholz D, Mauz-Körholz C, Wallace WH, Leblanc T |
Risk and Response Adapted Treatment Guidelines for Managing First Relapsed and Refractory Classical Hodgkin Lymphoma in Children and Young People. Recommendations from the EuroNet Pediatric Hodgkin Lymphoma Group. |
HemaSphere 2020, 4:e329 |
|
| The objective of this guideline is to aid clinicians in making individual salvage treatment plans for pediatric and adolescent patients with first relapse or refractory (R/R) classical Hodgkin lymphoma (cHL). While salvage with standard dose chemotherapy followed by high dose chemotherapy and autologous stem cell transplant is often considered the standard of care in adult practice, pediatric practice adopts a more individualized risk stratified and response adapted approach to salvage treatment with greater use of non-transplant salvage. Here, we present on behalf of the EuroNet Pediatric Hodgkin Lymphoma group, evidence and consensus-based guidelines for standardized diagnostic, prognostic and response procedures to allocate children and adolescents with R/R cHL to stratified salvage treatments. |
| Dürken M, Finckenstein FG, Janka GE |
Bone marrow transplantation in hemophagocytic lymphohistiocytosis. |
Leukemia & lymphoma 2001, 41(1-2): 89 |
|
| Two important syndromes of hemophagocytic lymphohistiocytosis (HLH) have to be considered in infants and young children with recurrent fever, organomegaly and cytopenias. Familial hemophagocytic lymphohistiocytosis (FHLH) is a genetically heterogeneous autosomal recessive disease with histiocytic and lymphocytic infiltrations in multiple organs and is currently curable only by bone marrow transplantation (BMT). Secondary HLH most commonly results from viral infections and some patients may be cured by treating the causative organism, others will need chemotherapy and immunosuppression. Since infections can also trigger disease episodes in FHLH, making the correct diagnosis can prove difficult. The published experience of BMT in HLH is reviewed. Taken together, cure of the majority of patients with HLH by matched related BMT, unrelated or haploidentical BMT is possible. Incomplete resolution of disease activity does not necessarily impede a successful outcome. Central nervous system involvement will eventually develop in many HLH patients and may cause considerable morbidity. Appropriate early treatment and a timely BMT will hopefully decrease mortality rates and improve neurodevelopmental outcome in this disease. |
| Due-Tonnessen BJ, Helseth E, Scheie D, Skullerud K, Aamodt G, Lundar T |
Long-term outcome after resection of benign cerebellar astrocytomas in children and young adults (0-19 years): report of 110 consecutive cases. |
Pediatr Neurosurg 2002, 37: 71 |
|
| Dübbers M, Simon T, Berthold F, Fischer J, Volland R, Hero B, Cernaianu G |
Retrospective analysis of relapsed abdominal high-risk neuroblastoma. |
Journal of pediatric surgery 2018, 53: 558 |
|
| The impact of abdominal topography and surgical technique on resectability and local relapse pattern of relapsed abdominal high-risk neuroblastoma (R-HR-NB) is not clearly defined. |
| Duffner PK, Cohen ME |
Extraneural metastases in childhood brain tumors. |
Ann Neurol 1981, 10: 261 |
|
| Duffner PK, Krischer JP, Sanford RA, Horowitz ME, Burger PC, Cohen ME, Friedman HS, Kun LE |
Prognostic factors in infants and very young children with intracranial ependymomas. |
Pediatr Neurosurg 1998, 28: 215-22. Review |
|
