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  • 1
    In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 2322-2322
    Abstract: Abstract 2322 New onset of AD have been reported after autologous and allogeneic HSCT and AD patients (pt) treated by HSCT may be at higher risk for developing a secondary AD. A single US centre study showed that more profound T cell depleting conditioning with antithymocyte globulin (ATG) or alemtuzumab enhanced the risk of secondary AD after HSCT for primary AD. We therefore aimed at specifying the incidence, nature and risk factors for secondary AD after autologous or allogeneic HSCT for a primary AD. Methods: Retrospective analysis of AD pts treated by HSCT as reported to the EBMT data management system ProMISe until November 2009. Each EBMT participating centre was asked to identify all pts having developed at least one AD and those not having developed AD after HSCT as controls with complete detailed information on HSCT and outcome of original disease and treatment and outcome of secondary AD for cases. Cumulative incidence curves were used to estimate incidence of AD considering death as a competing event. Associations of patients and graft characteristics with secondary AD were evaluated by multivariate analyses, using Cox proportional hazards. All tests were two-sided. The type I error rate was fixed at 0.05 to determinate factors associated with time to event outcomes. Results (median, extremes): Out of 338 patients from 26 centres in 12 European countries, 33 developed at least one secondary AD within 569 (19-1489) days after HSCT, 305 pts without secondary AD served as controls. Characteristics of both groups are in table 1. The cumulative incidence of secondary AD after HSCT for primary AD was 6.5 (±1) % after 3 years and 11.1 (±2) % after 5 years. Diagnoses of secondary AD were thyroiditis (n=13), autoimmune hemolytic anemia (AIHA) (n=4), autoimmune thrombopenia (n=3), acquired hemophilia (n=3), Graves' disease, rheumatoid arthritis, sarcoidosis, antiphospholipid syndrome and psoriatic arthritis in 2 pts each and myasthenia gravis and vasculitis in 1 pt each. Two pts developed two secondary AD. After multivariate analysis age younger than 33 years p=0.016 (overall median age at HSCT), primary systemic lupus erythematosus (SLE) p= 0.003, ex vivo manipulation p= 0.015 and HSCT performed after the year 2002 p=0.02 remained as risk factors for secondary AD. At last follow-up within 5.9 years (0.25-15 years) after HSCT, 28/33 pts with secondary AD were alive and 257/305 nonAD pts. 0ne Systemic Sclerosis pt and one Multiple Sclerosis transplanted pt died from secondary embolic antiphospholipid syndrome and acquired hemophilia respectively. 26 primary AD pts received specific therapy after HSCT for their secondary AD. The pts with acquired hemophilia received steroids plus cyclophosphamide and additional Rituximab or ivIG or plasmapheresis, those with immune thrombocytopenia responded to steroids. One pt with thrombocytopenia followed by AIHA needed additional immunosuppression and Rituximab. Two pts with AIHA received steroids, cyclophosphamide and additional Rituximab, and one case also ivIG and ultimately allogeneic HSCT for secondary AID. At last follow-up, 12 pts remained in remission of secondary AD without treatment, 15 pts needed ongoing therapy, 3 pts had persistent secondary AD without therapy. This first multicenter study after HSCT for primary AD showed that secondary AD occurred in 10% of 338 pts after HSCT and led to death in 2 pts. Younger age and SLE as primary AD were significant risk factors for secondary AD, but contrary to previous single centre US experience, conditioning with ATG or alemtuzumab did not increase the secondary AD risk. Secondary AD after HSCT should be added to the post transplant follow up clinical parameters. Disclosures: Lenhoff: Celgene: Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2010
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  • 2
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 4357-4357
    Abstract: Abstract 4357 Background This retrospective study evaluates outcomes of patients (pts) treated with autologous stem cell transplantation (ASCT) and subsequent therapy for relapsed/refractory Hodgkin lymphoma (HL) who underwent ASCT in 7 transplant centres in Czech Republic. Patients and methods 194 pts with relapsed/refractory HL treated with ASCT (184 single, 10 tandem) between 01/2000 and 06/2009 were analyzed. Overall survival (OS) and progression-free survival (PFS) since the time of ASCT were evaluated according to Kaplan-Meier methods. Outcome of pts relapsing after ASCT was evaluated since the time of relapse. Different salvage modalities after ASCT and their impact on survival were compared with log-rank test. Results Median age of pts at time of ASCT was 33 (range 18-66) years. Best response observed after ASCT: complete remission (CR) in 124 pts (64%), partial remission (PR) in 35 pts (18%), stable disease (SD) in 2 pts (1%) and relapse/ progression in 33 pts (17%). Median follow-up was 44 months (m)(range, 3-108). Projected 5-year OS was 71% (median not reached) and PFS 54% (median 86m). Overall 70 pts progressed/relapsed after ASCT and allogeneic stem cell transplantation (alloSCT) was planned in 38 of them, but carried out only in 25 pts (3 myeloablative and 22 reduced intensity regimens). 