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  • Vogel, Wichard  (18)
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  • 1
    Language: English
    In: Rheumatology, 12/10/2016, p.kew319
    ISSN: 1462-0324
    E-ISSN: 1462-0332
    Source: Oxford University Press (via CrossRef)
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  • 2
    In: Rheumatology, 2017, Vol. 56(3), pp.451-456
    Description: Objectives. To evaluate the effect of autologous stem cell transplantation (aSCTrans) on antibody (Ab) reactivity towards topo I in patients with SSc, and to see whether it may correlate with clinical outcome after aSCTrans. Methods. Eighteen anti-topo/Scl70–positive patients with SSc in whom non-myeloablative aSCTrans had been performed were analysed. Seven patients showed good response without relapse for several years (group 1), eight primarily responded but later relapsed and three did not respond (group 2). A total of 74 sera were analysed at different time points and tested by ELISA against full length ( fl ) topo I, truncated ( tr ) topo I and a previously identified immunodominant epitope covering amino acid 489–573. Results. Eighty-three percent had IgG Abs to topo fl and topo tr . Ab reactivity significantly decreased after aSCTrans, but remained positive in 10 of the 11 patients followed for up to 24 months. The decrease did not correlate with the clinical outcome after aSCTrans. Fifty-six percent of the patients reacted with topo489–573, and reactivity was nearly confined to group 2. There was no correlation between Ab reactivity towards topo fl or topo489–573 and the modified Rodnan Skin Score before aSCTrans or its decrease after aSCTrans. Conclusions. Although aSCTrans is a good treatment option in patients with progressive SSc, it does not abrogate Ab reactivity towards topo I. The presence of anti-topo489–573 Abs before aSCTrans may indicate a less favourable course after aSCTrans.
    Keywords: Systemic Sclerosis ; Autologous Stem Cell Transplantation ; Anti - Topoisomerase I Antibodies ; Immunodominant Epitope
    ISSN: 1462-0324
    E-ISSN: 1462-0332
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  • 3
    In: Rheumatology, 2014, Vol. 53(5), pp.919-922
    Description: Objective. The aim of this study was to find a new and less cardiotoxic conditioning regimen for high-dose chemotherapy and autologous stem cell transplantation (aSCT) in patients with severe SSc and pre-existing cardiac involvement. Methods. Six patients with cardiac involvement were treated for SSc with a conditioning regimen including reduced-dose CYC plus the non-cardiotoxic alkylant thiotepa. All patients received an implantable cardioverter defibrillator (ICD) before aSCT. The response at months 6 and 12 was measured according to reduction of the modified Rodnan skin score (mRSS). CT histography was used to monitor pulmonary manifestations, as were echocardiography, N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin for the cardiac involvement. Cardiac events were defined as death or hospitalisation due to heart failure or appropriate discharge of the ICD. Results. Between December 2008 and May 2012, four male and two female patients with a median age of 41 years received aSCT. The median mRSS significantly decreased from 26.5 to 18 and 17.5 at month 6 and 12, respectively. The total lung volume also significantly improved. Within the median follow-up of 1.6 years (range 1–3.8) two patients experienced a relapse of SSc, which results in a progression-free survival rate of 66.6%. Three patients experienced ICD discharge. Conclusion. For patients with SSc and cardiac involvement, the use of thiotepa and reduced-dose CYC is feasible and effective. The rate of ICD discharge underlines the need for protection in these endangered patients. This preliminary experience allowed us to use this regimen for our currently recruiting prospective trial (NCT01895244).
