- Author: Bradley W Lash, MD; Chief Editor: Emmanuel C Besa, MD more...
Hodgkin lymphoma is a potentially curable lymphoma. The World Health Organization classifies Hodgkin lymphoma into five gty: nodular sclerosing, mixed cellularity (see the image below), lymphocyte depleted, lymphocyte rich, and nodular lymphocyte-predominant.
Signs and symptoms
Features of Hodgkin lymphoma include the following:
Unexplained weight loss, unexplained fever, night sweats
Chest pain, cough, shortness of breath
Pain at sites of nodal disease
Back or bone pain
Nodular sclerosis Hodgkin lymphoma (NSHL) has a strong genetic component and has often previously been diagnosed in the family
Palpable, painless lymphadenopathy in the cervical area, axilla, or inguinal area
Involvement of the Waldeyer ring (back of the throat, including the tonsils) or occipital (lower rear of the head) or epitrochlear (inside the upper arm near the elbow) area
Splenomegaly and/or hepatomegaly
Superior vena cava syndrome may develop in patients with massive mediastinal lymphadenopathy
Central nervous system symptoms or signs may be due to paraneoplastic syndromes, including cerebellar degeneration, neuropathy, Guillain-Barre syndrome or multifocal leukoencephalopathy
See Clinical Presentation for more detail.
Laboratory tests include the following:
Complete blood cell count studies for anemia, lymphopenia, neutrophilia, or eosinophilia
Erythrocyte sedimentation rate
A test for HIV is important because antiviral therapies can improve disease outcomes in HIV-positive patients  ; screening for hepatitis B and C should also be considered
Serum levels of cytokines (interleukin [IL]-6, IL-10) and soluble CD25 (IL-2 receptor) correlate with tumor burden, systemic symptoms, and prognosis
Imaging studies include the following:
Plain radiographs: Measurement of mediastinal mass in relationship to thoracic diameter on posteroanterior and lateral chest radiographs remains the gold standard
Computed tomography: Chest radiography has been largely replaced by CT scanning; on CT scans of the chest, abdomen, and pelvis, possible abnormal findings include enlarged lymph nodes, hepatomegaly and/or splenomegaly, lung nodules or infiltrates, and pleural effusions
Positron emission tomography: Considered essential to the initial staging of Hodgkin lymphoma
A histologic diagnosis of Hodgkin lymphoma is always required. An excisional lymph node biopsy is recommended because the lymph node architecture is important for histologic classification.
When a patient presents with neck lymphadenopathy and risk factors for a head and neck cancer, a fine-needle aspiration is usually advised as the initial diagnostic step, followed by excisional biopsy if squamous cell histology is excluded.
Bone marrow biopsies are indicated in some cases. Bone marrow involvement is more common in elderly patients and those with advanced-stage disease, systemic symptoms, or a high-risk histology.
Central nervous system evaluation by lumbar puncture and magnetic resonance imaging should be performed if symptoms or signs of CNS involvement are present.
The Ann Arbor classification is used most often for Hodgkin lymphoma, as follows:
Stage I: A single lymph node area or single extranodal site
Stage II: 2 or more lymph node areas on the same side of the diaphragm
Stage III: Lymph node areas on both sides of the diaphragm
Stage IV: Disseminated or multiple involvement of the extranodal organs
See also the Medscape Reference article Hodgkin Lymphoma Staging.
See Workup for more detail.
General treatment principles include the following:
Hematopoietic stem cell transplantation
See also the Medscape article Hodgkin Lymphoma Treatment Protocols.
Published guidelines from the National Comprehensive Cancer Network (NCCN), the European Society for Medical Oncology (ESMO), and the International Harmonization Project provide consensus opinions from leading experts on evidence-based approaches to the diagnosis and treatment of Hodgkin lymphoma. See Hodgkin Lymphoma Guidelines.
The radiation fields used in the treatment of Hodgkin lymphoma are generally defined as follows:
Involved-field radiation (IFRT): Radiation field that encompasses all of the clinically involved regions (eg, the mediastinum and the low-supraclavicular fields)
Involved-site radiation (ISRT): Radiation field that includes pre- and post-chemotherapy nodal volumes plus a 1.5-cm margin of healthy tissue; ISRT is largely replacing IFRT
Involved-node radiation (INRT): Radiation field that includes pre- and post-chemotherapy nodal volumes plus a 1-cm margin of healthy tissue
The following induction regimens are given as initial treatment for Hodgkin lymphoma:
MOPP (mechlorethamine, vincristine, procarbazine, prednisone)
ABVD (Adriamycin [doxorubicin], bleomycin, vinblastine, dacarbazine)
Stanford V (doxorubicin, vinblastine, mustard, bleomycin, vincristine, etoposide, prednisone)
BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone)
When induction chemotherapy fails, or patients experience relapse, salvage chemotherapy is generally given. Salvage regimens incorporate drugs that are complementary to those that failed during induction therapy. Commonly used salvage regimens include the following:
ICE (ifosfamide, carboplatin, etoposide)
DHAP (cisplatin, cytarabine, prednisone)
ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin)
High-dose chemotherapy at doses that ablate the bone marrow is feasible with reinfusion of the patient's previously collected hematopoietic stem cells or infusion of stem cells from a donor source. Historically, hematopoietic stem cells have been obtained from bone marrow, but they are now typically obtained by pheresis of peripheral blood lymphocytes. A validated and relatively safe conditioning regimen for autologous transplantation is the BEAM regimen (carmustine [BCNU], etoposide, cytarabine, melphalan).
