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Research Interests: Adolescent, Medicine, Anxiety, Prospective studies, Humans, and 15 moreFemale, Organ Transplantation, Male, Psychosocial, Liver Transplantation, Lung, Clinical Sciences, Aged, Middle Aged, Bone Marrow Transplantation, Adult, Analysis of Variance, ANXIETY, Personal Satisfaction, and Lung Transplantation
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The use of appropriate antigenic peptides for the most common human major histocompatibility complex (MHC) alleles is required for the amplification of the autologous cytotoxic compartment and the development of cytotoxic T cell-mediated... more
The use of appropriate antigenic peptides for the most common human major histocompatibility complex (MHC) alleles is required for the amplification of the autologous cytotoxic compartment and the development of cytotoxic T cell-mediated immunity. The human A2 allele of the MHC plays an important role for the identification of peptide-specific cytotoxic T cells (CTL) against tumor and viral epitopes. Computer-based prediction algorithms, which are available on the Internet, have already proved to be applicable for the identification of novel CTL epitopes. Using the bioinformatics approach, the authors have identified the novel influenza matrix protein-derived and HLA-A3-restricted 9-mer peptide RLEDVFAGK capable of inducing peptide specific CTL reactivity. Peripheral blood mononuclear cells (PBMC) from healthy individuals and patients with lung cancer were pulsed with this peptide and with the well-characterized HLA-A2-restricted influenza A virus matrix peptide58–66 GILGFVFTL. Usin...
Research Interests: Algorithms, Immunology, Immune response, Biology, Medicine, and 15 moreCell Culture, In Vitro, Humans, Polymerase Chain Reaction, Immunotherapy, Antigen Presentation, Immunization, CTL, Major histocompatibility complex, Predictive value of tests, Interferon gamma, Orthomyxoviridae, Human leukocyte antigen, epitope, and lung neoplasms
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Chronic granulomatous disease (CGD) is a primary immunodeficiency resulting in life-threatening infections and inflammatory complications. Allogeneic hematopoietic cell transplantation (allo-HCT) can cure the disease, but the indication... more
Chronic granulomatous disease (CGD) is a primary immunodeficiency resulting in life-threatening infections and inflammatory complications. Allogeneic hematopoietic cell transplantation (allo-HCT) can cure the disease, but the indication to transplant remains controversial. We performed a retrospective multicenter study of 712 patients with CGD who underwent allo-HCT transplantation from March 1993 through December 2018. We studied 635 children (aged <18 years) and 77 adults. Median follow-up was 45 months. Median age at transplantation was 7 years (range, 0.1-48.6). Kaplan-Meier estimates of overall survival (OS) and event-free survival (EFS) at 3 years were 85.7% and 75.8%, respectively. In multivariate analysis, older age was associated with reduced survival and increased chronic graft-versus-host disease. Nevertheless, OS and EFS at 3 years for patients ≥18 years were 76% and 69%, respectively. Use of 1-antigen-mismatched donors was associated with reduced OS and EFS . No sign...
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BACKGROUND Data on individualized immunosuppressive protocols for the pediatric heart recipients are missing in Europe. To contribute to this very small but specialized field, we describe the use of induction therapy (IT) in pediatric... more
BACKGROUND Data on individualized immunosuppressive protocols for the pediatric heart recipients are missing in Europe. To contribute to this very small but specialized field, we describe the use of induction therapy (IT) in pediatric heart transplant patients in Switzerland and the retrospective outcomes. METHOD This is a retrospective national database analysis of children <19 years of age at time of heart transplantation (HT) from 05/2008-01/2018. Use of IT or no IT, use of steroids, calculated panel reactive antibodies (cPRA) and outcomes (Mortality, post-transplant lymphoproliferative disease (PTLD), rejection rates) were studied within a mean follow-up period of 2.9 years (0.2-8.1 years). RESULTS All 32 patients (12♂, 20♀), median age at HT of 6.4 years (24 days - 18 years) received IT using either polyclonal antibodies (ATG; 72%) or interleukin-2 receptor antagonist (anti-IL-2R mAb; 28%). Length of treatment was median of 4 (1-63) days. At time of HT all patients received steroids, while at discharge 32% and one year after HT 19%. Kaplan-Meier analysis of survival revealed a one-year survival of 86%. Three out of 7 patients with elevated cPRA (43%) died. Median time to first treated rejection was 19.4 months (±60.5 SD) without significant difference if treated with anti-IL-2R mAb or ATG (p:0.5). No development of PTLD, chronic renal failure needing ongoing renal replacement therapy or diabetes mellitus were recorded. DISCUSSION This is the first report of the national practice use of IT within Switzerland. It reveals a high use of IT, no development of PTLD and a low use of steroids at one-year post HT.
