Kooperativer Bibliotheksverbund

In: Bone Marrow Transplantation, Springer Science and Business Media LLC, Vol. 53, No. 9 ( 2018-9), p. 1188-1192

Type of Medium: Online Resource

ISSN: 0268-3369 , 1476-5365

URL: Article

DOI: 10.1038/s41409-018-0135-3

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2018

detail.hit.zdb_id: 2004030-1

In: International Journal of Stroke, SAGE Publications

Abstract: Adenovirus-based COVID-19 vaccines are extensively used in low- and middle-income countries (LMICs). Remarkably, cases of cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) have rarely been reported from LMICs. Aims: We studied the frequency, manifestations, treatment, and outcomes of CVST-VITT in LMICs. Methods: We report data from an international registry on CVST after COVID-19 vaccination. VITT was classified according to the Pavord criteria. We compared CVST-VITT cases from LMICs to cases from high-income countries (HICs). Results: Until August 2022, 228 CVST cases were reported, of which 63 were from LMICs (all middle-income countries [MICs]: Brazil, China, India, Iran, Mexico, Pakistan, Turkey). Of these 63, 32 (51%) met the VITT criteri a, compared to 103 of 165 (62%) from HICs. Only 5 of the 32 (16%) CVST-VITT cases from MICs had definite VITT, mostly because anti-platelet factor 4 antibodies were often not tested. The median age was 26 (interquartile range [IQR] 20–37) versus 47 (IQR 32–58) years, and the proportion of women was 25 of 32 (78%) versus 77 of 103 (75%) in MICs versus HICs, respectively. Patients from MICs were diagnosed later than patients from HICs (1/32 [3%] vs. 65/103 [63%] diagnosed before May 2021). Clinical manifestations, including intracranial hemorrhage, were largely similar as was intravenous immunoglobulin use. In-hospital mortality was lower in MICs (7/31 [23%, 95% confidence interval (CI) 11–40] ) than in HICs (44/102 [43%, 95% CI 34–53], p = 0.039). Conclusions: The number of CVST-VITT cases reported from LMICs was small despite the widespread use of adenoviral vaccines. Clinical manifestations and treatment of CVST-VITT cases were largely similar in MICs and HICs, while mortality was lower in patients from MICs.

Type of Medium: Online Resource

ISSN: 1747-4930 , 1747-4949

URL: Article

DOI: 10.1177/17474930231182901

Language: English

Publisher: SAGE Publications

Publication Date: 2023

detail.hit.zdb_id: 2211666-7

In: Neurocritical Care, Springer Science and Business Media LLC

Abstract: Clinical observations indicated that vaccine-induced immune thrombosis with thrombocytopenia (VITT)-associated cerebral venous sinus thrombosis (CVST) often has a space-occupying effect and thus necessitates decompressive surgery (DS). While comparing with non-VITT CVST, this study explored whether VITT-associated CVST exhibits a more fulminant clinical course, different perioperative and intensive care unit management, and worse long-term outcome. Methods This multicenter, retrospective cohort study collected patient data from 12 tertiary centers to address priorly formulated hypotheses concerning the clinical course, the perioperative management with related complications, extracerebral complications, and the functional outcome (modified Rankin Scale) in patients with VITT-associated and non-VITT CVST, both with DS. Results Both groups, each with 16 patients, were balanced regarding demographics, kind of clinical symptoms, and radiological findings at hospital admission. Severity of neurological symptoms, assessed with the National Institute of Health Stroke Scale, was similar between groups at admission and before surgery, whereas more patients with VITT-associated CVST showed a relevant midline shift (≥ 4 mm) before surgery (100% vs. 68.8%, p  = 0.043). Patients with VITT-associated CVST tended to undergo DS early, i.e., ≤ 24 h after hospital admission ( p  = 0.077). Patients with VITT-associated CVST more frequently received platelet transfusion, tranexamic acid, and fibrinogen perioperatively. The postoperative management was comparable, and complications were evenly distributed. More patients with VITT-associated CVST achieved a favorable outcome (modified Rankin Scale ≤ 3) at 3 months ( p  = 0.043). Conclusions Although the prediction of individual courses remains challenging, DS should be considered early in VITT-associated CVST because an overall favorable outcome appears achievable in these patients.

