Hemophagocytic lymphohistiocytosis and associations with malignancies
In immune homeostasis, natural killer cells and cytotoxic T cells are responsible for clearance of virus-infected and tumor transformed cells, but also for turning off the immune response. Patients with familial hemophagocytic lymphohistiocytosis (HLH) have impaired cytotoxic function due to genetic...
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Inst för kvinnors och barns hälsa / Dept of Women's and Children's Health
2023
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ftkarolinskainst:oai:openarchive.ki.se:10616/48619 2024-02-04T10:03:19+01:00 Hemophagocytic lymphohistiocytosis and associations with malignancies Haara Löfstedt, Alexandra 2023-05-10 application/pdf http://hdl.handle.net/10616/48619 eng eng Inst för kvinnors och barns hälsa / Dept of Women's and Children's Health I. Cancer risk in relatives of patients with a primary disorder of lymphocyte cytotoxicity: a retrospective cohort study. Löfstedt A, Chiang SCC, Onelöv E, Bryceson YT, Meeths M, Henter J-I. Lancet Haematol. 2015;2:e536–42. ::doi::10.1016/S2352-3026(15)00223-9 ::pmid::26686408 ::isi::000366033900012 II. Haploinsufficiency of UNC13D increases the risk of lymphoma. Löfstedt A, Ahlm C, Tesi B, Bergdahl IA, Nordenskjöld M, Bryceson YT, Henter J-I, Meeths M. Cancer. 2019;125:1848-1854. ::doi::10.1002/cncr.32011 ::pmid::30758854 ::isi::000467473000015 III. Malignancy-associated hemophagocytic lymphohistiocytosis in Sweden: Incidence, characteristics and survival. Löfstedt A, Jädersten M, Meeths M, Henter J-I. [Submitted] 978-91-8017-039-0 http://hdl.handle.net/10616/48619 info:eu-repo/semantics/openAccess info:eu-repo/semantics/doctoralThesis dok 2023 ftkarolinskainst 2024-01-10T23:37:08Z In immune homeostasis, natural killer cells and cytotoxic T cells are responsible for clearance of virus-infected and tumor transformed cells, but also for turning off the immune response. Patients with familial hemophagocytic lymphohistiocytosis (HLH) have impaired cytotoxic function due to genetic aberrations in genes in the perforindependent cytotoxic pathway. This results in an inability to turn off the immune response and, typically, a fatal hyperinflammation, often with onset already during the first months of life. The only curative treatment is hematopoietic stem cell transplantation. Patients with hypomorphic, ‘milder’, mutations in HLH-causing genes often have later onset of disease. Notably, an increased risk of hematological malignancies has been reported in these patients. The hyperinflammation of HLH can also occur in individuals without known Mendelian genetic predisposition. In these cases, often occurring later in life, it is termed ‘secondary HLH’ and it is most often triggered by an infection or a malignancy. In paper I we established the incidence of malignancies in relatives to patients with familial HLH by combining two incidence studies of familial HLH in Sweden with the Swedish multigeneration register and the Swedish national cancer register. We report an almost three-fold increased incidence rate of all cancers in mothers of patients with HLH compared to matched controls (4.4 vs 1.6, p=0.0014). In paper II we investigated individuals diagnosed with lymphoma in a defined population in northern Sweden. We found a higher prevalence of the most common HLH-causing aberration in Sweden, an inversion of UNC13D, in patients with lymphoma (3.1% vs 1%, p=0.002). In paper III, we investigated the incidence of secondary HLH in patients with malignancies. All patients with an ICD-10 diagnosis of HLH and cancer between 1997 and 2018 were identified from the Swedish inpatient register and the Swedish cancer register. During the 22 years studied, the incidence increased 10-fold, and at least 0.6% of ... Doctoral or Postdoctoral Thesis Northern Sweden Karolinska Institutet: Publications |
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Open Polar |
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Karolinska Institutet: Publications |