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Background Influenza vaccination efficacy is reduced after hematopoietic stem cell transplantation (HSCT) and patient factors determining vaccination outcomes are still poorly understood. Methods We investigated the antibody response to... more
Background Influenza vaccination efficacy is reduced after hematopoietic stem cell transplantation (HSCT) and patient factors determining vaccination outcomes are still poorly understood. Methods We investigated the antibody response to seasonal influenza vaccination in 135 HSCT patients and 69 healthy volunteers (HVs) in a prospective observational multicenter cohort study. We identified patient factors associated with hemagglutination inhibition titers against A/California/2009/H1N1, A/Texas/2012/H3N2, and B/Massachusetts/2012 by multivariable regression on the observed titer levels and on seroconversion/seroprotection categories for comparison. Results Both regression approaches yielded consistent results but regression on titers estimated associations with higher precision. HSCT patients required 2 vaccine doses to achieve average responses comparable to a single dose in HVs. Prevaccination titers were positively associated with time after transplantation, confirming that HSCT p...
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Imatinib mesylate (Gleevec®) has changed the treatment of chronic myelogenous leukemia (CML), but allogeneic stem cell transplantation (SCT) is still considered the only curative therapy. Moreover, several reports indicate that imatinib... more
Imatinib mesylate (Gleevec®) has changed the treatment of chronic myelogenous leukemia (CML), but allogeneic stem cell transplantation (SCT) is still considered the only curative therapy. Moreover, several reports indicate that imatinib mesylate may also induce complete remission in relapsed CML following SCT, but it is not known, whether imatinib mesylate can be stopped after achieving complete remission. We report a patient who is in a complete molecular remission 4 months after withdrawal of imatinib mesylate therapy. A 41-year old man was diagnosed with Philadelphia chromosome (Ph)-positive CML in first chronic phase without additional cytogenetic abnormalities. Hydroxyurea therapy was started and he received allogeneic SCT from an HLA-identical and sex-matched sibling donor within one year after the initial diagnosis. The conditioning regimen consisted of cyclophosphamide and total body irradiation (12Gy). A combination with cyclosporin A (CsA) and methotrexate was administered...
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Introduction: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disease characterized by impairment of the phagocyte NADPH-oxidase complex, resulting in deficient microbial killing and life-threatening bacterial and... more
Introduction: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disease characterized by impairment of the phagocyte NADPH-oxidase complex, resulting in deficient microbial killing and life-threatening bacterial and fungal infections. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative approach, but it can be complicated by graft failure, graft versus-host disease (GvHD) and transplant-related mortality (TRM). In order to define prognostic risk factors in this setting, the IEWP of the EBMT performed a large retrospective registry study on 600 pediatric and adult patients with CGD undergoing allo-HSCT. Patients and Methods: We analyzed the outcome of patients with CGD who received allo-HSCT in EBMT centers between 1993 and 2017. The main end-points of the study were overall survival (OS) and event-free survival (EFS; events were death and primary or secondary engraftment failure) according to patient's age, donor type, stem cel...
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The occurrence of late events [i.e. secondary malignancies (SM)] after therapy is of special relevance in patients with Hodgkin«s lymphoma (HL) as the median age of this population is quite low and first line therapy is curative in a high... more
The occurrence of late events [i.e. secondary malignancies (SM)] after therapy is of special relevance in patients with Hodgkin«s lymphoma (HL) as the median age of this population is quite low and first line therapy is curative in a high proportion of them. Autologous stem cell transplantation (ASCT) is the standard of care for patients with HL in first relapse and chemosensitive disease and for those patients who demonstrate to be primary refractory. The administration of chemotherapy +/- radiotherapy is a risk factor for the development of SM and, high dose chemoradiotherapy given as conditioning regimen before stem cell infusion can further increase this risk. In this retrospective study we have analyzed the incidence of SM as well as of the different subtypes [acute leukemias (AL) / myelodisplastic syndromes – myeloproliferative disorders (MDS-MPD), lymphomas and solid tumors (ST)] in more than 2000 HL patients undergoing an ASCT with a very long follow up after transplantation...
