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  • 1
    Language: English
    In: Journal of Cancer Research and Clinical Oncology, 2011, Vol.137(9), pp.1293-1300
    Description: Byline: Maraike Rommeley (1), Baerbel Spies-Weisshart (1), Kristina Schilling (1), Andreas Hochhaus (1), Herbert G. Sayer (1), Sebastian Scholl (1) Keywords: Neutrophils; Monocytes; Innate immune system; CD14+CD16+; Allogeneic PBSCT Abstract: Purpose The aim of the study was to investigate the recovery of the innate immune system within the first 100 days after allogeneic peripheral blood stem cell transplantation (PBSCT) and to elucidate a potential correlation with such important events as severe infectious complications or graft-versus-host disease (GvHD). Methods In 30 consecutive patients who underwent allogeneic PBSCT, absolute numbers of neutrophils and monocytes were determined and different functional analyses performed at different time points (day +30, +60 and +90, respectively). The capacity to phagocyte Escherichia coli (E. coli) as well as the induction of oxidative burst after incubation with different stimuli (Phorbol-12-myristate-13-acetate PMA, the chemotactic peptide N-formyl-Met-Leu-Phe f-MLP or opsonized E. coli) were analysed after engraftment. Results There was a rapid reconstitution concerning the capability of both neutrophils and monocytes to phagocyte E. coli without a significant increase between day +30 and +90. In contrast, a twofold increase of monocyte oxidative burst after incubation with PMA at day +90 was observed (P = 0.017). Furthermore, the ability of neutrophils to induce oxidative burst after ingestion with E. coli was impaired on day +30 with a significant functional reconstitution on day +60 (P = 0.01). The oxidative burst activity following incubation with f-MLP did not show significant changes after stem cell engraftment. Analysis of numeric reconstitution of CD14+CD16+ monocytes demonstrated a potential correlation with a decreased incidence of chronic GvHD. Conclusion The functional recovery of neutrophils and monocytes in the early period after allogeneic PBSCT differs not only concerning phagocytosis and oxidative burst but also with respect to the stimulus and the cell population that was analysed for oxidative burst activity. The subset of CD16+CD14+ monocytes might be a predictor for a reduced risk of chronic GvHD. Author Affiliation: (1) Abteilung Hamatologie/Onkologie, Klinik fur Innere Medizin II, Universitatsklinikum Jena, Erlanger Allee 101, 07740, Jena, Germany Article History: Registration Date: 26/05/2011 Received Date: 11/03/2011 Accepted Date: 26/05/2011 Online Date: 29/06/2011
    Keywords: Neutrophils ; Monocytes ; Innate immune system ; CD14+CD16+ ; Allogeneic PBSCT
    ISSN: 0171-5216
    E-ISSN: 1432-1335
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  • 2
    Language: English
    In: Journal of Neurological Surgery Part B: Skull Base, 09/09/2016, Vol.77(S 02), suppl
    ISSN: 2193-6331
    E-ISSN: 2193-634X
    Source: Thieme Publishing Group (via CrossRef)
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  • 3
    In: Laryngo-Rhino-Otologie, 2017, Vol.96(11)
    In: Laryngo-Rhino-Otologie, 2017, Vol.96(11), pp.787-789
    Keywords: Carcinoid Tumor–Diagnosis ; Chronic Disease–Pathology ; Diagnosis, Differential–Surgery ; Endoscopy–Diagnosis ; Female–Pathology ; Humans–Surgery ; Magnetic Resonance Imaging–Diagnosis ; Middle Aged–Pathology ; Nasal Obstruction–Surgery ; Nasal Polyps–Diagnosis ; Neoplasm Staging–Pathology ; Paranasal Sinus Neoplasms–Surgery ; Rhinitis–Diagnosis ; Sinusitis–Pathology ; Tomography, X-Ray Computed–Surgery ; Tomography, X-Ray Computed–Diagnosis ; Tomography, X-Ray Computed–Pathology ; Tomography, X-Ray Computed–Surgery;
    ISSN: 0935-8943
    E-ISSN: 1438-8685
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  • 4
    Language: English
    In: Journal of Cancer Research and Clinical Oncology, 2013, Vol.139(8), pp.1397-1404
    Description: PURPOSEThe existence of platelet-derived growth factor (PDGF) receptor autoantibodies in systemic sclerosis is conflicting, and such antibodies were also detected in patients with chronic graft-versus-host disease (GvHD) after allogeneic peripheral blood stem cell transplantation (PBSCT). We therefore aimed to screen for PDGF receptor autoantibodies in patients with chronic GvHD. PATIENTS AND METHODSWe evaluated the existence of PDGF receptor autoantibodies in 39 patients, while 17 patients presented with a limited and 8 patients with an extensive chronic GvHD, respectively. Furthermore, 14 out of 39 patients had no chronic GvHD. RESULTSWe detected at least low levels of PDGF receptor autoantibodies in nearly all (35 of 39) patients after allogeneic PBSCT. Interestingly, only one of six patients with high levels of PDGF receptor autoantibodies presented with an extensive chronic GvHD, while the remaining six patients had no clinical signs of chronic GvHD. Thus, there was no correlation between the quantitative detection of antibodies directed against the PDGF receptor and the presence or severity of chronic GvHD. CONCLUSIONPlatelet-derived growth factor receptor autoantibodies could easily be detected in patient sera. Nevertheless, we did not observe any correlation between the presence of PDGF receptor autoantibodies and the severity of chronic GvHD in patients who underwent allogeneic PBSCT.
