| 1. |
|
|
| 2. |
|
|
| 3. |
- Hartmann, Karin, et al.
(författare)
-
Cutaneous manifestations in patients with mastocytosis : Consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology
- 2016
-
Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 137:1, s. 35-45
-
Tidskriftsartikel (refereegranskat)abstract
- Cutaneous lesions in patients with mastocytosis are highly heterogeneous and encompass localized and disseminated forms. Although a classification and criteria for cutaneous mastocytosis (CM) have been proposed, there remains a need to better define subforms of cutaneous manifestations in patients with mastocytosis. To address this unmet need, an international task force involving experts from different organizations (including the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology) met several times between 2010 and 2014 to discuss the classification and criteria for diagnosis of cutaneous manifestations in patients with mastocytosis. This article provides the major outcomes of these meetings and a proposal for a revised definition and criteria. In particular, we recommend that the typical maculopapular cutaneous lesions (urticaria pigmentosa) should be subdivided into 2 variants, namely a monomorphic variant with small maculopapular lesions, which is typically seen in adult patients, and a polymorphic variant with larger lesions of variable size and shape, which is typically seen in pediatric patients. Clinical observations suggest that the monomorphic variant, if it develops in children, often persists into adulthood, whereas the polymorphic variant may resolve around puberty. This delineation might have important prognostic implications, and its implementation in diagnostic algorithms and future mastocytosis classifications is recommended. Refinements are also suggested for the diagnostic criteria of CM, removal of telangiectasia macularis eruptiva perstans from the current classification of CM, and removal of the adjunct solitary from the term solitary mastocytoma.
|
|
| 4. |
- Sharrack, Basil, et al.
(författare)
-
Autologous haematopoietic stem cell transplantation and other cellular therapy in multiple sclerosis and immune-mediated neurological diseases : updated guidelines and recommendations from the EBMT Autoimmune Diseases Working Party (ADWP) and the Joint Accreditation Committee of EBMT and ISCT (JACIE)
- 2020
-
Ingår i: Bone Marrow Transplantation. - : Springer Nature. - 0268-3369 .- 1476-5365. ; 55:2, s. 283-306
-
Tidskriftsartikel (refereegranskat)abstract
- These updated EBMT guidelines review the clinical evidence, registry activity and mechanisms of action of haematopoietic stem cell transplantation (HSCT) in multiple sclerosis (MS) and other immune-mediated neurological diseases and provide recommendations for patient selection, transplant technique, follow-up and future development. The major focus is on autologous HSCT (aHSCT), used in MS for over two decades and currently the fastest growing indication for this treatment in Europe, with increasing evidence to support its use in highly active relapsing remitting MS failing to respond to disease modifying therapies. aHSCT may have a potential role in the treatment of the progressive forms of MS with a significant inflammatory component and other immune-mediated neurological diseases, including chronic inflammatory demyelinating polyneuropathy, neuromyelitis optica, myasthenia gravis and stiff person syndrome. Allogeneic HSCT should only be considered where potential risks are justified. Compared with other immunomodulatory treatments, HSCT is associated with greater short-term risks and requires close interspeciality collaboration between transplant physicians and neurologists with a special interest in these neurological conditions before, during and after treatment in accredited HSCT centres. Other experimental cell therapies are developmental for these diseases and patients should only be treated on clinical trials.
|
|
| 5. |
|
|
| 6. |
- Valent, Peter, et al.
(författare)
-
European Competence Network on Mastocytosis (ECNM) : 10-year jubilee, update, and future perspectives
- 2012
-
Ingår i: Wiener Klinische Wochenschrift. - : Springer Science and Business Media LLC. - 0043-5325 .- 1613-7671. ; 124:23-24, s. 807-814
-
Tidskriftsartikel (refereegranskat)abstract
- The European Competence Network on Mastocytosis (ECNM) was initiated in 2002 as a multidisciplinary and multinational cooperative approach to increase awareness and to improve diagnosis and therapy of mastocytosis. The network is composed of local centers, physicians, and scientists who have dedicated their work to patients with mastocytosis. A strategic goal of the ECNM is to provide the best available information about the disease to patients and physicians. During the past 10 years, the ECNM has expanded to various countries and contributed successfully to the development of markers, definitions, and standards in the field of mastocytosis. Members of the ECNM organized Annual Meetings in Europe and two Working Conferences on Mastocytosis in Vienna (in 2005 and 2010), and initiated and supported several preclinical and clinical trials. In all these activities, representatives of the ECNM cooperate closely with their US colleagues, with patient-organizations in Europe and in the USA, and with other scientific networks. The ECNM also launched a mastocytosis registry that has been activated in 2012. Using the central database of this registry, cooperative multicenter studies, which should include sufficient numbers of patients and robust evaluations, will be conducted. These studies will increase our knowledge about optimal management and therapy of patients with mastocytosis in the future.
|
|
| 7. |
- Valent, Peter, et al.
(författare)
-
European Competence Network on Mastocytosis (ECNM) : 20-Year Jubilee, Updates, and Future Perspectives
- 2023
-
Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 2213-2198 .- 2213-2201. ; 11:6, s. 1706-1717
-
Tidskriftsartikel (refereegranskat)abstract
- In 2002, the European Competence Network on Mastocytosis (ECNM) was launched as a multidisciplinary collaborative initiative to increase the awareness and to improve diagnosis and management of patients with mast cell (MC) disorders. The ECNM consists of a net of specialized centers, expert physicians, and scientists who dedicate their work to MC diseases. One essential aim of the ECNM is to timely distribute all available information about the disease to patients, doctors, and scientists. In the past 20 years, the ECNM has expanded substantially and contributed successfully to the development of new diagnostic concepts, and to the classification, prognostication, and treatments of patients with mastocytosis and MC activation disorders.
|
|
| 8. |
- Afram, Gabriel, et al.