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We describe the phenomenon of waning of focal hepatic and/or splenic lesions on abdominal computed tomographic (CT) scan during neutropenia in patients with chronic disseminated candidiasis. After observation of the phenomenon in one... more
We describe the phenomenon of waning of focal hepatic and/or splenic lesions on abdominal computed tomographic (CT) scan during neutropenia in patients with chronic disseminated candidiasis. After observation of the phenomenon in one patient, a total of five cases were prospectively monitored with serial CT scans. After the diagnosis of disseminated candidiasis, hepatic lesions decreased in size and conspicuousness in three patients, while in two others they disappeared completely during a subsequent chemotherapy-induced neutropenia. After recovery of the neutrophils, the lesions reappeared or increased in conspicuousness in all five patients. Of three patients treated with a second cycle of myeloablative chemotherapy, lesions again decreased in two patients during neutropenia and increased again in one patient after neutrophil recovery. In all five patients, candidiasis eventually resolved after prolonged antifungal treatment. In chronic disseminated candidiasis, hepatic or splenic...
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3281 Poster Board III-1 Introduction: In the two consecutive German CML studies III and IIIA (recruitment periods from 1995 to 2001 and 1997 to 2004), eligible patients were assigned to early HSCT by genetic randomization according to... more
3281 Poster Board III-1 Introduction: In the two consecutive German CML studies III and IIIA (recruitment periods from 1995 to 2001 and 1997 to 2004), eligible patients were assigned to early HSCT by genetic randomization according to availability of a matched related donor. After randomization, 113 patients of study III (84% of 135) and 144 of study IIIA (87% of 166) were eventually transplanted in first chronic phase (CP) using a related donor. Despite comparable transplantation protocols and most centers participating in both studies, survival probabilities in study IIIA were significantly better, even when adjusted for the established EBMT risk score (Gratwohl et al., Lancet 1998 [1]), p + 0.0097. For further explanation, the German Registry for Stem Cell Transplantation (DRST) and the Swiss Transplant Working Group for Blood and Marrow Transplantation (STABMT) were asked for data support. Patients and Methods: The main sample characteristics of the 257 transplanted CML study pa...
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Hematopoietic cell transplant (HCT) recipients are at increased risk for infections. Staphylococcus aureus (SA) colonizes 20-50% of healthy individuals and is a risk factor for subsequent invasive SA infections. Colonization rates in... more
Hematopoietic cell transplant (HCT) recipients are at increased risk for infections. Staphylococcus aureus (SA) colonizes 20-50% of healthy individuals and is a risk factor for subsequent invasive SA infections. Colonization rates in patients undergoing allogeneic HCT and clinical relevance for the time of aplasia and severely reduced immune function following HCT are not known. Only some retrospective data on methicillin-resistant SA infection rates are available. In this study, we prospectively assessed the prevalence of SA colonization in 110 consecutive patients before and during allo-HCT in a single-center observational study from June 2013 to January 2016. All patients undergoing allo-HCT were screened for nasal, pharyngeal and inguinal SA colonization weekly beginning at the time of admission to the transplant unit until neutrophil recovery. After swabs for the initial SA screening were taken all patients were put on oral gentamicin and vancomycin for gut decontamination unti...
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BACKGROUND: The outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) improved markedly with the introduction of tyrosine kinase inhibitors (TKIs), which allow achieving high rate of... more
BACKGROUND: The outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) improved markedly with the introduction of tyrosine kinase inhibitors (TKIs), which allow achieving high rate of molecular remissions. However, allogeneic hematopoietic stem cell transplantation (allo-SCT) performed in first complete remission still remains a standard of care. In a recent study we demonstrated significant improvement of results of autologous hematopoietic stem cell transplantation (auto-SCT) in the era of TKIs [Giebel S, et al.; Eur J Cancer 2014;50:411-7]. The goal of the current analysis was to compare results of auto-SCT and allo-SCT for adult patients with Ph+ ALL in first molecular remission. PATIENTS AND METHODS: 569 adult patients with Ph+ ALL, treated between 2007-2014 with either auto-SCT (n=67), allo-SCT from matched sibling donor (MSD, n=255) or unrelated donor (URD, n=247) were included in the analysis. The median age for respective grou...
