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Hodgkins Disease

  

About Lymphoma > Types of Lymphoma > Hodgkins Lymphoma

Last update: 05/15/2008

TOPIC SEARCH: PubMed: Diagnosis | Review | Therapies | Prognosis | Refractory
  
 
Overview | Treatment | Risk Factors | Clinical Trials | Prognosis & Survival | Research News
Overview of 
Lymphoma

What is lymphoma? Briefly, lymphomas result when DNA damage or changes occurs to an immune cell (a lymphocyte) that alters the behavior of the cells. 

The damage to DNA results in the abnormal production of proteins that prevents the cells from dying when they should, or causes sustained rapid cell division that produces more of its kind. 

These malignant cells then may accumulate to form tumors that may enlarge the lymph nodes or spread to other areas of the lymphatic system, such as the spleen or bone marrow.

Lymphoma can also spread or first appear outside the lymphatic system -- and is called extranodal disease. 

Also see

Lymphoma simplified

Lymphatic System
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Hodgkin's Lymphoma

A hallmark of cancer cells is that they have growth and survival advantages over normal cells. Their cell division is not balanced by cell death. The abnormal cells may eventually form lumps called tumors.

All lymphomas involve lymphocytes (white blood cells) that have developed errors causing these cells to have growth and survival advantages over normal cells of the same type. Therefore these cells will accumulate to form tumors in the lymphatic system and blood. Most often the areas of presentation are limited to the lymphatic system, but not always. 

What is the difference between Hodgkin's lymphoma and non-Hodgkin's lymphoma?

The difference is in the type of lymphocytes involved - the cell of origin.

In Hodgkin's disease, the abnormal lymphocyte is the Reed-Sternberg cell (a B lymphocyte). This particular lymphocyte isn't found in other types of lymphomas.  All other types of lymphomas are called non-Hodgkin's (NHL).  There are about 30 subtypes of NHL.

Identifying the correct type of lymphoma is important because treatment for Hodgkin's and non-Hodgkin's can be very different. Pathologists can distinguish between Hodgkin's and non-Hodgkin's by examining the cell sample from a biopsy under a microscope.

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Incidence

"The American Cancer Society estimates that 7,350 men and women (3,980 men and 3,370 women) will be diagnosed with Hodgkin's lymphoma.

From 1998-2002, the median age at diagnosis for Hodgkin's lymphoma was 37 years of age. Approximately 12.5% were diagnosed under age 20; 32.9% between 20 and 34; 19.0% between 35 and 44; 12.0% between 45 and 54; 7.8% between 55 and 64; 8.4% between 65 and 74; 5.8% between 75 and 84; and 1.6% 85+ years of age."

Source: SEER - Stat Fact Sheet 2006

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Symptoms of Hodgkin's Lymphoma  

painless swelling in the neck, armpits or groin 

night sweats

unexplained fever

unexplained weight loss

unexplained fatigue

cough or difficulty in breathing

persistent itch all over the body (pruritus)

NOTE: These symptoms are common to many conditions other than Hodgkin's disease. A definite diagnosis can only be made by removing an enlarged lymph node or part of it and examining the cells. This test is known as a biopsy. It is a very small operation and is commonly done under local anesthesia.

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Staging

Staging describes how wide spread the disease is. Hodgkin's disease is characterized by contiguous (side-by-side) spread. Metastasis - dissemination to all areas - is a late event. 

hodgclinic.gif (6487 bytes) 
Anne Arbor staging for Hodgkin's Lymphoma - Virginia.edu
click to enlarge illustration
  

Stage I
Single node region (or extranodal) site
Stage II
Two or more lymph nodes on same side of diaphragm
Stage III
Lymph Nodes (sites) on both sides of the diaphragm
Stage IV
Multiple or disseminated spread

Incidence of Hodgkin's Lymphoma

Type
New Cases 
Deaths per year 
Survival 5/10/15 year
Hodgkin's 7,000 1,400 83% &  74% & 66%

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Categories of Hodgkin's Lymphoma

Nodular Sclerosis
Mixed Cellularity
Lymphocyte Depleted
Lymphocyte Predominant
Nodular Lymphocyte Predominant Hodgkin's Disease (NLPHD

"B-cell lymphoproliferative disorder distinct from classical HD

Uncommon, accounting for approximately 5-7% of all cases of HD;  

