0000000000018104
AUTHOR
Hermann Einsele
showing 39 related works from this author
Allogeneic Stem Cell Transplant Versus Tandem High-Dose Melphalan for Front-Line Treatment of Deletion 13q14 Myeloma – An Interim Analysis of the Ger…
2009
Abstract Abstract 51 Background Allogeneic stem cell transplantation (allo SCT), a treatment modality based on transfer of immunocompetent donor lymphocytes offers curative potential to subjects with a variety of hematological cancers. In multiple myeloma (MM), high-dose melphalan followed by autologous stem cell transplantation (auto SCT) is adopted as a standard of care. However, it remains palliative since virtually all patients (pts) relapse and renders allo SCT an option of interest. Deletion of chromosome 13q14 (13q-) in MM has been shown to negatively impact prognosis. Therefore, improvement of therapy for 13q- pts is highly desirable. Patients and methods A prospective two-arm multi…
P046 Deconstructing HLA-C mismatch in hematopoietic stem cell transplantation
2016
Contrary to other HLA loci, allele vs antigen mismatches in HLA-C appear to differentially impact HSCT outcome. Aim of this study was to investigate the independent role of other factors characterizing a patient’s HLA-C non-shared allele, in HSCT outcome as well as their distribution in allele vs antigen mismatched cases. 288 9/10 HLA-C mismatched unrelated transplant pairs, were additionally genotyped by sequence based typing for rs9264942(C/T) and rs67384697(ins/del), which are considered surrogate markers of HLA-C expression levels. A proxy MFI model as previously described (Petersdorf et al., Blood 2014), was also implemented in the analysis. All patient non-shared alleles were characte…
Tumor Regression in Cancer Patients by Very Low Doses of a T Cell–Engaging Antibody
2008
Previous attempts have shown the potential of T cells in immunotherapy of cancer. Here, we report on the clinical activity of a bispecific antibody construct called blinatumomab, which has the potential to engage all cytotoxic T cells in patients for lysis of cancer cells. Doses as low as 0.005 milligrams per square meter per day in non–Hodgkin's lymphoma patients led to an elimination of target cells in blood. Partial and complete tumor regressions were first observed at a dose level of 0.015 milligrams, and all seven patients treated at a dose level of 0.06 milligrams experienced a tumor regression. Blinatumomab also led to clearance of tumor cells from bone marrow and liver. T cell–engag…
Donors with KIR-Bx Haplotypes Improve Outcome of Unrelated Hematopoietic Stem Cell Transplantation for Recipients with a Myeloid Malignant Disease an…
2015
relapse, or transplant related mortality (TRM) (p1⁄40.2, p1⁄40.1, p1⁄40.08, respectively). To investigate why higher CPSS scores were associated with higher mortality, we performed analysis restricted to patients with relapse following HCT. Those with intermediate-2/high riskhadnearly two-fold increase in riskof death after relapse compared to thosewith low/intermediate1 CPSS scores. Corresponding rates for low/intermediate-1 risk groups,OSat1year, 3years, and5yearswere61%,48%, and44% respectivelyand for intermediate-2/high riskgroupswere 38%, 32%, and19%respectively.OSofpatientswho receivedpre-HCT treatment with hypomethylating agents, chemotherapy, or both was not different compared to th…
Antimicrobial prophylaxis in allogeneic bone marrow transplantation. Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Societ…
2005
Patients undergoing allogeneic stem cell transplantation are at high risk for infection with a variety of pathogens during different phases of the procedure. Bacteria and fungi predominate the first phase until engraftment. During the second phase, from engraftment to about day 100, major infectious problems are caused by fungi and cytomegalovirus. Both pathogens remain important under continued immunosuppression, however, in the late post-transplantation period infections with encapsulated bacteria may become a problem. In this review the Infectious Diseases Working Party of the DGHO gives recommendations for prophylaxis of infections under allogeneic stem cell transplantation with drugs a…