    Keywords: PDGF receptor ; Autoantibodies ; Chronic GvHD ; Allogeneic PBSCT
    ISSN: 0171-5216
    E-ISSN: 1432-1335
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  • 5
    In: Clinical Case Reports, May 2016, Vol.4(5), pp.505-508
    Description: Positive galactomannan tests in patients who underwent chemotherapy without any clinical signs of a fungal infection should lead the clinician to consideration of a false‐positive test result. Oral nutritional supplements may be a cause, especially in the case of concomitant disturbance of the gastrointestinal mucosal barrier because of mucositis. Positive galactomannan tests in patients who underwent chemotherapy without any clinical signs of a fungal infection should lead the clinician to consideration of a false‐positive test result. Oral nutritional supplements may be a cause, especially in the case of concomitant disturbance of the gastrointestinal mucosal barrier because of mucositis.
    Keywords: Autologous Stem Cell Transplantation ; Enteral Nutrition ; Galactomannan ; Invasive Fungal Infection
    ISSN: 2050-0904
    E-ISSN: 2050-0904
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  • 6
    Language: English
    In: Acta Haematologica, December 2015, Vol.135(1), pp.1-10
    Description: Background: Posterior reversible encephalopathy syndrome (PRES) is a rare but serious complication after allogeneic hematopoietic stem cell transplantation (alloHSCT). Among others, calcineurin inhibitors (CNI) for prophylaxis of graft-versus-host disease (GvHD) may promote the development of PRES, but the pathomechanism is still controversial. Discontinuation of CNI facilitates remission of symptoms but might contribute to the unfavorable prognosis of PRES due to an elevated incidence of GvHD. Methods: This is a case series of 7 patients with PRES from a retrospective analysis of 146 consecutive patients who received alloHSCT for hematologic malignancies. Results: At the onset of PRES, all patients presented a systemic infection, while no influence was seen for underlying disease, conditioning regimen, donor type, or GvHD. Discontinuation of CNI and control of the blood pressure reversed neurological symptoms in 6 patients, while 1 patient died from septic multiorgan failure. After bridging with prednisolone and/or mycophenolic acid, replacement of CNI by the mammalian target of rapamycin (mTOR) inhibitor everolimus effectively prevented severe GvHD without recurrence of PRES. Conclusions: A systemic infection/inflammation may be an important cause of PRES. Prophylaxis of GvHD by the mTOR inhibitor everolimus in case of PRES after alloHSCT demonstrated promising results but needs to be validated in larger cohorts.
    Keywords: Case Report ; Allogeneic Stem Cell Transplantation ; Everolimus ; Graft-Versus-Host Prophylaxis ; Posterior Reversible Encephalopathy Syndrome ; Medicine ; Anatomy & Physiology
    ISSN: 0001-5792
    E-ISSN: 1421-9662
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  • 7
    In: European Journal of Haematology, September 2014, Vol.93(3), pp.247-259
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/ejh.12311/abstract Byline: Jochen J. Frietsch, Sebastian Dornaus, Thomas Neumann, Sebastian Scholl, Volker Schmidt, Christa Kunert, Herbert G. Sayer, Andreas Hochhaus, Paul La Rosee Keywords: myelodysplastic syndrome; autoimmune; autoimmunity; myelodysplasia; immunotherapy Abstract Introduction Myelodysplastic syndrome (MDS) comprises a heterogeneous group of clonal disorders of haematopoietic stem cells, characterised by dysplastic haematopoiesis and dysregulated apoptosis resulting in various degrees of cytopenia, whereas canonical cytologic, cytogenetic and histopathologic findings guiding the diagnosis MDS are widely accepted, the MDS-phenotype can be masked by coexisting/paraneoplastic immunologic disease. Autoimmune disorders have an estimated incidence of 10% among patients suffering from MDS and are causally related to increased morbidity and mortality, younger age at diagnosis and more complex genetics. Conversely, systemic inflammatory disorders may be an early manifestation of MDS, show good response to immunosuppressive therapy and frequently disappear during the course of specific haematologic therapy. Objective Monocentric report on clinical phenotypes found in MDS or bone marrow failure with paraneoplastic inflammatory disease. Methods Clinical case reports and systematic review about MDS pathophysiology and treatment. Results We report eight patients diagnosed with MDS or bone marrow failure, who presented with paraneoplastic autoimmune diseases. Six of eight patients were treated with the hypomethylating agent 5-azacytidine, three of which achieved meaningful response with regard to inflammation control and haematologic recovery. Conclusions As paraneoplastic syndromes are often mistakenly diagnosed as idiopathic autoimmune disorders, we propose that coexistence of an underlying myelodysplastic syndrome should be considered early in the diagnostic work up. 5-Azacytidine is effective in controlling paraneoplastic inflammation.