Toxicities associated with treatment regimens include the following:
Hematologic toxicity: Anemia (need for transfusion), thrombocytopenia, increased risk of infection (febrile neutropenia); myelodyplasia or acute leukemia
Pulmonary toxicity, particularly if bleomycin or thoracic radiation are used; increased risk of lung cancer or fibrotic lung disease, particularly in smokers
Cardiac toxicity from anthracycline therapy; congestive heart failure from treatment; increased risk of coronary artery disease
Infectious: Long-term increased risk of infection from splenectomy (rarely done in current practice), long-term immunodeficiency from treatment effects
Cancer: Increased risk of secondary cancers, particularly breast cancer in young women treated with mediastinal radiation; increased risk of sarcomas in radiation fields
Neurologic: Chemotherapy-induced neuropathy, muscular atrophy
Psychiatric: Depression and anxiety related to diagnosis and complications from treatment
Hodgkin lymphoma (formerly, Hodgkin disease) is a potentially curable lymphoma with distinct histology, biologic behavior, and clinical characteristics. The disease is defined in terms of its microscopic appearance (histology) (see the image below) and the expression of cell surface markers (immunophenotype). (See Pathophysiology.)
To diagnose Hodgkin lymphoma a histologic evaluation is always required, and an excisional lymph node biopsy is recommended for this purpose (see Workup). Various imaging studies are used to stage the patient.
Treatment for Hodgkin lymphoma is with multiagent chemotherapy, with or without radiation therapy. Treatment seeks to balance the risk of treatment failure with the risk of treatment side effects (see Treatment).
See also the Medscape Reference topic Pediatric Hodgkin Disease.
The World Health Organization (WHO) classifies Hodgkin lymphoma into five types. Nodular sclerosing, mixed cellularity, lymphocyte depleted, and lymphocyte rich are the four types referred to as classical Hodgkin lymphoma. The fifth type, nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), is a distinct entity with unique clinical features and a different treatment paradigm.
In classical Hodgkin lymphoma, the neoplastic cell is the Reed-Sternberg cell (see the image below).[7, 8] Reed-Sternberg cells comprise only 1-2% of the total tumor cell mass. The remainder is composed of a variety of reactive, mixed inflammatory cells consisting of lymphocytes, plasma cells, neutrophils, eosinophils, and histiocytes.
Most Reed-Sternberg cells are of B-cell origin, derived from lymph node germinal centers but no longer able to produce antibodies. Hodgkin lymphoma cases in which the Reed-Sternberg cell is of T-cell origin are rare, accounting for 1-2% of classical Hodgkin lymphoma.
The Reed-Sternberg cells consistently express the CD30 (Ki-1) and CD15 (Leu-M1) antigens. CD30 is a marker of lymphocyte activation that is expressed by reactive and malignant lymphoid cells and was originally identified as a cell surface antigen on Reed-Sternberg cells. CD15 is a marker of late granulocytes, monocytes, and activated T-cells that is not normally expressed by cells of B lineage.
Classical Hodgkin lymphoma
Classical Hodgkin lymphoma is classified into the following 4 types:
Nodular sclerosing Hodgkin lymphoma (NSHL)
Mixed-cellularity Hodgkin lymphoma (MCHL)
Lymphocyte-depleted Hodgkin lymphoma (LDHL)
Lymphocyte-rich classical Hodgkin lymphoma (LRHL)
Nodular sclerosing Hodgkin lymphoma
In NSHL, which constitutes 60-80% of all cases of Hodgkin lymphoma, the morphology shows a nodular pattern. Broad bands of fibrosis divide the node into nodules. The capsule is thickened. The characteristic cell is the lacunar-type Reed-Sternberg cell, which has a monolobated or multilobated nucleus, a small nucleolus, and abundant pale cytoplasm.
NSHL is frequently observed in adolescents and young adults. It usually involves the mediastinum (see the image below) and other supradiaphragmatic sites.
Mixed-cellularity Hodgkin lymphoma
In MCHL, which constitutes 15-30% of cases, the infiltrate is usually diffuse. Reed-Sternberg cells are of the classical type (large, with bilobate, double or multiple nuclei, and a large, eosinophilic nucleolus). MCHL commonly affects the abdominal lymph nodes and spleen. Patients with this histology typically have advanced-stage disease with systemic symptoms. MCHL is the histologic type most commonly observed in patients with human immunodeficiency virus (HIV) infection.
Lymphocyte-depleted Hodgkin lymphoma
LDHL constitutes less than 1% of cases. The infiltrate in LDHL is diffuse and often appears hypocellular. Large numbers of Reed-Sternberg cells and bizarre sarcomatous variants are present.
LDHL is associated with older age and HIV-positive status. Patients usually present with advanced-stage disease. Epstein-Barr virus (EBV) proteins are expressed in many of these tumors. Many cases of LDHL diagnosed in the past were actually non-Hodgkin lymphomas, often of the anaplastic large-cell type.
Lymphocyte-rich classical Hodgkin lymphoma
LRHL constitutes 5% of cases. In LRHL, Reed-Sternberg cells of the classical or lacunar type are observed, with a background infiltrate of lymphocytes. It requires immunohistochemical diagnosis. Some cases may have a nodular pattern. Clinically, the presentation and survival patterns are similar to those for MCHL.
Nodular lymphocyte-predominant Hodgkin lymphoma
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) constitutes 5% of cases. It is a distinct clinical entity and is not considered part of the classical Hodgkin lymphoma. Typical Reed-Sternberg cells are either infrequent or absent in NLPHL. Instead, lymphocytic and histiocytic (L&H) cells, or "popcorn cells" (their nuclei resemble an exploded kernel of corn), are seen within a background of inflammatory cells, which are predominantly benign lymphocytes (see the image below). Unlike Reed-Sternberg cells, L&H cells are positive for B-cell antigens, such as CD20, and are negative for CD15 and CD30.
A diagnosis of NLPHL needs to be supported by immunohistochemical studies, because it can appear similar to LRHL or even some non-Hodgkin lymphomas.