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3748 Introduction: By genetic randomization according to availability of a matched related donor, the two consecutive German CML studies III and IIIA (recruitment from 1995 to 2001 and from 1997 to 2004) evaluated the role of early HSCT... more
3748 Introduction: By genetic randomization according to availability of a matched related donor, the two consecutive German CML studies III and IIIA (recruitment from 1995 to 2001 and from 1997 to 2004) evaluated the role of early HSCT compared to medical treatment. Transplantation in first chronic phase (1st CP) was performed in 113 of 135 patients (84%) randomized to HSCT in study III and in 144 of 166 (87%) patients in study IIIA. Although transplantation protocols were comparable and most centers participated in both studies, even after adjustment for the established EBMT risk score (Gratwohl et al., Lancet 1998 [1]), post-transplant survival probabilities in study IIIA were significantly higher (p = 0.0073). Patients and Methods: Our aim was the evaluation of these survival differences. The German Registry for Stem Cell Transplantation and the Swiss Blood Stem cell Transplants Group provided data for an independent assessment of survival after first HSCT with a related donor p...
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We present an exemplary case of an immunocompromised patient with pulmonary mucormycosis successfully treated by a combination of surgical removal of the mucor and urokinase to control the recurring hemothorax. The use of urokinase in... more
We present an exemplary case of an immunocompromised patient with pulmonary mucormycosis successfully treated by a combination of surgical removal of the mucor and urokinase to control the recurring hemothorax. The use of urokinase in hemothoraces is a way to reduce repetitive surgeries in weak patients.
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Allogeneic haematopoietic stem cell transplantation (alloHSCT) is considered a standard treatment for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) achieving complete remission after induction... more
Allogeneic haematopoietic stem cell transplantation (alloHSCT) is considered a standard treatment for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) achieving complete remission after induction containing tyrosine kinase inhibitors (TKIs). We retrospectively compared results of myeloablative alloHSCT from either matched sibling donor (MSD) or unrelated donor (URD) with autologous (auto) HSCT for adults with Ph+ ALL in molecular remission, treated between 2007 and 2014. In univariate analysis, the incidence of relapse at 2 years was 47% after autoHSCT, 28% after MSD-HSCT and 19% after URD-HSCT (P = 0.0002). Respective rates of non-relapse mortality were 2%, 18%, and 22% (P = 0.001). The probabilities of leukaemia-free survival were 52%, 55% and 60% (P = 0.69), while overall survival rates were 70%, 70% and 69% (P = 0.58), respectively. In multivariate analysis, there was a trend towards increased risk of overall mortality after MSD-HSCT (hazard...
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In 1997, the Swiss Blood Stem Cell Transplantation Group (SBST) initiated a mandatory national registry for all haematopoietic stem cell transplants (HCTs) in Switzerland. As of 2016, after 20 years, information was available for 7899... more
In 1997, the Swiss Blood Stem Cell Transplantation Group (SBST) initiated a mandatory national registry for all haematopoietic stem cell transplants (HCTs) in Switzerland. As of 2016, after 20 years, information was available for 7899 patients who had received an HCT (2781 allogeneic [35%] and 5118 autologous [65%]). As some patients had more than one transplant the total number of transplants was 3067 allogeneic and 6448 autologous. We compared patient characteristics and outcome of the first decade (1997-2006) and second decade (2007-2016) of the registry. There were numerous changes over time. For allogeneic HCT, transplant rates, and therefore use of HCT technology, increased from 14 to 21.8 HCTs per 1 million inhabitants per year from the first to the second decade. Likewise autologous HCTs increased from 24.8 to 37.2 annually corrected for population growth. Allogeneic transplant recipients were older (38.4 vs 48.3 years) and more frequently had unrelated donors in the second ...
