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  • American Society of Hematology  (11)
  • Galicier, Lionel  (11)
  • 1
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    HLA-DRB1*11: a Strong Risk Factor for Acquired Severe ADAMTS13 Deficiency-Related Idiopathic Thrombotic Thrombocytopenic Purpura in Caucasians.
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 2412-2412
    Details
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 2412-2412
    Abstract: Abstract 2412 Poster Board II-387 Acquired idiopathic thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy (TMA) resulting from excessive von Willebrand factor (VWF)-mediated platelet clumping and capillary occlusion in relation with an autoantibody-mediated defect in the VWF-cleaving protease ADAMTS13. So far, the mechanisms leading to the loss of tolerance of the immune system against ADAMTS13 remain unknown. The usually switched isotype of the secreted anti-ADAMTS13 antibodies implies a cooperation between T lymphocytes and B lymphocytes and thus a recognition by T cell receptors of ADAMTS13 epitopes bound to human leukocyte antigen (HLA) molecules. We therefore hypothesized that particular HLA alleles may be involved in the process leading to a loss of tolerance of the immune system against ADAMTS13. Particularly, alleles within class I A and B loci and class II DRB1 and DQB1 loci are those most frequently associated with susceptibility to autoimmune diseases. We have compared medium resolution typing of HLA class I (HLA-A, B) and II (HLA-DRB1, DQB1) loci in 61 Caucasian patients with idiopathic TTP and a documented severe ( 〈 5%) acquired, autoantibody-mediated, ADAMTS13 deficiency to 132 healthy Caucasian volunteer donors Caucasian individuals and to 42 Caucasian patients with atypical hemolytic uremic syndrome (HUS) who displayed a detectable ADAMTS13 activity. The frequency of HLA-A, -B and -DQB1 alleles was comparable between patients with acquired idiopathic TTP, healthy individuals and patients with other forms of TMA. By contrast, the HLA DRB1*11 allele was observed in 62% of patients with acquired idiopathic TTP, whereas the usually reported incidence of this allele ranges from 13.5% to 24.5%, with the lower incidence in Asian/Pacific Islanders and Caucasians and the greater incidence in Afro-Caribbeans (http://www.allelefrequencies.net). Comparison to our group of healthy individuals confirmed this striking difference, which was statistically significant (20%, P = 10-7, odd ratio [OR] = 6.43, CI95% =2.3-12.7). The increased incidence of DRB1*11 in acquired idiopathic TTP was also significant when compared to patients with a diagnosis of atypical HUS (17%, P= 6×10-5). By contrast, DRB1*11 frequency in this latter group was comparable to this observed in healthy individuals (P = n.s). All patients were heterozygous for this allele. We also observed a decreased incidence of the DRB1*04 allele in acquired idiopathic TTP when compared to healthy individuals (10% versus 30%, respectively, Pcorr = 0.025). DRB1*04, resulting in the DR53 antigen when associated with DRB4, could thus be involved as a protective allele in acquired idiopathic TTP, as suggested in a previous work. We found no association between DRB1*11 and clinical features of autoimmunity, central nervous system involvement, antinuclear antibodies, anti-ADAMTS13 inhibitors, flare-up and relapse episodes and survival. Of note, the association between DRB1*11 with acquired idiopathic TTP was not observed in Afro-Caribbeans (3/12, 25%, p=0.04). High resolution typing of DRB1*11 allele revealed that both DRB1*1101 and DRB1*1104 alleles were significantly over-represented, suggesting that the generic DRB1*11 (and not the DRB1*11 alleles) is the predisposing factor. The DRB1*11 was reported to be a risk factor for systemic sclerosis, early-onset juvenile chronic arthritis and sarcoidosis, and protective against multiple sclerosis and pemphigus vulgaris. Accordingly, we found no patient with one of those 2 latter diseases in our French National TTP registry, whereas a past history of systemic sclerosis, sarcoidosis and juvenile chronic arthritis was observed in 1 case each. Our findings propose DRB1*11 as a strong risk factor for acquired idiopathic TTP in Caucasians. Indeed, the autoimmune response in acquired idiopathic TTP may involve the recognition by T cells of a class II region of DRB1*11, bound to a peptide fragment of ADAMTS13. We also suggest that acquired idiopathic TTP represents a subset of TMA with specific genetic risk factors, distinguishing it from the other forms of idiopathic TMA. The incomplete rate of concordance may be explained by other yet unexplored mechanisms, including additional predisposing genes and environmental triggers. Forthcoming genomewide association studies should lead to the identification of additional alleles associated with the risk of acquired idiopathic TTP. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V114.22.2412.2412
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 2
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    First-Line Rituximab Efficacy and Safety in Patients with Acquired Idiopathic Thrombotic Thrombocytopenic Purpura Experiencing a Non Optimal Response to Therapeutical Plasma Exchange: Results of a Prospective Multicenter Phase 2 Study From the French Reference Center for the Management of Thrombotic Microangiopathies.
