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Hägglund, Hans
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Publications (10 of 20) Show all publications
Valent, P., Elberink, J. N. G., Gorska, A., Lange, M., Zanotti, R., van Anrooij, B., . . . Sperr, W. R. (2019). The Data Registry of the European Competence Network on Mastocytosis (ECNM): Set Up, Projects, and Perspectives. Journal of Allergy and Clinical Immunology: In Practice, 7(1), 81-87
Open this publication in new window or tab >>The Data Registry of the European Competence Network on Mastocytosis (ECNM): Set Up, Projects, and Perspectives
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2019 (English)In: Journal of Allergy and Clinical Immunology: In Practice, ISSN 2213-2198, E-ISSN 2213-2201, Vol. 7, no 1, p. 81-87Article, review/survey (Refereed) Published
Abstract [en]

Mastocytosis is a unique hematologic neoplasm with complex biology and pathology and a variable clinical course. The disease can essentially be divided into cutaneous mastocytosis (CM) and systemic mastocytosis (SM). In adults, SM is diagnosed in most cases and manifests as either indolent or advanced disease. Patients with advanced SM have an unfavorable prognosis with reduced survival. However, so far, little is known about the prevalence of various categories of SM and about prognostic factors. In an attempt to learn more about the behavior and evolution of various forms of CM and SM, the European Competence Network on Mastocytosis (ECNM) initiated a mastocytosis registry in 2012. In this article, the set up and start phase of this registry are described. Until 2018, more than 3000 patients from 12 countries and 25 centers have been enrolled. In a majority of all patients, robust follow-up data and relevant clinical end points are available. Using this data set, a series of registry projects have been launched, with the aim to validate previously identified diagnostic and prognostic variables and to identify new disease-related and patient-related parameters in various forms of mastocytosis. Moreover, the core data set of the registry will be useful to establish multiparametric scoring systems through which prognostication and individualized management of patients with mastocytosis should improve in the foreseeable future. (C) 2019 American Academy of Allergy, Asthma & Immunology

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2019
Keywords
Mastocytosis, Prognosis, WHO classification, Diagnostic criteria, Therapy
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-375609 (URN)10.1016/j.jaip.2018.09.024 (DOI)000454522500010 ()30416055 (PubMedID)
Funder
German Research Foundation (DFG), HA 2393/6-1
Available from: 2019-01-31 Created: 2019-01-31 Last updated: 2019-01-31Bibliographically approved
Burman, J., Tolf, A., Hägglund, H. & Askmark, H. (2018). Autologous haematopoietic stem cell transplantation for neurological diseases. Journal of Neurology, Neurosurgery and Psychiatry, 89(2), 147-155
Open this publication in new window or tab >>Autologous haematopoietic stem cell transplantation for neurological diseases
2018 (English)In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 89, no 2, p. 147-155Article, review/survey (Refereed) Published
Abstract [en]

Neuroinflammatory diseases such as multiple sclerosis, neuromyelitis optica, chronic inflammatory demyelinating polyneuropathy and myasthenia gravis are leading causes of physical disability in people of working age. In the last decades significant therapeutic advances have been made that can ameliorate the disease course. Nevertheless, many affected will continue to deteriorate despite treatment, and the costs associated with disease-modifying drugs constitute a significant fiscal burden on healthcare in developed countries. Autologous haematopoietic stem cell transplantation is a treatment approach that aims to ameliorate and to terminate disease activity. The erroneous immune system is eradicated using cytotoxic drugs, and with the aid of haematopoietic stem cells a new immune system is rebuilt. As of today, more than 1000 patients with multiple sclerosis have been treated with this procedure. Available data suggest that autologous haematopoietic stem cell transplantation is superior to conventional treatment in terms of efficacy with an acceptable safety profile. A smaller number of patients with other neuroinflammatory conditions have been treated with promising results. Herein, current data on clinical effect and safety of autologous haematopoietic stem cell transplantation for neurological disease are reviewed.

Keywords
clinical neurology, haematology, multiple sclerosis, myasthenia, neuropathy
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-336956 (URN)10.1136/jnnp-2017-316271 (DOI)000424004400007 ()28866625 (PubMedID)
Available from: 2017-12-19 Created: 2017-12-19 Last updated: 2019-01-25Bibliographically approved
Afram, G., Perez Simon, J. A., Remberger, M., Caballero-Velazquez, T., Martino, R., Luis Pinana, J., . . . Hägglund, H. (2018). Reduced intensity conditioning increases risk of severe cGVHD: identification of risk factors for cGVHD in a multicenter setting. Medical Oncology, 35(6), Article ID 79.
Open this publication in new window or tab >>Reduced intensity conditioning increases risk of severe cGVHD: identification of risk factors for cGVHD in a multicenter setting
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2018 (English)In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 35, no 6, article id 79Article in journal (Refereed) Published
Abstract [en]