37 pts were scheduled for other salvage therapy, 4 pts underwent second ASCT and 4 pts did not receive further treatment. Median survival of 70 pts since relapse after ASCT was 16.9 months. Median survival since relapse after ASCT in pts with or without alloSCT was 31.8 and 12.4 months respectively, but the difference was not statistically significant. Overall 51/194 (26.3%) pts died. 11 of 124 pts died in continuous remission after ASCT due to non-relapse mortality including transplant related mortality in 8pts (6.4%). 40/70 relapsed/refractory pts died: 29 in relapse/progression (20 after salvage treatment, 9 after alloSCT) and 11 pts due to non-relapse mortality (5 after salvage treatment and 6 after alloSCT). Conclusion Efficacy of ASCT was confirmed in 113/194 surviving pts (58%) in continuous remission. Median survival of relapsed pts following ASCT was 16.9 m. AlloSCT seems to improve survival in relapsed/refractory patients, although the difference is not statistically significant. New drugs should be offered to patients failing transplantation treatment. Disclosures: Trneny: GSK: Consultancy; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Fresenius: Consultancy; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 16, No. 6 ( 2010-06), p. 685-693
    Abstract: There are multiple sclerosis patients who suffer from an aggressive course of the disease with severe relapses and rapid accumulation of disability despite adequate treatment. In such cases high-dose immunoablation with autologous haematopoietic stem cell transplantation (ASCT) may be considered. Our objective was to report our experience with 26 multiple sclerosis patients treated with ASCT within the years 1998—2008. Twenty-six patients (Expanded Disability Status Scale 2.5—7.5 (median 6.0), multiple sclerosis duration 2—19 years (median 7)) with aggressive multiple sclerosis underwent autologous haematopoietic stem cell transplantation. Stem cells were mobilized by high-dose cyclophosphamide and granulocyte colony-stimulating factor, BEAM (carmustine, etoposide, cytarabine, melphalan) was used for immunoablation. Patients were evaluated at baseline and every six months post ASCT for adverse events and clinical outcome. Follow-up period was 11—132 months (median 66). Progression-free survival was calculated using the Kaplan— Meier method. At 3 and 6 years of follow-up 70.8% and 29.2% of patients respectively were free of progression. Patients with relapsing multiple sclerosis course, disease duration 〈 5 years and age 〈 35 years had a more favourable outcome. There was no death within 100 days after ASCT. We conclude that ASCT represents a viable and effective treatment option for aggressive multiple sclerosis.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2010
    detail.hit.zdb_id: 2008225-3
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  • 4
    In: Blood, American Society of Hematology, Vol. 118, No. 6 ( 2011-08-11), p. 1693-1698
    Abstract: To specify the incidence and risk factors for secondary autoimmune diseases (ADs) after HSCT for a primary AD, we retrospectively analyzed AD patients treated by HSCT reported to EBMT from 1995 to 2009 with at least 1 secondary AD (cases) and those without (controls). After autologous HSCT, 29 of 347 patients developed at least 1 secondary AD within 21.9 (0.6-49) months and after allogeneic HSCT, 3 of 16 patients. The observed secondary ADs included: autoimmune hemolytic anemia (n = 3), acquired hemophilia (n = 3), autoimmune thrombocytopenia (n = 3), antiphospholipid syndrome (n = 2), thyroiditis (n = 12), blocking thyroid-stimulating hormone receptor antibody (n = 1), Graves disease (n = 2), myasthenia gravis (n = 1), rheumatoid arthritis (n = 2), sarcoidosis (n = 2), vasculitis (n = 1), psoriasis (n = 1), and psoriatic arthritis (n = 1). After autologous HSCT for primary AD, the cumulative incidence of secondary AD was 9.8% ± 2% at 5 years. Lupus erythematosus as primary AD, and antithymocyte globulin use plus CD34+ graft selection were important risk factors for secondary AD by multivariate analysis. With a median follow-up of 6.2 (0.54-11) years after autologous HSCT, 26 of 29 patients with secondary AD were alive, 2 died during their secondary AD (antiphospholipid syndrome, hemophilia), and 1 death was HSCT-related. This European multicenter study underlines the need for careful management and follow-up for secondary AD after HSCT.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    In: Clinical Lymphoma Myeloma and Leukemia, Elsevier BV, Vol. 17, No. 1 ( 2017-02), p. e124-
    Type of Medium: Online Resource
    ISSN: 2152-2650
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 2540998-0
    detail.hit.zdb_id: 2193618-3
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  • 6
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2007
    In:  Journal of Genetics Vol. 86, No. 2 ( 2007-8), p. 169-171
    In: Journal of Genetics, Springer Science and Business Media LLC, Vol. 86, No. 2 ( 2007-8), p. 169-171
    Type of Medium: Online Resource
    ISSN: 0022-1333 , 0973-7731
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2007
    detail.hit.zdb_id: 2162772-1
    SSG: 12
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  • 7
    In: JAMA, American Medical Association (AMA), Vol. 322, No. 2 ( 2019-07-09), p. 123-
    Type of Medium: Online Resource
