UK Hodgkin's lymphoma incidence statistics

UK Hodgkin's lymphoma incidence statistics

This page contains Hodgkin's lymphoma incidence statistics by age and sex, subtype, trends over time and geographic variation.The ICD code for Hodgkin's lymphoma is ICD9 201, ICD10 C81.

Overall Hodgkin's lymphoma incidence

Hodgkin’s lymphoma accounts for about 0.5% of all cancers diagnosed in the UK, yet it is one of the most common cancers among older children and adolescents. Hodgkin's lymphoma is also one of the most curable forms of cancer.

This section deals with Hodgkin's lymphoma in adults. Hodgkin's lymphoma statistics for children are presented in the childhood cancer section.

Hodgkin's lymphoma is a type of cancer affecting the lymphatic system ( Figure 1.1).

Figure 1.1: The lymphatic system showing sites commonly affected by Hodgkin's lymphoma

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There are around 1,600 new cases of Hodgkin’s lymphoma diagnosed each year in the UK, accounting for only 1 in 200 cases of all cancers diagnosed. Table 1.11-4 shows the numbers and rates of new cases of Hodgkin's Lymphoma in the UK and its constituent countries.

Table 1.1: Number of new cases and rates of Hodgkin's lymphoma, UK

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Hodgkin's lymphoma incidence by age and sex

In the UK there are two peaks in the age-specific incidence of Hodgkin’s lymphoma, one in young people aged 20-25 and another in older adults aged 75-80 years. ( Figure 1.21-4). Incidence rates for Hodgkin’s lymphoma in UK males are higher than in females. Hodgkin’s lymphoma is the third most commonly diagnosed cancer in people aged 15-29 years, and the sixth most commonly diagnosed cancer in children under 15.

It has been estimated that the lifetime risk of developing Hodgkin's lymphoma is 1 in 448 for men and 1 in 596 for women in the UK. These were calculated in May 2009 using incidence and mortality data for 2001-2005. 10

Figure 1.2: Numbers of new cases and age-specific incidence rates by sex, Hodgkin's lymphoma, UK

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Subtypes of Hodgkin's lymphoma

There are several different pathologic types of Hodgkin’s lymphoma recognised. The commonest is Classical Hodgkin’s Lymphoma which is further sub-divided into nodular sclerosis, mixed cellularity, lymphocyte-rich, and lymphocyte-depleted types 5. Nodular sclerosing Hodgkin’s lymphoma accounts for nearly 60% of all newly diagnosed cases of the disease, and the mixed cellularity subtype accounts for around 15% of cases. Lymphocyte-rich constitute around 10% of cases and the lymphocyte-deplete type is uncommon. The other, much less common, type of Hodgkin’s lymphoma described in the WHO classification is nodular lymphocyte-predominant Hodgkin’s lymphoma which constitutes only 5% of all cases of the disease 6.

The incidence of Hodgkin’s lymphoma subtypes varies by age-group and socio-economic status 6. Mixed cellularity disease is more common, especially at younger ages, in poorer countries, while the incidence of nodular sclerosis is higher in more affluent populations. In the UK, incidence rates for nodular sclerosis peak in young adults. Female rates are higher in adolescence and young adulthood, this gender difference is reversed by age 30 after which male rates are higher ( Figure 1.37).

Figure 1.3: Incidence of Nodular Sclerosing and Mixed Cellularity subtypes of Hodgkin's lymphoma by age and sex, England, 1995-2001

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The age-specific incidence of the mixed cellularity subtype of Hodgkin’s lymphoma increases steeply up to age 20 and then remains at around 0.5-0.7 and 0.3-0.5 per 100,000 population in males and females respectively. The incidence increases with age but is consistently higher for men than for women ( Figure 1.37).

Hodgkin's lymphoma incidence trends

Since the mid-1970s age-standardised incidence rates for Hodgkin’s lymphoma in Britain have decreased, however, since the mid-1980s they have remained unchanged at around 3 per 100,000 males and 2 per 100,000 females Figure 1.4.