Chronic graft-versus-host disease (cGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Aim is to identify risk factors for the development of cGVHD in a multicenter setting. Patients transplanted between 2000 and 2006 were analyzed (n = 820). Donors were HLA-identical siblings (57%), matched unrelated donors (30%), and HLA-A, B or DR antigen mismatched (13%). Reduced intensity conditioning (RIC) was given to 65% of patients. Overall incidence of cGVHD was 46% for patients surviving more than 100 days after HSCT (n = 747). Older patient age [HR 1.15, p < 0.001], prior acute GVHD [1.30, p = 0.024], and RIC [1.36, p = 0.028] increased overall cGVHD. In addition, RIC [4.85, p < 0.001], prior aGVHD [2.14, p = 0.001] and female donor to male recipient [1.80, p = 0.008] increased the risk of severe cGVHD. ATG had a protective effect for both overall [0.41, p < 0.001] and severe cGVHD [0.20, p < 0.001]. Relapse-free survival (RFS) was impaired in patients with severe cGVHD. RIC, prior aGVHD, and female-to-male donation increase the risk of severe cGVHD. ATG reduces the risk of all grades of cGVHD without hampering RFS. GVHD prophylaxis may be tailored according to the risk profile of patients.

Keywords
ATG, Graft-versus-host disease (GVHD), Risk factor
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-356856 (URN)10.1007/s12032-018-1127-2 (DOI)000432040700002 ()29696461 (PubMedID)
Available from: 2018-08-15 Created: 2018-08-15 Last updated: 2018-08-15Bibliographically approved
Pahnke, S., Larfors, G., Axdorph-Nygell, U., Fischer-Nielsen, A., Haastrup, E., Heldal, D., . . . Hägglund, H. (2018). Short-term side effects and attitudes towards second donation: A comparison of related and unrelated haematopoietic stem cell donors. Journal of clinical apheresis, 33(3), 226-235
Open this publication in new window or tab >>Short-term side effects and attitudes towards second donation: A comparison of related and unrelated haematopoietic stem cell donors
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2018 (English)In: Journal of clinical apheresis, ISSN 0733-2459, E-ISSN 1098-1101, Vol. 33, no 3, p. 226-235Article in journal (Refereed) Published
Abstract [en]

The Nordic Register of Haematopoietic Stem Cell Donors (NRHSD) has registered related and unrelated donors from 10 transplant centres in Sweden, Norway, Finland and Denmark since 1998. We present a prospective, observational study of 1,957 donors, focusing mainly on the differences between related and unrelated donors. Related donors are reported to have more comorbidities, but similar side effects compared with unrelated donors. Side effects after BM or PBSC donation are generally of short duration and in this study no deaths, myocardial infarctions, splenic ruptures, or thromboembolic events are reported. Interestingly, related donors express more hesitancy towards donating again when asked 1 month after donation.

Keywords
bone marrow donation, granulocyte colony stimulating factor, healthy donors, peripheral blood stem cell donation
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-342995 (URN)10.1002/jca.21576 (DOI)000441439100003 ()28833474 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2018-02-24 Created: 2018-02-24 Last updated: 2018-10-12Bibliographically approved
Ajeganova, S., Tesfa, D., Hägglund, H., Fadeel, B., Vedin, I., Zignego, A. L. & Palmblad, J. (2017). Effect of FCGR polymorphism on the occurrence of late-onset neutropenia and flare-free survival in rheumatic patients treated with rituximab. Arthritis Research & Therapy, 19, Article ID 44.
Open this publication in new window or tab >>Effect of FCGR polymorphism on the occurrence of late-onset neutropenia and flare-free survival in rheumatic patients treated with rituximab
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2017 (English)In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 19, article id 44Article in journal (Refereed) Published
Abstract [en]