| The Pediatric Oncology Group (1986-1990) conducted a study in which 48 children <3 years of age with intracranial ependymomas were treated with prolonged postoperative chemotherapy (CT) and delayed RT. Thirty-one children, 0-23 months of age at diagnosis (Gp A) received 2 years of CT followed by RT; while 17 children, 24-36 months of age at diagnosis (Gp B) received CT for 1 year followed by radiation. One-year survivals were 87% (Gp A) and 94% (Gp B) and 2-year survivals were 67% (Gp A) and 82% (Gp B). In subsequent years a significant divergence in survivals according to age has been noted (p = 0.04). Five-year survivals were 25.7% (Gp A) vs. 63.3% (Gp B). The curves began to diverge 1 year following diagnosis. Other than age, the only significant prognostic factor was degree of surgical resection: 5-year survivals were 66% (total resection) vs. 25% (subtotal resection). Neither the presence of metastases, degree of anaplasia nor the degree of surgical resection varied significantly according to age at diagnosis. The most likely reason for the difference in survivals between the two age groups relates to the timing of radiation following CT, i.e., 1-year delay in children 24-36 months of age compared to a 2-year delay in children 0-23 months of age. An alternative but less likely hypothesis is that ependymomas in the younger children have a more aggressive biology. In contrast, survivals in the 24- to 36-month group are much better than previous reports in the literature suggesting that prolonged postoperative CT may allow both a delay in CRT as well as provide improved survivals. Based on these results, future treatment trials should emphasize maximal surgical resection and a delay in radiation of no more than 1 year. |
| Dumas G, Habibi A, Onimus T, Merle JC, Razazi K, Mekontso Dessap A, Galactéros F, Michel M, Frémeaux Bacchi V, Noizat Pirenne F, Bartolucci P |
Eculizumab salvage therapy for delayed hemolysis transfusion reaction in sickle cell disease patients. |
Blood 2016, 25; 127: 1062 |
|
| Dunst J, Paulussen M, Jürgens H |
Lung irradiation for Ewing's sarcoma with pulmonary metastases at diagnosis. |
Strahlenther Onkol 1993, 169: 621 |
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| Dunst J, Jabar S, Paulussen M, Jürgens H |
Local therapy of Ewing sarcoma. |
Klin Pädiatr 1994, 206: 277 |
|
| Dunst J, Jürgens H, Sauer R, Pape H, Paulussen M, Winkelmann W, Rübe C |
Radiation therapy in Ewing's sarcoma. |
Int J Radiat Oncol Biol Phys 1995, 32: 919 |
|
| Dunst J, Hoffmann C, Ahrens S, Jürgens H |
Operation oder Radiotherapie bei prognostisch günstigen Ewing-Sarkomen? |
Strahlenther Onkol 1996, 172: 244 |
|
| Dunst J, Hoffmann C, Ahrens S, Jürgens H |
Surgery versus radiotherapy in Ewing's sarcoma with good prognosis. Analysis of the CESS-86 data. |
Strahlenther Onkol 1996, 172: 244 |
|
| Dunst J, Ahrens S, Paulussen M, Rübe C, Winkelmann W, Zoubek A, Harms D, Jürgens H |
Second malignancies after treatment for Ewing's sarcoma. |
Int J Radiation Oncol Biol 1998, 42: 379 |
|
| Dunkel IJ, Aledo A, Kernan NA, Kushner B, Bayer L, Gollamudi SV, Finlay JL, Abramson DH |
Successful treatment of metastatic retinoblastoma. |
Cancer 2000, 89: 2117 |
|
| BACKGROUND: In the past, patients with metastatic retinoblastoma have had a poor prognosis when treated with conventional modalities. In the current study, the authors evaluated the use of combined intensive conventional chemotherapy, high dose chemotherapy with autologous stem cell rescue (ASCR), and radiation therapy. METHODS: Four patients with metastatic retinoblastoma were treated. All had orbital and bone marrow metastases. In addition, three patients had bone metastases and two patients had liver metastases. None had central nervous system disease. Patients received intensive conventional chemotherapy that included vincristine, cyclophosphamide, etoposide, and either cisplatin or carboplatin. Stem cells were harvested after bone marrow disease was no longer detectable. High dose chemotherapy with carboplatin (500 mg/m(2)/day x 3 days or area under the curve = 7 via the Calvert formula) and thiotepa (300 mg/m(2)/day x 3 days) with (n = 3 patients) or without (n = 1 patient) etoposide (250 mg/m(2)/day x 3 days) was administered with ASCR. Sites that originally harbored bulky disease were irradiated after recovery from the high dose chemotherapy. RESULTS: The therapy was associated with substantial acute hematopoietic and mucosal toxicities. At last follow-up, all four patients had survived event free from 46-80 months after the diagnosis of metastatic disease. CONCLUSIONS: The treatment strategy described in the current study is effective for patients with metastatic retinoblastoma that does not involve the central nervous system. However, a multicenter trial should be considered to evaluate it in a larger group of patients. |
