Mats Brune

Mats Brune
University of Gothenburg | GU · Section of Hematology

MD PhD

About

167
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Publications

Publications (167)
Article
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The aim of this prospective, international multicenter, pseudorandomized study comparing RICT HCT to standard-of-care chemotherapy in intermediate- or high-risk AML patients 50–70 years using the donor versus no-donor concept. Part 1 included only patients with potential family donors (RD) at the date of HLA-typing of the first potential sibling or...
Preprint
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The aim of this prospective, international multicenter, pseudorandomized study using the donor versus no-donor concept to compare RICT HCT to standard-of-care chemotherapy in intermediate- or high risk AML patients 50 – 70 years in CR1. Part 1 included only patients with potential family donors (RD) at the date of HLA-typing of the first potential...
Article
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Cyclosporine-A (CsA) is used to prevent acute graft-versus-host disease (aGvHD). European Society for Blood and Marrow transplantation (EBMT) recommends a CsA target serum concentration of 200–300 µg/L during the first month after allogeneic hematopoietic stem cell transplantation (HSCT). With this study, we investigated whether a median CsA concen...
Article
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Background The natural killer (NK) complex (NKC) harbors multiple genes such as KLRC1 (encoding NKG2A) and KLRK1 (encoding NKG2D) that are central to regulation of NK cell function. We aimed at determining to what extent NKC haplotypes impact on NK cell repertoire and function, and whether such gene variants impact on outcome of IL-2-based immunoth...
Article
Background: Revaccination against tetanus and diphtheria after allogeneic hematopoietic stem cell transplant (HCT) is usually effective, but the duration of the immunity is unknown. Objective: To study humoral immunity to tetanus and diphtheria in long-term survivors and to provide knowledge regarding the need for boosters. Study design: The m...
Article
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Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematological diseases are at risk of severe disease and death from COVID-19. To determine the safety and immunogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines, samples from 50 infection-naïve allo-HSCT recipients (median 92 months from transplantation, range 7-34...
Article
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Introduction Genital chronic graft‐vs‐host disease (cGvHD) is a common late effect after allogeneic stem cell transplantation. In a previous cross‐sectional study, prevalence, signs and symptoms of genital and extra‐genital cGvHD were accounted for in a cohort of 42 women. Classifications of cGvHD were performed as per the National Institutes of He...
Article
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Natural killer cells are important effector cells in the immune response against myeloid malignancies. Previous studies show that the expression of activating NK cell receptors is pivotal for efficient recognition of blasts from patients with acute myeloid leukemia (AML) and that high expression levels impact favorably on patient survival. This stu...
Article
Introduction Our aim was to assess response and side effects of 4 doses of TBE vaccine to patients (pts) after allo- and autologous stem cell transplantation (SCT). PATIENTS: Included were 104 pts with leukaemia, myeloma and lymphoma, median age 61 yrs. METHODS: Vaccine (FSME-Immun®) was given at 9, 10, 12, and 21 months post-transplant. Serum samp...
Article
Background: Contemporary studies have identified >1 cycle of induction chemotherapy to induce complete remission (CR) as an independent risk factor for relapse and mortality in younger adults with acute myeloid leukemia (AML; Othus et al., Leukemia 2019). This study aimed at defining the potential impact of previous induction chemotherapy on the cl...
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Two decades after the introduction of tyrosine kinase inhibitors (TKI), a sizeable portion of patients with chronic myeloid leukemia (CML) in chronic phase (CP) still undergo allogeneic stem cell transplantation (allo-HSCT). We investigated the indications for allo-HSCT, clinical outcome, management of relapse, and post-transplant TKI treatment in...
Article
Introduction: After chemotherapy, children with acute lymphocytic leukemia lose immunity and need revaccination against tetanus and diphtheria. However, little is known about immunity in adult patients after treatment for hematological malignancies. In this study, we assessed serology levels against polio, diphtheria and tetanus in adult patients...
Article
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Immunotherapy with histamine dihydrochloride and low-dose interleukin-2 (HDC/IL-2) reduces the risk of relapse in the post-chemotherapy phase of acute myeloid leukemia (AML). Here we report the results of exploratory analyses of the clinical efficacy of HDC/IL-2 in AML with focus on the impact of karyotype aberrations in leukemic cells. Post-hoc an...
Article
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Secondary AML (s-AML), including AML with an antecedent hematologic disorder (AHD-AML) and therapy-related AML (t-AML), constitutes a large proportion of patients with AML and is considered to confer a dismal prognosis. The role of allogeneic hematopoietic cell transplantation (HCT) in patients with s-AML and the extent to which HCT is performed in...
