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  • Dreger, Peter  (48)
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  • 1
    Language: English
    In: Current Hematologic Malignancy Reports, 2012, Vol.7(1), pp.3-12
    Description: Chronic lymphocytic leukemia (CLL) shows a heterogeneous clinical course, which can be explained in part by prognostic factors. Most patients do not need treatment at the time of first diagnosis. The identification of prognostic factors is of major interest if strategies can be devised to treat patients according to their individual risk profile or biological subgroup. Currently, in spite of a wealth of prognostic factors, individualized treatment approaches in different genetic or risk groups are the exemption in CLL. This review summarizes the most important prognostic and predictive factors in CLL, with particular emphasis on factors affecting treatment decisions in clinical trials and routine practice.
    Keywords: Chronic lymphocytic leukemia ; CLL ; Predictive factors ; Allogeneic ; Early treatment ; Maintenance ; Consolidation ; 17p deletion ; 11q deletion ; TP53 ; IGHV ; MRD
    ISSN: 1558-8211
    E-ISSN: 1558-822X
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  • 2
    In: British Journal of Haematology, November 2013, Vol.163(4), pp.496-500
    Description: Recurrent gene mutations contribute to the pathogenesis of chronic lymphocytic leukaemia (). We developed a next‐generation sequencing (NGS) platform to determine the genetic profile, intratumoural heterogeneity, and clonal structure of two independent cohorts. ,, and were most frequently mutated (16·3%, 16·9%, 10·7%). We found evidence for subclonal mutations in 67·5% of cases with mutations of cancer consensus genes. We observed selection of subclones and found initial evidence for convergent mutations in . Our data suggest that assessment of (sub)clonal structure may need to be integrated into analysis of the mutational profile in .
    Keywords: Chronic Lymphocytic Leukaemia ; Convergent Mutation ; Tp53 ; Sf3b1 ; Notch1
    ISSN: 0007-1048
    E-ISSN: 1365-2141
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  • 3
    Language: English
    In: Cancer, May 1, 2011, Vol.117(9), p.1901(10)
    Keywords: Mantle Cell Lymphoma -- Care And Treatment ; Mantle Cell Lymphoma -- Patient Outcomes ; Mantle Cell Lymphoma -- Research ; Stem Cell Transplantation -- Patient Outcomes ; Stem Cell Transplantation -- Research ; Cancer Recurrence -- Patient Outcomes ; Cancer Recurrence -- Research
    ISSN: 0008-543X
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  • 4
    Language: English
    In: Blood, 17 January 2013, Vol.121(3), pp.440-6
    Description: Patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) have a poor prognosis with conventional chemotherapy. In the present study, we retrospectively analyzed the outcome of patients with BPDCN who underwent allogeneic stem cell transplantation (allo-SCT) or autologous stem cell transplantation (auto-SCT). A total of 39 patients (allo-SCT, n = 34; auto-SCT, n = 5) were identified in the European Group for Blood and Marrow Transplantation registry. The 34 allo-SCT patients had a median age of 41 years (range, 10-70) and received transplantations from sibling (n = 11) or unrelated donors (n = 23) between 2003 and 2009. MAC was used in 74% of patients. Nineteen allo-SCT patients (56%) received transplantations in first complete remission. The 3-year cumulative incidence of relapse, disease-free survival, and overall survival was 32%, 33%, and 41%, respectively. By univariate comparison, being in first remission at allo-SCT favorably influenced survival, whereas age, donor source, and chronic GVHD had no significant impact. We conclude that high-dose therapy followed by allo-SCT from related or unrelated donors can provide durable remission even in elderly patients with BPDCN. However, it remains to be shown if graft-versus-malignancy effects can contribute significantly to BPDCN control after allo-SCT.