(författare)
-
Higher response rates in patients with severe chronic skin graft-versus-host disease treated with extracorporeal photopheresis
- 2019
-
Ingår i: Central European Journal of Immunology. - : TERMEDIA PUBLISHING HOUSE LTD. - 1426-3912 .- 1644-4124. ; 44:1, s. 84-91
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Different forms of graft-versus-host disease (GVHD) remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The prognosis for steroid-refractory chronic GVHD (cGVHD) remains poor. Our aim was to evaluate extracorporeal photopheresis (ECP) treatment in cGVHD patients with different organ involvement to detect subgroups of patients with the best response.Material and methods: Thirty-four patients who underwent HSCT and developed moderate (n = 7) or severe (n = 27) steroid-refractory or steroid-dependent cGVHD treated with ECP were included in the analysis. A matched cGVHD control patient group untreated with ECP was collected for comparison.Results: Compared to the control group and the stable/progressive disease (SD/PD) patients, individuals with complete/partial remission have higher overall survival and lower transplant-related mortality. Furthermore, patients with complete and partial remission (CR/PR) had significantly higher levels of albumin and platelets after ECP treatment compared to patients with stable or progressive cGVHD (SD/PD). Corticosteroid treatment and other immunosuppressive agents could successfully be tapered in the CR/PR group compared to the SD/PD patients. In this study patients with skin cGVHD are those with the highest rate of CR/PR after ECP treatment.Conclusions: Our results suggest that ECP treatment is safe and effective for patients with predominantly skin, oral and liver cGVHD.
|
|
| 9. |
- Afram, Gabriel, et al.
(författare)
-
Reduced intensity conditioning increases risk of severe cGVHD : identification of risk factors for cGVHD in a multicenter setting
- 2018
-
Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 35:6
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 10. |
- Ajeganova, Sofia, et al.
(författare)
-
Effect of FCGR polymorphism on the occurrence of late-onset neutropenia and flare-free survival in rheumatic patients treated with rituximab
- 2017
-
Ingår i: Arthritis Research & Therapy. - : BIOMED CENTRAL LTD. - 1478-6362. ; 19
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Broesby-Olsen, Sigurd, et al.
(författare)
-
Multidisciplinary Management of Mastocytosis : Nordic Expert Group Consensus
- 2016
-
Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 96:5
-
Tidskriftsartikel (refereegranskat)abstract
- Mastocytosis is a heterogeneous group of diseases defined by an increased number and accumulation of mast cells, and often also by signs and symptoms of mast cell activation. Disease subtypes range from indolent to rare aggressive forms. Mastocytosis affects people of all ages and has been considered rare; however, it is probably underdiagnosed with potential severe implications. Diagnosis can be challenging and symptoms may be complex and involve multiple organ-systems. In general it is advised that patients should be referred to centres with experience in the disease offering an individualized, multidisciplinary approach. We present here consensus recommendations from a Nordic expert group for the diagnosis and general management of patients with mastocytosis.
|
|
| 14. |
- Burman, Joachim, et al.
(författare)
-
Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis : the Swedish experience
- 2014
-
Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - London, United Kingdom : BMJ Publishing Group Ltd. - 0022-3050 .- 1468-330X. ; 85:10, s. 1116-1121
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Autologous haematopoietic stem cell transplantation (HSCT) is a viable option for treatment of aggressive multiple sclerosis (MS). No randomised controlled trial has been performed, and thus, experiences from systematic and sustained follow-up of treated patients constitute important information about safety and efficacy. In this observational study, we describe the characteristics and outcome of the Swedish patients treated with HSCT for MS.Methods: Neurologists from the major hospitals in Sweden filled out a follow-up form with prospectively collected data. Fifty-two patients were identified in total; 48 were included in the study and evaluated for safety and side effects; 41 patients had at least 1 year of follow-up and were further analysed for clinical and radiological outcome. In this cohort, 34 patients (83%) had relapsing-remitting MS, and mean follow-up time was 47 months.Results: At 5 years, relapse-free survival was 87%; MRI event-free survival 85%; expanded disability status scale (EDSS) score progression-free survival 77%; and disease-free survival (no relapses, no new MRI lesions and no EDSS progression) 68%. Presence of gadolinium-enhancing lesions prior to HSCT was associated with a favourable outcome (disease-free survival 79% vs 46%, p=0.028). There was no mortality. The most common long-term side effects were herpes zoster reactivation (15%) and thyroid disease (8.4%).Conclusions: HSCT is a very effective treatment of inflammatory active MS and can be performed with a high degree of safety at experienced centres.
|
|
| 15. |
- Burman, Joachim, 1974-, et al.
(författare)
-
Autologous haematopoietic stem cell transplantation for neurological diseases
- 2018
-
Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 89:2, s. 147-155
-
Forskningsöversikt (refereegranskat)abstract
- 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.
|
|
| 16. |
- Carlsson, G, et al.