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 890-890
    Details
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 890-890
    Abstract: Abstract 890 Background: Acquired idiopathic thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy (TMA) resulting from an autoantibody-mediated defect in the von Willebrand factor-cleaving protease ADAMTS13. Therapeutical monoclonal antibodies directed against B-lymphocytes (rituximab) provided interesting results on preliminary studies. Objectives: We assessed rituximab efficacy and safety in adult patients with acquired idiopathic TTP who experienced a non optimal response to daily TPE, as defined by a refractory disease at day 5 or a flare-up of the disease within the first 15 days of standard intensive TPE treatment. Design: We conducted a prospective multicenter open-label single arm phase 2 trial. Patients with a non optimal response received 4 rituximab infusions at days 1, 4, 8 and 15, along with daily TPE continuation (R+ group). Peripheral blood B-lymphocyte count was evaluated before each rituximab administration, and then at 3, 6, 9 and 12 months. Outcome from the first TPE session was compared to this of 57 historical patients (R- group) treated by TPE alone (36 cases) or associated with vincristine (21 cases) for the same indication. ADAMTS13 activity was assessed at 3, 6, 9 and 12 months in both groups. Results: Both groups had comparable features on admission. Twenty-two patients were included to receive rituximab. All received 4 rituximab infusions. One patient died in a context of refractory disease, whereas the 21 others achieved durable remission. The median time to durable platelet count recovery was 20 days (extremes: 14-33), which required a median plasma volume of 950 mL/kg (extremes: 310-1940). The median time from the first rituximab infusion to durable platelet count recovery was 10 days (extremes: 5-27). All patients recovered platelet count before day-35. No relapse was observed during the first year. However, 3 (14.3%) patients relapsed after a mean follow-up of 21.2±13.8 months. In R- group, 4 patients died beyond day-5. The mean time to platelet count recovery and the mean plasma volume required to achieve remission did not significantly differ between survivors in R+ and R- groups (p=0.28 and 0.67, respectively). However, 13 (21.6%) patients of R- group were still thrombocytopenic at day-35 (p=0.01). Rituximab allowed a profound and sustained peripheral blood B-cell depletion as early as day day-4 despite associated daily plasmapheresis. Peripheral blood B-cells were undetectable from day-8 to the 6th or 9th month, and recovered at 1 year. Consistently, ADAMTS13 activity was significantly higher at 3, 6 and 9 months in R+ patients (85% [0-150] , 90% [42-150], and 89% [92-125] , respectively) when compared to R- patients (49% [0-150], 54% [0-130] and 40% [0-90], respectively, p 〈 0.01, 〈 0.05 and 〈 0.001, respectively), which correlated with significantly lower levels of serum anti-ADAMTS13 antibodies (16 [0-77], 8 [0-18] and 10 [0-25] U/L, respectively, in R+ group and 44 [7-100] , 33 [12-100] and 34 [10-130] U/L, respectively, in R- group; p=0.003, 0.007 and 0.04, respectively). However, these differences vanished at 12 months. Neither patient experienced side effects related to rituximab during infusions. No patient developed hypogammaglobulinemia. No significant infectious complications occurred during follow-up. Conclusion: In patients with acquired idiopathic TTP, rituximab allows to shorten treatment duration in slow responders and prevents 1-year relapses by allowing a higher increase in ADAMTS13 activity. However, rituximab does not prevent long term relapses. Whether rituximab should be introduced systematically on diagnosis or only in patients identified as being slow responders with standard treatment remains a matter of debate which should be accurately assessed through larger, randomized trials. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V114.22.890.890
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
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  • 3
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    Idiopathic Thrombotic Microangiopathies: Antinuclear Antibodies, Platelet Count and Creatinin Level Can Predict a Severe ADAMTS13 Deficiency.