    Keywords: Dendritic Cells -- Pathology ; Hematologic Neoplasms -- Pathology ; Hematopoietic Stem Cell Transplantation -- Methods ; Precursor Cell Lymphoblastic Leukemia-Lymphoma -- Pathology
    ISSN: 00064971
    E-ISSN: 1528-0020
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  • 5
    Language: English
    In: Blood, 21 September 2017, Vol.130(12), pp.1477-1480
    Keywords: Peripheral Blood Stem Cell Transplantation ; Leukemia, Lymphocytic, Chronic, B-Cell -- Therapy
    ISSN: 00064971
    E-ISSN: 1528-0020
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  • 6
    In: International Journal of Cancer, 15 September 2016, Vol.139(6), pp.1402-1413
    Description: We tested the hypothesis that proliferative activity of hematopoietic stem cells has impact on survival in newly diagnosed patients with myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (AML). RNA expression profiles of CD34 cells were analyzed in 125 MDS patients and compared to healthy controls. Prognostic impact on overall survival (OS) of mRNA proliferation signatures established for solid tumor cells was analyzed retrospectively. For validation on the protein level, immunofluorescence and immunohistochemistry analyses in bone marrow (BM) biopsies were performed, and an independent cohort of 223 MDS and secondary AML patients was investigated. Lower proliferative activity correlated with the expression of cyclin‐dependent kinase inhibitor 1C () and with shorter OS ( 〈 0.001). In multivariable analysis, higher expression was associated with worse OS ( = 0.02). On the BM level, a total of 84 (38%) patients showed CDKN1C protein expression before start of treatment. Patient, disease and treatment characteristics did not differ between CDKN1C‐positive and ‐negative patients. Positive CDKN1C BM status was associated with shorter OS in multivariable analysis (HR 1.54,  = 0.04). There was an interaction between CDKN1C BM status and subsequent treatment with negative impact on OS being most pronounced in patients receiving conventional cytotoxic chemotherapy ( = 83, 2‐year OS 30% 58%,  = 0.002). In conclusion, low‐proliferative phenotype and expression were associated with shorter OS. CDKN1C protein expression in the BM of newly diagnosed, treatment‐naïve MDS and secondary AML patients was identified as a prognostic factor for poor survival in patients treated with antiproliferative chemotherapy. What's new? Leukemia stem cells (LSC) tend to divide slowly. However, conventional chemotherapy usually targets rapidly dividing cells. In this study of patients with myelodysplastic syndrome (MDS) and secondary acute myeloid leukemia (AML), the authors found that patients whose bone marrow had lower proliferative activity and higher expression of CDKN1C had shorter overall survival (OS), especially after treatment with standard chemotherapy. CDKN1C may thus be a useful prognostic biomarker for poor survival, and may help clinicians select patients who are most likely to benefit from aggressive treatment regimens.
    Keywords: Cdkn1c ; P57 ; Survival ; Chemotherapy ; Mds ; Aml
    ISSN: 0020-7136
    E-ISSN: 1097-0215
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  • 7
    In: Transplantation, 2015, Vol.99(5), pp.1065-1071
    Description: BACKGROUND: The impact of nutritional status on outcome of allogeneic stem cell transplantation (alloSCT) is controversial. This study investigates the influence of pretransplant weight loss and serologic indicators of nutritional homeostasis on relapse and death of acute myeloid leukemia (AML) after alloSCT. METHODS: Pretransplant weight loss along with serum levels of total serum protein (TSP), albumin, C-reactive protein, and leptin were collected retrospectively in a training cohort (n = 149) and correlated with clinical outcome. Metabolic risk groups were defined and tested in an independent validation cohort (n = 167). RESULTS: We identified pretransplant weight loss and TSP as strong independent predictors of relapse and death. Patients in the metabolic high-risk group (low TSP and weight loss) had an increased risk for relapse (P = 0.0002) and death (P = 0.002), but a similar risk for acute graft-versus-host disease. Weight loss coincided with reduced pretransplant serum leptin levels. The adverse influence of weight loss and high metabolic risk on relapse and overall survival could be confirmed in the validation cohort and similarly in patients with less than or more than 5% blasts before alloSCT. Multivariate analysis of both cohorts revealed a hazard ratio for relapse of 7.78 (2.59–23.36, P = 0.0003) in the metabolic high risk group. CONCLUSION: Altered nutritional homeostasis before alloSCT correlates with recurrence of AML after transplantation. Studies addressing pretransplant nutritional interventions to reduce AML relapse rates are warranted.