(författare)
-
Hematopoietic stem cell transplantation in severe congenital neutropenia
- 2011
-
Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 56:3, s. 444-451
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Severe congenital neutropenia (SCN) is an immunodeficiency characterized by disturbed myelopoiesis and an absolute neutrophil count (ANC) <0.5 × 10(9)/L. SCN is also a premalignant condition; a significant proportion of patients develop myelodysplastic syndrome or leukemia (MDS/L). Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for SCN.PROCEDURE:Since 2004, eight HSCT have been performed in seven patients at our center. The indications were transformation to MDS/L (n = 2), granulocyte colony-stimulating factor receptor (CSF3R) mutation(s) (n = 2), granulocyte colony-stimulating factor (G-CSF) resistance (n = 2), and at the patient's own request (n = 1).RESULTS:The mean age at transplantation was 13 years (2.8-28 years) (mean follow-up 32 months, range 21-60). Three patients harbored ELANE mutations, three HAX1 mutations, and in one patient no causative mutation was identified. Two of the ELANE mutations were novel mutations. Three patients initially received myeloablative conditioning and four had reduced intensity conditioning (RIC). Three grafts were from HLA-identical siblings, three from matched unrelated donors and two were cord blood units. Engraftment occurred in all patients. Two of seven (29%) patients died; both had MDS/L and both were among the three that underwent myeloablative conditioning. One patient has chronic GVHD 2 years post-transplant.CONCLUSIONS:The role of HSCT should be explored further in patients with SCN. In particular, the influence of the conditioning regime needs to be evaluated in a larger cohort of patients.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
- Greco, Raffaella, et al.
(författare)
-
Autologous hematopoietic stem cell transplantation in neuromyelitis optica : A registry study of the EBMT Autoimmune Diseases Working Party
- 2015
-
Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 21:2, s. 189-197
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Neuromyelitis optica (NMO) is an inflammatory autoimmune disorder of the central nervous system, hallmarked by pathogenic anti-aquaporin 4 antibodies. NMO prognosis is worse compared with multiple sclerosis.OBJECTIVE:The European Group for Blood and Marrow Transplantation (EBMT) Autoimmune Diseases Working Party (ADWP) conducted a retrospective survey to analyze disease outcome following autologous stem cell transplantation (ASCT).METHODS:This retrospective multicenter study assessed the efficacy and safety of ASCT in 16 patients suffering from refractory NMO reported to the EBMT registry between 2001 and 2011.RESULTS:Fifteen patients were successfully mobilized with cyclophosphamide (Cy) and G-CSF, one with G-CSF alone. All patients received an unmanipulated autologous peripheral blood stem cell graft, after conditioning with BEAM plus anti-thymocyte globulin (ATG, n = 9 patients), thiotepa-Cy (n = 3) or Cy (200 mg/kg) plus ATG (n = 4). After a median follow-up of 47 months, three of 16 cases were progression and treatment free, while in the remaining 13 patients further treatments were administered for disability progression or relapse after ASCT. Altogether, relapse-free survival at three and five years was 31% and 10%, respectively, while progression-free survival remained 48% at three and five years.CONCLUSIONS:In these NMO patients, highly resistant to conventional treatment, ASCT allows for temporary control of the disease, despite a tendency to progress or relapse in the long term.
|
|
| 22. |
- Gubrianska, Danica, et al.
(författare)
-
Bone and hormonal status 10 years post-allogeneic bone marrow transplantation
- 2019
-
Ingår i: Clinical Transplantation. - : WILEY. - 0902-0063 .- 1399-0012. ; 33:12
-
Tidskriftsartikel (refereegranskat)abstract
- Bone loss and endocrine dysfunction are potential late complications of allogeneic stem cell transplant (allo-SCT); however, scant information concerning the long-term effects in SCT adult patients is available. In the present study, we evaluated bone status, expressed as bone mineral density (BMD), and endocrine functions including PTH, TSH, free T4, testosterone, SHBG, FSH, LH, and IGF-1, in 20 adult leukemia patients >10 years after allo-SCT. A low BMD (Z score <-2.0) was observed in two patients; two patients had osteoporotic fractures, and two had a unilateral avascular necrosis of the femoral head. Elevated PTH was observed in 30% of patients, and 25-hydroxy vitamin D (25(OH)D) was low (<50 nmol/L) in 45% of the patients. The majority of the patients had thyroid tests within the reference range, while elevated FSH values were present in 8 of 12 males. We conclude that adult leukemia patients have relatively well-preserved BMD >10 years post-allo-SCT. Prophylactic treatment of osteoporosis should be individualized, but control of BMD is necessary for long-term follow-up. Control of PTH and vitamin D levels before and after allo-SCT is recommended, and vitamin D supplementation should be considered if indicated. Estrogen replacement therapy is a routine treatment in females, whereas gonadal function in males requires further investigation.
|
|
| 23. |
|
|
| 24. |
- Gülen, T, et al.
(författare)
-
High prevalence of anaphylaxis in patients with systemic mastocytosis : a single-centre experience
- 2014
-
Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 44:1, s. 121-129
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Systemic mastocytosis (SM) is a clonal mast cells disorder characterized by the proliferation, accumulation and activation of mast cells in extracutaneous tissues. The clinical picture is heterogeneous and may range from asymptomatic to potentially fatal anaphylactic reactions due to excessive mast cell mediator release.OBJECTIVE: The aim of this study was to investigate the prevalence and trigger factors of anaphylactic reactions among adult SM patients. We also explored the clinical spectrum of mast cell mediator-related symptoms in patients with SM.METHODS: This descriptive study was performed among 84 consecutive adult (≥ 18 years) patients those were diagnosed with SM according to WHO criteria. Sixty-six of the patients also underwent a comprehensive allergy work-up.RESULTS: Sixty of 84 patients with SM (71%) had bone marrow mast cell aggregates and fulfilled the major criteria for SM and 76 patients (91%) had indolent disease. Simultaneous occurrence of cutaneous mastocytosis was observed in 59 patients (70%). Thirty-six patients (43%) had had at least one episode of an anaphylactic reaction. The clinical courses of the reactions were usually severe and patients often presented with syncope attacks (72%). Most patients reacted after hymenoptera venom stings (19/36; 53%). In 39% (14/36), a clear aetiology could not be determined. While males and females were equally frequent among the patients with SM, anaphylaxis patients showed a male predominance (61%). Anaphylactic reactions occurred more frequently in patients without cutaneous engagement. The rate of allergy sensitization was significantly higher in SM patients with anaphylaxis as compared with non-anaphylaxis SM patients, 70% vs. 23%, respectively (P = 0.0002).CONCLUSIONS AND CLINICAL RELEVANCE: Anaphylaxis is more prevalent in patients with SM, predominantly in patients with atopic SM. Hymenoptera venom-induced and idiopathic anaphylaxis were the most frequent elicitors. Our findings implicate that all mastocytosis patients with anaphylaxis should undergo detailed allergological assessment before considering treatment and preventive measures.
|
|
| 25. |
- Gülen, T, et al.