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 3923-3923
    Details
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 3923-3923
    Abstract: Severe ADAMTS13 deficiency in thrombotic microangiopathies (TMA) was reported with a variable frequency, which ranges from 13% to 50%. Whether clinical presentation allows to predict accurately severe ADAMTS13 deficiency remains a matter of controversy. To assess this question, we considered all adult (≥ 18 year-old) patients with idiopathic TMA and ADAMTS13 deficiency ( & lt; 15% of normal activity) of our Registry, whose clinical characteristics were compared with those of patients with idiopathic TMA and a detectable (≥ 15% normal activity) ADAMTS13 activity. Inclusion criteria were the association of a microangiopathic hemolytic anemia ( & lt; 12 g/dL) with a thrombocytopenia ( & lt; 150 × 109/L), and no other identifiable cause for cytopenias (transplantation, cancer and chemotherapy, or HIV infection). Patients were included prospectively from October, 2000, to January, 2007, from 17 National centers. One hundred and thirty-five patients were consecutively included. One hundred and two had a severe ADAMTS13 deficiency (58/96 had a plasma inhibitor), and 33 had a detectable ADAMTS13 activity (mean ADAMTS13 activity: 52.7± 29%). Patients with a severe ADAMTS13 deficiency were younger, displayed a lower platelet count and creatinin level, and presented more frequently antinuclear antibodies (ANA) at diagnosis (39.9± 15 versus 49.6± 17.9 year-old, 20± 19.2 versus 56.6± 42.9 × 109/L, 127± 106 versus 425± 335 μmol/L, and 61.8% versus 24.4%, respectively, p & lt;0.001 in all cases). Chronic renal failure occurred more frequently among patients with a detectable ADAMTS13 activity (19.2% versus 1.1%, p & lt;0.001). In a multivariate logistic analysis, patients with severe ADAMTS13 deficiency were more likely to have ANA (Estimated Odds ratio [OR] 4.81, 95% confidence interval [CI] 1.5–15.4), a lower platelet count (OR 0.98, 95% CI 0.96–1), and a lower creatinin level (OR 0.99, 95% CI 0.98–0.99) than patients with detectable ADAMTS13 activity (p & lt; 0.01, 0.14, and & lt; 0.01, respectively). Positive ANA with a platelet count & lt;31 × 109/L and a creatinin level & lt;194 μmol/L represented a set of criteria that allowed to identify patients with a severe ADAMTS13 deficiency with 52% sensitivity, but with a high specificity, at 97%. These criteria had a high positive predictive value for a severe ADAMTS13 deficiency, at 98.2%, and a negative predictive value of 39.5%. ANA, platelet count and creatinin level can predict accurately a severe acquired ADAMTS13 deficiency in idiopathic TMA. This set of criteria may be helpful in the management of patients that require targeted therapies, in association with plasma exchanges.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V110.11.3923.3923
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 4
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    Preemptive Rituximab Infusions Efficiently Prevent Relapses In Acquired Thrombotic Thrombocytopenic Purpura. Experience Of The French Thrombotic Microangiopathies Reference Center
    American Society of Hematology ; 2013
    In:  Blood Vol. 122, No. 21 ( 2013-11-15), p. 448-448
    Details
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 448-448
    Abstract: Acquired thrombotic thrombocytopenic purpura (TTP) results from a severe, antibody-mediated, deficiency in the von Willebrand factor-cleaving protease ADAMTS13. Rituximab is increasingly used in this indication in patients with a suboptimal response to plasma exchange. When severe acquired ADAMTS13 deficiency persists during remission, the estimated incidence rate is of 0.4/year. So far, it is still controversial whether preemptive rituximab efficiently prevents relapses in these patients. Patients and methods We defined two groups of patients with a history of acquired TTP who displayed a persistent severe ADAMTS13 deficiency during remission. Patients of group 1 were treated with preemptive infusions of rituximab. Patients of group 2 were managed in centers in which preemptive rituximab infusions were not the standard of care. The relapse incidence was evaluated and compared between both groups. Patients were treated according to National recommendations and enrolled from 12 French centers during a 12-year period. Patients were explored for ADAMTS13 activity and peripheral B-cell count every 3 months. Only patients with a 〉 12-month follow-up after rituximab administration are reported here. Median (25th - 75th percentile) was determined for all continuous variables. Wilcoxon’s test was used to compare continuous variables and the chi-square test or Fisher’s exact test to compare binary data. Relapse-free survival was compared between both groups using the Kaplan-Meier