| Dunst J, Ahrens S, Paulussen M, Burdach S, Jürgens H |
Prognostic impact of tumor perfusion in MR-imaging studies in Ewing tumors. |
Strahlenther Onkol 2001, 177: 153 |
|
| Dunkel IJ, Jubran RF, Gururangan S, Chantada GL, Finlay JL, Goldman S, Khakoo Y, O'Brien JM, Orjuela M, Rodriguez-Galindo C, Souweidane MM, Abramson DH |
Trilateral retinoblastoma: potentially curable with intensive chemotherapy. |
Pediatric blood & cancer 2010, 54: 384 |
|
| Trilateral retinoblastoma has been lethal in virtually all cases previously reported. We describe a series of 13 patients treated with intensive chemotherapy, defined as the intention to include high-dose chemotherapy with autologous hematopoietic stem cell rescue. |
| Dworzak MN, Buldini B, Gaipa G, Ratei R, Hrusak O, Luria D, Rosenthal E, Bourquin JP, Sartor M, Schumich A, Karawajew L, Mejstrikova E, Maglia O, Mann G, Ludwig WD, Biondi A, Schrappe M, Basso G, International-BFM-FLOW-network |
AIEOP-BFM consensus guidelines 2016 for flow cytometric immunophenotyping of Pediatric acute lymphoblastic leukemia. |
Cytometry. Part B, Clinical cytometry 2017 Feb 10; |
|
| Dzietko M, Schara U, Felderhoff-Müser U |
Perinataler Schlaganfall und Sinusvenenthrombose: Klinik, Diagnostik und therapeutische Ansätze. |
Monatsschr Kinderheilkd 2017, 7: 596 |
|
| Dörr H, Koch A, Sauerwald T, Beck J |
Endocrine dysfunction after brain tumor therapy in children. |
Late Sequelae in Oncology 1995, 59 |
|
| Dörr H, Koch A, Kühl J, Müller H, Beck J |
Endocrinologic after-care of brain tumor patients. |
Klin Pädiatr 1996, 208: 197 |
|
| Dördelmann M, Reiter A, Zimmermann M, Fengler R, Henze G, Riehm H, Schrappe M |
Intermediate dose methotrexate is as effective as high dose methotrexate in preventing isolated testicular relapse in childhood acute lymphoblastic leukemia. |
J Pediatr Hematol Oncol 1998, 20: 444 |
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| Dördelmann M, Schrappe M, Reiter A, Zimmermann M, Graf N, Schott G, Lampert F, Harbott J, Niemeyer C, Ritter J, Dörffel W, Nessler G, Kühl J, Riehm H |
Down's syndrome in childhood acute lymphoblastic leukemia. |
Leukemia 1998, 12: 645 |
|
| Dörffel W, Albrecht M, Lüders H, Marciniak H, Parwaresch R, Schwarze E, Trauzeddel R, Havers W, Henze G, Janka-Schaub G, Mann G, Niemeyer C, Pötter R, Schellong G, Selle B, Treuner J, Ruhl U |
Multi-national therapy study for Hodgkin's disease in children and adolescents GPOH-DH 95. Interim report after 2 1/2 years. |
Klin Pädiatr 1998, 210: 212 |
|
| Dörffel W |
Morbus Hodgkin im Kindesalter. Interdisziplinäre Leitlinien der Deutschen Krebsgesellschaft und der Deutschen Gesellschaft für Pädiatrische Onkologie und Hämatologie. |
Forum 2000, 15: 44 |
|
| Dörffel W |
Morbus Hodgkin im Kindesalter. |
Interdisziplinäre Leitlinie der Deutschen Krebsgesellschaft und der Deutschen Gesellschaft für Pädiatrische Onkologie und Hämatologie 2001 |
|
| Dörffel W |
Morbus Hodgkin im Kindesalter. In: Qualitätssicherung in der Onkologie - Diagnostik und Therapie maligner Erkrankungen. Kurzgefasste interdisziplinäre Leitlinien. |
Zugschwerdt Verlag München 3. Aufl. 2002, 409 |
|
| Dörffel W |
Morbus Hodgkin im Kindesalter. |
Interdisziplinäre Leitlinie der Deutschen Krebsgesellschaft und der Deutschen Gesellschaft für Pädiatrische Onkologie und Hämatologie 2005 |
|
| Dübbers A, Schulze-Westhoff P, Kurzknabe E, Creutzig U, Ritter J, Boos J |
Asparaginase synthetase in paediatric acute leukemias. |
Haematology and Blood Transfusion 1997, 39: 530 |
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| Dübbers A, Würthwein G, Müller H, Schulze-Westhoff P, Winkelhorst M, Kurzknabe E, Lanvers C, Pieters R, Kaspers G, Creutzig U, Ritter J, Boos J |
Asparagine synthetase activity in paediatric acute leukaemias. |
Br J Haematol 2000, 109: 427 |
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