    Keywords: Systemic Sclerosis ; Stem Cell Transplantation ; Treatment ; Cyclophosphamide ; Ct Histography ; Thiotepa ; Heart
    ISSN: 1462-0324
    E-ISSN: 1462-0332
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  • 4
    Language: English
    In: Clinical and experimental rheumatology, 2018, Vol.36 Suppl 113(4), pp.28-35
    Description: To evaluate the effect of autologous stem cell transplantation (aSCT) on antibody (ab) reactivity towards linear epitopes of topoisomerase-I (topo-I/Scl70) in patients with systemic sclerosis (SSc) and to correlate antibody reactivities with clinical outcome after aSCT. Fourteen anti-topo-I/Scl70-positive SSc-patients were analysed before and after non-myeloablative aSCT. Five patients showed ongoing good response (group 1), 9 had primarily responded but later relapsed or did not respond (group 2). Patients' sera were tested by ELISA against full length (fl) topo-I and 45 overlapping 25-mer peptides. Furthermore, for comparison sera from patients with anti-topo-I-negative SSc (n=12), other collagen disorders (n=6), and from 21 healthy controls (HC) were analysed. Anti-topo-I-positive SSc-sera showed significantly higher IgG-reactivity as compared to HC towards 34 of the 45 peptides. Especially peptide 39 (aa647-671) emerged as a immunodominant epitope being recognised predominantly by anti-topo-I-positive SSc-sera. Reactivity towards 17 of the 45 peptides decreased after aSCT in group 1- and 2-patients. Before aSCT, group 1-patients had lower antibody reactivity towards peptide 39 than group 2-patients. There was no change in peptide-specificity after aSCT. Reactivity towards topo-I-epitopes is heterogeneous in SSc, but peptide 39 (aa647-671) may be another immunodominant epitope besides the published epitope aa489-573. Antibody reactivity to this peptide 39 was higher in group 2- than in group 1-patients. Peptide recognition pattern did not change after aSCT.
    Keywords: Immunodominant Epitopes ; Stem Cell Transplantation ; Autoantibodies -- Immunology ; DNA Topoisomerases, Type I -- Immunology ; Immunoglobulin G -- Immunology ; Scleroderma, Systemic -- Surgery
    ISSN: 0392-856X
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 5
    Language: English
    In: Clinical and experimental rheumatology, 2017, Vol.35 Suppl 104(2), pp.11-12
    Keywords: Multidetector Computed Tomography ; Stem Cell Transplantation ; Scleroderma, Systemic -- Diagnostic Imaging ; Thymus Gland -- Diagnostic Imaging
    ISSN: 0392-856X
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 6
    Language: English
    In: The Journal of rheumatology, February 2012, Vol.39(2), pp.269-75
    Description: Autologous stem cell transplantation (aSCT) for systemic sclerosis (SSc) has been shown to be effective in recent reports. This aggressive approach and the disease itself are associated with a high mortality. We report our experiences in 26 consecutive patients. Between 1997 and 2009, 26 patients were scheduled for aSCT. Our standard transplant regimen consists of cyclophosphamide (CYC) and granulocyte colony-stimulating factor (GCSF) for mobilization and CYC plus antithymocyte globulin for conditioning before the retransfusion of CD34 selected stem cells. The major outcome variable was the response to treatment [reduction of modified Rodnan skin score (mRSS) by 25%] at Month 6. Secondary endpoints were the transplant-related mortality and the progression-free survival. Significant skin and lung function improvement of the mRSS was achieved in 78.3% of patients at Month 6. The overall response rate was 91%, as some patients improved even after Month 6. Three patients died between mobilization and conditioning treatment, 2 due to severe disease progression and 1 whose death was considered treatment-related (i.e., GCSF or CYC toxicity). Depending on definitions, transplant-related mortality was 4% and treatment-related mortality 11%. Seven patients experienced a relapse during the 4.4 years of followup. The progression-free survival was 74%. Four patients died during followup and the most frequent causes of death were pulmonary and cardiac complications of SSc. aSCT led to significant improvement in most patients with SSc. The procedure requires further optimization; hence we are modifying our screening and treatment strategy. To minimize infectious complications, CYC for mobilization and GCSF were reduced. We intensified our screening for cardiac involvement and modified our conditioning regimen in case of cardiac involvement.
    Keywords: Hematopoietic Stem Cell Transplantation -- Methods ; Scleroderma, Systemic -- Surgery
    ISSN: 0315-162X
    E-ISSN: 14992752
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  • 7
    Language: English
    In: Annals of Hematology, 2016, Vol.95(6), pp.973-983
    Description: Myelofibrosis (MF) is a rare disease responsible for an increasing ineffective hematopoesis by a progressive fibrosing process in the bone marrow. The only curative treatment option is allogeneic hematopoietic cell transplantation (HCT). In this single-center analysis, we evaluated retrospectively 54 consecutive patients suffering from primary or secondary MF which underwent HCT from 1997 to 2014 after either myeloablative (MAC, n  = 19) or reduced-intensity conditioning (RIC, n  = 35). Overall survival (OS) and disease-free survival (DFS) after 3 years was 54/53 % for RIC versus 63/58 % for MAC ( p  = 0.8/0.97). Cumulative incidence of relapse was 34 % after RIC and 8 % after MAC ( p  = 0.16). Three-year non-relapse mortality (NRM) was 15 % after RIC and 34 % after MAC ( p  = 0.29). We found that RIC was associated with a lower incidence of acute graft versus host disease (GvHD; II–IV 26 vs. 0 %, p  = 0.004). Evaluation of prognostic relevance of the Dynamic International Prognostic Scoring System (DIPSS) score showed a significant better OS in patient with risk score ≤3 versus 〉3 (after 3 years, 71 vs. 39 %, p  = 0.008). While similar OS and DFS were observed with MAC or RIC, the use of RIC resulted in lower incidence of acute GvHD. RIC regimens may be therefore the preferred conditioning approach for allogeneic HCT in patients with MF.