    ISSN: 0098-7484
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    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2019
    detail.hit.zdb_id: 2958-0
    detail.hit.zdb_id: 2018410-4
    SSG: 5,21
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  • 8
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 2881-2881
    Abstract: Introduction: Chronic graft-versus-host-disease (cGvHD) is a major complication of allogeneic hematopoietic stem cell transplantation (HSCT) and a leading cause of non-relapse mortality due to profound immunodeficiency. The approach currently used to establish the diagnosis of cGvHD depends almost exclusively on the clinical history, physical examination, and histopathologic confirmation. Biology-based markers for confirmation of diagnosis or monitoring progression of cGvHD are urgently warranted. The pathogenesis of cGvHD is poorly understood. Mounting evidence implies a role of B-cells in this autoimmune-like disorder. In this study we analyzed whether changes in B-cell subpopulations in the peripheral blood (PB) of HSCT recipients could serve as a biomarker for immune-modulatory consequences of cGvHD. Methods: Within six months 70 consecutive patients (45 men, 25 women; median age 47.5 years) with complete donor cell engraftment a median of 45.5 (range, 5–149) months after allogeneic HSCT were enrolled including 21 never having cGvHD and 49 with cGvHD (35 active and/or progressive, 14 resolved at study entry). The latter received standard anti-infective prophylaxis and immunosuppressive therapy with a median duration of 36 (range, 3–104) months. A third of patients with active/progressive cGvHD had more than 2 organs involved. Evaluations in the study consisted of clinical parameters including cGvHD severity and treatment, serum immunoglobulin (Ig) levels, and infections. PB was analyzed by multiparameter flow cytometry to define B-lymphocytes (CD19+), which were further subdivided by staining for surface Ig (IgD+/M+) and the B-cell memory marker CD27+ and more immature B-lymphocytes (CD19+/CD21−). Results: No significant differences in absolute B, T, and NK-cell counts between the groups with and without cGvHD were seen. However, the relative number of both class-switched and non-class-switched memory B-cells was significantly lower (below 3%) in patients with active cGvHD compared to patients never having cGvHD (up to 7%) (p 〈 0.001, c2 =22.0 for class-switched and p=0.002, c2 =9.2 for non-class-switched). Absolute cell counts confirmed these findings (10.3 vs. 27.2 cells/uL, p=0.02 for class-switched and 12.1 vs. 22.1 cells/ul, p=0.047 for non-class-switched). Significantly more patients with active cGvHD had elevated numbers of immature CD19+/CD21− B-cells ( 〉 15% cut-off) than the groups with resolved or never having cGvHD (37% vs 21% vs 9%, p=0.024). In patients with 〉 15% immature CD19+/CD21− B-cells significantly more severe infections (according to NCI-CTC Infection module grade III–IV) were seen compared to patients with low CD19+/CD21− B-cell counts (p=0.002, c2 =9.5). In the group of active cGvHD 12/13 (92%) patients with 〉 15% CD19+/CD21− B-cells compared to 4/22 (18%) patients with ≤ 15% CD19+/CD21− B-cells experienced severe infections (p 〈 0.001, c2 =18.1). First results in an ongoing prospective study showed an increase of memory B-cell numbers in patients with decreasing cGvHD activity. Discussion: Monitoring of class-switched and non-class-switched memory B-cells may allow measuring of disease activity of chronic GvHD. In combination with assessment of immature CD19+/CD21− B-cells new insights into immune-modulatory consequences of cGvHD focusing on B-cell defects and activation status are possible.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    In: Multiple Sclerosis Journal, SAGE Publications, Vol. 21, No. 2 ( 2015-02), p. 189-197
    Abstract: Neuromyelitis optica (NMO) is an inflammatory autoimmune disorder of the central nervous system, hallmarked by pathogenic anti-aquaporin 4 antibodies. NMO prognosis is worse compared with multiple sclerosis. Objective: The European Group for Blood and Marrow Transplantation (EBMT) Autoimmune Diseases Working Party (ADWP) conducted a retrospective survey to analyze disease outcome following autologous stem cell transplantation (ASCT). Methods: This retrospective multicenter study assessed the efficacy and safety of ASCT in 16 patients suffering from refractory NMO reported to the EBMT registry between 2001 and 2011. Results: Fifteen patients were successfully mobilized with cyclophosphamide (Cy) and G-CSF, one with G-CSF alone. All patients received an unmanipulated autologous peripheral blood stem cell graft, after conditioning with BEAM plus anti-thymocyte globulin (ATG, n = 9 patients), thiotepa-Cy ( n = 3) or Cy (200 mg/kg) plus ATG ( n = 4). After a median follow-up of 47 months, three of 16 cases were progression and treatment free, while in the remaining 13 patients further treatments were administered for disability progression or relapse after ASCT. Altogether, relapse-free survival at three and five years was 31% and 10%, respectively, while progression-free survival remained 48% at three and five years. Conclusions: In these NMO patients, highly resistant to conventional treatment, ASCT allows for temporary control of the disease, despite a tendency to progress or relapse in the long term.