    Keywords: Nutritional Status ; Acute Myeloid Leukemia ; Stem Cell Transplantation ; Survival ; Graft-Versus-Host Reaction ; Homeostasis ; Serum Proteins ; Serum Levels ; Leptin ; Multivariate Analysis ; Risk Factors ; Albumin ; Risk Groups ; Blast ; C-Reactive Protein ; Transplantation;
    ISSN: 0041-1337
    E-ISSN: 15346080
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  • 8
    Language: English
    In: Clinical cancer research : an official journal of the American Association for Cancer Research, 15 January 2012, Vol.18(2), pp.417-31
    Description: Environmental conditions in lymph node proliferation centers protect chronic lymphocytic leukemia (CLL) cells from apoptotic triggers. This situation can be mimicked by in vitro stimulation with CD40 ligand (CD40L) and interleukin 4 (IL-4). Our study investigates the impact of the drug leflunomide to overcome apoptosis resistance of CLL cells. CLL cells were stimulated with CD40L and IL-4 and treated with fludarabine and the leflunomide metabolite A771726. Resistance to fludarabine-mediated apoptosis was induced by CD40 activation alone stimulating high levels of BCL-XL and MCL1 protein expression. Apoptosis resistance was further enhanced by a complementary Janus-activated kinase (JAK)/STAT signal induced by IL-4. In contrast, CLL proliferation required both a CD40 and a JAK/STAT signal and could be completely blocked by pan-JAK inhibition. Leflunomide (A771726) antagonized CD40L/IL-4-induced proliferation at very low concentrations (3 μg/mL) reported to inhibit dihydroorotate dehydrogenase. At a concentration of 10 μg/mL, A771726 additionally attenuated STAT3/6 phosphorylation, whereas apoptosis of CD40L/IL-4-activated ("resistant") CLL cells was achieved with higher concentrations (IC(50): 80 μg/mL). Apoptosis was also effectively induced by A771726 in clinically refractory CLL cells with and without a defective p53 pathway. Induction of apoptosis involved inhibition of NF-κB activity and loss of BCL-XL and MCL1 expression. In combination with fludarabine, A771726 synergistically induced apoptosis (IC(50): 56 μg/mL). We thus show that A771726 overcomes CD40L/IL-4-mediated resistance to fludarabine in CLL cells of untreated as well as clinically refractory CLL cells. We present a possible novel therapeutic principle for attacking chemoresistant CLL cells.
    Keywords: Drug Resistance, Neoplasm ; Aniline Compounds -- Pharmacology ; Antineoplastic Agents -- Pharmacology ; Apoptosis -- Drug Effects ; Hydroxybutyrates -- Pharmacology ; Leukemia, Lymphocytic, Chronic, B-Cell -- Drug Therapy ; Vidarabine -- Analogs & Derivatives
    ISSN: 1078-0432
    E-ISSN: 15573265
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  • 9
  • 10
    Language: English
    In: European Journal of Cancer, July 2016, Vol.62, pp.1-8
    Description: The aim of this study was to determine the value of upfront autologous transplantation (ASCT) in elderly patients (60–79 years) with myeloma. We analysed relative survival (RS) of patients diagnosed in 1998–2011 and treated with ASCT within 12 months after diagnosis in Germany (n = 3591; German Registry of Stem Cell Transplantation) and compare RS with survival of myeloma patients diagnosed in the same years in Germany (n = 13,903; population-based German Cancer Registries). Utilisation of ASCT has increased rapidly between 2000–2002 and 2009–2011 (60–64years: 7.0–43.0%; 65–69 years: 6.6–23.7%; 70–79 years: 0.4–4.0%). Comparison of 5-year RS of patients from the general German myeloma population who have survived the first year after diagnosis with 5-year RS of patients treated with ASCT revealed higher survival for transplanted patients among all age groups (60–64: 59.2% versus 66.1%; 65–69: 57.4% versus 61.7%; 70–79: 51.0% versus 56.6%). RS increased strongly between 2003–2005 and 2009–2011 for the general German myeloma population (+8.5%) and for patients treated with ASCT (+11.8%). Differences in RS between these groups increased over time from +1.9% higher age-standardised survival in transplanted patients in 2003–2005 to 5.2% higher survival in 2009–2011. We conclude that upfront ASCT might be a major contributor to improved survival for elderly myeloma patients in Germany.
    Keywords: Multiple Myeloma ; Elderly ; Autologous Stem Cell Transplantation ; Population-Based Survival Analysis ; Medicine
    ISSN: 0959-8049
    E-ISSN: 1879-0852
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