    Keywords: Reduced intensity conditioning ; Myeloablative conditioning ; Hematopoietic cell transplantation ; Myelofibrosis
    ISSN: 0939-5555
    E-ISSN: 1432-0584
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  • 8
  • 9
    Language: English
    In: Annals of Hematology, 2016, Vol.95(1), pp.115-124
    Description: We report a retrospective single-center analysis of 112 consecutive patients that underwent allogeneic hematopoietic cell transplantation (HCT) after reduced-intensity conditioning (RIC) with fludarabine (FLU) and busulfan (BU) for the treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and myeloproliferative syndrome (MPS) from 2005 to 2014. Three-year event-free survival (EFS) and overall survival (OS) were 46 and 58 %, respectively. Patients ≥60 years of age showed a similar outcome compared to younger patients (3-year OS 55 vs. 61 %, p  = 0.96; 3-year EFS 46 vs. 46 %, p  = 0.82). Cumulative incidence of non-relapse mortality (NRM) at 3 years adjusted for relapse as competing risk was 25 % for patients aged 〈60 years and 15 % for older patients ( p  = 0.15). Infusions of higher CD34 + blood stem cell doses were associated with a significantly better outcome in the elderly subgroup (3-year OS 82 vs. 39 %, p  = 0.007). Moreover, complete donor chimerism at day +100 was associated with a significantly improved survival (3-year OS 69 vs. 23 %, p  = 0.003). In conclusion, our data suggest that RIC with FLU/BU enables long-term disease-free survival even in an elderly patient population. Age has no negative impact on the outcome of allogeneic HCT, and decision for transplant should be based on disease risk and performance status rather than age alone.
    Keywords: Allogeneic HCT ; RIC ; Myeloid malignancies ; Aged patients ; Fludarabine ; Busulfan
    ISSN: 0939-5555
    E-ISSN: 1432-0584
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  • 10
    Language: English
    In: Annals of the New York Academy of Sciences, June 2007, Vol.1106, pp.262-71
    Description: The isolation of mesenchymal stem cells (MSC) from primary tissue is hampered by the limited selectivity of available markers. So far, CD271 is one of the most specific markers for bone marrow (BM)-derived MSC. In search of additional markers, monoclonal antibodies (mAbs) with specificity for immature cells were screened by flow cytometry for their specific reactivity with the rare CD271(+) population. The recognized CD271(+) populations were fractionated by fluorescence-activated cell sorting and the clonogenic capacity of the sorted cells was analyzed for their ability to give rise to CFU-F. The results showed that only the CD271(bright) but not the CD271(dim) population contained CFU-F. Two-color flow cytometry analysis revealed that only the CD271(bright) population was positive for the established MSC markers CD10, CD13, CD73, and CD105. In addition, a variety of mAbs specific for novel and partially unknown antigens selectively recognized the CD271(bright) population but no other BM cells. The new MSC-specific molecules included the platelet-derived growth factor receptor-beta (CD140b), HER-2/erbB2 (CD340), frizzled-9 (CD349), the recently described W8B2 antigen, as well as cell-surface antigens defined by the antibodies W1C3, W3D5, W4A5, W5C4, W5C5, W7C6, 9A3, 58B1, F9-3C2F1, and HEK-3D6. In conclusion, the described markers are suitable for the prospective isolation of highly purified BM-MSC. These MSC may be used as an improved starting population for transplantation in diseases like osteogenesis imperfecta, cartilage repair, and myocardial infarction.
    Keywords: Cell Culture Techniques -- Methods ; Cell Separation -- Methods ; Mesenchymal Stem Cells -- Cytology
    ISSN: 0077-8923
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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