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Research Interests: Microbiology, Medical Microbiology, Biology, Adolescent, Medicine, and 15 moreAcute Myeloid Leukemia, Humans, Female, Male, Chemoprevention, Antimicrobial chemotherapy, Aged, Middle Aged, Adult, Immunocompromised host, Antifungal Agents, Open Label, Adverse effect, Dosing, and Myelodysplastic syndromes
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Atypical chronic myeloid leukaemia (aCML) is an aggressive malignancy for which allogeneic haematopoietic stem cell transplantation (allo-HSCT) represents the only curative option. We describe transplant outcomes in 42 patients reported... more
Atypical chronic myeloid leukaemia (aCML) is an aggressive malignancy for which allogeneic haematopoietic stem cell transplantation (allo-HSCT) represents the only curative option. We describe transplant outcomes in 42 patients reported to the European Society for Blood and Marrow Transplantation (EBMT) registry who underwent allo-HSCT for aCML between 1997 and 2006. Median age was 46 years. Median time from diagnosis to transplant was 7 months. Disease status was first chronic phase in 69%. Donors were human leucocyte antigen (HLA)-identical siblings in 64% and matched unrelated (MUD) in 36%. A reduced intensity conditioning was employed in 24% of patients. T-cell depletion was applied in 87% and 26% of transplants from MUD and HLA-identical siblings, respectively. According to the EBMT risk-score, 45% of patients were 'low-risk', 31% 'intermediate-risk' and 24% 'high-risk'. Following allo-HSCT, 87% of patients achieved complete remission. At 5 years, relaps...
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In 2009, international nutritional societies published practice guidelines on screening and nutritional support for patients undergoing stem cell transplantation. Little is known about how these guidelines are implemented in clinical... more
In 2009, international nutritional societies published practice guidelines on screening and nutritional support for patients undergoing stem cell transplantation. Little is known about how these guidelines are implemented in clinical practice. We performed a nationwide survey with the aim of understanding current practice patterns, differences between clinical practice, and international recommendations as well as barriers to the use of nutritional therapy. We performed a qualitative survey including all centers across Switzerland offering allogeneic (n = 3) or autologous (n = 7) stem cell transplantation. We focused on in-house protocols pertaining to malnutrition screening, indications for nutritional support, types of nutritional therapy available and provided, and recommendations regarding neutropenic diets. All centers offering allogeneic, and most of the centers offering autologous transplantation, had a malnutrition screening tool, mainly the nutritional risk score (NRS 2002) method. Only one center does not provide nutritional support. There is wide variation regarding start and stop of nutritional therapy as well as route of delivery, with five centers recommending parenteral nutrition and five centers recommending enteral nutrition as a first step. Although all centers offering allogeneic transplantation, and approximately every other autologous transplant center, used a neutropenic diet, specific recommendations regarding the type of food and food handling showed significant variation. This Swiss survey found wide variation in the use of nutritional therapy in patients undergoing stem cell transplantation, with low adherence overall to current practice guidelines. Understanding and reducing barriers to guideline implementation in clinical practice may improve clinical outcomes. Close collaboration of centers will facilitate future research needed to improve current practice and ensure high quality of treatment.
Research Interests: Nutrition, Diet, Medicine, Transplantation, Malnutrition, and 13 moreHumans, Patient Compliance, Switzerland, Intensive Care Medicine, Medical Nutrition Therapy, Parenteral Nutrition, Nutrition Policy, GuideLine, Hematopoietic Stem Cell Transplantation, Nutritional Support, Surveys and Questionnaires, Nutrition assessment, and Medical and Health Sciences
Curative chemotherapy approaches in patients with malignancies and platelet (PLT) transfusion refractoriness due to alloimmunization may be hampered by the lack of suitable PLT donors. For these patients, transfusion of cryopreserved... more
Curative chemotherapy approaches in patients with malignancies and platelet (PLT) transfusion refractoriness due to alloimmunization may be hampered by the lack of suitable PLT donors. For these patients, transfusion of cryopreserved autologous PLTs is an option, but is time- and resource-consuming. We aimed at further simplifying this process. A retrospective single-center analysis was conducted on the transfusion of cryopreserved autologous PLTs in nine female alloimmunized, PLT transfusion-refractory patients treated for acute leukemia (n = 8) and non-Hodgkin&amp;amp;amp;amp;amp;amp;#39;s lymphoma (n = 1). No additional processing was used before transfusion, and most notably, washing and centrifugation steps were omitted. Clinical efficacy and safety, as well as a flow cytometric assessment of structural and functional PLT changes, were analyzed. A total of 40 autologous PLT concentrates were thawed at bedside and transfused a median of 32 (range, 9 to 994) days after cryopreservation. No major bleeds and no severe dimethyl sulfoxide toxicity were observed. The median PLT count increments did not differ 1 and 18 to 24 hours after transfusion and reached 6 × 10(9) /L (interquartile range [IQR], 3 × 10(9) -7.5 × 10(9) /L) and 6 × 10(9) /L (IQR, 2.5 × 10(9) -9.5 × 10(9) /L), respectively. Cryopreservation resulted in partial activation of one-third of the PLTs. In vitro stimulation with strong agonists induced additional full activation of cryopreserved PLTs: median, 55% (IQR, 42%-60%) after thrombin and 39% (IQR, 36%-39%) after convulxin. The transfusion of cryopreserved autologous PLTs is feasible and safe. Despite the cryopreservation process, PLT functionality is partially maintained.