Chart showing the age standardised (European) incidence rates for Hodgkin's lymphoma, by sex, Great Britain

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One possible explanation for declining trends in the late 1970s-early 1980s is that some lymphomas previously registered as Hodgkin’s lymphoma are now classified as non-Hodgkin lymphoma5-8 for which there have been increasing trends over the last two decades (see non-Hodgkin lymphoma section). These trends are also reflected in the age-specific rates for Hodgkin’s lymphoma.

The UK Hodgkin's lymphoma incidence trend is shown in Figure 1.5.

Figure 1.5: Age standardised (European) incidence rates, Hodgkin's lymphoma, by sex, UK

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Geographic variation of Hodgkin's lymphoma incidence

There is wide international variation in the incidence of Hodgkin’s lymphoma, the variation is similar for males and females ( Figure 1.69). The highest rates are in Western Asia with rates in Yemen and Lebanon at >5.5 per 100,000, rates in the UK are around half these. In many parts of Asia, such as Bangladesh, Japan and China, incidence rates for Hodgkin’s lymphoma are <1 per 100,000 population.

Figure 1.6: Age-standardised incidence and mortality rates for Hodgkin's lymphoma in males, selected countries
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There are also variations in Hodgkin's Lymphoma incidence between the 25 countries of the European Union (EU) ( Figure 1.79). Within the EU the highest rates are in Austria and Greece and the lowest rates are in Spain and Slovakia. The reported incidence of Hodgkin’s lymphoma in the UK is one of the lowest in the EU and is significantly below the EU average.

Figure 1.7: Age standardised incidence rates, Hodgkin's lymphoma, by sex, EU

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Updated: 01/06/2009 0:00

UK Hodgkin's lymphoma mortality statistics

This page presents Hodgkin's lymphoma mortality statistics by age and sex, trends over time and geographic variation.

Hodgkin's lymphoma mortality by age and sex

In 2007 there were 311 deaths from Hodgkin’s lymphoma in the UK ( Table 2.11-3).

Number of deaths and mortality rates for Hodgkin's lymphoma in the UK

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The incidence peak of Hodgkin’s lymphoma observed in young adults in the UK is not reflected in the mortality rates. The patterns in age-specific mortality reflect the much better survival rates for Hodgkin’s lymphoma in young adults. The Hodgkin's lymphoma mortality rates rise with increasing age, most rapidly after age 55 years and peak in those aged over 80 years ( Figure2.11-3).

Numbers of deaths and age-specific mortality rates by sex for Hodgkin's lymphoma in the UK

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Hodgkin's lymphoma mortality trends

Since the early 1970s there have been large decreases in the death rates for Hodgkin’s lymphoma in the UK. From 1971-2007, The age-standardised mortality rate for Hodgkin’s lymphoma fell from 2.2 to 0.4 per 100,000 males, and from 1.1 to 0.4 per 100,000 females ( Figure 2.21-3).

Age-standardised (European) mortality rates for Hodgkin's lymphoma, by sex in the UK

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The biggest declines in Hodgkin's lymphoma mortality rates have been in young and middle aged adults, with the smallest falls in those over 70.

Geographic variation of Hodgkin's lymphoma mortality

Within the EU there is less variation in Hodgkin's lymphoma mortality than there is for incidence and the UK has significantly lower rates than the EU average ( Figure 2.34).

Figure 2.3: Age-standardised mortality rates for Hodgkin's lymphoma , by sex, EU countries, 2002 estimates

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Because in most developed countries Hodgkin’s lymphoma can be successfully treated, the international variation in incidence is not reflected in variation in mortality rates.

In less developed countries there is an average of one death for every two cases of Hodgkin's lymphoma, while in more developed countries there is an average of one death for every four cases.

In countries such as Yemen and Lebanon, where the Hodgkin's lymphoma incidence is high and the best treatment is not available to many people, mortality rates are high. Many countries with low incidence and poor survival have mortality rates similar to countries with higher incidence but better survival, for example the Hodgkin's lymphoma incidence rates in India are around a third of the UK rates but mortality rates are very similar ( Figure 2.44).