Most cases are clinically indolent; not associated with systemic B symptoms

Close clinical follow-up and a low threshold for repeat biopsy is not an unreasonable course for these patients. The subsequent development of a hematolymphoid neoplasm in patients with antecedent nodular LPHD should alert one to the possible presence of a DLCL of B- lineage."  hitchcock.org

Also see PubMed | ClinicalTrials.gov
Source: gucfm.georgetown.edu
Infradiaphragmatic versus supradiaphragmatic Hodgkin lymphoma: a retrospective review of 1114 patients. Leuk Lymphoma. 2005 Dec;46(12):1715-20. PMID: 16263573
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CD20 expression in Hodgkin's Lymphoma
CD20 Expression in Hodgkin and Reed-Sternberg Cells of Classical Hodgkin’s Disease: Associations With Presenting Features and Clinical Outcome jco.org 
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Prognostic indicators in  Hodgkin's Lymphoma
NEW: Prognostic impact of bone involvement in Hodgkin lymphoma.
Neoplasma. 2008;55(2):96-100. PMID: 18237246 Medscape

...  bone involvement is a relatively common finding in HL and is not an independent adverse prognostic factor. Key words: Hodgkin lymphoma - bone involvement - prognostic factors.
NEW: Better Prognosis for Patients with Lymphocyte-predominant Hodgkin’s Lymphoma patient.cancerconsultants.com 

"In order to better understand characteristics of LPHL [Lymphocyte-predominant HL], researchers from Germany conducted an analysis of 8,298 HL patients treated within a German medical trial to compare patient characteristics and treatment outcomes among cHL [classical HL) patients and others diagnosed with LPHD . "
Hodgkin's lymphoma in the elderly: The results of 10 years of follow-up.
Leuk Lymphoma. 2006 Aug;47(8):1518-22. PMID: 16966262
Hodgkin disease survival in Europe and the U.S.: prognostic significance of morphologic groups. Cancer. 2006 Jul 15;107(2):352-60. PMID: 16770772 

Morphology distribution varied markedly across Europe and much less in the U.S., with nodular sclerosis less common in Europe (45.9%) than the U.S. (61.7%). The RER data showed that patients who had lymphocyte depletion, NOS, and mixed cellularity had a significantly worse prognoses compared with patients who had nodular sclerosis, whereas patients who had lymphocyte predominance had the best prognosis.
MAL [a gene also expressed in mediastinal (thymic) large B-cell lymphoma] is expressed in a subset of Hodgkin lymphoma and identifies a population of patients with poor prognosis. Am J Clin Pathol. 2006 May;125(5):776-82. PMID: 16707382 

"Expression correlated with nodular sclerosis subtype, and within this subtype, with grade 2 histology."
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Resources
About  cancerbacup.org.uk | nci.nih.gov 
Hodgkin’s Lymphoma: Evolving Concepts 
with Implications for Practice  asheducationbook.org
Ralph M. Meyer, Richard F. Ambinder and Sigrid Stroobants
An overview of HD: pleiad.umdnj.edu
Online support forum: forums.webmagic.com 
Foundations  KDH Hodgkin's Disease Foundation.org 
Risk Factors

 

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Risk Factors

What causes Hodgkin's disease is not known.  Risk factors associated with contracting this kind of blood cancer include:

Inborn immune deficiency diseases

Acquired immunodeficiency from AIDS or immunosuppressive drugs

Living in Western countries, being of higher social class, more educated

Genetic pre-disposition, clusters are noted in siblings with similar HLA genotypes

Infection with Epstein-Barr Virus (EBV) history is noted in up to 40% of patients developing Hodgkin's. 
 
Elevated levels of the IgG and IgA immunoglobulins against the EBV capsid antigen are noted 3 months to 12 years prior to clinical Hodgkin's development.
 
Components of the EBV genome have been noted in the cellular DNA of the Reed-Stemberg cell (Ref. Weiss NEJM 320: 502 1989). 

However, the EBV is not noted in all patients and may be merely a marker of the poorer cellular immunity (but intact humoral immunity) seen in Hodgkin's patients. 1

"The most important risk factors are: 1) genetic; 2) Epstein-Barr virus (infectious mononucleosis); 3) congenital and acquired immunodeficiency; 4) occupational exposure (the wood industry).