Background: The causes and mechanisms of late-onset neutropenia (LON) following rituximab treatment in patients with rheumatic diseases are not known. In this study, we aimed to investigate the role of established Fc gamma receptor gene (FCGR) polymorphisms and B-cell-activating factor (BAFF) gene promoter polymorphisms for the development of LON and for the efficacy of rituximab in patients with rheumatic diseases. Methods: A single-center case-control retrospective study was nested in a cohort of 214 consecutive patients with rheumatic diseases treated with rituximab. Eleven patients presented with LON. Fifty non-LON control subjects were matched by diagnosis, age, sex, and treatments. Single-nucleotide polymorphisms of FCGR (FCGR2A 131H/R, FCGR2B 232I/T, FCGR3A 158V/F) and BAFF promoter polymorphism -871C/T were analyzed with polymerase chain reaction-based techniques, and serum immunoglobulin M (IgM) and BAFF levels were analyzed by enzyme-linked immunosorbent assay. Flare-free survival was related to LON occurrence and polymorphisms. Results: The FCGR3A V allele, but not other FCGR polymorphisms, correlated with the occurrence of LON; each V allele conferred a fourfold increased OR for LON (p = 0.017). FCGR3A 158V/V and presentation with LON were associated with a longer flare-free survival (p = 0.023 and p = 0.031, respectively). FCGR3A 158V/V was related to lower IgM levels (p = 0.016). Serum BAFF levels showed no relationship with LON and BAFF -871C/T promoter polymorphism. There was a tendency toward longer flare-free survival in patients with the BAFF -871T/T allotype compared with the C/T or C/C allotypes (p = 0.096). Conclusions: The results of the present study suggest that presentation with LON may be a result of the intrinsic efficacy of rituximab in patients with rheumatic diseases. LON could indicate a longer biological and therapeutic activity of rituximab modulated by a certain genotypic polymorphism: the high-affinity FCGR3A V allele. This genotype and the occurrence of LON are both related to longer flare-free survival, suggestive of common mechanisms for LON and duration of response to rituximab. The role of the BAFF -871C/T promoter polymorphism in LON occurrence is unclear.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD, 2017
Keywords
Late-onset neutropenia, Rituximab, FCGR, BAFF, Polymorphism, Rheumatic disease
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:uu:diva-320256 (URN)10.1186/s13075-017-1241-0 (DOI)000396276000003 ()28270182 (PubMedID)
Funder
The Karolinska Institutet's Research FoundationStockholm County CouncilSwedish Rheumatism Association
Available from: 2017-04-19 Created: 2017-04-19 Last updated: 2017-11-29Bibliographically approved
Machaczka, M., Hägglund, H., Staver, E., Joks, M., Hassan, M., Wahlin, B. E. & Nygell, U. A. (2017). G-CSF mobilized peripheral blood stem cell collection for allogeneic transplantation in healthy donors: Analysis of factors affecting yield. Journal of clinical apheresis, 32(6), 384-391
Open this publication in new window or tab >>G-CSF mobilized peripheral blood stem cell collection for allogeneic transplantation in healthy donors: Analysis of factors affecting yield
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2017 (English)In: Journal of clinical apheresis, ISSN 0733-2459, E-ISSN 1098-1101, Vol. 32, no 6, p. 384-391Article in journal (Refereed) Published
Abstract [en]

Mobilized PBSC are the main source for allogeneic HSCT. We aimed to evaluate factors that affect CD34+ cell yield including the donor's age, gender, BSA, processed blood volume and the method of G-CSF dose calculation. Data from 170 healthy donors were analyzed. The concentration of CD34+ cells in the peripheral blood (PB) and the processed volume of blood were significantly correlated to CD34+ cells yield (P<.00005 and P<.001, respectively). The G-CSF dose per m(2) was significantly correlated to the concentration of CD34+ cells in the PB (P=.0003) and in the product (P=.01). Smaller BSA and less processed volume were found among female donors, who were given lesser G-CSF dose perm(2), and showed lower yield compared to men. However, multivariate analysis of the yield showed that only the concentration of CD34+ cells in the PB and the processed volume remained independent significant.

Place, publisher, year, edition, pages
WILEY, 2017
Keywords
collection, healthy donors, G-CSF, mobilization, PBSC donation
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-342662 (URN)10.1002/jca.21524 (DOI)000415743800002 ()28101890 (PubMedID)
Available from: 2018-02-27 Created: 2018-02-27 Last updated: 2018-02-27Bibliographically approved
Machaczka, M., Hägglund, H., Staver, E., Joks, M., Hassan, M., Wahlin, B. E. & Nygell, U. A. (2017). G-CSF mobilized peripheral blood stem cell collection for allogeneic transplantation in healthy donors: Analysis Of Factors Affecting Yield. Paper presented at 43rd Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT), MAR 26-29, 2017, Marseille, FRANCE. Bone Marrow Transplantation, 52(Supplement: 1), S139-S139
Open this publication in new window or tab >>G-CSF mobilized peripheral blood stem cell collection for allogeneic transplantation in healthy donors: Analysis Of Factors Affecting Yield
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2017 (English)In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 52, no Supplement: 1, p. S139-S139Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2017
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-351610 (URN)10.1038/bmt.2017.134 (DOI)000424355301030 ()
Conference
43rd Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT), MAR 26-29, 2017, Marseille, FRANCE
Note

In: Abstracts From The 43RD Annual Meeting Of The Europeansociety For Blood And Marrow Transplantation:Physicians—Posters Session (P001-P738).

Meeting Abstract: P131.