Figure 2.4 Age-standardised incidence and mortality rates for Hodgkin's lymphoma in males, selected countries, 2002 estimates

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Updated: 01/05/2009 0:00

Hodgkin's lymphoma survival statistics

This page presents Hodgkin's lymphoma survival statistics, including one and five year survival rates, and survival by age at diagnosis.

Hodgkin's lymphoma - one and five year survival rates

Trends in Hodgkin's lymphoma survival rates for patients diagnosed in England and Wales present an encouraging picture of improving prognosis for people with Hodgkin’s lymphoma ( Figure 3.11, 2) that is also reflected in survival rates from else wherein the UK 3.

The overall five-year age-standardised relative survival rate for patients diagnosed with Hodgkin's lymphoma in England between 1996-1999 was 80%. The data show that survival rates fall by around 8% between five and ten years after diagnosis 1.

Figure 3.1: Age-standardised relative survival by sex, for patients diagnosed with Hodgkin's lymphoma, England & Wales, 1971-75 to 1996-99

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Hodgkin's lymphoma survival rates by age at diagnosis

There are large differences in Hodgkin’s lymphoma survival rates by age, in patients aged 15-49 five-year relative survival rates were 87% in men and 92% in women, compared to 27% and 32% respectively in those over 70 ( Figure 3.22). Hodgkin's Lymphoma survival rates tend to be a little better in women than men.

Figure 3.2: Relative survival by sex and age group, for patients diagnosed with Hodgkin's lymphoma, England & Wales, 1996-1999

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Updated: 24/06/2005 0:00

Hodgkin's lymphoma risk factors

This page presents the risk factors for Hodgkin's lymphoma including genetics, infectious agents, the immune system,social and environmental factors and other factors.

The possible causes of Hodgkin’s lymphoma, and the predisposing factors are not understood well and the disease remains poorly characterised at a cellular and molecular level.

Genetics and risk of Hodgkin's lymphoma

Racial differences in the incidence of Hodgkin’s lymphoma have been documented in several countries, particularly in the USA, where the incidence is lower in blacks than in whites 1, 2. A 99-fold increased risk has been reported in the identical twins of people who have had Hodgkin’s lymphoma. 3 Studies also show up to a seven-fold increased risk in people with a parent or sibling diagnosed with Hodgkin's lymphoma or with any blood or lymphatic cancer. 22-24

Risks for nodular sclerosis Hodgkin’s lymphoma have been associated with certain HLA class II loci although the data are inconsistent 4.

Infectious agents and risk of Hodgkin's lymphoma

Early serological and subsequent molecular studies have demonstrated an association between Hodgkin’s lymphoma and infection with Epstein Barr Virus (EBV). The DNA of the virus can be found in 26% to 50% of cases that are positive for EBV, this being much more common in the paediatric and older adult patients, and lower in young adults ( Figure 4.113, 14).

Figure 4.1: Proportion of EBV-associated Hodgkin's lymphoma cases by age group

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Consistent with this observation, evidence of EBV is more often found with mixed cellularity than with nodular sclerosis Hodgkin’s lymphoma.

The risk is increased three-fold after a diagnosis of infectious mononucleosis (glandular fever). 17

The immune system and risk of Hodgkin's lymphoma

People with HIV infection or AIDS have an 11-fold increased risk of Hodgkin’s lymphoma 15. Other groups with reduced immunity, for example after organ transplantation, also show an excess risk 15.

Individuals with a diagnosis of certain autoimmune conditions, including rheumatoid arthritis, systemic lupus erythematosus and sarcoidosis, have an increased risk of Hodgkin's lymphoma. 18-21

Social and environmental factors and risk of Hodgkin's lymphoma

An increased risk of Hodgkin’s lymphoma is associated with indicators of affluence in childhood such as small family size, standard of maternal education and single family housing 7-11.

While it has been proposed that late exposure to a common infectious agent may be responsible for this association, no agent has been identified.