Article
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Allogeneic stem cell transplantation (SCT) as primary treatment for aplastic anemia (AA) is being increasingly used. Yet, age, stem cell source, and donor type are important outcome factors. We have recently performed a nationwide cohort study of all patients with AA in Sweden diagnosed from 2000 to 2011 and now present outcome data on SCT patients...
Article
Background For AML (excluding APL), there has until recently been no major changes in AML‐specific drug therapy, but improvements of supportive care and access to allogeneic transplantation (SCT). Aims We aimed to analyze changes in survival from AML (non‐APL) over the period 1997–2016, and to identify and characterize patient subsets with greater...
Article
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Natural killer (NK) cell function is regulated by inhibitory receptors, such as the family of killer immunoglobulin-like receptors (KIRs) and the NKG2A/CD94 heterodimer. These receptors recognize cognate HLA class I molecules on potential target cells, and recent studies imply that an HLA-B dimorphism at position −21 in the gene segment encoding th...
Article
Background and study design. Reduced intensity conditioning transplantation (RICT) is a commonly applied treatment option for AML patients >50 years of age. Prospective, controlled studies comparing RICT with standard chemotherapy are warranted. In this study, we aimed to prevent selection biases. Thus, patients were included prior to HLA typing of...
Article
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Mutations in NPM1 can be used for minimal residual disease (MRD) analysis in acute myeloid leukemia (AML). We here applied a newly introduced method, deep sequencing, allowing for simultaneous analysis of all recurrent NPM1 insertions and thus constituting an attractive alternative to multiple PCRs for the clinical laboratory. We retrospectively us...
Article
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Human cytomegalovirus (CMV) infection is reported to promote NK cell differentiation and education. The CMV-induced generation of highly differentiated adaptive-like NK cells has been proposed to impact favorably on the maintenance of remission in patients with acute myeloid leukemia (AML) after allogeneic stem cell transplantation (allo-SCT). The...
Article
Introduction: Female genital chronic graft-versus-host disease (cGvHD) is a complication of allogeneic hematopoietic cell transplantation (alloHCT) for blood malignancies. Unattended inflammation and fibrosis in the vulva and vagina may lead to total vaginal stenosis. The course and treatment of genital cGvHD was observed in this population-based...
Article
Objectives: Antithymocyte globulin (ATG)-based immunosuppression remains a cornerstone in aplastic anaemia (AA) treatment. However, most ATG studies are not population-based and knowledge about real-world results concerning response and outcome could offer important information for treating physicians. Methods: We have recently performed a natio...
Article
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Regulatory T cells (Tregs) have been proposed to dampen functions of anti-neoplastic immune cells and thus promote cancer progression. In a phase IV trial (Re:Mission Trial, NCT01347996, http://www.clinicaltrials.gov) 84 patients (age 18–79) with acute myeloid leukemia (AML) in first complete remission (CR) received ten consecutive 3-week cycles of...
Article
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Aplastic anemia is a rare life-threatening disease. However, since the introduction of immunosuppressive therapy and allogeneic stem cell transplantation, the outcome has improved considerably, and the 5-year survival is reported to be 70-80% in selected patient cohorts. Yet, contemporary population-based data on incidence and survival are lacking....
Article
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Interactions between killer-immunoglobulin-like receptors (KIRs) and their HLA class I ligands are instrumental in natural killer (NK) cell regulation and protect normal tissue from NK cell attack. Human KIR haplotypes comprise genes encoding mainly inhibitory receptors (KIR A) or activating and inhibitory receptors (KIR B). A substantial fraction...
Article
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Low androgen levels may contribute to sexual dysfunction in women after allogeneic hematopoietic cell transplantation (alloHCT). However, data on serum androgens in women after alloHCT are limited. The aim of this study was to assess androgen levels and their association with chronic GvHD (cGvHD) and glucocorticoid (GC) therapy. Included were 65 al...
Article
We have previously reported on the efficacy of the JAK1/2 inhibitor ruxolitinib in corticosteroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) in 95 patients (pts) (Leukemia 2015;29(10):2062-8). To assess long-term follow-up results, we collected data from the same pts treated in 19 centers in Europe and the US. Pts we...
Article
Introduction: Aplastic anemia (AA) is a rare life-threatening disease but since the introduction of immunosuppressive therapy (IST) and allogeneic stem cell transplantation (alloHCT), the outcome in selected patient cohorts has improved considerably with a 5-year overall survival of 70-80 %. However, there is a lack of contemporary population-based...