estimator with the corresponding 95% confidence interval. Results Forty-eight patients (20.6%) with a history of acquired TTP displayed a persistent severe ADAMTS13 deficiency on remission or experienced a subsequent severe ADAMTS13 deficiency (24 cases each) after a median follow-up of 17 months (12-29 months). Anti-ADAMTS13 antibodies concentration was 44 U/mL (24-59 U/mL). Thirty patients received preemptive infusions of rituximab (group 1), whereas 18 others had no therapeutical intervention (group 2). In group 1, 16 patients experienced a past history of TTP with a median number of 2 (1-3) episodes, corresponding to a relapse incidence of 0.22 (0-0.57)/year. Rituximab infusions were performed 14.5 months (6.5-27.4 months) after the last TTP episode. A median number of 4 (1-4) rituximab infusions were performed. The median follow-up between the first preemptive infusion of rituximab and the last ADAMTS13 evaluation is of 36 months (24-65 months). After preemptive rituximab administration, only 3 patients experienced a clinical relapse (0 [0] episode/year), corresponding to a significant reduction in the relapse incidence (P 〈 .01). ADAMTS13 activity was 58.5% (30.5%-86.3%). Three months after the first rituximab infusion, ADAMTS13 activity was 46% (30-68); it further increased until the 12th month, and subsequently decreased. Accordingly, B-cell lymphocytes remained undetectable until the 6th month, and progressively increased at the 9th month to reach normal values at the 18th month. Nine patients (30%) required one (5 cases), two (2 cases), three (1 case) or ten (1 case) additional courses of rituximab for a further decrease or a persistent undetectable ADAMTS13 activity, which allowed to maintain a detectable ADAMTS13 activity in all but one patients. The time between two consecutive courses of rituximab was 26 months (5-59 months). At the end of follow-up, ADAMTS13 activity remained normal in 18 patients; 10 patients had a moderate ADAMTS13 deficiency, and 2 patients had a persistently undetectable ADAMTS13 activity. In four patients (13%), rituximab alone failed to increase durably ADAMTS13 activity, which required additional immunosuppressive drugs. In group 2, 14 patients relapsed after a 66-month follow-up (36-105 months), corresponding to a higher relapse incidence than in patients who received preemptive infusions of rituximab (0.23 [0.1-0.46] relapse/year, P 〈 .01). Moreover, 2 patients died of TTP in group 2, whereas no fatal outcome was recorded in group 1. Relapse free survival over time was significantly longer in group 1 (Log-rank test: P = .049). Five patients experienced adverse effects including benign infections in 2 cases. Conclusion Rituximab efficiently prevents TTP relapses in most patients with a persistent acquired ADAMTS13 deficiency, with acceptable side effects. Disclosures: Off Label Use: Rituximab Rituximab may prevent relapses in acquired thrombotic thrombocytopenic purpura.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V122.21.448.448
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
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  • 5
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    Preemptive rituximab infusions after remission efficiently prevent relapses in acquired thrombotic thrombocytopenic purpura
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 2 ( 2014-07-10), p. 204-210
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 2 ( 2014-07-10), p. 204-210
    Abstract: Patients with a history of acquired TTP and persistent severe ADAMTS13 deficiency during remission are at high risk of relapse and death. Preemptive infusions of rituximab in remission significantly decrease TTP relapse rate.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2014-01-550244
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 6
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    Preemptive rituximab prevents long-term relapses in immune-mediated thrombotic thrombocytopenic purpura
    American Society of Hematology ; 2018
    In:  Blood Vol. 132, No. 20 ( 2018-11-15), p. 2143-2153
    Details
    In: Blood, American Society of Hematology, Vol. 132, No. 20 ( 2018-11-15), p. 2143-2153
    Abstract: TTP patients who display persistent and severe ADAMTS13 deficiency after remission have a relapse rate of 74% during long-term follow-up. Preemptive rituximab can decrease TTP relapses in 85% of patients with a favorable benefit-risk balance.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2018-04-840090
    RVK:
    XA 33000
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    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
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  • 7
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    Immune thrombotic thrombocytopenic purpura in older patients: prognosis and long-term survival