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Case reports and series suggest hematopoietic stem cell transplantation (HSCT) may benefit some patients with Crohn disease. To evaluate the effect of autologous HSCT on refractory Crohn disease. Parallel-group randomized clinical trial... more
Case reports and series suggest hematopoietic stem cell transplantation (HSCT) may benefit some patients with Crohn disease. To evaluate the effect of autologous HSCT on refractory Crohn disease. Parallel-group randomized clinical trial conducted in 11 European transplant units from July 2007 to September 2011, with follow-up through March 2013. Patients were aged 18 to 50 years with impaired quality of life from refractory Crohn disease not amenable to surgery despite treatment with 3 or more immunosuppressive or biologic agents and corticosteroids. All patients underwent stem cell mobilization before 1:1 randomization to immunoablation and HSCT (n = 23) or control treatment (HSCT deferred for 1 year [n = 22]). All were given standard Crohn disease treatment as needed. Sustained disease remission at 1 year, a composite primary end point comprising clinical remission (Crohn Disease Activity Index (CDAI) <150 [range, 0-600]), no use of corticosteroids or immunosuppressive or biolo...
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ABSTRACT
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Die Autoimmunhämolytischen Anämien (AIHA) sind seltene aber potentiell lebensbedrohliche Erkrankungen, die einer raschen Abklärung und Therapie bedürfen. Die Diagnose wird durch den gleichzeitigen Nachweis einer Hämolyse und von... more
Die Autoimmunhämolytischen Anämien (AIHA) sind seltene aber potentiell lebensbedrohliche Erkrankungen, die einer raschen Abklärung und Therapie bedürfen. Die Diagnose wird durch den gleichzeitigen Nachweis einer Hämolyse und von antierythrozytären Autoantikörpern gestellt. Der wichtigste diagnostische Test in der Abklärung einer AIHA ist der direkte Antiglobulin Test (DAT, direkter Coombs-Test). AIHA können gemäß der optimalen Wirktemperatur der antierythrozytären Autoantikörper in AIHA vom Wärme- respektive vom Kältetyp und aufgrund ihrer Ätiologie in primäre oder sekundäre AIHA unterteilt werden. Da die AIHA nicht selten mit einer Grundkrankheit assoziiert ist, muss gezielt nach dieser gesucht werden, bevor von einer primären AIHA gesprochen werden kann. Die Therapie unterscheidet sich je nach Typ der AIHA. Bei den häufigeren Wärme-Antikörpern besteht die Erstlinientherapie neben der Behandlung der Grundkrankheit in der Gabe von systemischen Kortikosteroiden und in zweiter Linie i...
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A 42 year old female was diagnosed with an acute myelogenous leukemia (AML) with recurrent genetic abnormality (inversion 3q26; EVI1 overexpression) and high dose chemotherapy (3+7) was initiated. On day 17 bone marrow examination showed... more
A 42 year old female was diagnosed with an acute myelogenous leukemia (AML) with recurrent genetic abnormality (inversion 3q26; EVI1 overexpression) and high dose chemotherapy (3+7) was initiated. On day 17 bone marrow examination showed leukemia persistence. Chemotherapy was continued with a second cycle on day 18. A CT scan at diagnosis revealed an infiltrate of the right upper lobe and microbiological cultures obtained from a bronchoalveolar lavage identified Aspergillus fumigatus. The patient was treated empirically with antibiotics and voriconazole for invasive aspergillosis. A follow up CT scan on day 7 of the second chemotherapy cycle showed improvement of the pulmonary infiltrates. Therapy with voriconazole was continued, the dosage was increased due to insufficient plasma levels. Ten days later the patient developed rapidly progressive respiratory failure requiring intubation and was transferred to the medical intensive care unit. The CT showed progression of the pulmonary ...