(författare)
-
Mastocytosis : the puzzling clinical spectrum and challenging diagnostic aspects of an enigmatic disease
- 2016
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 279:3, s. 211-228
-
Forskningsöversikt (refereegranskat)abstract
- Mastocytosis is a complex disorder characterized by the accumulation of abnormal mast cells (MC) in the skin, bone marrow and/or other visceral organs. The clinical manifestations result from MC-derived mediators and, less frequently, from destructive infiltration of MCs. Patients suffer from a variety of symptoms including pruritus, flushing and life-threatening anaphylaxis. Whilst mastocytosis is likely to be suspected in a patient with typical skin lesions [i.e. urticaria pigmentosa (UP)], the absence of cutaneous signs does not rule out the diagnosis of this disease. Mastocytosis should be suspected in cases of recurrent, unexplained or severe insect-induced anaphylaxis or symptoms of MC degranulation without true allergy. In rare cases, unexplained osteoporosis or unexplained haematological abnormalities can be underlying feature of mastocytosis, particularly when these conditions are associated with elevated baseline serum tryptase levels. The diagnosis is based on the World Health Organization criteria, in which the tryptase level, histopathological and immunophenotypic evaluation of MCs and molecular analysis are crucial. A somatic KIT mutation, the most common of which is D816V, is usually detectable in MCs and their progenitors. Once a diagnosis of systemic mastocytosis (SM) is made, it is mandatory to assess the burden of the disease, its activity, subtype and prognosis, and the appropriate therapy. Mastocytosis comprises seven different categories that range from indolent forms, such as cutaneous and indolent SM, to progressive forms, such as aggressive SM and MC leukaemia. Although prognosis is good in patients with indolent forms of the disease, patients with advanced categories have a poor prognosis.
|
|
| 26. |
- Gülen, T, et al.
(författare)
-
Systemic mastocytosis : progressive evolution of an occult disease into fatal mast cell leukemia
- 2012
-
Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 29:5, s. 3540-3546
-
Tidskriftsartikel (refereegranskat)abstract
- Systemic mastocytosis (SM) may be associated with a clonal hematopoietic non-mast cell-lineage disease (AHNMD). SM and AHNMD even may be clonally related. This report contributes to a better understanding of the different morphological aspects of SM by demonstrating that various AHNMDs can be detected in one patient during the course of disease. Routinely processed biopsy specimens of bone marrow and spleen removed from a 63-year-old man were investigated including a broad panel of immunohistochemical stainings. KIT codon 816 mutation analysis was carried out by melting point analysis of nested PCR products amplified from DNA of pooled microdissected mast cells. The histomorphological features of the initial bone marrow showed diffuse infiltration by hairy cell leukemia (HCL). Occult SM was only detected retrospectively by demonstration of a slight diffuse increase in loosely scattered, spindle-shaped mast cells carrying the activating point mutation KIT ( D816V ). In the second bone marrow, core biopsy removed about two years later HCL had been completely eradicated, while a diagnosis of SM-AHNMD with multifocal compact mast cell infiltrates associated with a myeloproliferative neoplasm (MPN) and significant increase in eosinophilic granulocytes was established. The third and last bone marrow biopsy specimen lacked the features of both MPN and HCL but showed progression into a secondary mast cell leukemia (MCL) with a focal sarcomatous component. To the best of the authors' knowledge, this is the first description of a case of SM-AHNMD with coexisting hematological neoplasms of lymphatic and myeloid origin initially presenting as occult disease and terminating as secondary MCL.
|
|
| 27. |
- Gülen, T, et al.
(författare)
-
The presence of mast cell clonality in patients with unexplained anaphylaxis
- 2014
-
Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 44:9, s. 1179-1187
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The mechanisms by which mast cells in patients with unexplained anaphylaxis (UEA) are triggered remain elusive. Onset of episodes is unpredictable and often recurrent. The substantial overlap between the clinical manifestations of UEA and clonal mast cell disorders (CMD) suggests an association between these rare disorders. The two forms of CMD characterized to date are systemic mastocytosis (SM) and monoclonal mast cell activation syndrome (MMAS).OBJECTIVE: To examine the hypothesis that the pathogenesis of UEA reflects the presence of aberrant subpopulations of mast cells.METHODS: Thirty (14 men, 16 women) patients (≥ 18 years) suffering from UEA and with no signs of cutaneous mastocytosis were recruited. Patients underwent an initial complete allergy work-up to confirm the diagnosis of UEA. Level of baseline serum tryptase (sBT) and total IgE were determined. In addition, a bone marrow examination was performed on all 30 patients to investigate possible underlying CMD.RESULTS: Fourteen (47%) of our cases (nine men, five women) were diagnosed with CMD: 10 with SM and four with MMAS. Four of the 10 patients with SM had mast cell aggregates in their bone marrow. All patients with SM exhibited a sBT level > 11.4 ng/mL, whereas this level was elevated in only two of those with MMAS and four with UAE but not diagnosed with CMD. Total IgE levels were lower in the group of patients with CMD (P < 0.03).CONCLUSION AND CLINICAL RELEVANCE: The pathogenic mechanism underlying UEA could be explained by the presence of immunophenotypically aberrant mast cells with clonal markers in 47% of our subjects, indicating that clonal mast cell disorders are present in a substantial subset of these patients. Thus, the presence of CMD should be considered in patients with UEA if they have an elevated level of sBT (≥ 11.4 ng/mL) and cardiovascular symptoms such as syncope.
|
|
| 28. |
- Gülen, Theo, et al.