"Epstein Barr virus (EBV) is associated with around one-third of Hodgkin's lymphoma (HL) cases and this association is believed to be causal."

"The increased risk of NHL and HL among individuals with a family history of hematopoietic malignancy was approximately twofold for both lymphoma types."

  1. [Risk factors for Hodgkin's lymphomas] An Esp Pediatr. 2001 Sep;55(3):239-43. Review. Spanish. PMID: 11676899
  2. Risk factors for Hodgkin's lymphoma by EBV status and significance of detection of EBV genomes in serum of patients with EBV-associated Hodgkin's lymphoma.
    Leuk Lymphoma. 2003;44 Suppl 3:S27-32. Review. PMID: 15202522 | Related articles
  3. Characteristics of Hodgkin's lymphoma after infectious mononucleosis.
    N Engl J Med. 2003 Oct 2;349(14):1324-32. PMID: 14523140
  4. Family history of hematopoietic malignancy and risk of lymphoma.
    J Natl Cancer Inst. 2005 Oct 5;97(19):1466-74. PMID: 16204696 | Related articles
Resources
  1. About risk factors  cancergroup.com   
  2. Epstein-Barr virus (EBV) associated lymphomas  Related abstracts
    The three main types of EBV-associated B-cell lymphoma are Burkitt lymphoma, Hodgkin lymphoma and post-transplant lymphomas
Treatments & Long Term Side Effects
Questions for your doctor
  Patients Against Lymphoma
General, Treatment & Side Effects, and Tests

&

Treatment Overview
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Generally, Hodgkins disease is treated with chemotherapy or radiotherapy. Sometimes, both are given.  Treatment depends on the stage of the disease, it's location in the body, symptoms, and the age and general health of the patient. 

TREATMENT - Standard of care
Early Favorable Hodgkin's Lymphoma  Cancer.gov
Early Unfavorable Hodgkin's Lymphoma  Cancer.gov
Advanced Favorable Hodgkin's Lymphoma  Cancer.gov
Advanced Unfavorable Hodgkin's Lymphoma  Cancer.gov
Recurrent Adult Hodgkin’s Lymphoma  Cancer.gov
NEW: NCCN Treatment Guidelines http://www.nccn.org  pdf 
NEW: Gemcitabine in the treatment of Hodgkin lymphoma - Abstract 2008
A systematic overview of radiation therapy effects in Hodgkin's lymphoma.
Acta Oncol. 2003;42(5-6):589-604. Review. PMID: 14596517 
Hodgkin's Lymphoma: Basing the Treatment on the Evidence (2001)  asheducationbook.org
Evidence-Based Management of Hodgkin's Disease 
from Cancer Control: Journal of the Moffitt Cancer Center
Results of Conventional Therapy  medscape.com 
Overview  NCI.gov  
Guidance for Parents on Childhood cancers by NCI   Large PDF file | PDF-Help
Articles on Refractory HD  PubMed
A parent's guide to children's cancer  CancerBACUP
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Long Term Side Effects

TOPIC SEARCH: PubMed

"Successfully treated children and adolescents with Hodgkin's disease have a substantial risk for the occurrence of subsequent neoplasms. The most frequent SMNs (skin, thyroid, and breast) are readily detected by physical examination and available screening procedures." 1
 
  1. Second Malignant Neoplasms After Treatment for Hodgkin's Disease  Medscape free login req.
  2. A systematic overview of radiation therapy effects in Hodgkin's lymphoma.
    Acta Oncol. 2003;42(5-6):589-604. Review. PMID: 14596517
  3. A systematic overview of chemotherapy effects in Hodgkin's disease.
    Acta Oncol. 2001;40(2-3):185-97. Review. PMID: 11441931
  4. Late cardiotoxicity after treatment for Hodgkin's lymphoma. 
    Blood. 2006 Nov 21; PMID: 17119114 
  5.  Individualized estimates of second cancer risks after contemporary radiation therapy for Hodgkin lymphoma. Cancer. 2007 Oct 16; PMID: 17941006 

    Contemporary IFRT is predicted to substantially reduce risk of secondary breast and lung cancer compared with mantle RT, with considerable variation in risk among individuals. Individualized prospective risk estimates could facilitate patient-specific counseling and the development of more effective RT techniques.