Other factors and risk of Hodgkin's lymphoma

People with a previous non-Hodgkin's lymphoma have a four to 16-fold increased risk of Hodgkin's lymphoma. 25-27

Case-control studies show that alcohol consumption protects against Hodgkin's lymphoma, but more evidence is needed before this can be considered an established risk factor. 28-30

Updated: 17/10/2008 0:00

Hodgkin's lymphoma symptoms and treatment

This page presents information on the symptoms and treatment of Hodgkin's lymphoma, including staging and prognostic factors and treatment, at early stage, and advanced stage.

Symptoms of Hodgkin's lymphoma

The most common presenting symptom for Hodgkin’s lymphoma is painless lymph node enlargement, most frequently involving nodes on the neck. More generalised lymph node enlargement is also common, but systemic spread to the liver, lungs, bone marrow and other organs is usually a late event.

Although localised disease usually occurs in lymph nodes above the diaphragm, isolated infradiaphragmatic disease may occur, and tends to be more common with the lymphocytepre dominant type.

Characteristic systemic symptoms, known as ‘B’symptoms, are unexplained fevers, drenching night sweats, and weight loss of >10% of total body weight. Presence of these symptoms is an adverse prognostic factor.

Other characteristic symptoms of Hodgkin's lymphoma, although less clearly associated with poor prognosis, are fatigue, generalised pruritus, and alcohol-induced pain in affected lymph nodes.

Staging and prognostic factors of Hodgkin's lymphoma

The lymphatic spread of Hodgkin’s lymphoma usually occurs in a step-wise fashion to contiguous lymph nodes. Anatomical staging, based on the Ann Arbor system ( Table 5.11), has largely determined treatment decisions. The suffix ‘B’ is added to the stage category for patients with systemic symptoms (i.e. fever, night sweats and weight loss), while patients without systemic symptoms are designated ‘A’.

Although stage and constitutional systems are still important factors, other prognostic factors have refined treatment decisions, which are now rarely based on anatomical stage only.

Table 5.1: Summary of Ann Arbor staging system

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For patients with early stage (I and IIA) Hodgkin's Lymphoma, prognostic groups are based on histological subtype, age, sex, number of sites of disease, the presence of bulky disease in the mediastinum and presence or absence of consititutional (B) symptoms. An example, as described by the EORTC, is shown in Table 5.22.

Table 5.2: Prognostic groups in early stage HD (EORTC)

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For patients with advanced stage (IIB-IVB) Hodgkin's Lymphoma, the International Prognostic Factors Project has been developed 3. This is summarised in Table 5.33 and Figure 5.13.

For patients with none of the adverse factors, five-year failure free survival (FFS) was 84%. The presence of each factor reduces the five-year FFS by about 8%. This model forms a basis for risk-stratified treatment of advanced stage Hodgkin’s lymphoma in clinical trials.

Table 5.3: Adverse prognostic factors in advanced HD according to the International Prognostic Factors Project

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Figure 5.1: Tumour control rates according to number of risk factors from the International Prognostic Factors Project on Advanced Hodgkin's lymphoma

Figure 5.1: Tumour control rates according to the number of risk factors from the International Prognostic Factors Project on Advanced Hodgkin's lymphoma

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Treatment of Hodgkin's lymphoma

Major advances in the understanding of the possible causes and treatment of Hodgkin’s lymphoma in recent years have led to large reductions in mortality. The outlook for the majority of patients with Hodgkin's Lymphoma is now very good.

In addition, the recognition of the long-term side-effects of the original chemotherapy and radiotherapy regimens used for Hodgkin’s lymphoma have resulted in the development of new approaches with a lower incidence of long-term effects such as infertility and the development of second malignancy. This represents a major advance in a disease for which many life-years can potentially be lost by premature death as a result of treatment toxicity.

The use of extended field radiotherapy and/or alkylating agent-based chemotherapy, e.g. MOPP (mustine, vincristine procarbazine, prednisone), has resulted in high long- term disease free - and overall - survival rates for patients with Hodgkin’s lymphoma 4, 5. However, it is now recognised that each of these treatments is associated with significant long-term toxicity - of major importance in a disease which mainly affects young adults 6, 7.