Research Interests: Gastroenterology, Treatment Outcome, Adolescent, Medicine, Stem Cell Transplantation, and 15 moreTransplantation, Humans, Female, Male, Follow-up studies, T lymphocytes, Neutrophils, Adult, Time Factors, B Lymphocytes, Hematopoietic Stem Cell Transplantation, Chronic Granulomatous Disease, Respiratory function tests, High risk, and Medical and Health Sciences
The transfusion of homologous blood carries well-known risks that have prompted efforts to develop alternative techniques. Such measures are of particular interest to patients undergoing elective procedures. A total of 204 patients, out... more
The transfusion of homologous blood carries well-known risks that have prompted efforts to develop alternative techniques. Such measures are of particular interest to patients undergoing elective procedures. A total of 204 patients, out of 1470 patients who consecutively underwent major craniomaxillofacial procedures under general anesthesia over a two-year period, were enrolled in a prospective protocol to reduce homologous transfusion requirements when a blood loss in excess of 500 ml was anticipated. The data were compared with the results of a retrospective control group (n=2890) covering major procedures during the previous four years, when blood-saving measures were applied occasionally, but not based on a global strategy. Techniques for the reduction of homologous transfusions were acute normovolemic hemodilution, controlled moderate hypotension, cell saver and predeposit autologous blood. In addition, preoperative administration of human recombinant erythropoietin was introduced during the last year of the study. These techniques were applied individually or in combination, depending on contraindications specific for each technique, using invasive monitoring in order to maintain intraoperative hemodynamic stability. The goal of this study was to examine the extent to which homologous transfusions may be reduced with the systematic application of transfusion-sparing techniques. Of 204 patients qualifying for the transfusion-sparing protocol, 30 received homologous transfusions. In comparison to the control group, utilization of transfusion-sparing techniques had doubled. The overall reduction in the use of homologous transfusions was highly significant. When acute normovolemic hemodilution, controlled moderate hypotension and the cell saver were used in combination, a greater reduction in homologous transfusions was achieved than with the use of either a single modality or combination of any two. No transfusions were required in patients pretreated with erythropoietin.
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Little is known of health-relevant behaviour among long-term survivors of haematological disorders treated with haematopoietic SCT. This comparative cross-sectional multicentre study aimed (1) to explore the prevalence of selected... more
Little is known of health-relevant behaviour among long-term survivors of haematological disorders treated with haematopoietic SCT. This comparative cross-sectional multicentre study aimed (1) to explore the prevalence of selected behaviours in this group and (2) to compare them with those of the general population. Self-reported data of 376 survivors (mean age: 50.4 (s.d. = 12.8); median 7 years postallogeneic SCT (interquartile range (IQR) = 8.9; range 1-33) were compared with controls derived from the Swiss Health Survey 2007 by propensity score matching. Survivors were more physically inactive (26.8% vs 12.5%; P ⩽ 0.001) and consumed fewer portions of vegetables (⩾ 3 pieces: 10% vs 21.6%; P < 0.001), fruits (⩾ 3 pieces: 6.5% vs 10.6%; P < 0.001) and fish (31.2% vs 60.9% weekly fish dish; P < 0.001). More survivors consumed dairy products daily (92.5% vs 62.9%; P < 0.001), used sun protection regularly (94.5% vs 85.3%, P < 0.001) and had received influenza vaccinat...
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Transplant patients are exposed to many different types of mental and social stress. The study investigates these patients' need for psychosocial counselling. At 6 months and again at 12 months following either a lung, liver or... more
Transplant patients are exposed to many different types of mental and social stress. The study investigates these patients' need for psychosocial counselling. At 6 months and again at 12 months following either a lung, liver or bone-marrow transplantation, 76 patients were questioned about their need for psychosocial counselling. The measuring instruments employed were: SF-36 (quality of life), FLZ (life satisfaction), HADS-D (anxiety/depression), and F-SoZu K-14 (social support). The need for psychosocial counselling in all three patient groups was at its greatest before transplantation. It amounted to 42.9 % (lung transplantation patients), 50.0 % (liver transplantation patients) and 26.7 % (bone marrow transplantation patients). Six months after transplantation, the need for counselling in all patient groups had quite clearly decreased. Among liver transplant patients, however, it increased again between the sixth and twelfth months. The need for counselling in all patient gr...