    Keywords: Myelodysplastic Syndrome ; Autoimmune ; Autoimmunity ; Myelodysplasia ; Immunotherapy
    ISSN: 0902-4441
    E-ISSN: 1600-0609
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  • 8
    Language: English
    In: Journal of Cancer Research and Clinical Oncology, 2016, Vol.142(12), pp.2603-2610
    Description: To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s00432-016-2270-9 Byline: Nils Winkelmann (1), Max Desole (1,2), Inken Hilgendorf (1), Thomas Ernst (1), Herbert G. Sayer (1,3), Christa Kunert (1), Lars-Olof Mugge (1), Andreas Hochhaus (1), Sebastian Scholl (1) Keywords: Myeloma; Cyclophosphamide; Stem cell mobilization Abstract: Introduction Even in the era of proteasome inhibitors and immunomodulatory drugs, the autologous stem cell transplantation after high-dose melphalan continues to represent a standard approach for myeloma patients in first-line therapy. Different mobilization chemotherapies before stem cell apheresis have been published while cyclophosphamide at a dose level of up to 4 g/m.sup.2 has been evaluated and is commonly applied. In contrast, lower dose levels of cyclophosphamide (e.g., 1.5 g/m.sup.2) did not result in a sufficient collection of stem cells. Methods We retrospectively analyzed the impact of "intermediate-dose" (ID-CY, 2.5 g/m.sup.2) versus "high-dose" (HD-CY, 4 g/m.sup.2) cyclophosphamide in 101 (48 vs. 53) consecutively evaluable myeloma patients (median age 59 years, range 32--72 years) who underwent stem cell mobilization after induction chemotherapy. Successful stem cell harvest was defined as a stem cell yield of at least 5 million CD34 cells per kg bodyweight. Evaluation of toxicity especially considered infectious complications and hematological toxicity in both subgroups. Results Successful stem cell mobilization was achieved in 40 of 48 (83 %) and 44 of 53 (83 %) patients, respectively. The median time to apheresis (11 vs. 12 days) and the median CD34 content of stem cell harvest (8.3 vs. 7.6 million CD34 cells per kg bodyweight) did not differ significantly between both groups. There was a significant difference of WBC nadir in favor of the cyclophosphamide regimen with 2.5 g/m.sup.2 (0.8 vs. 0.3 Gpt/L, p = 0.021), and neutropenic fever was more often observed in patients who received 4 g/m.sup.2 cyclophosphamide (34 vs. 15 %, p = 0.078). Importantly, after induction chemotherapy using the VCD regimen (bortezomib, cyclophosphamide, dexamethasone), successful stem cell mobilization was achieved in 26 of 29 (90 %) patients treated with 2.5 g/m.sup.2 and 21 of 25 (84 %) patients receiving 4 g/m.sup.2 cyclophosphamide, respectively. Conclusions ID-CY is safe and highly effective for stem cell mobilization in patients with newly diagnosed myeloma and associated with a reduced toxicity compared to HD-CY. Author Affiliation: (1) Klinik fur Innere Medizin II (Abteilung Hamatologie und Internistische Onkologie), Universitatsklinikum Jena, Am Klinikum 1, 07740, Jena, Germany (2) HELIOS Klinikum Emil von Behring, Berlin, Germany (3) HELIOS Klinikum, Erfurt, Germany Article History: Registration Date: 10/09/2016 Received Date: 09/08/2016 Accepted Date: 10/09/2016 Online Date: 17/09/2016
    Keywords: Myeloma ; Cyclophosphamide ; Stem cell mobilization
    ISSN: 0171-5216
    E-ISSN: 1432-1335
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  • 9
    Language: English
    In: Journal of Cancer Research and Clinical Oncology, 2017, Vol.143(2), pp.337-345
    Description: To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s00432-016-2290-5 Byline: Maximilian Fleischmann (1), Ulf Schnetzke (1), Karin G. Schrenk (1), Volker Schmidt (1,2), Herbert G. Sayer (1,2), Inken Hilgendorf (1), Andreas Hochhaus (1), Sebastian Scholl (1) Keywords: AML; FLT3-ITD; Allogeneic transplantation; Tyrosine kinase inhibitor Abstract: Background Activating mutations of the receptor tyrosine kinase FLT3 (fms-related tyrosine kinase 3) reflect the most frequent molecular aberration in acute myeloid leukemia (AML). In particular, FLT3 internal tandem duplications (FLT3-ITD) are characterized by an unfavorable prognosis and allogeneic stem cell transplantation (allogeneic SCT) in first complete remission is recommended. In case of imminent or frank relapse following allogeneic SCT, treatment with FLT3 tyrosine kinase inhibitors (TKI) constitutes a promising clinical approach to induce