    Type of Medium: Online Resource
    ISSN: 1352-4585 , 1477-0970
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2015
    detail.hit.zdb_id: 2008225-3
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  • 10
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 502-502
    Abstract: Abstract 502 Background and Aims: Rituximab has become an essential component of FL treatment, either in combination with chemotherapy or as maintenance. However, there is not much data available regarding the influence of prior rituximab on the survival of patients after ASCT. In addition, there is no consensus regarding the best type of high-dose regimen. The aim of this study is to assess the outcome of patients with FL having ASCT according to the high-dose regimen and previous treatment with rituximab. Patients and Methods: Between 1995 and 2007, 7910 patients with FL had their 1st ASCT and were reported to the EBMT registry. A full data set was available for 2233 patients who had ASCT with either TBI containing regimens or BEAM, and constitute the study group. Overall survival (OS) and event-free survival (EFS) were determined using the Kaplan-Meier method, and curves were compared by log-rank test. In multivariate analysis, the relevance of prognostic factors was estimated using Cox regression model. Incidence of relapse (IR) and non-relapse mortality (NRM) were calculated by cumulative incidence curves compared by Gray's test. Multivariate analysis of IR and NRM used Fine and Gray model. Results: Six hundred and eighty patients received a TBI-containing regimen, and 1553 patients BEAM. Seven hundred and thirteen patients (32%) had been treated with monoclonal antibodies (MoAb) before ASCT (confirmed as rituximab in 665). Patients who had TBI were younger (median age: 47) than patients who underwent BEAM (median age: 49; p 〈 0.001), and were transplanted in 1st remission more frequently (61%) than BEAM patients (44%, p 〈 0.001). In contrast, more patients treated with BEAM had received MoAb prior to ASCT (37%) than TBI patients (21%, p 〈 0.001). Peripheral blood was the source of stem cells in 98% of patients having BEAM in comparison with 92% of patients having TBI (p 〈 0.001). After a median follow-up of 60 months, the median overall survival (OS) for the whole group was 146 months and the median EFS, 72 months. Multivariate models for analysis of prognostic value of TBI were all adjusted on disease status at transplant, age, previous MoAb, time from diagnosis to ASCT, and source of stem cell and significant risk factors are shown in the table. In addition there was a trend for patients receiving TBI to have a better OS than patients receiving BEAM (p=0.06). Moreover, females had better EFS (p = 0.011) and OS (p = 0.058) in univariate analysis. However, the gender survival curves did not fulfil the proportional hazards assumption and thus the multivariate analysis of OS and EFS were stratified on gender allowing no estimation of its effect on outcome. Conclusions: In contrast to observations made in patients autografted before 1995 (Montoto Leukemia 2007), in the present series (with a shorter follow-up) the beneficial effect of TBI over BEAM in terms of relapse prevention was not counteracted by an increased NRM, resulting in a significantly better EFS with TBI in the rituximab era. Unlike reported for aggressive lymphoma, use of MoAb (rituximab) prior to ASCT had no detrimental impact on outcome and in fact was associated with significantly better OS. The superior survival of female patients in the rituximab era needs to be confirmed in further studies. Disclosures: Blaise: Laboratoire Pierre Fabre: Research Funding; Celgene: Research Funding. Rambaldi:Italfarmaco S.p.A.: Consultancy, Honoraria. Gribben:Roche: Honoraria; Celgene: Honoraria; GSK: Honoraria; Mundipharma: Honoraria; Gilead: Honoraria; Pharmacyclics: Honoraria. Montoto:Genentech: Research Funding; Roche: Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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