The etiology of Hodgkin lymphoma is unknown. Infectious agents, particularly Epstein-Barr virus (EBV), may be involved in the pathogenesis.[9, 10] Depending on the study, data show that up to 30% of cases of classical Hodgkin lymphoma may be positive for EBV proteins. In addition, a case control study supports an increased risk of classical Hodgkin lymphoma after EBV infection, with a risk of approximately 1 in 1000 cases.
The incidence of EBV positivity varies with subtype. Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) rarely expresses EBV proteins, whereas in classical Hodgkin lymphoma, EBV positivity is most common in the mixed-cellularity variant. However, the exact mechanism by which EBV can lead to Hodgkin lymphoma is not known.
HIV-positive patients also have a higher incidence of Hodgkin lymphoma compared with HIV-negative patients. However, Hodgkin lymphoma is not considered an AIDS-defining neoplasm.
Genetic predisposition plays a role in the pathogenesis of Hodgkin lymphoma. Approximately 1% of patients with Hodgkin lymphoma have a family history of the disease, and siblings of an affected individual have a 3- to 7-fold increased risk of developing the disease. Most evidence for a genetic etiology has been established in the distinct subtype of nonsclerosing Hodgkin lymphoma (NSHL). NSHL has been shown to be one of the most heritable types of neoplasm, with a 100-fold increased risk in identical twins.[16, 17]
There is evidence that NSHL may result from an atypical immune response to a virus or other trigger, in an individual with a genetic predisposition to such a response. For decades, specific human leukocyte antigen (HLA) class II genotypes, including HLA-DRB1 and HLA-DQB1, have been known to be associated with NSHL, and this has been confirmed by genome-wide association studies. Several single-nucleotide polymorphisms in the 6p21.32 region, which is rich in genes associated with immune function, have also been associated with NSHL risk.
United States statistics
Information regarding the incidence and mortality of Hodgkin lymphoma in the United States can be found at the National Cancer Institute (NCI) Surveillance Epidemiology and End Results (SEER) database Website. The NCI reports that rates of new Hodgkin lymphoma cases have been falling on average 1.2% each year over the last 10 years. As of 2009-2013, the age-adjusted incidence is 2.6 cases per 100,000 population. Death rates have been falling on average 2.6% each year over 2004-2013.
Data are also collected by the American Cancer Society (ACS).
The worldwide incidence of Hodgkin lymphoma has remained relatively stable. In Europe and other developed countries, the incidence parallels US data.[23, 24] United Kingdom data from 2013 show a crude incidence rate of 3.5 cases per 100,000 males and 2.6 cases per 100,000 females.
Race-, sex-, and age-related differences in incidence
Hodgkin lymphoma incidence rates in the United States vary by race and sex. In general, incidence is higher in males than in females. The sex predilection is most pronounced in children, with 85% of cases affecting boys. The lowest incidence is found in Asians and Pacific Islanders.
The incidence of Hodgkin lymphoma varies with age, with a clear bimodal distribution that is consistent across most countries and studies. The initial peak is in young adults (15-34 years) and older adults (>55 years). There is also a difference in subtype based on age, with young adults having nodular sclerosing Hodgkin lymphoma (NSHL) and older adults tending to have MCHL.
Patient prognosis is largely based on the stage of the disease and various prognostic factors, which may be defined differently across various major cooperative groups (eg, German Hodgkin's Study Group [GHSG] vs European Organisation for Research and Treatment of Cancer [EORTC] and others). (See also Staging, under Workup.)
The SEER data report an 86.2% overall 5-year survival rate from 2006-2012. Table 1 summarizes the stage distribution and 5-year relative survival at diagnosis for the same period for all races and both sexes. In addition to the stage of the disease, many factors contribute to the likelihood of survival from Hodgkin lymphoma (see Staging). Factors that influence prognosis include patient age, presence or absence of B symptoms, stage of disease, and elevation of erythrocyte sedimentation rate.
Table 1. Stage Distribution and 5-Year Relative Survival by Stage at Diagnosis for All Races and Both Sexes: 2006-2012 (Open Table in a new window)
|Stage at Diagnosis||Stage Distribution, %||5-year Relative Survival, %|
|Localized (confined to primary site)||16||91.5|
|Regional (spread to regional lymph nodes)||40||93.1|
|Distant (cancer has metastasized)||39||77.3|
|Source: National Cancer Institute. SEER stat fact sheets: Hodgkin lymphoma. Available at: http://www.seer.cancer.gov/statfacts/html/hodg.html. Accessed: May 19, 2016|
The most commonly used prognostic system is the International Prognostic System (IPS), which uses the following variables to The most commonly used prognostic system is the International Prognostic System (IPS), which uses the following variables to determine prognosis :
Serum albumin less than 4 g/dL
Hemoglobin less than 10.5 g/dL
Age of 45 years or older
Stage IV disease (Ann Arbor classification)
White blood cell (WBC) count greater than 15,000/mm 3
Absolute lymphocyte count less than 600/mm 3, less than 8% of the total WBC count, or both
Each of the above variables is assigned 1 point. The total number of points for prognostic factors is used to determine risk. When applied to a group of 5141 patients with Hodgkin lymphoma the IPS produced the following groups of 5-year survival rates :
0 prognostic factors: 84%
1 prognostic factor: 77%
2 prognostic factors: 67%
3 prognostic factors: 60%
4 prognostic factors: 51%
5 or more prognostic factors: 42%
These results have been validated in other populations as well, including in patients undergoing stem cell transplant.[31, 32] However this scoring system is most applicable to patients with advanced-stage disease (stages III and IV).