Type of Medium: Online Resource

ISSN: 1541-6933 , 1556-0961

URL: Article

DOI: 10.1007/s12028-023-01782-6

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2023

detail.hit.zdb_id: 2176033-0

In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 4165-4165

Abstract: Abstract 4165 Introduction: Hematopoietic cell transplantation (HCT) is the treatment of choice for many hematological malignancies and often the only curative option. Despite continuous expansion of unrelated donor registries worldwide, not all patients have a matched donor available and single antigen mismatched donors are used for patients at high risk of relapse or progression. However, it remains unclear whether or not single-antigen mismatched and matched unrelated donor transplantations generate comparable clinical outcomes. Here, we present the results of a unicentre analysis approaching this question. Patients and Methods: The outcome of all patients transplanted from unrelated donors between 2000 and 2009 at the University Hospital in Leipzig was analyzed. A total of 206 patients with a median age of 38 (range 18–58) years with acute leukemias, chronic myeloid leukemia, myelodysplastic syndrome or non Hodgkin`s lymphoma were treated with a myeloablative regimen consisting of 12 Gy fractionated total body irradiation (n=189) or busulfan 16mg/m2 (n=17) in combination with cyclophosphamide. All patients received antithymocyte globulin during the conditioning regimen and graft-versus-host prophylaxis with cyclosporine and short course methotrexate. Donors were considered matched according to the typing available at the time of transplantation: Antigen typing in class I and allele typing in class II was available prior to 2006 and 10/10 4 digit HLA typing thereafter. Donors were considered matched if no HLA-antigen mismatch was detected. One hundred and fifty five patients were matched for the HLA loci A, B, C, DRB1 and DQB1 at the antigen level, while 39 patient/donor pairs had a single antigen mismatch and 12 a mismatch of two or more antigens. Disease stage, comorbidity index and Gratwohl score were well balanced in both groups. Results: After a median follow-up of 49 months, 54% of the 206 patients were alive. Most interestingly, there was no difference in overall survival (OS) at 5 years between HCT with matched and HCT with mismatched donors [52% vs 49% respectively (p=0.48)]. Also similar were event free survival (EFS) at 47% vs. 39% (p=0.44), relapse incidence (RI) 34% vs. 50% (p=0.22) and non-relapse mortality (NRM) 28% vs. 22% (p=0.81) in the matched versus mismatched donors. Acute graft versus host disease (GvHD) grade one or two occurred in 58% of all patients, while 14% had grade three or four and 28% had no signs of acute GvHD. The incidence of GvHD was comparable after antigen mismatched and antigen matched HCT. As expected, there was a significantly better OS, PFS and lower NRM for patients with early (n=104) vs. advanced disease (p=0.02) and patients with high resolution typing vs. low resolution typing (n=99; P=0.04). Even within these subgroups, however, the use of a single antigen mismatched donor did not worsen the results. Conclusion: In this unicenter analysis a comparable outcome was found after single antigen mismatched HCT compared to matched unrelated donor HCT. An antigen mismatched donor seems to be an acceptable option for patients with high risk malignant disease for whom no fully matched donor is available Disclosures: No relevant conflicts of interest to declare.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V118.21.4165.4165

Language: English

Publisher: American Society of Hematology

Publication Date: 2011

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: European Stroke Journal, SAGE Publications

Abstract: Cerebral venous sinus thrombosis associated with vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is a severe disease with high mortality. There are few data on sex differences in CVST-VITT. The aim of our study was to investigate the differences in presentation, treatment, clinical course, complications, and outcome of CVST-VITT between women and men. Patients and methods: We used data from an ongoing international registry on CVST-VITT. VITT was diagnosed according to the Pavord criteria. We compared the characteristics of CVST-VITT in women and men. Results: Of 133 patients with possible, probable, or definite CVST-VITT, 102 (77%) were women. Women were slightly younger [median age 42 (IQR 28–54) vs 45 (28–56)], presented more often with coma (26% vs 10%) and had a lower platelet count at presentation [median (IQR) 50x10 9 /L (28–79) vs 68 (30–125)] than men. The nadir platelet count was lower in women [median (IQR) 34 (19–62) vs 53 (20–92)] . More women received endovascular treatment than men (15% vs 6%). Rates of treatment with intravenous immunoglobulins were similar (63% vs 66%), as were new venous thromboembolic events (14% vs 14%) and major bleeding complications (30% vs 20%). Rates of good functional outcome (modified Rankin Scale 0-2, 42% vs 45%) and in-hospital death (39% vs 41%) did not differ. Discussion and conclusions: Three quarters of CVST-VITT patients in this study were women. Women were more severely affected at presentation, but clinical course and outcome did not differ between women and men. VITT-specific treatments were overall similar, but more women received endovascular treatment.