P043 HLA-DPB matching and donor cytomegalovirus positive (CMV+) status: An “unconventional alliance” associated with a decreased relapse incidence in…
2017
Aim While the role of HLA-DPB1 (DP) compatibility in uHSCT regarding graft versus host disease (GVHD)- and graft versus leukaemia (GVL)-effects has been extensively discussed, its interaction with donor CMV status (dCMV), remains elusive. The aim of this study was, to investigate the impact of dCMV status in DP matched (DPM) and mismatched (DPMM) uHSCT. Methods 1749 HSCT transplant (Tx) pairs were DP genotyped with an exon 2 amplicon based NGS approach in order to assess their DP matching status. CMV sero-status as well as clinical data were retrieved from the German Stem Cell Registry. Overall survival (OS), relapse incidence (RI) and chronic GvHD (cGvHD) were defined as endpoints, while s…
Diagnosis of invasive fungal infections in hematology and oncology
2003
Invasive fungal infections are a primary cause of morbidity and mortality in patients with hematological malignancies. Establishing a definite diagnosis of invasive fungal infection in febrile neutropenic patients is particularly challenging and time-consuming, but a delay of antifungal treatment leads to higher mortality. This situation has lead to the strategy of initiation "empirical" antifungal therapy prior to the detection of fungi. Meanwhile, improvements in diagnostic procedures are achieved, especially with imaging techniques and non-culture based methods which include antigen-based assays, metabolite detection and molecular detection of fungal DNA from body fluid samples using con…
Immune response to the 23-valent polysaccharide pneumococcal vaccine after the 7-valent conjugate vaccine in allogeneic stem cell transplant recipien…
2009
The current recommendations for active immunization after stem cell transplant (SCT) include 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7) from 3 months after transplant, followed by a 23-valent polysaccharide pneumococcal vaccine (PPV23). However, until now, the immune response to PPV23 after PCV7 has not been assessed after SCT. In the EBMT IDWP01 trial, 101 patients received 1 dose of PPV23 at 12 or 18 months, both after 3 doses of PCV7. The efficacy of PPV23 was assessed 1 month later and at 24 months after transplant by the pneumococcal serotype 1 and 5 antibody levels. Serotype 1 and 5 are not included in PCV7. Although the geometric mean concentrations were significantly …
Kinetics of Renal Function during Induction in Newly Diagnosed Multiple Myeloma: Results of Two Prospective Studies by the German Myeloma Study Group…
2021
Background: Preservation of kidney function in newly diagnosed (ND) multiple myeloma (MM) helps to prevent excess toxicity. Patients (pts) from two prospective trials were analyzed, provided postinduction (PInd) restaging was performed. Pts received three cycles with bortezomib (btz), cyclophosphamide, and dexamethasone (dex
Diagnosis and antimicrobial therapy of pulmonary infiltrates in febrile neutropenic patients
2003
Patients with severe neutropenia lasting for more than 10 days, who develop fever and pulmonary infiltrates, are at high risk of treatment failure and infection-related death, under conventional broad-spectrum antibiotics. Early supplementation by a systemic antifungal therapy active against Aspergillus spp. has been shown to markedly improve their clinical outcome. Prognosis is significantly influenced by early identification of lung infiltrates by means of high-resolution thoracic computed tomography. Non-culture based diagnostic procedures using a highly sensitive Sandwich ELISA assay to detect circulating galactomannan, or PCR techniques to amplify circulating fungal DNA, may facilitate…
Phase II study of bortezomib, cyclophosphamide and dexamethasone as induction therapy in multiple myeloma: DSMM XI trial.