Before beginning treatment, patients with Hodgkin lymphoma should be counseled about the potential complications of therapy, including the risk of cardiac disease, lung toxicity, and secondary cancers. Patients should also be apprised of the potential loss of fertility that may arise from treatments such as MOPP (mechlorethamine, vincristine, procarbazine, prednisone) chemotherapy, escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) chemotherapy, and pelvic irradiation, so that they may explore fertility-preserving options such as sperm banking, oral contraceptive use, or oophoropexy. Although less likely, infertility can also occur with ABVD therapy (Adriamycin [doxorubicin], bleomycin, vinblastine, dacarbazine).
Female patients who have received chest radiation therapy should be encouraged to perform regular breast self-examinations. All patients should be counseled on health habits that may help reduce the risk of cancer and cardiovascular disease, including avoidance of smoking, control of lipids, and the use of sunscreen.
Although splenectomy is uncommon with modern therapy, any patient who has undergone this procedure needs to be counseled about vaccination needs and their long-term risk of infection.
Patients should understand the risk of psychosocial problems that may affect survivors of Hodgkin lymphoma. Consultations with social workers, psychologists, and psychiatrists may be helpful.
Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2001.
Hentrich M, Maretta L, Chow KU, et al. Highly active antiretroviral therapy (HAART) improves survival in HIV-associated Hodgkin's disease: results of a multicenter study. Ann Oncol. 2006 Jun. 17(6):914-9. [Medline]. [Full Text].
[Guideline] NCCN Clinical Practice Guidelines in Oncology: Hodgkin Lymphoma. Version 2.2016. National Comprehensive Cancer Network. Available at http://www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf. Accessed: May 19, 2016.
[Guideline] Eichenauer DA, Engert A, André M, Federico M, Illidge T, Hutchings M, et al. Hodgkin's lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014 Sep. 25 Suppl 3:iii70-5. [Medline]. [Full Text].
Schmitz N, Pfistner B, Sextro M, et al. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: a randomised trial. Lancet. 2002 Jun 15. 359(9323):2065-71. [Medline].
Thomas RK, Re D, Wolf J, Diehl V. Part I: Hodgkin's lymphoma--molecular biology of Hodgkin and Reed-Sternberg cells. Lancet Oncol. 2004 Jan. 5(1):11-8. [Medline].
Re D, Kuppers R, Diehl V. Molecular pathogenesis of Hodgkin's lymphoma. J Clin Oncol. 2005 Sep 10. 23(26):6379-86. [Medline].
Gutensohn N, Cole P. Childhood social environment and Hodgkin's disease. N Engl J Med. 1981 Jan 15. 304(3):135-40. [Medline].
Hjalgrim H, Smedby KE, Rostgaard K, et al. Infectious mononucleosis, childhood social environment, and risk of Hodgkin lymphoma. Cancer Res. 2007 Mar 1. 67(5):2382-8. [Medline].
Staal SP, Ambinder R, Beschorner WE, Hayward GS, Mann R. A survey of Epstein-Barr virus DNA in lymphoid tissue. Frequent detection in Hodgkin's disease. Am J Clin Pathol. 1989 Jan. 91(1):1-5. [Medline].
Hjalgrim H, Askling J, Rostgaard K, Hamilton-Dutoit S, Frisch M, Zhang JS, et al. Characteristics of Hodgkin's lymphoma after infectious mononucleosis. N Engl J Med. 2003 Oct 2. 349(14):1324-32. [Medline].
Weiss LM, Chen YY, Liu XF, Shibata D. Epstein-Barr virus and Hodgkin's disease. A correlative in situ hybridization and polymerase chain reaction study. Am J Pathol. 1991 Dec. 139(6):1259-65. [Medline]. [Full Text].
Pallesen G, Hamilton-Dutoit SJ, Rowe M, Young LS. Expression of Epstein-Barr virus latent gene products in tumour cells of Hodgkin's disease. Lancet. 1991 Feb 9. 337(8737):320-2. [Medline].
Goldin LR, Pfeiffer RM, Gridley G, Gail MH, Li X, Mellemkjaer L, et al. Familial aggregation of Hodgkin lymphoma and related tumors. Cancer. 2004 May 1. 100(9):1902-8. [Medline].
Harty LC, Lin AY, Goldstein AM, Jaffe ES, Carrington M, Tucker MA, et al. HLA-DR, HLA-DQ, and TAP genes in familial Hodgkin disease. Blood. 2002 Jan 15. 99(2):690-3. [Medline].
Mack TM, Cozen W, Shibata DK, Weiss LM, Nathwani BN, Hernandez AM, et al. Concordance for Hodgkin's disease in identical twins suggesting genetic susceptibility to the young-adult form of the disease. N Engl J Med. 1995 Feb 16. 332(7):413-8. [Medline].
Mueller NE, Grufferman S. Hodgkin lymphoma. Schottenfeld D, Fraumeni JF Jr , eds. Cancer Epidemiology and Prevention. New York, NY: Oxford University Press; 2006. 872-97.
Enciso-Mora V, Broderick P, Ma Y, Jarrett RF, Hjalgrim H, Hemminki K, et al. A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3). Nat Genet. 2010 Dec. 42(12):1126-30. [Medline].
Cozen W, Li D, Best T, Van Den Berg DJ, Gourraud PA, Cortessis VK, et al. A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32. Blood. 2012 Jan 12. 119(2):469-75. [Medline]. [Full Text].
National Cancer Institute. SEER stat fact sheets: Hodgkin lymphoma. Available at http://www.seer.cancer.gov/statfacts/html/hodg.html. Accessed: May 19, 2016.
Sant M, Allemani C, Tereanu C, De Angelis R, Capocaccia R, Visser O, et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood. 2010 Nov 11. 116(19):3724-34. [Medline].
Correa P, O'Conor GT. Epidemiologic patterns of Hodgkin's disease. Int J Cancer. 1971 Sep 15. 8(2):192-201. [Medline].