Type of Medium: Online Resource

ISSN: 2396-9873 , 2396-9881

URL: Article

DOI: 10.1177/23969873231185213

Language: English

Publisher: SAGE Publications

Publication Date: 2023

detail.hit.zdb_id: 2851287-X

In: Journal of Cancer Research and Clinical Oncology, Springer Science and Business Media LLC, Vol. 142, No. 1 ( 2016-1), p. 317-324

Type of Medium: Online Resource

ISSN: 0171-5216 , 1432-1335

URL: Article

DOI: 10.1007/s00432-015-2050-y

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2016

detail.hit.zdb_id: 1459285-X

In: Hämostaseologie, Georg Thieme Verlag KG, Vol. 40, No. 01 ( 2020-02), p. 119-127

Abstract: Introduction In 2005 the Kompetenznetz Hämorrhagische Diathese Ost published epidemiologic data about patients with haemophilia A (HA) and haemophilia B (HB) in the eastern part of Germany. This study provides data about the development of treatment in these patients over the past 10 years. Methods Data from 12 haemophilia centres in eastern Germany were retrospectively collected for the year 2015 from patients' records. Results We evaluated 413 patients (115 children, 298 adults) with HA or HB. A total of 286 patients (69.2%) had severe haemophilia (patients with severe haemophilia, PWSH). Compared with 2005, the proportion PWSH on prophylaxis increased from 90% to 98.8% in children and from 64% to 80.2% in adults. The use of plasma-derived factor concentrates decreased from 〉 70% to 55.3% in children and to 55.1% in adults. Mean annual factor consumption in PWSH without inhibitor was higher in 2015 compared with 2005 (children with HA: 151,489 vs. 98,894; adults with HA: 217,151 vs. 151,394; children with HB: 105,200 vs. 64,256; adults with HB: 159,185 vs. 85,295). Median annualized bleeding (annualized bleeding rate, ABR) and joint bleeding rates (annualized joint bleeding rate, AJBR) in 2015 were 2 and 0 in children and 3 and 0 in adults, respectively. In 2015 only one child (1.2%) but 101 (53.2%) adults with severe haemophilia were anti-hepatitis C virus (anti-HCV) positive. The rate of anti-HCV positive patients with active hepatitis C dropped from 63.8% to 12.9%. Conclusions Within the last decade more patients with severe haemophilia were switched to a prophylactic regimen going along with a moderate increase in factor consumption achieving a low ABR and AJBR.