The use of radiotherapy, particularly to the mediastinum, produces an increased risk of second malignancies such as lung and breast cancer, pulmonary fibrosis, and coronary heart disease 8-11. The use of alkylating agent-based chemotherapy increases the risks of secondary leukaemia, non-Hodgkin lymphoma, infertility, and premature ovarian failure 12-15.

A major emphasis of recent trials in Hodgkin’s lymphoma has therefore been to reduce radiation fields, and to introduce alternative chemotherapy regimens containing fewer alkylating agents.

At present, Ann Arbor stage 16, is still a major determinant of therapy, although risk stratification according to the factors mentioned above is used increasingly in clinical trial design, and routine practice.

Treatment of early stage Hodgkin's lymphoma

Combined modality treatment with short duration chemotherapy followed by involved field radiotherapy is the approach taken for most patients.

Evidence from clinical trials shows that the use of brief duration combination chemotherapy such as ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), with limited (involved field) radiotherapy produces good long-term overall Hodgkin's Lymphoma survival rates of 70% and 90%, with less potential for long-term toxicity 17 than the previous approach using extended field radiotherapy alone 18.

The emphasis for current clinical trials is to determine whether therapy may be reduced further without compromising Hodgkin's lymphoma cure rates, perhaps using newer imaging techniques such as Positron-Emission Tomography (PET) scanning to determine responses at an early stage.

Treatment of advanced stage Hodgkin's lymphoma

Combination chemotherapy is the primary modality of treatment for advanced Hodgkin’s lymphoma.

Involved field irradiation is often used to treat residual masses at the completion of systemic treatment 16, although it does not seem useful for patients in whom complete remission is achieved. 17 ABVD is now recognised as the standard regimen for advanced Hodgkin’s lymphoma, producing five-year failure free survival rates of 65-80 %, depending on the selection of patients 21, 22.

Recent studies of the use of more dose intensive regimens such as BEACOPP 23, 24used in conjunction with involved field radiotherapy, have produced five-year overall Hodgkin's Lymphoma survival rates of up to 90%, albeit with a high risk of permanent infertility and some risk of secondary acute leukaemia 23. These regimens are now being compared with standard therapy in randomized clinical trials.

High dose chemotherapy with autologous stem cell transplantation is now widely used in patients with relapsed or refractory disease 25, 26.

In addition to the chemotherapy regimens described above, recent advances in the understanding of Hodgkin’s lymphoma at the cellular and molecular level have resulted in new antibody-based approaches being developed, including the use of immunotoxins. These are mostly directed at the CD30 antigen, expressed on RS cells 27, 28.

Clinical trials are in progress to test the efficacy of such antibodies against recurrent disease 29, 30.

Updated: 27/12/2007 0:00

References

UK Hodgkin's lymphoma incidence statistics

  1.  Office for National Statistics. Cancer Statistics registrations: Registrations of cancer diagnosed in 2004, England. Series MB1 no.37.2009.
  2.  Cancer Incidence, Mortality and Survival Data. Information and Statistics Division, NHS Scotland, 2009. ISD Online. 2009 Information and Statistics Division, NHS Scotland.
  3.  Welsh Cancer Intelligence and Surveillance Unit. Cancer Incidence in Wales. 2009
  4.   Northern Ireland Cancer Registry 2009. Cancer Incidence and Mortality
  5.  Adami, H.O., D. Hunter, and D. Trichopoulos, eds. Textbook of Cancer Epidemiology. 2002, Oxford University Press: New York.
  6.  Yung, L. and D. Linch, Hodgkin's lymphoma. The Lancet, 2003. 361(9361): p. 943-951.
  7.  Office for National Statistics, Cancer Statistics registrations: Registrations of cancer diagnosed in 2001, England. Series MB1 no.32, Table 7, 2004
  8.  Swerdlow, A.J., I. dos Santos Silva, and R. Doll, Cancer Incidence & Mortality in England & Wales: trends and risk factors. 2001: Oxford University Press.
  9.   GLOBOCAN 2002. Cancer Incidence, Mortality and Prevalence Worldwide (2002 estimates)
  10.  Statistical Information Team, Cancer Research UK, 2009