Cancer Research UK. Hodgkin lymphoma - UK incidence statistics. Available at http://www.cancerresearchuk.org/cancer-info/cancerstats/types/hodgkinslymphoma/incidence/#Overall. Accessed: May 19, 2016.
Ries LAG, Kosary CL, Hankey BF, Miller BA, Harras A, Edwards BK, et al. SEER Cancer Statistics Review, 1973-1994. Available at http://seer.cancer.gov/csr/1973_1994/. Accessed: September 27, 2012.
Howlader N, Noone AM, Krapcho M, et al, eds. Bethesda, Md: National Cancer Institute. Bethesda, et al. SEER Cancer Statistics Review, 1975-2008. (Based on November 2010 SEER data submission, posted to the SEER Website, 2011.). Available at http://seer.cancer.gov/csr/1975_2008/. Accessed: September 27, 2012.
Das P, Ng A, Constine LS, Hodgson DC, Mendenhall NP, Morris DE, et al. ACR Appropriateness Criteria on Hodgkin's lymphoma: favorable prognosis stage I and II. J Am Coll Radiol. 2008 Oct. 5(10):1054-66. [Medline]. [Full Text].
Das P, Ng A, Constine LS, Advani R, Flowers C, Friedberg J, et al. ACR Appropriateness Criteria(R) on Hodgkin's lymphoma-unfavorable clinical stage I and II. J Am Coll Radiol. 2011 May. 8(5):302-8. [Medline]. [Full Text].
Hasenclever D, Diehl V. A prognostic score for advanced Hodgkin's disease. International Prognostic Factors Project on Advanced Hodgkin's Disease. N Engl J Med. 1998 Nov 19. 339(21):1506-14. [Medline]. [Full Text].
Bierman PJ, Lynch JC, Bociek RG, Whalen VL, Kessinger A, Vose JM, et al. The International Prognostic Factors Project score for advanced Hodgkin's disease is useful for predicting outcome of autologous hematopoietic stem cell transplantation. Ann Oncol. 2002 Sep. 13(9):1370-7. [Medline].
Swerdlow SH, Campo E, Harris NL, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: IARC Press; 2008.
Menard F, Besson C, Rince P, et al. Hodgkin lymphoma-associated hemophagocytic syndrome: a disorder strongly correlated with Epstein-Barr virus. Clin Infect Dis. 2008 Aug 15. 47(4):531-4. [Medline].
Juweid ME, Stroobants S, Hoekstra OS, Mottaghy FM, Dietlein M, Guermazi A, et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol. 2007 Feb 10. 25(5):571-8. [Medline].
Juweid ME, Stroobants S, Hoekstra OS, et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol. 2007 Feb 10. 25(5):571-8. [Medline]. [Full Text].
Vassilakopoulos TP, Angelopoulou MK, Constantinou N, Karmiris T, Repoussis P, Roussou P, et al. Development and validation of a clinical prediction rule for bone marrow involvement in patients with Hodgkin lymphoma. Blood. 2005 Mar 1. 105(5):1875-80. [Medline].
Cosset JM, Henry-Amar M, Meerwaldt JH, Carde P, Noordijk EM, Thomas J, et al. The EORTC trials for limited stage Hodgkin's disease. The EORTC Lymphoma Cooperative Group. Eur J Cancer. 1992. 28A(11):1847-50. [Medline].
Engert A, Plütschow A, Eich HT, Lohri A, Dörken B, Borchmann P, et al. Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma. N Engl J Med. 2010 Aug 12. 363(7):640-52. [Medline].
DeVita VT Jr. A selective history of the therapy of Hodgkin's disease. Br J Haematol. 2003 Sep. 122(5):718-27. [Medline].
Connors JM. State-of-the-art therapeutics: Hodgkin's lymphoma. J Clin Oncol. 2005 Sep 10. 23(26):6400-8. [Medline].
Advani R, Maeda L, Lavori P, et al. Impact of positive positron emission tomography on prediction of freedom from progression after Stanford V chemotherapy in Hodgkin's disease. J Clin Oncol. 2007 Sep 1. 25(25):3902-7. [Medline]. [Full Text].
Gallamini A, Hutchings M, Rigacci L, et al. Early interim 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography is prognostically superior to international prognostic score in advanced-stage Hodgkin's lymphoma: a report from a joint Italian-Danish study. J Clin Oncol. 2007 Aug 20. 25(24):3746-52. [Medline]. [Full Text].
Levine JM, Weiner M, Kelly KM. Routine use of PET scans after completion of therapy in pediatric Hodgkin disease results in a high false positive rate. J Pediatr Hematol Oncol. 2006 Nov. 28(11):711-4. [Medline].
Wilder RB, Ng A, Constine LS, et al, for the Expert Panel on Radiation Oncology-Hodgkin's Lymphoma. ACR Appropriateness Criteria(R) Hodgkin's lymphoma--stage III and IV [online publication]. Reston, Va: American College of Radiology; 2010. [Full Text].
Koeck J, Abo-Madyan Y, Lohr F, Stieler F, Kriz J, Mueller RP, et al. Radiotherapy for early mediastinal Hodgkin lymphoma according to the German Hodgkin Study Group (GHSG): the roles of intensity-modulated radiotherapy and involved-node radiotherapy. Int J Radiat Oncol Biol Phys. 2012 May 1. 83(1):268-76. [Medline].
Specht L, Yahalom J, Illidge T, Berthelsen AK, Constine LS, Eich HT, et al. Modern radiation therapy for Hodgkin lymphoma: field and dose guidelines from the international lymphoma radiation oncology group (ILROG). Int J Radiat Oncol Biol Phys. 2014 Jul 15. 89 (4):854-62. [Medline].