(författare)
-
The significance of diagnosing associated clonal mast cell diseases in patients with venom-induced anaphylaxis and the role of bone marrow investigation
- 2013
-
Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 3:1, s. 22-
-
Tidskriftsartikel (refereegranskat)abstract
- Hymenoptera venom allergy (HVA) represents a particular risk for exceptionally severe anaphylactic sting reactions in patients with clonal mast cell disorders (CMD). Nevertheless, conventional investigations are not sufficient to do accurate risk assessments. Increased levels of baseline serum tryptase (sBT) (>11.4 μg/L) is highly associated with severe anaphylactic reactions and with a possible underlying CMD. The measurement of baseline serum tryptase, thus, has opened the possibility to screen for CMD. In the present study, we sought to investigate whether bone marrow evaluation provides more accurate diagnosis in patients with HVA.Three patients of the same sex and similar age with HVA were enrolled in this clinical study. The patients underwent comprehensive allergy work-up including skin prick testing, measurements of serum total IgE concentrations and baseline serum tryptase. Bone-marrow biopsies were also performed in all three patients to assess underlying CMD.We evaluated characteristics of the bone marrow mast cells by pathology, flow cytometry and detection of D816V mutation by using current WHO-criteria, which led to changes in the final diagnosis compared to the assessments done by classical allergy work-up and measurements of sBT. Three distinct diagnostic outcomes including systemic mastocytosis, monoclonal mast cell activation syndrome and non-clonal HVA were revealed.We conclude that a bone marrow investigation is required for the correct diagnosis of hymenoptera venom-induced anaphylactic reactions in patients with elevated baseline tryptase levels (>11.4 μg/L), and this has important implications for management strategies.
|
|
| 29. |
- Hallböök, Helene, et al.
(författare)
-
Autologous and allogeneic stem cell transplantation in adult ALL : The Swedish Adult ALL Group experience
- 2005
-
Ingår i: Bone Marrow Transplantation. - London : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 35:12, s. 1141-1148
-
Tidskriftsartikel (refereegranskat)abstract
- Adult patients with acute lymphoblastic leukaemia (ALL) have been treated according to national protocols in Sweden since 1986. Stem cell transplantation (SCT) has been recommended in first remission for patients with risk factors for relapse, and for standard risk patients only after relapse. In this retrospective study, the results of autologous and allogeneic SCT in these populations were evaluated. In total, 187 patients with a median age of 34 years (17-66 years) underwent SCT. The 5-year disease-free survival (DFS), for all patients, was 26% (Confidence intervals (CI) 20-32%). The 5-year DFS was higher for patients transplanted in first remission 32% (CI 24-40%) compared to 14% (CI 5-23%; P<0.0001) in patients transplanted beyond first remission. No significant differences in DFS (P=0.06) were determined between autologous, related donor and unrelated donor SCT in the whole cohort. A lower relapse rate was counterbalanced by higher treatment-related mortality in patients undergoing allogeneic SCT. In Philadelphia-positive ALL, allogeneic SCT was superior to autologous SCT, with a 5-year DFS of 30% (CI 12-47%) vs 0% (P=0.04). Limited chronic graft-versus-host-disease (GVHD) was associated with an improved DFS of 53% (CI 38-69%) compared to no chronic GVHD of 22% (CI 10-36%; P=0.0008), indicating a clinically important graft-versus-leukaemia effect.
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
- Harrysson, Lars, et al.
(författare)
-
Cancer, a relational disease exploring the needs of relatives to cancer patients
- 2019
-
Ingår i: International Journal of Qualitative Studies on Health and Well-being. - : Informa UK Limited. - 1748-2631 .- 1748-2623. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Syfte: I denna kvalitativa studie studerade vi erfarenheter bland familjemedlemmar till cancerpatienter. Vårt syfte var att undersöka och differentiera deras behov från de behov som cancer patienten uppvisar.Metod: Fem fokusintervjuer och sex individuella narrativa intervjuer med 17 familje medlemmar till cancerpatiener i Sverige genomfördes och jämförda med 19 intervjuer med cancerpatienter. Vår analys var inspirerad av klassisk grundad teori.Resaultat: Familjemedlemmar till cancerpatienter uppvisade egen sjukdom kopplad till höga stressnivåer och svårigheter att erkänna egen stress till följd av pågående jämförelser med cancerpatienten. Familjemedlemmar var fastlåsta i en momentan terrorlik situation där de blev den sjukes skyddsnät. En upplevd oförmåga till att förbättra den sjukes hälsa och välmående bidrog till känslor av skukld. Önskan om att allt skulle vara över var inbäddat i skam då slutet innebar möjlig död.Slutsatser: Genom att erkänna cancer som en sjukdom som påverkar både kropp och relationer kan familjemedlemmar ges kontroll över sina egna kamper skilda från patientens upplevelser. Vi definierar skillnaderi behov mellan cancer patienter och anhöriga. De anhöriga till cancerpatienter kan ges stöd i att utveckla balanserade strategier för mindre stress, ökad trygghet och stunder av förnöjsamhet.
|
|
| 33. |
- Hulegardh, E., et al.
