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  • Fricke, Hj  (12)
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  • 1
    Language: English
    In: Journal of Cancer Research and Clinical Oncology, 2011, Vol.137(4), pp.733-738
    Description: Byline: Nils Winkelmann (1), Iver Petersen (2), Michael Kiehntopf (3), Hans Joerg Fricke (1), Andreas Hochhaus (1), Ulrich Wedding (1) Keywords: Geriatric assessment; Malignant lymphoma; Comorbidity; Survival; Prognostic value Abstract: Purpose The prevalence of elderly and comorbid patients (pts) with malignant lymphoma (ML) will steadily increase in future. Elderly patients comprise a heterogeneous population. Comprehensive geriatric assessment (CGA) is an established diagnostic tool in geriatric medicine. However, the prognostic value in patients with ML is unclear. We sought to establish a relationship between results of CGA and survival time in patients with ML. Methods Newly diagnosed patients with ML and indication for chemotherapeutical treatment were prospectively recruited in an observational trial. In addition to usual diagnostic work up, a CGA including activities of daily living (ADL), instrumental activities of daily living (IADL) and comorbidities was performed. Association of patients' characteristics and results of CGA with survival were analysed according to Kaplan--Meier method and in a multivariate Cox-regression analysis. Results About 143 patients were included, median age was 63 years, 63 patients were women. Median follow-up of surviving patients was 62 months. Sixty-six patients died within this time. Advanced age, poor Karnofsky performance status, dependence in ADL and IADL and presence of severe comorbidity were significantly associated with shorter survival time. In a Cox-regression analysis, IADL (HR 2.1 95% CI 1.1--3.9) and comorbidity (HR 1.9 95% CI 0.9--3.9) were independent and strongest associated with survival time. Conclusion Results of CGA, such as IADL and comorbidities, are prognostic variables for survival of patients with ML. Results should be validated in homogeneous clinical groups and if confirmed included in diagnostic and therapeutic algorithm. Author Affiliation: (1) Klinik fur Innere Medizin II, Abteilung Hamatologie und internistische Onkologie, Universitatsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany (2) Institut fur Pathologie, Universitatsklinikum Jena, Ziegenmuhlenweg 1, 07743, Jena, Germany (3) Institut fur Klinische Chemie und Laboratoriumsdiagnostik, Universitatsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany Article History: Registration Date: 18/06/2010 Received Date: 27/05/2010 Accepted Date: 18/06/2010 Online Date: 03/07/2010
    Keywords: Geriatric assessment ; Malignant lymphoma ; Comorbidity ; Survival ; Prognostic value
    ISSN: 0171-5216
    E-ISSN: 1432-1335
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  • 2
    Language: English
    In: Annals of Hematology, 2011, Vol.90(4), pp.473-475
    ISSN: 0939-5555
    E-ISSN: 1432-0584
    Source: Springer Science & Business Media B.V.