 

Clinical Trials
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ClinicalTrials.gov
All studies
Newly diagnosed or untreated
Recurrent
Prognosis and Survival
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TOPIC SEARCH : ASCO | Medscape | PubMedPubMed - stage IV Bulky

About survival statistics:  Statistics cannot predict what will happen to you or a loved one.  Each patient and case is unique, and treatment outcomes can vary from one person to another.  Indeed, not even your doctor can tell you for sure what will happen.  The term '5 year survival' is used often.  It relates to the proportion of people in research studies who were still alive 5 years after diagnosis. Patients who live 6,  10,  or 30 years after diagnosis are also in this group. Also see Jay Gould's encouraging essay: The Median isn't the Message
 

Tumor microenvironment and mitotic checkpoint are key factors in the outcome of classical Hodgkin lymphoma. Blood. 2006 Mar 21; PMID: 16551964 
Prognosis of bulky Hodgkin's disease treated with chemotherapy alone or combined with radiotherapy. Cancer Surv. 1985;4(2):439-58. PMID: 2430700 
Research News
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NEW: outcomes: min-SCT: Superiority of reduced-intensity allogeneic transplantation over conventional treatment for relapse of Hodgkin's lymphoma following  autologous stem cell transplantation

This study compares outcome of reduced-intensity conditioned transplant (RIT) with outcome of conventional non-transplant therapy in patients with Hodgkin's lymphoma relapsing following autograft.

There were 72 patients in two groups who had relapsed, and received salvage therapy with chemotherapy radiotherapy. 

One group (n=38) then underwent alemtuzumab-containing RIT. The second group-historical controls (n=34), relapsing before the advent of RIT-had no further high-dose therapy.

This group was required to respond to salvage therapy and live for over 12 months post-relapse, demonstrating potential eligibility for RIT, had this been available.

Overall survival (OS) from diagnosis was superior following RIT
(48% at 10 years versus 15% ; P=0.0014),

as was survival from autograft
(65% at 5 years versus 15% ; P0.0001).

For the RIT group, OS at 5 years from allograft was 51% , and in chemoresponsive patients was 58% , with current progression-free survival of 42% .

Responses were seen in 8 of 15 patients receiving donor lymphocyte infusions (DLI) for relapse/progression, with durable remission in five patients at median follow-up from DLI of 45 months (28-55).

These data demonstrate the potential efficacy of RIT in heavily pre-treated patients whose outlook with conventional therapy is dismal, and provide evidence of a clinically relevant graft-versus-lymphoma effect.


full text: http://www.nature.com/bmt/journal/v41/n9/full/1705977a.html 

Outcomes (small study): mTOR Inhibition ( everolimus) for Relapsed or Refractory Hodgkin Lymphoma: Promising Single Agent Activity with Everolimus (RAD001). Session Type: ASH Poster Session, Board #745-II 

Oral everolimus has promising activity with acceptable toxicity in Hodgkin lymphoma. These results provide the rationale for additional studies with this novel class of agents and to integrate mTOR inhibitors into salvage treatment regimens for Hodgkin lymphoma.
Outcomes: Rituxan in relapsed lymphocyte-predominant Hodgkin Lymphoma: Long-term results of a phase-II trial of the German Hodgkin Lymphoma Study Group (GHSG). Blood. 2007 Oct 15; PMID: 17938252 

Thus, rituximab is highly effective in relapsed and refractory NLPHL. This study is registered at /www.klinisches-studienzentrum.de/trial/285 
Promising treatment target found in Hodgkin lymphoma  eurekalert.org 

Using gene microarray chips, the scientists looked for genes that were active in Reed-Sternberg cells but not in cells of another non-Hodgkin B-cell lymphoma.  The comparison revealed that a gene called Gal1 was up to 30 times more active in the Reed-Sternberg cells, causing them to secrete large quantities of a protein -- Gal1 or Galectin 1 -- that turns down the Th1 immune response.
Stem cell transplantation in Hodgkin lymphoma. 
Expert Rev Anticancer Ther. 2007 Mar;7(3):297-306. Review. PMID: 17338650
Outcome of Patients Experiencing Progression or Relapse After Primary Treatment With Two Cycles of Chemotherapy and Radiotherapy for Early-Stage Favorable Hodgkin's Lymphoma. J Clin Oncol. 2007 Apr 9;  PMID: 17420510 