2017
Summary We assessed the safety and efficacy of bortezomib, cyclophosphamide and dexamethasone (VCD) induction therapy in previously untreated multiple myeloma patients. A total of 414 patients received three 21-day cycles of VCD prior to autologous stem-cell transplantation (ASCT). Most common grade ≥3 adverse events were leucopenia (31·4%) and thrombocytopenia (6·8%). The overall response rate (ORR) by investigator-based assessment was 85·4%. Most patients (74%) underwent successful central laboratory-based molecular cytogenetic analysis. No clinically relevant differences in ORR post-induction were seen between patients with or without high-risk cytogenetic abnormalities (86·2% vs. 84·3%)…
Survival of elderly patients with multiple myeloma-Effect of upfront autologous stem cell transplantation
2016
Abstract Background The aim of this study was to determine the value of upfront autologous transplantation (ASCT) in elderly patients (60–79 years) with myeloma. Methods We analysed relative survival (RS) of patients diagnosed in 1998–2011 and treated with ASCT within 12 months after diagnosis in Germany (n = 3591; German Registry of Stem Cell Transplantation) and compare RS with survival of myeloma patients diagnosed in the same years in Germany (n = 13,903; population-based German Cancer Registries). Results Utilisation of ASCT has increased rapidly between 2000–2002 and 2009–2011 (60–64years: 7.0–43.0%; 65–69 years: 6.6–23.7%; 70–79 years: 0.4–4.0%). Comparison of 5-year RS of patients f…
Transfer of minimally manipulated CMV-specific T cells from stem cell or third-party donors to treat CMV infection after allo-HSCT.
2017
Cytomegalovirus (CMV) infection is a common, potentially life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed prospectively the safety and efficacy of stem cell-donor-or third-party-donor-derived CMV-specific T cells for the treatment of persistent CMV infections after allo-HSCT in a phase I/IIa trial. Allo-HSCT patients with drugrefractory CMV infection and lacking virus-specific T cells were treated with a single dose of ex vivo major histocompatibility complex-Streptamer-isolated CMV epitope-specific donor T cells. Forty-four allo-HSCT patients receiving a T-cell-replete (D+ repl; n = 28) or T-cell-depleted (D+ depl; n = 16) …
Antiviral prophylaxis in patients with haematological malignancies and solid tumours: Guidelines of the Infectious Diseases Working Party (AGIHO) of …
2006
Morbidity and mortality in patients with malignancies are increased by viral infections. These mostly are reactivations of asymptomatic latent infections. They primarily concern clinical entities associated with the reactivation of herpes viruses, such as varicella zoster virus (VZV) and cytomegalovirus (CMV). Respiratory tract infections caused by influenza, parainfluenza or respiratory syncytial virus (RSV) are less common. Since reactivation of latent infections has major clinical impact, antiviral prophylaxis is an attractive approach for patients expecting immunosuppression. The main risk factor for clinically relevant reactivation is profound disruption of cellular immune response. Du…
Multiple Myeloma Treatment in Real-world Clinical Practice: Results of a Prospective, Multinational, Noninterventional Study.
2018
© 2018 The Authors.
Guidelines for the management of cytomegalovirus infection in patients with haematological malignancies and after stem cell transplantation from the …
2018
Summary Cytomegalovirus is one of the most important infections to occur after allogeneic haematopoietic stem cell transplantation (HSCT), and an increasing number of reports indicate that cytomegalovirus is also a potentially important pathogen in patients treated with recently introduced drugs for hematological malignancies. Expert recommendations have been produced by the 2017 European Conference on Infections in Leukaemia (ECIL 7) after a review of the literature on the diagnosis and management of cytomegalovirus in patients after HSCT and in patients receiving other types of therapy for haematological malignancies. These recommendations cover diagnosis, preventive strategies such as pr…
Improved Safety with the Use of Subcutaneous Bortezomib in Combination with Panobinostat and Dexamethasone: Preliminary Data from a Panobinostat Glob…
2016
Abstract Introduction: Panobinostat (PAN) is a potent pan-deacetylase inhibitor that targets multiple myeloma (MM) cells via its epigenetic effects as well as its effect on the aggresome. In the PANORAMA 1 phase 3 trial, the combination of PAN, bortezomib (BTZ), and dexamethasone (Dex; PAN+BTZ+Dex) significantly increased progression-free survival compared with placebo plus BTZ and Dex, leading to approval in Europe of the combination for the treatment of patients with MM who have received ≥ 2 prior regimens, including BTZ and an immunomodulatory agent. The purpose of this expanded treatment protocol (ETP) is to further evaluate safety and to provide panobinostat prior to commercial availab…
Risk factors for breakthrough invasive fungal infection during secondary prophylaxis.