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In contrast to solid organ transplantation (SOT), ABO-histo blood group incompatibility is of minor importance for hematopoietic stem cell transplantation (HSCT). Patients receiving ABO-incompatible HSCT are at an increased risk for... more
In contrast to solid organ transplantation (SOT), ABO-histo blood group incompatibility is of minor importance for hematopoietic stem cell transplantation (HSCT). Patients receiving ABO-incompatible HSCT are at an increased risk for immune-mediated hematological complications including immediate and delayed hemolysis, late red blood cell engraftment and pure red cell aplasia, but seem not to have a worse overall survival or increased transplant-related mortality. This review gives an overview of the immunological mechanisms leading to complications associated with ABO-incompatible HSCT and describes approaches to prevent them. The current organ shortage in SOT stimulates the exploration of new strategies to expand the donor pool including ABO-incompatible SOT and xenotransplantation. Here, we discuss the hypothesis that ABO-incompatible transplantation may be viewed as a human in vivo model for the humoral immune mechanisms of antigen-mismatched transplantation. ABO-incompatible HSC...
Research Interests: Immunology, Biology, Medicine, Transplantation, Xenotransplantation, and 15 moreHumans, Organ Transplantation, Blood groups, Risk factors, Clinical Sciences, Red blood cell, Risk Factors, Immune Tolerance, Overall Survival, Hematopoietic Stem Cell, Hemolysis, Humoral Immunity, Hematopoietic Stem Cell Transplantation, Pure Red Cell Aplasia, and ABO Blood-Group System
Non-HLA immunogenetic polymorphisms may influence outcome of hematopoietic stem cell transplantation (HSCT). In this study, we have determined the role of TNFa, TNFd, IL-10, IL-1, IL-1Ra, and IL-4R polymorphisms in patients transplanted... more
Non-HLA immunogenetic polymorphisms may influence outcome of hematopoietic stem cell transplantation (HSCT). In this study, we have determined the role of TNFa, TNFd, IL-10, IL-1, IL-1Ra, and IL-4R polymorphisms in patients transplanted with HSC of an unrelated donor. The allelic variants of four SNPs (IL-10-1082, IL-1beta-511, IL-4R-3223, IL-4R-1902) and four microsatellites (TNFa, TNFd, IL-10-1064, IL-1Ra) were determined in 131 unrelated patient/donor pairs typed for HLA-A/B/C/DR/DQ (four digits). The allelic distribution of the polymorphisms was similar to that previously reported in Caucasoid populations. Patient and donor TNFd and patient IL-10-1064 polymorphisms correlated with mortality in univariate analysis. Patients with TNFd1/d2/d3 genotypes had 3-year survival rates of 65%. A gradual decrease in survival rates was observed for patients with TNFd3/d3 genotypes (50%, p=n.s.), TNFd4 (46%, P=0.08), and TNFd5 (33%, P=0.03). A multivariate analysis of 10/10 matched patients r...
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Foetal and neonatal alloimmune thrombocytopenia is caused by transplacental transfer of antibodies directed against platelet antigens and affects approximately 1 in 1000-2500 neonates. Clinically relevant complications are the... more
Foetal and neonatal alloimmune thrombocytopenia is caused by transplacental transfer of antibodies directed against platelet antigens and affects approximately 1 in 1000-2500 neonates. Clinically relevant complications are the intracranial haemorrhages that occur in 10-20% of cases. 20 platelet antigen systems are currently known. However, immunisation is most frequently seen against two of these (HPA-1a and HPA-5b). Treatment options include transfusion of compatible or, if these are not available while urgently needed, random donor platelets, intravenous immunoglobulin, and steroids. We report on a case of neonatal alloimmune thrombocytopenia due to an anti-HPA-1b antibody in the third pregnancy of a 31-year-old Caucasoid woman. The infant was treated with repeated maternal and random donor platelet transfusions and with a single dose of intravenous immunoglobulin.