hematologic remission without conventional chemotherapy. Patients and methods We retrospectively analyzed the response to induction chemotherapy and the outcome of 76 patients with FLT3-ITD-positive AML including 50 patients who underwent allogeneic SCT. Furthermore, efficacy of TKI treatment was evaluated in 18 patients (median age 54 years, range 21--74) with relapsed or refractory FLT3-ITD-positive AML. Results Response to induction chemotherapy in 76 FLT3-ITD-positive AML patients was characterized by a complete remission (CR) rate of 68%. In total, 50 of 76 patients (66%) underwent allogeneic SCT including 40 patients (80%) in CR. Relapse of AML was observed in 21 of 47 patients (45%) after allogeneic SCT with a median relapse-free survival (RFS) of 13 months (range 3--224) for patients with CR prior to or at day +30 after SCT. Myeloablative conditioning resulted in an improved median RFS of 29 months (4--217) as compared to a reduced intensity conditioning protocol prior to allogeneic SCT with a RFS of 8 months (1--197, P = 0.048), respectively. Median OS of FLT3-ITD-positive AML was 17 months (5--225) for patients who received an allogeneic SCT as compared to 9 months (1--184) for patients who did not undergo SCT. Response of FLT3-ITD-positive AML to sorafenib was characterized by only 3 of 18 patients achieving a bone marrow response (17%), while there was no response to second-line treatment with ponatinib. Conclusion This "real-life" data reflect the continuing challenge of FLT3-ITD-positive AML and confirm the poor outcome even after allogeneic SCT. Furthermore, efficacy of TKI treatment of relapsed or refractory FLT3-ITD AML is still limited and requires substantial improvement, e.g., by the introduction of second-generation inhibitors targeting constitutively active FLT3. Author Affiliation: (1) Klinik fur Innere Medizin II (Abteilung Hamatologie und Internistische Onkologie), Universitatsklinikum Jena, Am Klinikum 1, 07740, Jena, Germany (2) HELIOS Klinikum Erfurt, Erfurt, Germany Article History: Registration Date: 17/10/2016 Received Date: 25/09/2016 Accepted Date: 17/10/2016 Online Date: 24/10/2016
    Keywords: AML ; FLT3-ITD ; Allogeneic transplantation ; Tyrosine kinase inhibitor
    ISSN: 0171-5216
    E-ISSN: 1432-1335
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  • 10
    Language: English
    In: BMC Blood Disorders, 01 August 2012, Vol.12(1), p.9
    Description: Abstract Background This case report highlights the relevance of quantifying the BCR-ABL gene in cerebrospinal fluid of patients with suspected relapse of chronic myeloid leukemia in the central nervous system. Case presentation We report on a female patient with isolated central nervous system relapse of chronic myeloid leukemia (CML) during peripheral remission after allogeneic hematopoietic stem cell transplantation. The patient showed a progressive cognitive decline as the main symptom. MRI revealed a hydrocephalus and an increase in cell count in the cerebrospinal fluid (CSF) with around 50% immature blasts in the differential count. A highly elevated BCR-ABL/ ABL ratio was detected in the CSF, whilst the ratio for peripheral blood and bone marrow was not altered. On treatment of the malresorptive hydrocephalus with shunt surgery, the patient showed an initial cognitive improvement, followed by a secondary deterioration. At this time, the cranial MRI showed leukemic infiltration of lateral ventricles walls. Hence, intrathecal administration of cytarabine, methotrexate, and dexamethasone was initiated, which caused a significant decrease of cells in the CSF. Soon after, the patient demonstrated significant cognitive improvement with a good participation in daily activities. At a later time point, after the patient had lost the major molecular response of CML, therapy with dasatinib was initiated. In a further follow-up, the patient was neurologically and hematologically stable. Conclusions In patients with treated CML, the rare case of an isolated CNS blast crisis has to be taken into account if neurological symptoms evolve. The analysis of BCR-ABL in the CSF is a further option for the reliable detection of primary isolated relapse of CML in these patients.
    Keywords: Chronic Myeloid Leukemia ; CNS Relapse ; BCR-Abl ; Medicine
    ISSN: 1471-2326
    E-ISSN: 1471-2326
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