2008
BACKGROUND: Intensive chemotherapy with severe neutropenia is associated with invasive fungal infections (IFIs) leading to high mortality rates. During leukaemia induction chemotherapy, IFI often prohibited further curative treatment, thus predisposing for leukaemia relapse. Continuing myelosuppressive chemotherapy after diagnosis of IFI has become feasible with the now expanding arsenal of safe and effective antifungals. Secondary prophylaxis of IFI is widely administered, but reliable data on outcome and risk factors for recurrent IFI during subsequent chemotherapy are not available. This study determines risk factors for recurrent IFI in leukaemia patients. METHODS: From 25 European canc…
The Human Leukocyte Antigen-DPB1 Degree of Compatibility Is Determined by Its Expression Level and Mismatch Permissiveness: A German Multicenter Anal…
2021
T-cell epitope matching according to the TCE3 algorithm classifies HLA-DPB1 mismatches in permissive and non-permissive. This classification has been shown to be predictive for mortality and acute GvHD (aGvHD) events in large international cohorts. We retrospectively genotyped HLA-DPB1 in 3523 patients transplanted in Germany between 2000 and 2014 and in their unrelated donors using an Illumina amplicon-NGS based assay. Aim of the study was to evaluate DP-compatibility beyond the established TCE3 algorithm by assessing the combined effect of several DP-mismatch parameters on post-transplant outcome. We implemented an extended DP-mismatch assessment model where TCE3, DP allotype expression w…
Randomized Study of Early versus Late Immunization with Pneumococcal Conjugate Vaccine after Allogeneic Stem Cell Transplantation
2009
BACKGROUND: Invasive pneumococcal disease is a life-threatening complication after allogeneic stem cell transplantation, and at least 20% of cases occur within 1 year after transplantation. The 23-valent pneumococcal polysaccharide vaccine (PPV23) has limited efficacy, especially during the first year after transplantation. The immune response to the conjugated vaccines is expected to be better than that to the polysaccharide vaccine, but the optimal timing of vaccination is not defined. Our objective was to show that a 7-valent pneumococcal conjugate vaccine (PCV7; Prevnar) was not inferior when first given 3 months after transplantation, compared with when first given 9 months after trans…
Velcade, Intravenous Cyclophosphamide and Dexamethasone (VCD) Induction for Previously Untreated Multiple Myeloma (German DSMM XIa Trial).
2009
Abstract 131 Introduction. Autologous stem cell transplantation (ASCT) after cytoreductive induction is considered standard of care for younger patients (pts) with multiple myeloma (MM). The previous standard of induction, the Vincristin-Adriamycin-Dexamethasone (VAD) combination, achieves inferior results compared with induction regimens which combine the proteasome inhibitor Velcade (V = Bortezomib) with Dexamethasone (D)(=VD) and a cytostatic drug such as Doxorubicin (PAD = VD plus Doxorubicin). Velcade-based induction therapy was shown to translate into better myeloma control after high dose melphalan and to lead to prolonged progression-free survival. In order to find a more efficaciou…
Chronic graft-versus-host disease: long-term results from a randomized trial on graft-versus-host disease prophylaxis with or without anti-T-cell glo…
2011
Abstract Previous randomized graft-versus-host disease (GVHD)-prophylaxis trials have failed to demonstrate reduced incidence and severity of chronic GVHD (cGVHD). Here we reanalyzed and updated a randomized phase 3 trial comparing standard GVHD prophylaxis with or without pretransplantation ATG-Fresenius (ATG-F) in 201 adult patients receiving myeloablative conditioning before transplantation from unrelated donors. The cumulative incidence of extensive cGVHD after 3 years was 12.2% in the ATG-F group versus 45.0% in the control group (P < .0001). The 3-year cumulative incidence of relapse and of nonrelapse mortality was 32.6% and 19.4% in the ATG-F group and 28.2% and 33.5% in the contr…
Early detection of Toxoplasma infection by molecular monitoring of Toxoplasma gondii in peripheral blood samples after allogeneic stem cell transplan…
2004
International audience; Background. Isolated case reports have shown that recipients of allogeneic hematopoietic stem cell transplants ( HSCTs) who develop toxoplasmosis may have circulating Toxoplasma gondii DNA in peripheral blood before the onset of clinical symptoms. Methods. We prospectively studied 106 T. gondii - seropositive adult recipients of HSCTs for the incidence of reactivation of toxoplasmosis in the first 6 months after transplantation. Toxoplasmosis infection ( TI) was defined by a positive result of polymerase chain reaction ( PCR) of peripheral blood specimens, whereas toxoplasmosis disease ( TD) was defined as an invasive infection. Results. The incidence of TI was 16% (…
High-resolution HLA matching in hematopoietic stem cell transplantation: a retrospective collaborative analysis.