(författare)
-
Outcome after HSCT in Philadelphia chromosome positive acute lymphoblastic leukemia in Sweden : a population-based study
- 2014
-
Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 31:8, s. 66-
-
Tidskriftsartikel (refereegranskat)abstract
- Even in the tyrosine kinase inhibitor era, allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as standard care for adult Philadelphia (Ph) positive acute lymphoblastic leukemia (ALL). In this retrospective national study, we have reviewed the outcome after HSCT in Sweden for adult Ph-positive ALL between 2000 and 2009. In total, 51 patients with median age 42 (range 20-66) years underwent HSCT. Mainly allogeneic HSCT was performed (24 related donor, 24 unrelated donor and one cord blood), and only two patients were treated with an autologous HSCT. The 5-year OS was 51 (37-64) %. The probabilities of morphological relapse and non-relapse mortality (NRM) at 5 years were 36 (23-49) and 18 (9-29) %, respectively. For the allogeneic transplanted, the 5-year OS was for patients <40 years 70 (50-90) % and for patients >= 40 years 34 (16-52) %, p = 0.002. The 5-year probability of NRM was for patients <40 years 10 (2-28) % compared to 25 (11-42) % for patients >= 40 years (p = 0.04). Patients with chronic graft-versus-host disease (GVHD) had a 5-year morphological relapse probability of 20 (6-40) % compared to 59 (35-77) % for patients without chronic GVHD (p = 0.03). Age >= 40 years and the absence of chronic GVHD were confirmed as independent negative prognostic factors for relapse and non-relapse mortality in a multivariate analysis although the impact of chronic GVHD was significant only in the older age cohort.
|
|
| 34. |
- Håkansson, Irene, et al.
(författare)
-
Successful autologous haematopoietic stem cell transplantation for refractory myasthenia gravis - a case report
- 2017
-
Ingår i: Neuromuscular Disorders. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0960-8966 .- 1873-2364. ; 27:1, s. 90-93
-
Tidskriftsartikel (refereegranskat)abstract
- 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. (c) 2016 Elsevier B.V. All rights reserved.
|
|
| 35. |
- Hägglund, Hans, et al.
(författare)
-
Analysis of V600E BRAF and D816V KIT mutations in systemic mastocytosis
- 2014
-
Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 31:8, s. 123-
-
Tidskriftsartikel (refereegranskat)abstract
- Most patients with systemic mastocytosis (SM) carry a D816 V KIT mutation causing a ligand-independent activation of the receptor. Down-stream of KIT is several components known to be mutated in different malignancies. RAF is among the most frequently mutated kinases, where BRAF V600E mutation occurs in most hairy cell leukemias (HCL) and half of malignant melanomas. We investigated BRAF mutations in 36 subjects with different forms of SM, but could not detect BRAF mutation in any of the cases, not even in the mast cell lineage of a patient with V600E BRAF-positive HCL. Thus, although BRAF is commonly mutated it appears not to be present in SM.
|
|
| 36. |
- Hägglund, Hans, et al.
(författare)
-
Graft-versus-Mastocytosis Effect After Donor Lymphocyte Infusion : Proof of Principle.
- 2021
-
Ingår i: European Journal of Haematology. - : John Wiley & Sons. - 0902-4441 .- 1600-0609. ; 106:2, s. 290-293
-
Tidskriftsartikel (refereegranskat)abstract
- Advanced systemic mastocytosis is a relatively rare entity where allogeneic stem cell transplantation can lead to cure of the disease in selected patients. Delayed incomplete responses with graft versus mastocytosis effect were published in a few cases. In this particular patient's report, we describe the direct evidence and potency of graft versus mastocytosis effect of donor lymphocyte infusions in a patient with systemic mastocytosis with associated hematological neoplasm (SM-AHN). In a 53-year-old female patient, an allogeneic stem cell transplantation after conventional induction treatment was performed for transformed acute myeloid leukemia (AML) during the course of polycythemia vera. After 6 years of remission period of AML and PV, the patient developed aleukemic mast cell leukemia and JAK2 positive myeloproliferative neoplasm (SM-AHN). We were able to achieve a sustained complete remission of SM-AHN lasting for 6 years with only donor lymphocyte infusions in a status of mixed chimerism. The patient is in a good clinical condition and remission. The potent graft versus mastocytosis effect in this patient resembles the favorable effect of donor lymphocyte infusions in relapsing chronic myeloid leukemia patients after transplantation. This patient is, to our knowledge, the first case showing the proof of principle of graft versus mastocytosis effect.
|
|
| 37. |
- Hägglund, Hans, et al.
(författare)
-
Increased risk of malignant melanoma in patients with systemic mastocytosis?
- 2014
-
Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 94:5, s. 583-584
-
Tidskriftsartikel (refereegranskat)abstract
- Mastocytosis, a group of rare disorders that occur in bothchildren and adults, is characterised by abnormal growthand pathological accumulation of mast cells in one or moreorgans, most commonly the skin (1). Urticaria pigmentosa(UP) is the most common cutaneous variant. In cases ofextracutaneous involvement, systemic mastocytosis (SM)can be diagnosed on the basis of the criteria formulatedby the WHO. The course of SM in most patients (90%) isindolent, with more aggressive presentation in only a few.The incidence of cutaneous melanoma is increasingand although this malignancy and mastocytosis originatefrom 2 different types of cells (melanocytes from theneural crest and mast cells from haematopoetic stem cells,respectively) they share certain similarities, includingexpression of the transcription factors MITF and STAT3,and dependence of the growth factor receptor KIT and itsligand stem cell factor for their growth and development(2, 3). We have found 5 published case reports that suggesta relationship between these 2 pathologies. In the first,published in 1979, a patient with nodular mastocytosis de-veloped both melanocytoma and mastocytoma (4). In thesecond, UP and SM preceded a metastatic melanoma (5)and the third involved combined mastocytoma-junctionalnaevus (6). In the fourth case, malignant melanoma wasdiagnosed prior to SM (7). And finally, a patient withtelangiectasia macularis eruptive perstans (TEMP), arare form of cutaneous mastocytosis, was found to havea malignant melanoma (8).Here, we describe our 4 additional cases and discusspossible associations between these 2 diseases.