Type of Medium: Online Resource

ISSN: 0720-9355 , 2567-5761

URL: Article

DOI: 10.1055/s-0039-3399493

Language: English

Publisher: Georg Thieme Verlag KG

Publication Date: 2020

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 2109-2109

Abstract: Background: Recombinant porcine factor VIII (rpFVIII, susoctocog alfa, Obizur ®, Baxalta US Inc., a Takeda company, Lexington, MA, USA) is a recombinant, B-domain-deleted, porcine-sequence FVIII indicated for the treatment of bleeding episodes (BEs) in adults with acquired hemophilia A. Thirty to 40% of patients with congenital hemophilia develop inhibitors to human FVIII (hFVIII). rpFVIII has low cross-reactivity to anti-hFVIII antibodies and is predicted to provide functional FVIII activity in patients with congenital hemophilia A (CHA) with inhibitors (CHAWI). Aims: To evaluate the efficacy and safety of rpFVIII in patients with CHAWI undergoing surgical and other invasive procedures. Methods: This was a Phase 3, international, multicenter, single-arm, open-label study (NCT02895945). Eligible participants were male (aged 12-75 years) with severe (FVIII & lt;1%) or moderately severe (FVIII ≤2%) CHA and inhibitors to hFVIII, who required elective surgical, dental, or other invasive procedures; those with anti-porcine FVIII (anti-pFVIII) & gt;10 BU prior to surgery were excluded. Patients received a loading dose of rpFVIII 1-2 hours before surgery based on body weight, hematocrit, pFVIII inhibitor titer and type of surgery, followed by individualized dosing. The primary outcome was the proportion of all procedures with a good or excellent response (treatment success) on the global hemostatic efficacy assessment (GHEA) score, based on the full analysis set (FAS; surgeries with ≥1 available hemostatic assessment). The GHEA score comprises 3 individual surgeon/investigator-assessed ratings (excellent, good, fair, or none) summed to give the total GHEA score: intraoperative efficacy at the end of surgery (Day 0, GHEA1); postoperative efficacy on postoperative Day 1 (GHEA2); and perioperative efficacy up to 72 hours after the last postoperative dose of rpFVIII (GHEA3). Secondary efficacy outcomes included observed-versus-predicted operative blood loss, BEs, weight-adjusted rpFVIII administration, and adverse events (AEs). Analysis of safety was based on the safety analysis set (all patients who received any amount of rpFVIII). Results: Eight patients comprising the safety analysis set received ≥1 dose of rpFVIII from 8 sites in 5 countries (Table). Of these 8 patients, 7 underwent major surgeries and 1 was scheduled for a minor surgery but did not undergo the procedure because the target preoperative FVIII was not achieved. The FAS included the 7 patients with major surgeries. Of the 8 dosed patients, 5 completed the study. Six of 7 (85.7%; 95% confidence interval, 42.1-99.6%) surgeries achieved treatment success; 5 surgeries were rated excellent, and 1 was rated good. The mean (standard deviation) ratio of actual to expected average blood loss in the major surgeries was 0.97 (0.95) during the intraoperative period and 0.15 (0.22) during the postoperative period. Seven surgery-related BEs (FAS, intraoperative, n=1; postoperative, n=6) occurred in 3 patients during the study, with none requiring surgical intervention (n=2 moderate; n=3 major; n=2 missing severity). Overall, 6 of 8 patients experienced 17 AEs. Three patients had anamnestic reactions (increase in titer of ≥10 BU/mL from a measurable baseline) to hFVIII and pFVIII; 1 patient developed de novo pFVIII inhibitors; another 2 patients had anamnestic reactions to hFVIII and developed de novo pFVIII inhibitors. Eight serious adverse events (SAEs) were reported in 6 patients, of which 4 SAEs were considered related to rpFVIII (3 anti-pFVIII antibody positive; 1 anamnestic reaction to hFVIII and pFVIII). The unrelated remaining SAEs were anti-hFVIII antibody increased (n=2), bacterial infection (n=1) and haemarthrosis (n=1). Conclusions: Six of 7 patients who received the study drug and underwent a surgical procedure achieved hemostasis with rpFVIII during the intraoperative and immediate postoperative period. Most patients developed de novo inhibitors or anamnestic reactions. Thus, good hemostasis can be achieved with rpFVIII within the first days after surgery; other bypassing agents should be used if longer clotting factor correction is required. The study was terminated early due to feasibility reasons and the risks of anamnestic reactions that outweigh the benefit in this study population. Figure 1 Figure 1. Disclosures Pfrepper: BMS: Honoraria; CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer Healthcare: Membership on an entity's Board of Directors or advisory committees; Chugai: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Fujimori: Research Funding; LeoPharma: Research Funding. Windyga: Baxalta: Honoraria, Research Funding; Novo Nordisk: Honoraria, Research Funding; Rigel Pharmaceuticals: Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; Shire: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Alfasigma: Honoraria; Aspen: Honoraria; Bayer AG: Honoraria; Octapharma: Honoraria, Research Funding; Sanofi-Aventis: Honoraria, Research Funding; Sobi: Honoraria, Research Funding; Swixx BioPharma: Honoraria; Werfen: Honoraria; Alnylam Pharmaceuticals: Research Funding; Sanofi/Genzyme: Honoraria, Research Funding; Alexion: Honoraria; CSL Behring: Honoraria. Kavakli: Takeda: Consultancy, Other: Clinical Trial Support; Novo Nordisk A/S: Consultancy, Other: Clinical Trial Support; Roche: Consultancy, Other: Clinical Trial Support. Schutgens: Bayer: Research Funding; CSL Behring: Research Funding; Novo Nordisk: Research Funding; OctaPharma: Research Funding; Pfizer: Research Funding; Shire/Takeda: Research Funding. Baptista: Takeda Development Center Americas, Inc.: Current Employment; Takeda: Current equity holder in publicly-traded company. Badejo: Takeda Development Center Americas, Inc.: Current Employment; Takeda: Current equity holder in publicly-traded company. Ewenstein: Takeda Development Center Americas, Inc.: Current Employment; Takeda: Current equity holder in publicly-traded company. Jain: Takeda: Current equity holder in publicly-traded company; Takeda Development Center Americas, Inc.,: Current Employment. OffLabel Disclosure: This abstract includes discussion of the following investigational use of a drug: in the CHAWI study (NCT02895945), recombinant porcine factor VIII (susoctocog alfa) was not administered according to the dosing and administration information in the product label.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-146179