UK Hodgkin's lymphoma mortality statistics

  1.  Office for National Statistics, 2009  Mortality Statistics: Deaths registered in 2007
  2.  ISD Online, 2009  Cancer Incidence and Mortality data, 2007
  3.  Northern Ireland Statistics and Research Agency 2009  Northern Ireland Mortality data, 2007.
  4.  GLOBOCAN, 2002. Cancer Incidence, Mortality and Prevalence Worldwide (2002 estimates)

Hodgkin's lymphoma survival statistics

  1.  Coleman, M.P., et al. Cancer Survival Trends in England & Wales, 1971-1995 Deprivation & NHS Region. 1999:The Stationery Office.
  2.  Office for National Statistics. Cancer survival 23 less common sites 1991-1999 by age group.Accessed 2005 March
  3.  ISD Online Cancer Incidence, Mortality and Survival data. Information and Statistics Division, NHS Scotland, 2004.

Hodgkin's lymphoma risk factors

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  7.  Altieri, A., et al., Number of siblings and the risk of lymphoma, leukemia, and myeloma by histopathology. Cancer Epidemiol Biomarkers Prev, 2006. 15(7): p. 1281-6.
  8.  Petridou, E., et al., Incidence and characteristics of childhood Hodgkin's lymphoma in Greece: a nationwide study (Greece) Cancer Causes Control. 2006. 17(2): p. 209-15.
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  10.  Chang, E.T., et al., Childhood social environment and Hodgkin's lymphoma: new findings from a population-based case-control study Cancer Epidemiol Biomarkers Prev. 2004.13(8): p. 1361-70.
  11.  Chatenoud, L., et al., Number of siblings and risk of hodgkin's and other lymphoid neoplasms Cancer Epidemiol Biomarkers Prev. 2005. 14(2): p. 552.
  12.  Baris, D. and Zahm, S.H. Epidemiology of lymphomas. Curr Opin Oncol, 2000. 12(5): p. 383-94.
  13.  Jarrett, A.F., Armstrong A.A., Alexander E., Epidemiology of EBV and Hodgkin's lymphoma Annals of Oncology. 1996. p. S5-S10.
  14.  Baris, D. and Zahm, S.H., Epidemiology of lymphomas. Curr Opin Oncol, 2000. 12(5): p. 383-94.
  15.  Grulich, A.E., et al., Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet, 2007. 370(9581): p. 59-67.
  16.  Bierman, P.J., et al., Hodgkin's disease following solid organ transplantation. Ann Oncol, 1996. 7(3): p. 265-70.
  17.  Hjalgrim, H., et al., Risk of Hodgkin's disease and other cancers after infectious mononucleosis. J Natl Cancer Inst, 2000. 92(18): p. 1522-8.
  18.  Landgren, O., et al., Autoimmunity and susceptibility to Hodgkin lymphoma: a population-based case-control study in Scandinavia. J Natl Cancer Inst, 2006. 98(18): p. 1321-30.
  19.  Mellemkjaer, L., et al., Rheumatoid arthritis and cancer risk. Eur J Cancer, 1996. 32A(10): p. 1753-7.
  20.  Thomas, E., et al., Risk of malignancy among patients with rheumatic conditions. Int J Cancer, 2000. 88(3): p. 497-502.
  21.  Hakulinen, T., et al., Rheumatoid arthritis and cancer studies based on linking nationwide registries in Finland. Am J Med, 1985. 78(1A): p. 29-32.
  22.  Goldin, L.R., et al., Familial aggregation of Hodgkin lymphoma and related tumors. Cancer, 2004. 100(9): p. 1902-8.
  23.  Hemminki, K., and Czene, K., Attributable risks of familial cancer from the Family-Cancer Database. Cancer Epidemiol Biomarkers Prev, 2002. 11(12): p. 1638-44.
  24.  Chang, E.T., et al., Family history of hematopoietic malignancy and risk of lymphoma. J Natl Cancer Inst, 2005. 97(19): p. 1466-74.
  25.  Travis, L.B., et al., Second cancers among long-term survivors of non-Hodgkin's lymphoma. J Natl Cancer Inst, 1993. 85(23): p. 1932-7.
  26.  Travis, L.B., et al., Second cancers following non-Hodgkin's lymphoma. Cancer, 1991. 67(7): p. 2002-9.
  27.  Dong, C., and Hemminki, K., Second primary neoplasms among 53 159 haematolymphoproliferative malignancy patients in Sweden, 1958-1996: a search for common mechanisms. Br J Cancer, 2001. 85(7): p. 997-1005.
  28.  Besson, H., et al., Tobacco smoking, alcohol drinking and Hodgkin's lymphoma: a European multi-centre case-control study (EPILYMPH). Br J Cancer, 2006. 95(3): p. 378-84.
  29.  Nieters, A., et al., Tobacco and alcohol consumption and risk of lymphoma: results of a population-based case-control study in Germany. Int J Cancer, 2006. 118(2): p. 422-30.
  30.  Gorini, G.S.E., et al., Alcohol consumption and risk of Hodgkin's lymphoma and multiple myeloma: a multicentre case-control study. Ann Oncol, 2007. 18(1): p. 143-8.