2013
To validate current donor selection strategies based on previous international studies, we retrospectively analyzed 2646 transplantations performed for hematologic malignancies in 28 German transplant centers. Donors and recipients were high resolution typed for HLA-A, -B, -C, -DRB1, and -DQB1. The highest mortality in overall survival analysis was seen for HLA-A, -B, and DRB1 mismatches. HLA-DQB1 mismatched cases showed a trend toward higher mortality, mostly due to HLA-DQB1 antigen disparities. HLA incompatibilities at >1 locus showed additive detrimental effects. HLA mismatching had no significant effect on relapse incidence and primary graft failure. Graft source had no impact on surviv…
A Comparison of Aspergillus and Mucorales PCR Testing of Different Bronchoalveolar Lavage Fluid Fractions from Patients with Suspected Invasive Pulmo…
2018
ABSTRACT In patients with hematological malignancies, bronchoalveolar lavage fluid (BALF) specimens are commonly used for the diagnosis of mold infections. However, it is not clear whether the cell pellet (P) or the supernatant fraction (S) of the BALF specimen is optimal for molecular diagnostic testing. Thus, 99 BALF specimens were collected from 96 hematology patients with or without allogeneic hematopoietic stem cell transplant. The cell pellets and supernatants were processed alone and in combination (S/P) for testing by two fungus-specific real-time PCR assays compliant with international recommendations. The results achieved with S/P were revealed to be superior in comparison to thos…
Combining dasatinib with dexamethasone long-term leads to maintenance of antiviral and antileukemia specific cytotoxic T cell responses in vitro
2012
Maintaining graft versus leukemia (GvL) and antivirus responses of cytotoxic T cells (CTLs) while suppressing graft-versus-host disease (GvHD) remains a challenge after allogeneic bone marrow transplantation. Clinical observations indicate that combining glucocorticoids with multi-tyrosine-kinase inhibitors could be a successful therapeutic approach. We and others have shown that the BCR-ABL/SRC kinase inhibitor dasatinib may enhance or suppress T cells in vitro. In this report, we evaluated combination effects of dasatinib and dexamethasone on CD3 + and virus-specific CD8 + T cells directly ex vivo and on antigen-specific leukemia-reactive and alloreactive CD8 + T cell clones. Functional o…
OR26. Investigating the impact of patient’s non-shared HLA-C Allotype expression levels in A 9/10 Single HLA-C mismatched hematopoieticstem cell tran…
2018
Aim Petersdorf et al. reported in 2014 an association between patient high expressed HLA-C (C) allotypes and inferior HSCT outcome using an imputed C-expression model (Apps et al., 2013). This study aims at: a) examining the validity of Apps et al. model in Caucasians by using the same methodology in a sample of 400 healthy German blood donors. b) specifically investigating the effect of patient’s non-shared (PNS) C expression levels on outcome by applying C expression imputed data in a 9/10 HLA C-mismatched HSCT setting. Methods Buffy coats from 400 healthy German blood donors were tested by flow cytometry as previously described (Apps et al., 2013) in order to determine C expression on ly…
Bispecific T-Cell Engager (BiTE) Antibody Construct Blinatumomab for the Treatment of Patients With Relapsed/Refractory Non-Hodgkin Lymphoma : Final …
2016
Purpose Blinatumomab is a CD19/CD3 BiTE (bispecific T-cell engager) antibody construct for the treatment of Philadelphia chromosome–negative acute B-lymphoblastic leukemia. We evaluated blinatumomab in relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). Patients and Methods This 3 + 3 design, phase I dose-escalation study determined adverse events and the maximum tolerated dose (MTD) of continuous intravenous infusion blinatumomab in patients with relapsed/refractory NHL. Blinatumomab was administered over 4 or 8 weeks at seven different dose levels (0.5 to 90 μg/m2/day). End points were incidence of adverse events, pharmacokinetics, pharmacodynamics, and overall response rate. Results B…
Guidelines from the 2017 European Conference on Infections in Leukaemia for management of HHV-6 infection in patients with hematologic malignancies a…
2019