|
|
| 38. |
- Hägglund, Hans
(författare)
-
Risk-factors, prevention and treatment of early complications after allogeneic haematopoietic stem cell transplantation
- 1998
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aims of this thesis were to define risk factors for early complications after allogeneic haematopoietic stem cell transplantation (HSCT), such as bacteraemia during the aplastic phase, veno-occlusive disease in the liver (VOD) and acute graft-versus-host disease (GVHD). Furthermore, we wanted to evaluate new methods - e.g., intraosseous infusion, peripheral blood progenitor cell transplantation (PBPCT) and granulocyte-colony stimulating factor (G CSF) post-transplant treatment for a shorter neutropenic period. And finally, we aimed to evaluate the effects and side-effects of recombinant tissue plasminogen activator (rt-PA) treatment and liver transplantation for VOD. In 500 consecutive patients who underwent allogeneic HSCT in Huddinge Hospital between November 1975 and June 1995, receiving HSC from an unrelated donor was found to be the only significant risk factor (p<0.01). In 251 patients grafted between January 1990 and June 1995, the following risk factors were associated with an increased risk of hepatic veno occlusive disease in multivariate logistic regression analysis: norethisterone treatment after transplantation (p<0.001), bilirubin level >26 µmo/l before transplantation (0.002), HLA mismatched donor (p=0.003), previous abdominal irradiation (0.02) and busulphan treatment (0.02). Heparin prophylaxis (100 IE/kg/24 hours), given from the start of the conditioning regimen until one month after BMT or discharge, did not influence the incidence or mortality rate of VOD. In 291 patients grafted with marrow from HLA-identical sibling donors between November 1975 and June 1993, the main risk factors for acute GVHD in logistic regression, multivariate analysis were: immunosuppression with monotherapy (CsA or MTX) (p=0.01), pretransplant multiple-positive donor herpes virus serology (p=0.01), early engraftment (p=0.02) and CMV seropositivity in the recipient before BMT (p=0.04). Thirty-eight patients receiving marrow transplants from related donors were randomized to i.o. + i.v. (n=10), i.o. (n=8) or i.v. (n=20) infusions of bone marrow. We found a significant reduction in the number of days on TPN (p=0.03) and a tendency to a reduction in the number of days on antibiotics, using the i.o. technique (p=0.06). However, intraosseous, compared to intravenous administration of bone marrow, did not accelerate haematological recovery. Twenty-three recipients of peripheral blood progenitor cells (PBPC) were matched with 23 recipients of bone marrow (BM). Eleven in each group were recipients of unrelated HSC. A higher number of MNC (p<0.001), CD34+ (p=0.05), CD3+ (p<0.001) and CD56+ (p<0.001) cells in the graft, a reduced number of platelet transfusions (p=0.03) and a significant hastening of neutrophil (ANC >05x109/l, 12 vs. 17 days after HSCT, p<0.001) and platelet recoveries (>30x109/l, 15 vs 20 days, p=0.02) were seen in the PBPC group, compared to the BM group. Sixty-nine patients were randomized to G-CSF (5 µglkg/day) treatment, starting on day 0 (n=23), day +5 (n=23) and day +10 (n=23), respectively, after unrelated HSCT. G-CSF treatment starting on day +10 was found to be as effective in improving neutrophil recovery as starting on day +5 or on the day of transplantation (day 0). Starting treatment on day +10, rather than on day 0, reduced the costs of G-CSF by $1060. The 69 patients given G-CSF reached ANC>O.sx109/l a median of 5 days earlier than a retrospective control group of 30 recipients of unrelated HSC not given G-CSF (p=0.004), and they were discharged a median of 8 days earlier from hospital (p=0.04). Treatment with rt-PA (n=8), rt-PA+OLT (n=2) and OLT (n=1) for severe VOD was evaluated in 11 recipients of allogeneic bone marrow. Our findings suggest that rt-PA should not be given in high doses and not over a long period, because of the risk of severe haemorrhages. In patients with irreversible VOD, OLT may be considered in selected patients.
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
- Hägglund, Ruaridh, et al.
(författare)
-
Uppföljning av kvalitetsförändringar i ängs- och betesmarker via NILS : tillstånds- och förändringsskattningar baserade på data insamlade 2006-2015
- 2017
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- ”Uppföljning av kvalitetsförändringar i ängs- och betesmark via NILS” (nedan kallat kvalitetsuppföljningen) är ett uppdrag till SLU från Jordbruksverket att årligen inventera ett urval av ängs- och betesmarker i syfte att kunna följa kvaliteter i ängs- och betesmarker. Urvalet utgörs av objekt som inventerades i ängs- och betesmarksinventeringen i början av 2000-talet och som finns registrerade i Jordbruksverkets TUVA-databas1 . Urvalet av objekt har gjorts inom ramen för NILS (Nationell inventering av landskapet i Sverige) systematiskt utlagda 5x5 km rutor. I norra Sverige finns färre ängs och betesmarker än i södra och urvalet i norra Sverige genomfördes därför inom 15x15 km-rutor centrerade runt NILS 5x5 km-rutor för att öka chanserna till att få med ängs och betesmarksobjekt.Kvalitetsuppföljningen består av en provyteinventering och en transektinventering av fjärilar och humlor. I kvalitetsuppföljningen ingår 696 ängs- och betesmarksobjekt fördelat på 402 NILS-rutor, för fler detaljer över design och datainsamling i kvalitetsuppföljningen, se Eriksson m.fl. (2011).Denna rapport redovisar tillstånd och förändringsskattningar för fjärilar och humlor såväl som för data insamlade på provytorna under perioden 2006-2015.
|
|
| 44. |
|
|
| 45. |
|
|
| 46. |
- Juliusson, Gunnar, et al.