Hodgkin's lymphoma symptoms and treatment

  1.  Smithers, D.W., . Summary of papers delivered at the Conference on Staging in Hodgkin's Disease (Ann Arbor). Cancer Res, 1971. 31(11): p. 1869-70
  2.  Carde, P., et al., . Clinical staging versus laparotomy and combined modality with MOPP versus ABVD in early-stage Hodgkin's disease: the H6 twin randomized trials from the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group. J Clin Oncol, 1993. 11(11): p. 2258-72
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  7.  Goodrick, M.J., et al., Haematological toxicity compromises MOPP/ABVD chemotherapy in Hodgkin's disease. Clin Oncol (R Coll Radiol), 1991. 3(3): p. 151-4.
  8.  Travis, L.B., et al., Lung cancer following chemotherapy and radiotherapy for Hodgkin's disease. J Natl Cancer Inst, 2002. 94(3): p. 182-92.
  9.  Travis, L.B., et al., Breast cancer following radiotherapy and chemotherapy among young women with Hodgkin disease. Jama, 2003. 290(4): p. 465-75.
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  12.  Delwail, V., et al., Fifteen-year secondary leukaemia risk observed in 761 patients with Hodgkin's disease prospectively treated by MOPP or ABVD chemotherapy plus high-dose irradiation. Br J Haematol, 2002. 118(1): p. 189-94.
  13.  Ng, A.K., et al., Factors influencing treatment recommendations in early-stage Hodgkin's disease: a survey of physicians. Ann Oncol, 2004. 15(2): p. 261-9.
  14.  Franchi-Rezgui, P., et al., Fertility in young women after chemotherapy with alkylating agents for Hodgkin and non-Hodgkin lymphomas. Hematol J, 2003. 4(2): p. 116-20.
  15.  Thorneloe, W.F., Cytotoxic-induced ovarian failure in Hodgkin's disease. Jama, 1980. 244(5): p. 435.
  16.  Smithers, D.W., Summary of papers delivered at the Conference on Staging in Hodgkin's Disease (Ann Arbor). Cancer Res, 1971. 31(11): p. 1869-70.
  17.  Carde, P., et al., Clinical staging versus laparotomy and combined modality with MOPP versus ABVD in early-stage Hodgkin's disease: the H6 twin randomized trials from the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Group. J Clin Oncol, 1993. 11(11): p. 2258-72.
  18.  Engert, A., Schiller, P., Josting, A., Involved-field radiotherapy is equally effective and less toxic compared with extended-field radiotherapy after four cycles of chemotherapy in patients with early-stage unfavorable Hodgkin's lymphoma: results of the HD8 trial of the German Hodgkin's Lymphoma Study Group. in J Clin Oncol. 2003. p. 3601-08.
  19.  Loeffler, M., et al., Meta-analysis of chemotherapy versus combined modality treatment trials in Hodgkin's disease. International Database on Hodgkin's Disease Overview Study Group. J Clin Oncol, 1998. 16(3): p. 818-29.
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