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  • 3
    Language: English
    In: Journal of Cancer Research and Clinical Oncology, 2014, Vol.140(8), pp.1391-1397
    Description: Byline: Ulf Schnetzke (1), Peter Fix (3), Baerbel Spies-Weisshart (1), Karin Schrenk (1), Anita Glaser (2), Hans-Joerg Fricke (1), Paul Rosee (1), Andreas Hochhaus (1), Sebastian Scholl (1) Keywords: AML; Relapse; FLT3; Cyclophosphamide; Stem cell transplantation Abstract: Background Approximately, 70 % of adult patients with de novo acute myeloid leukemia (AML) achieve a complete remission (CR) while 10--20 % of AML are refractory to induction chemotherapy. Furthermore, a significant proportion of AML patients in CR will relapse during or after consolidation treatment. There is no evidence for a standard salvage regimen and most centers use a combination of an anthracycline and cytarabine (AraC). The aim of this study was to investigate the impact of two age-adjusted regimens containing AraC and cyclophosphamide applied for the treatment of relapsed or refractory AML. Patients and methods We retrospectively analyzed 60 patients (24 male, 36 female median age 56 years) with relapsed or refractory AML who were treated with a combination of AraC and cyclophosphamide monocentrically between October 2000 and January 2013. Two different protocols containing either high-dose (hAC) or intermediate-dose cytarabin (iAC) have been applied dependent on age and performance status. Results We demonstrate an overall response rate (CR + PR) induced by hAC and iAC of 56.7 %. Importantly, a complete remission rate (CR + CRp) of 52.2 % was found in patients who received the hAC regimen while only 8.8 % of patients achieved a CR following the iAC protocol (p 〈 0.001). The rate of refractory disease was 26.1 and 47.1 %, respectively. High-risk cytogenetics, i.e., a complex aberrant or monosomal karyotype had no effect on achievement of CR after hAC. In addition, there was no impact of activating FLT3 mutations on response to treatment according to the hAC regimen. In the cohort of patients treated with the iAC protocol, treatment-related mortality of 11.8 % within 60 days was observed but none of the patients who received the hAC regimen died within the first 2 months following chemotherapy. The toxicity profile was acceptable at both cytarabine dose levels. Importantly, 19 patients (82.6 %) of the hAC cohort underwent allogeneic hematopoietic stem cell transplantation (HSCT) as consecutive treatment. Conclusion The hAC regimen represents a promising therapeutic approach to induce a second CR in younger patients with relapsed or refractory AML prior to HSCT without using anthracyclines. Author Affiliation: (1) Abteilung Hamatologie und Internistische Onkologie, Klinik fur Innere Medizin II, Universitatsklinikum Jena, Erlanger Allee 101, 07747, Jena, Germany (2) Institut fur Humangenetik, Universitatsklinikum Jena, Jena, Germany (3) Abteilung Internistische Onkologie und Hamatologie, Zentralklinik Bad Berka, Bad Berka, Germany Article History: Registration Date: 28/03/2014 Received Date: 12/03/2014 Accepted Date: 28/03/2014 Online Date: 12/04/2014 Article note: Ulf Schnetzke and Peter Fix have contributed equally to this work.
    Keywords: AML ; Relapse ; FLT3 ; Cyclophosphamide ; Stem cell transplantation
    ISSN: 0171-5216
    E-ISSN: 1432-1335
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  • 4
    Language: English
    In: Annals of Hematology, 2011, Vol.90(7), pp.857-859
    Description: Byline: Ellen Ritter (1), Ralf A. Husain (2), Katrin Hinderhofer (4), Tino Prell (3), Hans-Jorg Fricke (1), Sebastian Scholl (1), Andreas Hochhaus (1), Paul La Rosee (1) Author Affiliation: (1) Abteilung Hamatologie und Onkologie, Klinik fur Innere Medizin II, Universitatsklinikum Jena, 07747, Jena, Germany (2) Klinik fur Kinder- und Jugendmedizin, Universitatsklinikum Jena, Jena, Germany (3) Hans-Berger-Klinik fur Neurologie, Universitatsklinikum Jena, Jena, Germany (4) Institut fur Humangenetik, Universitat Heidelberg, Heidelberg, Germany Article History: Registration Date: 09/10/2010 Received Date: 06/10/2010 Accepted Date: 09/10/2010 Online Date: 09/11/2010
    Keywords: Lymphomas -- Drug Therapy ; Lymphomas -- Genetic Aspects ; Ornithine ; Cancer Treatment;
    ISSN: 0939-5555
    E-ISSN: 1432-0584
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  • 5
    In: British Journal of Haematology, October 2012, Vol.159(1), pp.67-77
    Description: The efficacy of bendamustine chlorambucil in a phase trial of previously untreated patients with inet stage chronic lymphocytic leukaemia () was re‐evaluated after a median observation time of 54 months in ay 2010. Overall survival () was analysed for the first time. At follow‐up, investigator‐assessed complete response () rate (21·0% vs 10·8%), median progression‐free survival (21·2 vs 8·8 months; 65 years, responders and non‐responders. However, patients with objective response or a experienced a significantly longer than non‐responders or those without a . Significantly more patients on chlorambucil progressed to second/further lines of treatment compared with those on bendamustine (78·3% vs 63·6%; =0·004). The benefits of bendamustine over chlorambucil were achieved without reducing quality of life. In conclusion, bendamustine is significantly more effective than chlorambucil in previously untreated patients, with the achievement of a or objective response appearing to prolong . Bendamustine should be considered as a preferred first‐line option over chlorambucil for patients ineligible for fludarabine, cyclophosphamide and rituximab.