Noordijk EM, Carde P, Dupouy N, Hagenbeek A, Krol AD, Kluin-Nelemans JC, et al. Combined-modality therapy for clinical stage I or II Hodgkin's lymphoma: long-term results of the European Organisation for Research and Treatment of Cancer H7 randomized controlled trials. J Clin Oncol. 2006 Jul 1. 24(19):3128-35. [Medline].
Engert A, Schiller P, Josting A, Herrmann R, et al. 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... J Clin Oncol. 2003 Oct 1. 21(19):3601-8. [Medline].
Arakelyan N, Jais JP, Delwail V, Briere J, Moles-Moreau MP, Senecal D, et al. Reduced versus full doses of irradiation after 3 cycles of combined doxorubicin, bleomycin, vinblastine, and dacarbazine in early stage Hodgkin lymphomas: results of a randomized trial. Cancer. 2010 Sep 1. 116(17):4054-62. [Medline].
Canellos GP, Anderson JR, Propert KJ, et al. Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med. 1992 Nov 19. 327(21):1478-84. [Medline].
Horning SJ, Hoppe RT, Breslin S, et al. Stanford V and radiotherapy for locally extensive and advanced Hodgkin's disease: mature results of a prospective clinical trial. J Clin Oncol. 2002 Feb 1. 20(3):630-7. [Medline]. [Full Text].
Advani RH, Hong F, Fisher RI, Bartlett NL, Robinson KS, Gascoyne RD, et al. Randomized Phase III Trial Comparing ABVD Plus Radiotherapy With the Stanford V Regimen in Patients With Stages I or II Locally Extensive, Bulky Mediastinal Hodgkin Lymphoma: A Subset Analysis of the North American Intergroup E2496 Trial. J Clin Oncol. 2015 Jun 10. 33 (17):1936-42. [Medline].
Diehl V, Franklin J, Pfreundschuh M, et al. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease. N Engl J Med. 2003 Jun 12. 348(24):2386-95. [Medline]. [Full Text].
Viviani S, Zinzani PL, Rambaldi A, et al. ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned. N Engl J Med. 2011 Jul 21. 365(3):203-12. [Medline].
Bauer K, Skoetz N, Monsef I, Engert A, Brillant C. Comparison of chemotherapy including escalated BEACOPP versus chemotherapy including ABVD for patients with early unfavourable or advanced stage Hodgkin lymphoma. Cochrane Database Syst Rev. 2011 Aug 10. CD007941. [Medline].
Mounier N, Brice P, Bologna S, Briere J, Gaillard I, Heczko M, et al. ABVD (8 cycles) versus BEACOPP (4 escalated cycles ≥ 4 baseline): final results in stage III-IV low-risk Hodgkin lymphoma (IPS 0-2) of the LYSA H34 randomized trial. Ann Oncol. 2014 Aug. 25 (8):1622-8. [Medline].
Carde P, Karrasch M, Fortpied C, Brice P, Khaled H, Casasnovas O, et al. Eight Cycles of ABVD Versus Four Cycles of BEACOPPescalated Plus Four Cycles of BEACOPPbaseline in Stage III to IV, International Prognostic Score ≥ 3, High-Risk Hodgkin Lymphoma: First Results of the Phase III EORTC 20012 Intergroup Trial. J Clin Oncol. 2016 Apr 25. [Medline].
Edwards-Bennett SM, Jacks LM, Moskowitz CH, et al. Stanford V program for locally extensive and advanced Hodgkin lymphoma: the Memorial Sloan-Kettering Cancer Center experience. Ann Oncol. 2010 Mar. 21(3):574-81. [Medline].
Gayoso J, Balsalobre P, Pascual MJ, Castilla-Llorente C, López-Corral L, Kwon M, et al. Busulfan-based reduced intensity conditioning regimens for haploidentical transplantation in relapsed/refractory Hodgkin lymphoma: Spanish multicenter experience. Bone Marrow Transplant. 2016 May 9. [Medline].
Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH, et al. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015 May 9. 385 (9980):1853-62. [Medline].
Engert A, Franklin J, Eich HT, et al. Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin's lymphoma: final results of the GHSG HD7 trial. J Clin Oncol. 2007 Aug 10. 25(23):3495-502. [Medline]. [Full Text].
Herbst C, Rehan FA, Brillant C, Bohlius J, Skoetz N, Schulz H, et al. Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin's lymphoma: a systematic review. Haematologica. 2010 Mar. 95(3):494-500. [Medline]. [Full Text].
Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Wells WA, Winter JN, et al. ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma. N Engl J Med. 2012 Feb 2. 366(5):399-408. [Medline].
Hutchings M, Mikhaeel NG, Fields PA, Nunan T, Timothy AR. Prognostic value of interim FDG-PET after two or three cycles of chemotherapy in Hodgkin lymphoma. Ann Oncol. 2005 Jul. 16(7):1160-8. [Medline].
Hutchings M, Loft A, Hansen M, Pedersen LM, Buhl T, Jurlander J, et al. FDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma. Blood. 2006 Jan 1. 107(1):52-9. [Medline].
Advani RH, Horning SJ. Treatment of early-stage Hodgkin's disease. Semin Hematol. 1999 Jul. 36(3):270-81. [Medline].
von Tresckow B, Plutschow A, Fuchs M, Klimm B, Markova J, Lohri A, et al. Dose-intensification in early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD14 trial. J Clin Oncol. 2012 Mar 20. 30(9):907-13. [Medline].
Armitage JO. Early-stage Hodgkin's lymphoma. N Engl J Med. 2010 Aug 12. 363(7):653-62. [Medline].
Duggan DB, Petroni GR, Johnson JL, Glick JH, Fisher RI, Connors JM, et al. Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: report of an intergroup trial. J Clin Oncol. 2003 Feb 15. 21(4):607-14. [Medline].