Available from: 2018-06-08 Created: 2018-06-08 Last updated: 2018-06-08Bibliographically approved
Lyberg, K., Ali, H. A., Grootens, J., Kjellander, M., Tirfing, M., Arock, M., . . . Ungerstedt, J. (2017). Histone deacetylase inhibitor SAHA mediates mast cell death and epigenetic silencing of constitutively active D816V KIT in systemic mastocytosis.. OncoTarget, 8(6), 9647-9659
Open this publication in new window or tab >>Histone deacetylase inhibitor SAHA mediates mast cell death and epigenetic silencing of constitutively active D816V KIT in systemic mastocytosis.
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2017 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 6, p. 9647-9659Article in journal (Refereed) Published
Abstract [en]

Systemic mastocytosis (SM) is a clonal bone marrow disorder, where therapeutical options are limited. Over 90% of the patients carry the D816V point mutation in the KIT receptor that renders this receptor constitutively active. We assessed the sensitivity of primary mast cells (MC) and mast cell lines HMC1.2 (D816V mutated), ROSA (KIT WT) and ROSA (KIT D816V) cells to histone deacetylase inhibitor (HDACi) treatment. We found that of four HDACi, suberoyl anilide hydroxamic acid (SAHA) was the most effective in killing mutated MC. SAHA downregulated KIT, followed by major MC apoptosis. Primary SM patient MC cultured ex vivo were even more sensitive to SAHA than HMC1.2 cells, whereas primary MC from healthy subjects were less affected. There was a correlation between cell death and SM disease severity, where cell death was more pronounced in the case of aggressive SM, with almost 100% cell death among MC from the mast cell leukemia patient. Additionally, ROSA (KIT D816V) was more affected by HDACi than ROSA (KIT WT) cells. Using ChIP qPCR, we found that the level of active chromatin mark H3K18ac/H3 decreased significantly in the KIT region. This epigenetic silencing was seen only in the KIT region and not in control genes upstream and downstream of KIT, indicating that the downregulation of KIT is exerted by specific epigenetic silencing. In conclusion, KIT D816V mutation sensitized MC to HDACi mediated killing, and SAHA may be of value as specific treatment for SM, although the specific mechanism of action requires further investigation.

National Category
Cancer and Oncology Cell Biology
Identifiers
urn:nbn:se:uu:diva-311794 (URN)10.18632/oncotarget.14181 (DOI)000394181800062 ()28038453 (PubMedID)
Available from: 2017-01-02 Created: 2017-01-02 Last updated: 2017-11-29Bibliographically approved
Håkansson, I., Sandstedt, A., Lundin, F., Askmark, H., Pirskanen, R., Carlson, K., . . . Hägglund, H. (2017). Successful autologous haematopoietic stem cell transplantation for refractory myasthenia gravis - a case report. Neuromuscular Disorders, 27(1), 90-93
Open this publication in new window or tab >>Successful autologous haematopoietic stem cell transplantation for refractory myasthenia gravis - a case report
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2017 (English)In: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 27, no 1, p. 90-93Article in journal (Refereed) Published
Abstract [en]

Myasthenia gravis (MG) is an autoimmune disease, with immune reactivity against the post-synaptic endplate of the neuromuscular junction. Apart from symptomatic treatment with choline esterase blockers, many patients also require immunomodulatory treatment. Despite existing treatment options, some patients are treatment refractory. We describe a patient with severe MG refractory to corticosteroids, four oral immunosuppressants, cyclophosphamide, rituximab and bortezomib who was treated with autologous haematopoietic stem cell transplantation. Two years after this, the patient has significantly improved in objective tests and in quality of life and leads an active life. Diplopia is her only remaining symptom and she is completely free of medication for MG. We believe that autologous haematopoietic stem cell transplantation can be an effective therapeutic option for carefully selected cases of severe, treatment refractory MG.

National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-310817 (URN)10.1016/j.nmd.2016.09.020 (DOI)000393247400014 ()27863874 (PubMedID)
Available from: 2016-12-20 Created: 2016-12-20 Last updated: 2017-11-29Bibliographically approved
Ustun, C., Gotlib, J., Popat, U., Artz, A., Litzow, M., Reiter, A., . . . Valent, P. (2016). Consensus Opinion on Allogeneic Hematopoietic Cell Transplantation in Advanced Systemic Mastocytosis. Biology of blood and marrow transplantation, 22(8), 1348-1356
Open this publication in new window or tab >>Consensus Opinion on Allogeneic Hematopoietic Cell Transplantation in Advanced Systemic Mastocytosis
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2016 (English)In: Biology of blood and marrow transplantation, ISSN 1083-8791, E-ISSN 1523-6536, Vol. 22, no 8, p. 1348-1356Article in journal, Editorial material (Other academic) Published
National Category
Hematology Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-303423 (URN)10.1016/j.bbmt.2016.04.018 (DOI)000380417400003 ()27131865 (PubMedID)
Available from: 2016-11-21 Created: 2016-09-19 Last updated: 2018-01-13Bibliographically approved
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