    Keywords: Bendamustine ; Chlorambucil ; Chronic Lymphocytic Leukaemia ; Complete Response ; Overall Survival
    ISSN: 0007-1048
    E-ISSN: 1365-2141
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  • 6
    Language: English
    In: Journal of Cancer Research and Clinical Oncology, 2006, Vol.132(10), pp.665-671
    Description: Acute myeloid leukaemia (AML) is mainly affecting elderly patients. Elderly patients are increasingly affected by impairment of functional status (FS). FS is of prognostic relevance for survival in different tumours. Data for patients with AML are rare. Within a prospective trial we recruited patients with newly diagnosed AML and measured FS by two different methods: Karnofsky performance status (KPS) and instrumental activities of daily living (IADL). Sixty-three patients aged 19–85 years (median 61.1) were included. Twenty-three had prior myelodisplastic syndrome (MDS), 7 favourable, 17 unfavourable karyotype. Fifty received induction chemotherapy, 13 palliative chemotherapy. Median survival was 15.2 months (95% CI, 10.8–22.3) in all patients. Age, cytogenetic risk group, and impaired KPS and IADL significantly influenced median survival in univariate analysis. Impairment of IADL was the single most predictive variable. In multivariate analysis, impairment of IADL Score (HR:4.3, 95% CI 1.7–10.5, P  = 0.001) and of KPS (HR:4.8, 95% CI 1.9–12.3, P  = 0.001), and unfavourable cytogenetic risk group (HR:6.0, 95% CI 2.5–14.3, P  〈 0.001) significantly predicted median survival. In patients with AML, FS and not age is a major predictor of survival. The influence of FS is independent from cytogenetic risk group. IADL measurement adds information to KPS. The results have to be confirmed in a large sample of patients.
    Keywords: Acute myeloid leukaemia ; Functional status ; Chemotherapy ; Geriatric assessment ; Survival
    ISSN: 0171-5216
    E-ISSN: 1432-1335
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  • 7
    Language: English
    In: International Journal of Molecular Medicine, September 2009, Vol.24(3), pp.335-341
    Description: The impact of chromosome architecture in the formation of chromosome aberrations is a recent finding of interphase directed molecular cytogenetic studies. Also positive correlation of translocation frequencies and spatial proximity of chromosomes was described. Thus, disease specific chromosomal translocations could be due to tissue specific genomic organization. However, no three-dimensional interphase fluorescence in situ hybridization (FISH) studies for the nuclear architecture of bone marrow (BM) cells have previously been done. In this study, BM of three secondary acute myelogenous leukemia (AML) cases with trisomy 8 and otherwise normal karyotype were evaluated. Bone marrow cells of one AML and one ALL (acute lymphoblastic leukemia) case, peripheral blood lymphocytes and human sperm, all of them with normal karyotype, served as controls. Multicolor banding (MCB) probes for chromosomes 8 and 21 were applied in suspension-FISH (S-FISH). Interestingly, in myeloid bone marrow cells chromosomes 8 (di- and trisomic) and 21 tended to co-localize with their homologue chromosome(s), rather than to be separated. Thus, the co-localization of chromosomes 8 and 21 might promote a translocation providing a selective advantage of t(8;21) cells in AML-M2. In summary, the concept that tissue specific spatial proximity of chromosomes leads to enhanced translocation frequencies was further supported.
