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Hodgkin Lymphoma in children, adolescents and young adults
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Barnonkologi)
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Hodgkin lymphoma (HL) is a heterogeneous condition varying from engaging one single lymph node site to a widespread condition. The prognosis with contemporary treatment is excellent for the vast majority. However, the treatment might cause severe late adverse effects in a proportion of the affected individuals.

We evaluated all children and adolescents diagnosed in Sweden and registered in the Swedish Childhood Cancer Register over a period of 25 years. The incidence has been stable and the overall survival (OS) is very good, comparable to the best results in the world. Approximately ten percent encountered a relapse, but even after relapse the chances of survival were good. During the study period there were no detectable changes in survival estimates. The use of radiotherapy has decreased.

Epstein Barr virus (EBV) and numbers of eosinophils, mast cells and macrophages in the tumors were investigated in 98 cases. Young children were more likely to express EBV. In patients with advanced disease the mast cell and macrophage counts were higher and they also had more affected laboratory parameters. Patients with Nodular Lymphocyte Predominant Hodgkin Lymphoma did not express EBV in the tumor, had significantly lower numbers of eosinophils, mast cells and macrophages and less affected laboratory parameters compared to classical HL.

Outcome and clinical presentation were investigated in a cohort of children, adolescents and young adults in Sweden and Denmark and treatment in pediatric and adult departments was compared. OS and event-free survival (EFS) did not differ between the three age groups nor between pediatric and adult treatment. However, the Danish pediatric patients had lower EFS, which corresponded to less use of radiotherapy. Adolescents and young adults shared similar characteristics, while children presented differently with less advanced disease and male preponderance.

Hospitalization rates and outpatient visits after end of treatment were evaluated to see whether the excess need of resources described in the literature is evenly distributed among the survivors or whether it is limited to a smaller group. Most of the patients had a low burden of health care use and the relapsing patients were the main drivers of the excess need.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. , p. 67
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1314
Keywords [en]
Hodgkin, pediatric, adolescent, young adults, microenvironment, eosinophils, mast cells, macrophages, Sweden, late adverse effects
National Category
Cancer and Oncology
Research subject
Pediatrics; Medical Science; Oncology
Identifiers
URN: urn:nbn:se:uu:diva-316796ISBN: 978-91-554-9851-1 (print)OAI: oai:DiVA.org:uu-316796DiVA, id: diva2:1080930
Public defence
2017-05-05, Rosénsalen, Ingång 95/96, Akademiska sjukhuset, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2017-04-12 Created: 2017-03-12 Last updated: 2017-04-21
List of papers
1. Hodgkin lymphoma - a survey of children and adolescents treated in Sweden 1985-2009.
Open this publication in new window or tab >>Hodgkin lymphoma - a survey of children and adolescents treated in Sweden 1985-2009.
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2015 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, no 1, p. 41-8Article in journal (Refereed) Published
Abstract [en]