(författare)
-
Hematopoietic Stem Cell Transplantation Rates and Long-Term Survival in Acute Myeloid and Lymphoblastic Leukemia Real-World Population-Based Data From the Swedish Acute Leukemia Registry 1997-2006
- 2011
-
Ingår i: Cancer. - Philadelphia : Wiley-Blackwell. - 0008-543X .- 1097-0142. ; 117:18, s. 4238-4246
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: 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. METHODS: We evaluated alloSCT rates within the Swedish Acute Leukemia Registry, including 3899 adult patients diagnosed from 1997 through 2006 with a coverage of 98% and a median follow-up of 6.2 years. RESULTS: AlloSCT rates and survival decreased rapidly with age andgt;55 years. The 8-year overall survival (OS) was 65% in patients andlt;30 years and 38% in patients andlt;60 years and was similar for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Among 1073 patients andlt;60 years, alloSCT was performed in 42% and 49% of patients with AML and ALL, respectively. Two-thirds of the alloSCTs were performed in first complete remission, and half used unrelated donors, the same in AML and ALL. Regional differences in management and outcome were found: 60% of AML patients andlt;40 years received alloSCT in all parts of Sweden, but two-thirds of AML patients 40-59 years had alloSCT in one region compared with one-third in other regions (Pandlt;.001), with improved 8-year OS among all AML patients in this age cohort (51% vs 30%; P = .005). CONCLUSIONS: More Swedish AML patients received alloSCT, and long-term survival was better than in recently published large international studies, despite our lack of selection bias. There was no correlation between alloSCT rate and survival in ALL. In adult AML patients andlt;60 years of age, a high alloSCT rate was associated with better long-term survival, but there was no such correlation in ALL.
|
|
| 47. |
|
|
| 48. |
|
|
| 49. |
- Kennedy, Vanessa E., et al.
(författare)
-
Mast cell leukemia : clinical and molecular features and survival outcomes of patients in the ECNM Registry
- 2023
-
Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 7:9, s. 1713-1724
-
Tidskriftsartikel (refereegranskat)abstract
- Mast cell leukemia (MCL) is a rare subtype of systemic mastocytosis defined by >= 20% mast cells (MC) on a bone marrow aspirate. We evaluated 92 patients with MCL from the European Competence Network on Mastocytosis registry. Thirty-one (34%) patients had a diagnosis of MCL with an associated hematologic neoplasm (MCL-AHN). Chronic MCL (lack of C-findings) comprised 14% of patients, and only 4.5% had "leukemic MCL" (>= 10% circulating MCs). KIT D816V was found in 62/85 (73%) evaluable patients; 9 (11%) individuals exhibited alternative KIT mutations, and no KIT variants were detected in 14 (17%) subjects. Ten evaluable patients (17%) had an abnormal karyotype and the poor-risk SRSF2, ASXL1, and RUNX1 (S/A/R) mutations were identified in 16/36 (44%) patients who underwent next-generation sequencing. Midostaurin was the most common therapy administered to 65% of patients and 45% as first-line therapy. The median overall survival (OS) was 1.6 years. In multivariate analysis (S/A/R mutations excluded owing to low event rates), a diagnosis of MCL-AHN (hazard ratio [HR], 4.7; 95% confidence interval [CI], 1.7-13.0; P = .001) and abnormal karyotype (HR, 5.6; 95% CI, 1.4-13.3; P = .02) were associated with inferior OS; KIT D816V positivity (HR, 0.33; 95% CI, 0.11-0.98; P = .04) and midostaurin treatment (HR, 0.32; 95% CI, 0.08-0.72; P = .008) were associated with superior OS. These data provide the most comprehensive snapshot of the clinicopathologic, molecular, and treatment landscape of MCL to date, and should help further inform subtyping and prognostication of MCL.
|
|
| 50. |
- Kluin-Nelemans, Hanneke C., et al.
(författare)
-
Cytogenetic and molecular aberrations and worse outcome for male patients in systemic mastocytosis
- 2021
-
Ingår i: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 11:1, s. 292-303
-
Tidskriftsartikel (refereegranskat)abstract
- In systemic mastocytosis (SM), the clinical features and survival vary greatly. Patient-related factors determining the outcome in SM are largely unknown. Methods: We examined the impact of sex on the clinical features, progression-free survival (PFS), and overall survival (OS) in 3403 patients with mastocytosis collected in the registry of the European Competence Network on Mastocytosis (ECNM). The impact of cytogenetic and molecular genetic aberrations on sex differences was analyzed in a subset of patients. Results: Of all patients enrolled, 55.3% were females. However, a male predominance was found in a subset of advanced SM (AdvSM) patients, namely SM with an associated hematologic neoplasm (SM-AHN, 70%; p < 0.001). Correspondingly, organomegaly (male: 23% vs. female: 13%, p = 0.007) was more, whereas skin involvement (male: 71% vs. female: 86%, p = 0.001) was less frequent in males. In all patients together, OS (p < 0.0001) was significantly inferior in males, and also within the WHO sub-categories indolent SM, aggressive SM (ASM) and SM-AHN. PFS was significantly (p = 0.0002) worse in males when all patients were grouped together; due to low numbers of events, this significance persisted only in the subcategory smoldering SM. Finally, prognostically relevant cytogenetic abnormalities (10% vs. 5%, p = 0.006) or molecular aberrations (SRSF2/ASXLI/RUNXI profile; 63% vs. 40%, p = 0.003) were more frequently present in males. Conclusions: Male sex has a major impact on clinical features, disease progression, and survival in mastocytosis. Male patients have an inferior survival, which seems related to the fact that they more frequently develop a multi-mutated AdvSM associated with a high-risk molecular background.
|
|