    Keywords: Medicine;
    ISSN: 1107-3756
    E-ISSN: 1791244X
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  • 8
    In: European Journal of Haematology, March 2008, Vol.80(3), pp.208-215
    Description: Nucleophosmin (NPM1) and Flt3 internal tandem duplications (Flt3‐ITD mutations) represent the most frequent molecular aberrations in patients with acute myeloid leukemia (AML). While NPM1 mutations are associated with favourable prognosis in younger AML patients, Flt3‐ITD mutations reflect an unfavourable prognostic factor in these patients. So far, especially NPM1 mutations have not yet been evaluated exclusively in older patients. We retrospectively analysed the prevalence of NPM1 and Flt3‐ITD mutations and its association with complete remission (CR), and survival in 99 elderly patients (median age 71 yr, range 60–85 yr) newly diagnosed for AML. Primary treatment approach was curative in 54, and palliative in 38 patients, while seven patients received best supportive care only. The mean follow‐up of surviving patients was 600 d. Sixty‐seven patients were tested negative for NPM1 and Flt3‐ITD mutations (group 1), 16 patients carried only a NPM1 mutation (group 2) and nine patients had only a Flt3‐ITD mutation (group 3) while additional seven patients were positive for both aberrations (group 4). We can demonstrate a significant higher rate of CR comparing wildtype vs. NPM1 positive patients (40.5% for group 1 vs. 80.0% for group 2,  = 0.03) for patients receiving curative therapy. Interestingly, there is no significant difference in overall survival between group 1 and group 2 (Log‐rank test  = 0.22, median 440 d vs. 1125 d). In contrast, patients carrying a Flt3‐ITD mutation had a significant worse overall survival compared to wildtype patients ( = 0.03, median 210 d for group 3 + 4 vs. 634 d for group 1 + 2) while no difference of CR rate could be observed (42.8% vs. 48.9%,  = 0.91). As elderly but medically fit patients with AML carrying a NPM1 mutation have a high CR rate, age itself should not be a barrier for induction treatment. However, new therapeutic concepts of postremission therapy (e.g. allogeneic stem cell transplantation after dose‐reduced conditioning) should be considered for these patients in first CR.
    Keywords: Aml ; Npm1 ; Flt3‐Itd ; Elderly Patients ; Prognosis
    ISSN: 0902-4441
    E-ISSN: 1600-0609
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  • 9
    Language: English
    In: Blood, Vol.114, pp.934-935
    Keywords: Medicin Och Hälsovetenskap ; Klinisk Medicin ; Hematologi ; Medical And Health Sciences ; Clinical Medicine ; Hematology
    ISSN: 1528-0020
    ISSN: 00064971
    Source: SwePub (National Library of Sweden)
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  • 10
    Language: English
    In: Annals of Hematology, 2007, Vol.86(10), pp.763-765
    Description: Byline: Sebastian Scholl (1), Joachim Luftner (2), Lars-Olof Mugge (1), Volker Schmidt (1), Hans-Jorg Fricke (1), Klaus Hoffken (1) Author Affiliation: (1) Department of Internal Medicine II (Oncology/Hematology/Gastroenterology/Infectious Disease), Medical Faculty at Friedrich Schiller University, Erlanger Allee 101, 07740, Jena, Germany (2) Institute of Pathology, Meiningen, Germany Article History: Registration Date: 25/05/2007 Received Date: 17/12/2006 Accepted Date: 02/01/2007 Online Date: 17/07/2007
    Keywords: Sarcoma -- Diagnosis ; Sarcoma -- Genetic Aspects;
    ISSN: 0939-5555
    E-ISSN: 1432-0584
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