Johnson PW, Radford JA, Cullen MH, Sydes MR, Walewski J, Jack AS, et al. Comparison of ABVD and alternating or hybrid multidrug regimens for the treatment of advanced Hodgkin's lymphoma: results of the United Kingdom Lymphoma Group LY09 Trial (ISRCTN97144519). J Clin Oncol. 2005 Dec 20. 23(36):9208-18. [Medline].
Boleti E, Mead GM. ABVD for Hodgkin's lymphoma: full-dose chemotherapy without dose reductions or growth factors. Ann Oncol. 2007 Feb. 18(2):376-80. [Medline].
Wedgwood A, Younes A. Prophylactic use of filgrastim with ABVD and BEACOPP chemotherapy regimens for Hodgkin lymphoma. Clin Lymphoma Myeloma. 2007 Dec. 8 Suppl 2:S63-6. [Medline].
Saxman SB, Nichols CR, Einhorn LH. Pulmonary toxicity in patients with advanced-stage germ cell tumors receiving bleomycin with and without granulocyte colony stimulating factor. Chest. 1997 Mar. 111(3):657-60. [Medline].
Federico M, Luminari S, Iannitto E, Polimeno G, Marcheselli L, Montanini A, et al. ABVD compared with BEACOPP compared with CEC for the initial treatment of patients with advanced Hodgkin's lymphoma: results from the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial. J Clin Oncol. 2009 Feb 10. 27(5):805-11. [Medline].
Engert A, Haverkamp H, Kobe C, Markova J, Renner C, Ho A, et al. Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial. Lancet. 2012 May 12. 379(9828):1791-9. [Medline].
Horning SJ, Hoppe RT, Advani R, et al. Efficacy and late effects of Stanford V chemotherapy and radiotherapy in untreated Hodgkin's disease: mature data in early and advanced stage patients [abstract 308]. Blood. 2004. 104:92a.
Gordon LI, Hong F, Fisher RI, et al. Randomized phase III trial of ABVD vs. Stanford V /- radiation therapy in locally extensive and advanced stage Hodgkin's lymphoma... Blood (ASH Annual Meeting Abstracts). 2010. 116(21):185; (E2496) [abstract 415].
Hoppe RT. Hodgkin's disease--the role of radiation therapy in advanced disease. Ann Oncol. 1996. 7 Suppl 4:99-103. [Medline].
Loeffler M, Brosteanu O, Hasenclever D, Sextro M, Assouline D, Bartolucci AA, 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 Mar. 16(3):818-29. [Medline].
Aleman BM, Raemaekers JM, Tomisic R, Baaijens MH, Bortolus R, Lybeert ML, et al. Involved-field radiotherapy for patients in partial remission after chemotherapy for advanced Hodgkin's lymphoma. Int J Radiat Oncol Biol Phys. 2007 Jan 1. 67(1):19-30. [Medline].
Johnson PW, Sydes MR, Hancock BW, Cullen M, Radford JA, Stenning SP. Consolidation radiotherapy in patients with advanced Hodgkin's lymphoma: survival data from the UKLG LY09 randomized controlled trial (ISRCTN97144519). J Clin Oncol. 2010 Jul 10. 28(20):3352-9. [Medline].
Federico M, Bellei M, Brice P, Brugiatelli M, Nagler A, Gisselbrecht C, et al. High-dose therapy and autologous stem-cell transplantation versus conventional therapy for patients with advanced Hodgkin's lymphoma responding to front-line therapy. J Clin Oncol. 2003 Jun 15. 21(12):2320-5. [Medline].
Portlock CS. Nodular lymphocyte predominant Hodgkin's disease. Cancer Treat Res. 2006. 131:353-62. [Medline].
Schulz H, Rehwald U, Morschhauser F, et al. Rituximab in relapsed lymphocyte-predominant Hodgkin lymphoma: long-term results of a phase 2 trial by the German Hodgkin Lymphoma Study Group (GHSG). Blood. 2008 Jan 1. 111(1):109-11. [Medline]. [Full Text].
Eichenauer DA, Fuchs M, Pluetschow A, et al. Phase 2 study of rituximab in newly diagnosed stage IA nodular lymphocyte-predominant Hodgkin lymphoma: a report from the German Hodgkin Study Group. Blood. 2011 Oct 20. 118(16):4363-5. [Medline].
Savage KJ, Skinnider B, Al-Mansour M, Sehn LH, Gascoyne RD, Connors JM. Treating limited-stage nodular lymphocyte predominant Hodgkin lymphoma similarly to classical Hodgkin lymphoma with ABVD may improve outcome. Blood. 2011 Oct 27. 118(17):4585-90. [Medline].
Lavoie JC, Connors JM, Phillips GL, et al. High-dose chemotherapy and autologous stem cell transplantation for primary refractory or relapsed Hodgkin lymphoma: long-term outcome in the first 100 patients treated in Vancouver. Blood. 2005 Aug 15. 106(4):1473-8. [Medline]. [Full Text].
Gopal AK, Metcalfe TL, Gooley TA, et al. High-dose therapy and autologous stem cell transplantation for chemoresistant Hodgkin lymphoma: the Seattle experience. Cancer. 2008 Sep 15. 113(6):1344-50. [Medline].
Przepiorka D, van Besien K, Khouri I, et al. Carmustine, etoposide, cytarabine and melphalan as a preparative regimen for allogeneic transplantation for high-risk malignant lymphoma. Ann Oncol. 1999 May. 10(5):527-32. [Medline]. [Full Text].
Anderlini P, Saliba R, Acholonu S, et al. Fludarabine-melphalan as a preparative regimen for reduced-intensity conditioning allogeneic stem cell transplantation in relapsed and refractory Hodgkin''s lymphoma: the updated M.D. Anderson Cancer Center experience. Haematologica. 2008 Feb. 93(2):257-64. [Medline]. [Full Text].