Of the two human herpesvirus 6 (HHV-6) species, human herpesvirus 6B (HHV-6B) encephalitis is an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplant. Guidelines for the management of HHV-6 infections in patients with hematologic malignancies or post-transplant were prepared a decade ago but there have been no other guidelines since then despite significant advances in the understanding of HHV-6 encephalitis, its therapy, and other aspects of HHV-6 disease in this patient population. Revised guidelines prepared at the 2017 European Conference on Infections in Leukaemia covering diagnosis, preventative strategies and management of HHV-6 disease are n…
Polymorphisms within the TNFSF4 and mapkapk2 loci influence the risk of developing invasive aspergillosis: A two-stage case control study in the cont…
2020
Here, we assessed whether 36 single nucleotide polymorphisms (SNPs) within the TNFSF4 and MAPKAPK2 loci influence the risk of developing invasive aspergillosis (IA). We conducted a twostage case control study including 911 high-risk patients diagnosed with hematological malignancies that were ascertained through the aspBIOmics consortium. The meta-analysis of the discovery and replication populations revealed that carriers of the TNFSF4rs7526628T/T genotype had a significantly increased risk of developing IA (p = 0.00022). We also found that carriers of the TNFSF4rs7526628T allele showed decreased serum levels of TNFSF14 protein (p = 0.0027), and that their macrophages had a decreased fungi…
Impact of Donor Activating KIR Genes on HSCT Outcome in C1-Ligand Negative Myeloid Disease Patients Transplanted with Unrelated Donors-A Retrospectiv…
2017
Natural Killer cells (NK) are lymphocytes with the potential to recognize and lyse cells which escaped T-cell mediated lysis due to their aberrant HLA expression profiles. Killer cell immunoglobulin-like receptors (KIR) influence NK-cell activity by mediation of activating or inhibitory signals upon interaction with HLA-C (C1, C2) ligands. Therefore, absence of ligands for donor inhibitory KIRs following hematopoietic stem cell transplantation (HSCT) may have an influence on its outcome. Previous studies showed that C1 negative patients have a decreased HSCT outcome. Our study, based on a cohort of 200 C1-negative patients, confirmed these findings for the endpoints: overall survival (OS: H…
Donor Genetic Determinant of Thymopoiesis rs2204985 Impacts Clinical Outcome after Single HLA Mismatched HSCT
2021
Abstract Introduction: A common genetic variant within the TCRA-TCRD locus has been recently identified as a predictive factor of thymic function and T cell repertoire diversity (Clave et al., 2018). Specifically it was shown in a mouse model that transplantation of rs2204985 AA human hematopoietic stem cells (HSC) into immunodeficient mice led to lower thymocyte counts and poorer TCR diversity. T cell mediated pathways are known to play a significant role in immunological processes affecting HSCT outcome like GvL, GvH and infection. Aim of this study was to investigate the potential impact of donor rs2204985 genotype on patient's outcome after unrelated HSCT. Methods: The study included 2,…
Exogenous TNFR2 activation protects from acute GvHD via host T reg cell expansion
2015
Activation of TNFR2 with a novel agonist expands T reg cells in vivo and protects allo-HCT recipients from acute GvHD while sparing antilymphoma and antiinfectious properties of transplanted donor T cells.
Immune Response to the 23-Valent Polysaccharide Pneumococcal Vaccine (PPV23) after the 7-Valent Conjugate Vaccine (PCV7) in Allogeneic Stem Cell Tran…
2008
Abstract Background: Pneumococcal infections are causes of death after SCT. The IDWP01 trial compared early (E) vs late (L) pneumococcal immunization after allogeneic SCT, starting either at 3, or at 9 months post-transplant with 3 doses of PCV7 given at 1 month intervals,. This study has shown that the early immunization was not inferior in the proportion of responders one month after the last PCV7 dose. In addition, all patients received one dose of PPV23 after the 3 doses of PCV7 at 12 months and 18 months in the E and L groups, respectively. The goal of this supplementary analysis was to look at the immune response to the PPV23 according to the time of its administration. Methods: 158 p…
Matching for the MICA-129 polymorphism is beneficial in unrelated hematopoietic stem cell transplantation.