    American Society of Hematology ; 2019
    In:  Blood Vol. 134, No. 24 ( 2019-12-12), p. 2209-2217
    Details
    In: Blood, American Society of Hematology, Vol. 134, No. 24 ( 2019-12-12), p. 2209-2217
    Abstract: Prevel and colleagues examined the natural history of thrombotic thrombocytopenic purpura (TTP) in older adults, reporting that the geriatric TTP population experiences delayed diagnosis and more severe neurologic and renal impairment. Older patients also have greater short- and long-term mortality.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.2019000748
    RVK:
    XA 33000
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
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  • 8
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    A Prospective Phase II Trial of An L-Asparaginase Containing Regimen in Patients with Refractory or Relapsing Extra Nodal NK/T-Cell Lymphoma
    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 579-579
    Details
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 579-579
    Abstract: Extra nodal NK/T-cell lymphoma, nasal type, is an EBV-related highly aggressive disease with a poor outcome, especially when disseminated or recurrent after radiotherapy. L-Asparaginase seems to have a particular efficacy in this disease (Jaccard, 2008, Ann oncol). Nineteen patients with relapsing or refractory extra nodal NK/T-Cell Lymphoma, nasal type, were included in a multicentric prospective phase II trial using the Aspametdex regimen (E coli-L-asparaginase (Kidrolase®) 6000 UI/m2 IM at day 2,4,6,8, methotrexate 3 gr/m2 at day 1 and dexamethasone 40 mg at day 1 to 4 with 3 weeks cycles). Patients below 65 years of age and with a good performance status received 3 cycles and, in case of good response, an intensive treatment with the BEAM regimen and stem cell rescue. Other patients received up to 6 cycles of the Aspametdex protocol. Patients with localized disease received irradiation if not performed before inclusion. The histology was centrally reviewed and EBV viremia was regularly and centrally monitored. The response after 3 cycles was the primary end point. There were 14 men and 4 women (1 patient was excluded after pathologic review), median age was 59.5 (45 to 76), 7 were primary refractory, 11 were in relapse, 6 were in stage IV. Median number of cycles was 3 (1 to 6). Three patients who had an allergic reaction with L-asparaginase received further courses of Erwinia-asparaginase (Erwiniase®) (n= 3). Toxicity related to L-asparaginase was mild, mainly brief leucopenia (n=2), elevation of alanine aminotransferase (n=2) and venous thrombosis (n=1). Response was documented in 17/18 patients, 10 patients were in complete remission (CR) after treatment with L-asparaginase and 5 patients in partial remission. Five patients died of unrelated causes (n=1) or progression of disease (n=4). Thirteen patients are still alive with a median follow-up of 8 months (1 to 29), 5 responding patients progressed at 4, 5, 8, 8 and 22 months after treatment. Six patients are in persistent CR, 2 of these patients had received high dose therapy with autologous stem cell transplant and 1 patient received irradiation after L-asparaginase treatment. These data confirm the excellent activity of L-asparaginase-containing regimens in extranodal NK/T-cell lymphoma. This must be known because of the very poor prognosis of patients with disseminated or relapsing disease with conventional chemotherapy. First-line L-asparaginase combination therapy for extranodal NK/T-cell lymphoma should be tested in prospective trials.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V112.11.579.579
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
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  • 9
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    Development and Validation of a Predictive Model for Death in Acquired Severe ADAMTS13 Deficiency-Associated Idiopathic Thrombotic Thrombocytopenic Purpura: The French TMA Reference Center Experience
    American Society of Hematology ; 2011
    In:  Blood Vol. 118, No. 21 ( 2011-11-18), p. 2229-2229
    Details
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 2229-2229