Younes A, Bartlett NL, Leonard JP, Kennedy DA, Lynch CM, Sievers EL, et al. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med. 2010 Nov 4. 363(19):1812-21. [Medline]. [Full Text].
Chen R, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Klasa R, et al. Results of a Pivotal Phase 2 Study of Brentuximab Vedotin (SGN-35) in Patients with Relapsed or Refractory Hodgkin Lymphoma. American Society of Hematology (ASH) 52nd Annual Meeting: Abstract 283, presented December 6, 2010. American Society of Hematology. Available at http://ash.confex.com/ash/2010/webprogram/Paper30260.html. Accessed: August 22, 2011.
Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015 Jan 22. 372 (4):311-9. [Medline]. [Full Text].
Ansell S, et al. Nivolumab in Patients (Pts) with Relapsed or Refractory Classical Hodgkin Lymphoma (R/R cHL): Clinical Outcomes from Extended Follow-up of a Phase 1 Study (CA209-039). Blood. 2015. 126(23):[Full Text].
Wethal T, Lund MB, Edvardsen T, et al. Valvular dysfunction and left ventricular changes in Hodgkin's lymphoma survivors. A longitudinal study. Br J Cancer. 2009 Aug 18. 101(4):575-81. [Medline]. [Full Text].
Heidenreich PA, Schnittger I, Strauss HW, et al. Screening for coronary artery disease after mediastinal irradiation for Hodgkin's disease. J Clin Oncol. 2007 Jan 1. 25(1):43-9. [Medline]. [Full Text].
Milano MT, Li H, Constine LS, Travis LB. Survival after second primary lung cancer: a population-based study of 187 Hodgkin lymphoma patients. Cancer. 2011 Dec 15. 117(24):5538-47. [Medline].
Swerdlow AJ, Higgins CD, Smith P, et al. Second Cancer Risk After Chemotherapy for Hodgkin's Lymphoma: A Collaborative British Cohort Study. J Clin Oncol. 2011 Nov 1. 29(31):4096-104. [Medline].
Barbaro PM, Johnston K, Dalla-Pozza L, Cohn RJ, Wang YA, Marshall GM, et al. Reduced incidence of second solid tumors in survivors of childhood Hodgkin's lymphoma treated without radiation therapy. Ann Oncol. 2011 Dec. 22(12):2569-74. [Medline].
Behringer K, Breuer K, Reineke T, et al. Secondary amenorrhea after Hodgkin's lymphoma is influenced by age at treatment, stage of disease, chemotherapy regimen, and the use of oral contraceptives during therapy: a report from the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 2005 Oct 20. 23(30):7555-64. [Medline].
Sieniawski M, Reineke T, Josting A, et al. Assessment of male fertility in patients with Hodgkin's lymphoma treated in the German Hodgkin Study Group (GHSG) clinical trials. Ann Oncol. 2008 Oct. 19(10):1795-801. [Medline].
Kornblith AB, Herndon JE 2nd, Zuckerman E, et al. Comparison of psychosocial adaptation of advanced stage Hodgkin's disease and acute leukemia survivors. Cancer and Leukemia Group B. Ann Oncol. 1998 Mar. 9(3):297-306. [Medline].
Loge JH, Abrahamsen AF, Ekeberg, Kaasa S. Fatigue and psychiatric morbidity among Hodgkin's disease survivors. J Pain Symptom Manage. 2000 Feb. 19(2):91-9. [Medline].
Ng A, Constine LS, Advani R, Das P, Flowers C, Friedberg J, et al. ACR Appropriateness Criteria: follow-up of Hodgkin's lymphoma. Curr Probl Cancer. 2010 May-Jun. 34(3):211-27. [Medline]. [Full Text].
Andre M, Bosly A. BEACOPPescalated versus ABVD in advanced Hodgkin's lymphoma. Lancet Oncol. 2013 Aug 12. [Medline].
Younes A, Connors JM, Park SI, Hunder NNH, Ansell SM. Frontline therapy with brentuximab vedotin combined with ABVD or AVD in patients with newly diagnosed advanced stage Hodgkin lymphoma [abstract]. Proc ASH 2011;abstract 955. Available at http://abstracts.hematologylibrary.org/cgi/content/abstract/118/21/955?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=955.
American Cancer Society. Breast cancer: Can breast cancer be found early?. Available at http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-detection. Accessed: September 6, 2012.
Canioni D, Deau-Fischer B, Taupin P, et al. Prognostic significance of new immunohistochemical markers in refractory classical Hodgkin lymphoma: a study of 59 cases. PLoS One. 2009 Jul 22. 4(7):e6341. [Medline]. [Full Text].
Chang ET, Canchola AJ, Cockburn M, et al. Adulthood residential ultraviolet radiation, sun sensitivity, dietary vitamin D, and risk of lymphoid malignancies in the California Teachers Study. Blood. 2011 Aug 11. 118(6):1591-9. [Medline]. [Full Text].
Chen R, Gopal AK, Smith SE, et al. Results of a pivotal phase 2 study of brentuximab vedotin (SGN-35) in patients with relapsed or refractory Hodgkin lymphoma. Presented at: American Society of Hematology Annual Meeting; December 4-7, 2010; Orlando, Fla. Blood. 2010. 116(21):Abstract 283.
Eich HT, Diehl V, Gorgen H, et al. Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD11 trial. J Clin Oncol. 2010 Sep 20. 28(27):4199-206. [Medline].
|Stage at Diagnosis||Stage Distribution, %||5-year Relative Survival, %|
|Localized (confined to primary site)||16||91.5|
|Regional (spread to regional lymph nodes)||40||93.1|
|Distant (cancer has metastasized)||39||77.3|
|Source: National Cancer Institute. SEER stat fact sheets: Hodgkin lymphoma. Available at: http://www.seer.cancer.gov/statfacts/html/hodg.html. Accessed: May 19, 2016|