Article
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Bone Marrow Transplantation is a high quality, peer-reviewed journal covering all aspects of clinical and basic haemopoietic stem cell transplantation.
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Preventing relapse after chemotherapy remains a challenge in acute myeloid leukemia (AML). Eighty-four non-transplanted AML patients in first complete remission received relapse-preventive immunotherapy with histamine dihydrochloride and low-dose interleukin-2 in an international phase IV trial (ClinicalTrials.gov; NCT01347996). Blood samples were...
Article
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After allogeneic hematopoietic stem cell transplantation (allo-SCT), ocular GvHD is a common complication, typical symptoms being dry eye syndrome with features of fibrosis. In this study, we have identified and quantified two cell types-myofibroblasts (MFB) and polyploid (PP) cells-in the conjunctival surface of allo-SCT patients (pts) and have ex...
Article
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In a phase IV trial, eighty-four patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose human recombinant interleukin-2 (IL-2) to prevent relapse in the post-consolidation phase. Aspects of natural killer (NK) cell biology were analyz...
Article
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Despite major improvements in allogeneic hematopoietic cell transplantation over the last decades, corticosteroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) cause high mortality. Pre-clinical evidence indicates the potent anti-inflammatory properties of the JAK1/2 inhibitor ruxolitinib. In this retrospective survey,...
Article
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In a phase IV trial, eighty-four patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose human recombinant interleukin 2 (IL-2) for 18 months to prevent leukemic relapse. During cycles, the treatment resulted in expansion of CD56bright...
Article
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Background Influenza vaccination is generally recommended to hematopoietic stem cell transplant (HSCT) recipients. However, the seasonal subunit vaccination response is frequently sub-optimal and calls to examine alternate, more efficient vaccination systems. We compared the immunogenicity of an adjuvanted virosomal influenza and subunit vaccine i...
Article
Autologous hematopoietic cell transplantation (AHCT) is a standard of care in multiple myeloma (MM) patients aged <65 years. To understand age-related trends in utilisation and outcome of AHCT, we analysed 53 675 MM patients who underwent a first AHCT in 31 European countries between 1991 and 2010. The number of patients undergoing AHCT increased f...
Article
BACKGROUND AND METHODS. Immunotherapy with histamine dihydrochloride and low-dose interleukin-2 (HDC/IL-2) has been approved within the EU for relapse prevention in the post-consolidation phase of acute myeloid leukemia (AML) (Blood 108:88). We have performed a phase IV trial (Re:MISSION) to assess the immunomodulatory properties of this regimen an...
Article
The recent contribution by Michelis et al. convincingly shows that an early recovery of lymphocytes in blood following allogeneic hematopoietic cell transplantation heralds a reduced risk of relapse for patients with acute myeloid leukemia (AML) (1). In a multicenter phase III trial (n=320), post-consolidation therapy with histamine dihydrochloride...
Article
Background and Purpose: Natural killer (NK) cells are commonly dysfunctional in chronic myeloid leukemia (CML) and their status may determine the course of disease. We aimed to define the molecular mechanisms of leukemia-induced NK cell inhibition with focus on the role of CML cell-derived reactive oxygen species (ROS) and the poly(ADP-ribose) poly...
Article
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Using the National Institutes of Health (NIH) consensus document on criteria for chronic Graft-versus-Host Disease (cGvHD), we assessed the prevalence, symptoms and clinical features of female genital chronic Graft-versus-Host Disease (cGvHD) in a cross-sectional population-based study. Forty-two women were seen at 13-148 (median 80) months after H...
Article
Full-text available
Bone Marrow Transplantation is a high quality, peer-reviewed journal covering all aspects of clinical and basic haemopoietic stem cell transplantation.
Article
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Clinical management guidelines on malignant disorders are generally based on data from clinical trials with selected patient cohorts. In Sweden, more than 95% of all patients diagnosed with chronic myeloid leukemia (CML) are reported to the national CML registry, providing unique possibilities to compile population-based information. This report is...
Article
Cases of human herpesvirus type 6 (HHV-6) infection and disease were retrospectively analysed in a cohort of 97 allogeneic haematopoietic stem cell transplantation (allo-SCT) patients in Gothenburg, Sweden (1997-2001). Altogether 54 of 97 (56%) patients were tested for HHV-6. HHV-6 DNAemia was detected in 15 of the tested patients at a median of 76...
Article
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CML cells induce PARP-1 dependent parthanatos in NK cells, and inhibition of PARP-1 maintains lymphocyte viability and function. NK cells and T cells are commonly dysfunctional in CML, and their status may determine the course of disease. We aimed to define the molecular mechanisms of leukemia-induced immunosuppression with focus on the role of ROS...