    Abstract: Abstract 2229 Background: Acquired thrombotic thrombocytopenic purpura (TTP) is still associated with a 10–20% death rate, which did not significantly improve for more than 20 years despite a better awareness about this diagnosis. Usually, death occurs within the first days of management and so far, early prognostic factors of death could not be clearly identified. In this context, the accurate understanding of factors associated with a fatal outcome at the acute phase of the disease would help to better tailor initial treatment and further improve these results. Objective: To identify prognostic factors associated with 1-month death in TTP patients with acquired severe ( 〈 10% of normal activity) ADAMTS13 deficiency. Design: Prospective national cohort of adult (≥ 18 year-old) patients included between October, 2000, and December, 2008. A validation cohort of patients was set up from January, 2009 to March, 2010. Participants: 248 (analysis cohort) and 39 (validation cohort) consecutive adult TTP patients with acquired severe ADAMTS13 deficiency from 39 French centers. Measurements: 30-day mortality after treatment initiation according to characteristics at inclusion. Results: When compared to survivors, non-survivors (11%) were older (54.0 ± 19.4 versus 39.0 ± 15.5 year-old, respectively, P 〈 .001) and had more frequently a past history of arterial hypertension (37% versus 10%, respectively, P 〈 .001) and ischemic heart disease (19% versus 4%, respectively, P =.002). Prognosis was increasingly poor with age (p 〈 .004), particularly in patients ≥ 60 year-old. On presentation, cerebral manifestations were more frequent in non-survivors (81% versus 55%, respectively, P =.009) and serum creatinine level was higher (172 ± 123 versus 117 ± 91 μmol/L, respectively, P =.037). Death occurred after a few days (mean 7 days, interquartile range = [3, 12]), in a context of one or multiple organ failure in relation with an uncontrolled TTP. Platelet count between diagnosis and death did not significantly increase (20 ± 25×109/L versus 28 ± 46×109/L, respectively, P =.44). The most significant independent variables for determining death were age (P 〈 .001), cerebral involvement (stupor and seizure) and LDH level 〉 10 times normal value (P 〈 .04 for both). After computing the risk scores using these 3 variables (Table), patients were stratified into 3 distinctive risk groups regarding death: low, 0 and 1; intermediate, 2; and high, 3 and 4. The proportion of positive predictive value for 30-day death was 11–13% in the low risk group, 20% in the intermediate group, and 39–50% in the high risk group. This score was confirmed in the validation cohort using these variables, with higher values corresponding to increased risk of early death (P 〈 .01). Conclusions: A risk score for early death was defined in patients with TTP and validated on an independent cohort. This score should help to stratify early treatment and intensify patients with a worse prognosis. Importantly, we provide clear evidence that age is an important prognostic factor of TTP. Consequently, old patients with a diagnosis of TTP should benefit from more intensive supportive care and should be monitored more closely in intensive care units with more aggressive attention to cardiac and renal function. Disclosures: Rottensteiner: Baxter Innovations GmbH: Employment.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V118.21.2229.2229
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 10
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    Pathogenesis and treatment of xanthomatosis associated with monoclonal gammopathy
    American Society of Hematology ; 2011
    In:  Blood Vol. 118, No. 14 ( 2011-10-06), p. 3777-3784
    Details
    In: Blood, American Society of Hematology, Vol. 118, No. 14 ( 2011-10-06), p. 3777-3784
    Abstract: Xanthomas are a common manifestation of lipid metabolism disorders. They include hyperlipemic xanthoma, normolipemic xanthoma, and a related condition, necrobiotic xanthogranuloma (NXG). All 3 forms can be associated with monoclonal immunoglobulin (MIg). In an attempt to improve diagnosis, understanding, and treatment of this association, we retrospectively analyzed a personal series of 24 patients (2 hyperlipemic xanthoma, 11 normolipemic xanthoma, and 11 NXG) and 230 well-documented reports from the literature. With the exception of the nodules and plaques featured in NXG, the clinical presentation of xanthomatous lesions usually resembled that seen in common hyperlipidemic forms and could not be used to suspect MIg-associated xanthomas. Extracutaneous sites were not rare. The MIg was an IgG in 80% of cases. Myeloma was diagnosed in 35%. Hypocomplementemia with low C4 fraction was present in 80% of studied patients. Low C1 inhibitor serum levels were found in 53%. Cryoglobulinemia was detected in 27%. These abnormalities suggest immune complex formation because of interactions between the MIg and lipoproteins and argue in favor of a causal link between MIg and xanthomas. Monoclonal gammopathy therapy could thus be an option. Indeed, among the patients who received chemotherapy, hematologic remission was accompanied by improvement in xanthoma lesions in several cases.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2011-05-356907
    RVK:
    XA 33000
    RVK:
    XA 10000
    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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