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 2590-2590

Abstract: Background: Relapse of acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is frequently treated with 2nd allo-HSCT. Donor change has not yielded a significantly different outcome over choosing the original HLA-identical donor (Christopeit et al., JCO 2013). Using a haploidentical donor at second allo-HSCT might represent a feasible option (Tischer et al., BMT 2014) Study design and population: To define the role for second haploidentical allo-HSCT for AL relapsing after 1st allo-HSCT, a retrospective analysis was conducted 63 consecutive patients (female n=30, male n=33; AML n=51, ALL n=12) from 9 German centers were included. Median age was 40 years (range, 16-65). Grafts at 1st allo-HSCT were from matched related (32%), matched unrelated (33%), mismatch unrelated (18%), haploidentical donors (6%), and other donors, including cord blood (8%). Median duration of complete remission (CR) after 1st allo-HSCT was 414 days (range, 18-1633). Relapse was initially treated by cytoreductive chemotherapy in all cases; stage at start of conditioning for haploidentical second allo-HSCT was CR in 27%, active disease in 66% and not evaluated in 8%. Conditioning for second HSCT was myeloablative/reduced in 14%/86% To overcome the HLA barrier, 23 patients (36%) received ex vivo T-cell depletion (TCD), following either CD3/CD19 negative or CD34 positive selection. 4 patients received in vivo TCD only, two received no TCD at all, and 35 patients (55%) received high-dose cyclophosphamide post-transplant according to the Baltimore protocol. Results: Neutrophil engraftment was achieved after a median of 12 days (range, 8-26). 50 patients (78%) achieved CR after 2nd haploidentical allo-HSCT, out of which 23 (46%) relapsed again. After a median follow-up of 425 days, 47 patents had died, 22 from leukemia, and 25 from treatment-related causes. Kaplan-Meier estimated overall survival at one and two years from haploidentical second HSCT was 41+/-6% and 19+/-6%. Conclusions: Haploidentical second allo-HSCT is a promising approach to the treatment of AL relapse after first allogeneic transplant. OS rates at least comparable to alternative treatments were observed. Different strategies to overcome the HLA barrier seem feasible. This retrospective study was registered as NCT01997918 at clinicaltrials.gov. Maximilian Christopeit and Johanna Tischer as well as Wolfgang Bethge and Christoph Schmid contributed equally to this work. Disclosures No relevant conflicts of interest to declare.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V124.21.2590.2590

Language: English

Publisher: American Society of Hematology

Publication Date: 2014

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Haemophilia, Wiley, Vol. 28, No. 5 ( 2022-09), p. 687-693

Abstract: Guidelines recommend that patients with haemophilia should preferably receive vaccination subcutaneously. COVID‐19 and other vaccines, however, are only licenced for intramuscular application. Aims To assess the safety of intramuscular COVID‐19 vaccination in patients living with haemophilia. Methods Part A of this prospective observational study enrolled consecutive patients with haemophilia A (HA) and B (HB) of all ages and severities and assessed injection site bleeding and other complications within 30 days of vaccination. Part B enrolled patients providing informed consent for detailed data collection including medication and prophylaxis around the time of vaccination. Logistic regression was performed to assess potential risk factors for bleeding. Results Four hundred and sixty‐one patients were enrolled into part A. The primary endpoint injection site bleeding occurred in seven patients (1.5%, 95% confidence interval .7–3.1%). Comprehensive analysis of 214 patients (404 vaccinations, part B) revealed that 97% of patients with severe haemophilia had prophylaxis before vaccination, either as part of their routine prophylaxis or using additional doses. 56% and 30% of patients with moderate and mild haemophilia, respectively, received prophylaxis before vaccination. Among the seven bleeds recorded, three occurred when intramuscular vaccination was done without prophylaxis (odds ratio 12). Conclusions This is the first prospective study reporting on the safety of intramuscular vaccination in haemophilia. The rate of injection site bleeding was low in mild haemophilia, and in moderate and severe haemophilia if patients received factor prophylaxis.

Type of Medium: Online Resource

ISSN: 1351-8216 , 1365-2516

URL: Issue

URL: Article

DOI: 10.1111/hae.v28.5

DOI: 10.1111/hae.14586

Language: English

Publisher: Wiley

Publication Date: 2022

detail.hit.zdb_id: 2006344-1