Article
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Background: Viral infections are major complications after allogeneic hematopoietic stem cell transplantation (HSCT). During posttransplant immunosuppression the regular T-cell control is compromised. Even if treatment strategies against infections caused by herpes viruses such as cytomegalovirus, Epstein-Barr virus, and adenovirus have improved,...
Article
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Post-consolidation immunotherapy with histamine dihydrochloride and interleukin-2 has been shown to improve leukemia-free survival in acute myeloid leukemia in a phase 3 trial. For this study treatment efficacy was determined among 145 trial patients with morphological forms of acute myeloid leukemia defined by the French-American-British classific...
Article
The dysfunction of natural killer (NK) cells and T cells in acute myeloid leukemia (AML) determines the course of disease, but only limited information is available on the mechanisms of lymphocyte inhibition. This study aimed to evaluate to what extent malignant AML cells utilize NADPH-oxidase derived reactive oxygen species (ROS) as an immune evas...
Article
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Dysfunction of T cells and natural killer (NK) cells has been proposed to determine the course of disease in acute myeloid leukemia (AML), but only limited information is available on the mechanisms of lymphocyte inhibition. We aimed to evaluate to what extent human malignant AML cells use NADPH oxidase-derived reactive oxygen species (ROS) as an i...
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Although Hodgkin's lymphoma is a highly curable disease with modern chemotherapy protocols, some patients are primary refractory or relapse after first-line chemotherapy or even after high-dose therapy and autologous stem cell transplantation. We investigated the potential role of allogeneic stem cell transplantation in this setting. In this phase...
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T-prolymphocytic leukemia (T-PLL) has a very poor prognosis with conventional immunochemotherapy. Incidental reports suggest that allogeneic hematopoietic stem cell transplantation (allo-HSCT) might have a role in this disease. Therefore, the purpose of the present study was to analyze the outcome of transplants for T-PLL registered with the Europe...
Article
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Autologous stem cell transplantation (ASCT) consolidation remains the treatment of choice for patients with relapsed diffuse large B cell lymphoma. The impact of rituximab combined with chemotherapy in either first- or second-line therapy on the ultimate results of ASCT remains to be determined, however. This study was designed to evaluate the bene...
Article
Allogeneic stem cell transplantation (alloSCT) reduces relapse rates in acute leukemia, but outcome is hampered by toxicity. Population-based data avoid patient selection and may therefore substitute for lack of randomized trials. We evaluated alloSCT rates within the Swedish Acute Leukemia Registry, including 3899 adult patients diagnosed from 199...
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Between 1982 and 2009 a total of 92 patients with myelofibrosis (MF) in chronic phase underwent allo-SCT in nine Nordic transplant centers. Myeloablative conditioning (MAC) was given to 40 patients, and reduced intensity conditioning (RIC) was used in 52 patients. The mean age in the two groups at transplantation was 46±12 and 55±8 years, respectiv...
Article
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In trials designed to evaluate new therapies for hematologic malignancies, end points such as leukemia-free survival are often used as surrogates for overall survival in acute leukemia. We aimed to assess whether leukemia-free survival is an acceptable statistical surrogate for overall survival when applied to remission maintenance therapy for acut...
Article
Today, a number of therapeutic options are available as the patient with myeloma relapses from initial treatment with high-dose melphalan and autologous stem cell transplantation (ASCT). For patients who experience a durable response to primary ASCT, retreatment with high-dose melphalan is recommended by many current guidelines. Yet, toxicity is an...
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Data from a randomized multinational phase 3 trial of 320 adults with acute myeloid leukemia (AML) demonstrated that maintenance therapy with 3-week cycles of histamine dihydrochloride plus low-dose interleukin-2 (HDC/IL-2) for up to 18 months significantly improved leukemia-free survival (LFS) but lacked power to detect an overall survival (OS) di...
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Adenoviruses (AdV) have emerged as important causes of morbidity and mortality in patients after hematopoietic SCT (HSCT). Early diagnosis of the infection by detection of viral DNA may improve the prognosis. A surveillance strategy was evaluated for detection of AdV DNA by PCR in a prospective study of unselected allogeneic HSCT recipients. In par...
Article
Cytomegalovirus (CMV) is an important factor for morbidity and long-term outcome after allogeneic haematopoetic stem cell transplantation (allo-SCT). Cases of proven and probable CMV infection and disease among 97 allo-SCT recipients in Gothenburg, Sweden, 1997-2001, were analysed. CMV DNAemia was detected in 60 patients at a median of 30 days afte...