Relapse after primary treatment with two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine followed by RT is rare. In our analysis, results were influenced by a high treatment-related mortality rate. Additional studies are needed to define the optimal salvage therapy.
Long-term events in adult patients with clinical stage IA-IIA nonbulky Hodgkin's lymphoma treated with four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine and adjuvant radiotherapy: a single-institution 15-year follow-up. PMID: 17085663  

"Long-term events were mostly related to radiotherapy; the role of short ABVD chemotherapy was very limited, as documented by fertility preservation and lack of secondary myelodysplasia/leukemia."
LACE-conditioned autologous stem cell transplantation for relapsed or refractory Hodgkin's lymphoma: treatment outcome and risk factor analysis in 67 patients from a single centre.
Bone Marrow Transplant. 2006 Nov 20;  PMID: 17115062 

LACE followed by ASCT is an effective treatment for the majority of patients with chemosensitive relapsed Hodgkin's lymphoma and a proportion of chemorefractory patients also benefit.
Long-term outcome after radiotherapy alone for lymphocyte-predominant Hodgkin lymphoma. Cancer. 2005 Aug 10; PMID: 16094666 
Vanishing Bile Duct Syndrome in Hodgkin's Disease:
case report ~ Department of Internal Medicine and Hematology and Blood Transfusion Center, Universidade Estadual de Campinas, Campinas, Brazil  full text | Related PubMed articles
Results of a prospective randomized clinical trial of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by radiation therapy (RT) versus ABVD alone for stages I, II, and IIIA nonbulky Hodgkin disease. Blood. 2004 Dec 1;104(12):3483-9. Epub 2004 Dec 1. PMID: 15315964 | Related articles
Baseline Tumor Burden Predicts Clinical Outcome in Hodgkin Lymphoma  leukemia-lymphoma.org
Prognostic factors in Hodgkin's disease.
Leuk Lymphoma. 2004 Jun;45(6):1133-9. PMID: 15359992 | Related articles
Long Term Outcome in Adolescents with Hodgkin's Lymphoma: Poor Results using Regimens Designed for Adults. Leuk Lymphoma. 2004;45(8):1579-1585. PMID: 15370209
The clinical value of tumor burden at diagnosis in Hodgkin lymphoma.
Cancer. 2004 Sep 15 PMID: 15372482 
Strong impact of highly active antiretroviral therapy on survival in patients with human immunodeficiency virus-associated Hodgkin's disease. Br J Haematol. 2004 May;125(4):455-62. PMID: 15142115 | Related articles
Investigational EBV-based T-cell therapy   Related PubMed abstracts 
Efficacy of vinblastine, bleomycin, methotrexate (VBM) combination chemotherapy with involved field radiotherapy in early stage (I-IIA) Hodgkin disease patients. Leuk Lymphoma. 2003 Nov;44(11):1919-23. Review. PMID: 14738143 | Related articles
Increased serum levels of interleukin-9 correlate to negative prognostic factors in Hodgkin's lymphoma. Leukemia. 2003 Oct 9 [Epub ahead of print] PMID: 14562126 | More
Bispecific antibodies - novel investigative  treatment for refractory Hodgkin's disease  related abstracts
Involved-field radiotherapy for advanced Hodgkin's lymphoma.
N Engl J Med. 2003 Jun 12;348(24):2396-406. PMID: 12802025  PubMed
Epstein-Barr virus and other candidate viruses in the pathogenesis of Hodgkin's disease. Semin Hematol. 1999 Jul;36(3):260-9. Review.
PMID: 10462326  PubMed | Related Abstracts
Severe pruritus should be a B-symptom in Hodgkin's disease.
Cancer. 1983 May 15;51(10):1934-6. PMID: 6831358  PubMed
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.
PMID: 12586796  PubMed
Treatment of relapsed CD20+ Hodgkin lymphoma with the monoclonal antibody rituximab is effective and well tolerated: results of a phase 2 trial of the German Hodgkin Lymphoma Study Group. Blood 2003; 101: 420-424..  PubMed
 
Disclaimer:  The information presented on Lymphomation.org is not intended to be a substitute for 
professional medical advice or to replace your relationship with a physician.
For all medical concerns,  you should always consult your doctor. 
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