Abstract Background. Hodgkin lymphoma (HL) in children constitutes approximately 30% of all pediatric lymphomas in Sweden. The chance of cure is high, but the frequency of late effects has been considerable. Over recent years, efforts have been made to reduce treatment with maintained survival. Material and methods. All patients 0-17 years, identified in the Swedish Childhood Cancer Register as diagnosed between 1985 and 2009, were included. The material was analyzed using descriptive statistics and for survival estimates the Kaplan-Meier method was used. Results. Three hundred and thirty-four patients were identified during this time period. The median age was 14 years. Male sex was over-represented, especially in lower age groups and in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). In nodular sclerosis and in age group 15-17 years, female sex dominated. Most of the cases presented in stages I or II. B-symptoms were present in 38% of cHL, but only in 7% of NLPHL. The number of patients receiving radiotherapy has been significantly reduced during the period studied. The relapse rate in cHL was 10 ± 2% and in NLPHL 16 ± 7%. The relapse rate was significantly higher in cHL stage IIB compared to other stages in the same therapy group. In cHL 6% died, and in NLPHL 0%. The 5-, 10- and 20-year overall survival estimates in cHL were 96 ± 1%, 95 ± 1% and 90 ± 3%, respectively, with no significant difference when comparing different treatment regimens and time periods. The 5- and 10-year overall survival after relapse in cHL was 81 ± 8% and 75 ± 10%, respectively. Conclusion. During the period studied there is no indication of a decline in survival despite changes in treatment. Survival rates in Sweden are high, and even after relapse chances of cure are high. We were not able to identify any characteristics specific for the group of patients that did not survive.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-240256 (URN)10.3109/0284186X.2014.948058 (DOI)000346571700006 ()25203597 (PubMedID)
Available from: 2015-01-06 Created: 2015-01-06 Last updated: 2017-12-05Bibliographically approved
2. The role of tumour-infiltrating eosinophils, mast cells and macrophages in Classical and Nodular Lymphocyte Predominant Hodgkin Lymphoma in children
Open this publication in new window or tab >>The role of tumour-infiltrating eosinophils, mast cells and macrophages in Classical and Nodular Lymphocyte Predominant Hodgkin Lymphoma in children
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2016 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 97, no 5, p. 430-438Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: To study Hodgkin lymphoma (HL) microenvironment in a Swedish paediatric population and its relation to clinical parameters.

METHODS: Tumour tissue from classical HL (cHL) (n=87) and nodular lymphocyte predominant HL (NLPHL) (n=11) was investigated for Epstein-Barr Virus (EBV) and analysed for eosinophils, mast cells and macrophages.

RESULTS: In cHL, EBV positivity was more common in low age (p<0.001) and in mixed cellularity (MC) (p<0.001). Higher mast cell infiltration was seen in stage III-IV (p<0.001), and with presence of B-symptoms (p=0.01). Cases with high mast cell counts displayed higher erythrocyte sedimentation rate (ESR), lower haemoglobin and albumin levels. Higher macrophage infiltration was seen in stage III-IV (p=0.02) and there was elevated ESR and neutrophil count. All NLPHL cases were EBV negative, had lower rates of inflammatory cells and lower degree of inflammatory reaction in laboratory parameters. There was no difference in survival estimates with regard to infiltration of inflammatory cells.

CONCLUSIONS: Higher levels of mast cells and macrophages in cHL tumours reflected the clinical presentation in laboratory parameters, B-symptoms and more advanced stages. NLPHL differs from cHL in numbers of inflammatory cells in the tumour, and in laboratory parameters. This article is protected by copyright. All rights reserved.

Keywords
paediatric, Hodgkin, Microenvironment, mast cells, eosinophils, macrophages
National Category
Clinical Laboratory Medicine Basic Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-278917 (URN)10.1111/ejh.12747 (DOI)000388630800003 ()26872637 (PubMedID)
Funder
Swedish Childhood Cancer Foundation
Note

Both last authors contributed equally.

Available from: 2016-02-26 Created: 2016-02-26 Last updated: 2018-01-10Bibliographically approved
3. Hodgkin Lymphoma in children adolescents and young adults-a comparative study of clinical presentation and treatment outcome
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(English)Article in journal (Other academic) Submitted
Keywords
Hodgkin, pediatric, adolescent, radiotherapy, treatment
National Category
Cancer and Oncology
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-316792 (URN)
Available from: 2017-03-07 Created: 2017-03-07 Last updated: 2017-03-12
4. Late adverse effects in children, adolescents and young adults in relapsing and non-relapsing patients with Hodgkin lymphoma
Open this publication in new window or tab >>Late adverse effects in children, adolescents and young adults in relapsing and non-relapsing patients with Hodgkin lymphoma
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(English)Manuscript (preprint) (Other academic)
Keywords
Late effects, children, adolescents, young adults, hospitalisation, Hodgkin
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-316794 (URN)
Available from: 2017-03-07 Created: 2017-03-07 Last updated: 2017-03-13

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