2016
Major histocompatibility complex class I polypeptide-related sequence A (MICA) is a highly polymorphic ligand of the activating NKG2D receptor on natural killer (NK) cells, γδ-T cells, and NKT cells. MICA incompatibilities have been associated with an increased graft-versus-host disease (GVHD) incidence, and the MICA-129 (met/val) dimorphism has been shown to influence NKG2D signaling in unrelated hematopoietic stem cell transplantation (uHSCT). We investigated the effect of MICA matching on survival after uHSCT. We sequenced 2172 patients and their respective donors for MICA. All patients and donors were high-resolution HLA-typed and matched for 10/10 (n = 1379), 9/10 (n = 636), or 8/10 (n…
Detection of Fusarium Species in Clinical Specimens by Probe-Based Real-Time PCR
2019
The mold Fusarium is a ubiquitous fungus causing plant, animal and human infections. In humans, Fusarium spp. are the major cause of eye infections in patients wearing contact lenses or after local trauma. Systemic infections by Fusarium spp. mainly occur in immunosuppressed patients and can disseminate throughout the human body. Due to high levels of resistance to antifungals a fast identification of the causative agent is an urgent need. By using a probe-based real-time PCR assay specific for the genus Fusarium we analysed several different clinical specimens detecting Fusarium spp. commonly found in clinical samples in Germany. Also, a large collection of lung fluid samples of haematolog…
Human leukocyte antigen-E mismatch is associated with better hematopoietic stem cell transplantation outcome in acute leukemia patients
2017
The immunomodulatory role of human leukocyte antigen (HLA)-E in hematopoietic stem cell transplantation (HSCT) has not been extensively investigated. To this end, we genotyped 509 10/10 HLA unrelated transplant pairs for HLA-E, in order to study the effect of HLA-E as a natural killer (NK)-alloreactivity mediator on HSCT outcome in an acute leukemia (AL) setting. Overall survival (OS), disease free survival (DFS), relapse incidence (RI) and non-relapse mortality (NRM) were set as endpoints. Analysis of our data revealed a significant correlation between HLA-E mismatch and improved HSCT outcome, as shown by both univariate (53% vs. 38%, P=0.002, 5-year OS) and multivariate (hazard ratio (HR)…
Allogeneic hematopoietic cell transplantation in older myelofibrosis patients: A study of the chronic malignancies working party of EBMT and the Span…
2021
Allogeneic hematopoietic cell transplantation (allo-HCT) is increasingly used in older myelofibrosis (MF) patients, but its risk/benefit ratio compared to non-transplant approaches has not been evaluated in this population. We analyzed the outcomes of allo-HCT in 556 MF patients aged > 65years from the EBMT registry, and determined the excess mortality over the matched general population of MF patients > 65years managed with allo-HCT (n=556) or conventional drug treatment (n=176). The non-transplant cohort included patients with intermediate-2 or high risk DIPSS from the Spanish Myelofibrosis Registry. After a median follow-up of 3.4years, the estimated 5-year survival rate, non-relapse mor…
Prognostic Factors Affecting Outcome after Allogeneic Transplantation for Hematological Malignancies from Unrelated Donors: Results from a Randomized…
2012
Several prognostic factors for the outcome after allogeneic hematopoietic stem-cell transplant (HSCT) from matched unrelated donors have been postulated from registry data; however, data from randomized trials are lacking. We present analyses on the effects of patient-related, donor-related, and treatment-related prognostic factors on acute GVHD (aGVHD), chronic GVHD (cGVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS) in a randomized, multicenter, open-label, phase III trial comparing standard graft-versus-host-disease (GVHD) prophylaxis with and without pretransplantation ATG-Fresenius (ATG-F) in 201 adult patients receiving myeloablative co…