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ftkarolinskainst |
language |
English |
description |
In immune homeostasis, natural killer cells and cytotoxic T cells are responsible for clearance of virus-infected and tumor transformed cells, but also for turning off the immune response. Patients with familial hemophagocytic lymphohistiocytosis (HLH) have impaired cytotoxic function due to genetic aberrations in genes in the perforindependent cytotoxic pathway. This results in an inability to turn off the immune response and, typically, a fatal hyperinflammation, often with onset already during the first months of life. The only curative treatment is hematopoietic stem cell transplantation. Patients with hypomorphic, ‘milder’, mutations in HLH-causing genes often have later onset of disease. Notably, an increased risk of hematological malignancies has been reported in these patients. The hyperinflammation of HLH can also occur in individuals without known Mendelian genetic predisposition. In these cases, often occurring later in life, it is termed ‘secondary HLH’ and it is most often triggered by an infection or a malignancy. In paper I we established the incidence of malignancies in relatives to patients with familial HLH by combining two incidence studies of familial HLH in Sweden with the Swedish multigeneration register and the Swedish national cancer register. We report an almost three-fold increased incidence rate of all cancers in mothers of patients with HLH compared to matched controls (4.4 vs 1.6, p=0.0014). In paper II we investigated individuals diagnosed with lymphoma in a defined population in northern Sweden. We found a higher prevalence of the most common HLH-causing aberration in Sweden, an inversion of UNC13D, in patients with lymphoma (3.1% vs 1%, p=0.002). In paper III, we investigated the incidence of secondary HLH in patients with malignancies. All patients with an ICD-10 diagnosis of HLH and cancer between 1997 and 2018 were identified from the Swedish inpatient register and the Swedish cancer register. During the 22 years studied, the incidence increased 10-fold, and at least 0.6% of ... |
format |
Doctoral or Postdoctoral Thesis |
author |
Haara Löfstedt, Alexandra |
spellingShingle |
Haara Löfstedt, Alexandra Hemophagocytic lymphohistiocytosis and associations with malignancies |
author_facet |
Haara Löfstedt, Alexandra |
author_sort |
Haara Löfstedt, Alexandra |
title |
Hemophagocytic lymphohistiocytosis and associations with malignancies |
title_short |
Hemophagocytic lymphohistiocytosis and associations with malignancies |
title_full |
Hemophagocytic lymphohistiocytosis and associations with malignancies |
title_fullStr |
Hemophagocytic lymphohistiocytosis and associations with malignancies |
title_full_unstemmed |
Hemophagocytic lymphohistiocytosis and associations with malignancies |
title_sort |
hemophagocytic lymphohistiocytosis and associations with malignancies |
publisher |
Inst för kvinnors och barns hälsa / Dept of Women's and Children's Health |
publishDate |
2023 |
url |
http://hdl.handle.net/10616/48619 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
I. Cancer risk in relatives of patients with a primary disorder of lymphocyte cytotoxicity: a retrospective cohort study. Löfstedt A, Chiang SCC, Onelöv E, Bryceson YT, Meeths M, Henter J-I. Lancet Haematol. 2015;2:e536–42. ::doi::10.1016/S2352-3026(15)00223-9 ::pmid::26686408 ::isi::000366033900012 II. Haploinsufficiency of UNC13D increases the risk of lymphoma. Löfstedt A, Ahlm C, Tesi B, Bergdahl IA, Nordenskjöld M, Bryceson YT, Henter J-I, Meeths M. Cancer. 2019;125:1848-1854. ::doi::10.1002/cncr.32011 ::pmid::30758854 ::isi::000467473000015 III. Malignancy-associated hemophagocytic lymphohistiocytosis in Sweden: Incidence, characteristics and survival. Löfstedt A, Jädersten M, Meeths M, Henter J-I. [Submitted] 978-91-8017-039-0 http://hdl.handle.net/10616/48619 |
op_rights |
info:eu-repo/semantics/openAccess |
_version_ |
1789970629970100224 |