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)

Nodular Sclerosis

Mixed Cellularity

Lymphocyte Depleted (fixed)

The pathologic and clinical heterogeneity (variation) of lymphocyte-depleted Hodgkin's disease  http://bit.ly/40Jh7F 

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

	Biology, clinical course and management of nodular lymphocyte-predominant Hodgkin lymphoma   asheducationbook
	Nodular lymphocyte predominant Hodgkin lymphoma Review
	Origin and pathogenesis of nodular lymphocyte–predominant Hodgkin lymphoma as revealed by global gene expression analysis http://www.ncbi.nlm.nih.gov Also see PubMed | ClinicalTrials.gov

Infradiaphragmatic versus supradiaphragmatic Hodgkin lymphoma: a retrospective review of 1114 patients. Leuk Lymphoma. 2005 Dec;46(12):1715-20. PMID: 16263573

CD20 Expression in Hodgkin and Reed-Sternberg Cells of Classical Hodgkin’s Disease: Associations With Presenting Features and Clinical Outcome jco.org 

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.

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."

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 

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

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

Overview  NCI.gov  

NCCN Treatment Guidelines http://www.nccn.org  pdf (req. free registration)

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

Guidance for Parents on Childhood cancers by NCI PDF

A parent's guide to children's cancer  CancerBACUP

All studies

Newly diagnosed or untreated

Recurrent

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 

Panobinostat Produces Objective Responses in Advanced Hodgkin's Lymphoma http://bit.ly/bHEBIb

"Of 129 patients, 4 (3%) had a complete response to panobinostat, 29 (22%) had a partial response (defined as a reduction of tumor size by a least 50%), and 111 were deemed to have disease control (defined as a combination of complete and partial responses and stable disease)

A ceiling is likely going to be reached in relapsed/refractory patients, and the major questions are going to be: Is there sufficient independent activity for efficacy, such as in maintenance?" he said. "Is there synergy, and is it feasible to combine this agent with other therapies? And are there predictive biomarkers?"

HIV-associated Hodgkin's lymphoma (HIV-HL): Results of a prospective multicenter trial http://bit.ly/bpJmKE

"Conclusions: In pts with HIV-HL risk-adapted CT and concomitant HAART is feasible and effective. However, pts must closely be monitored for neutropenic infections. These data suggest that the prognosis of HIV-HD may approach results achieved in the HIV-negative population with HL."  (Which is very good indeed.)

March 2009: Developments in the management of Hodgkin's lymphoma, The Lancet, March 2010

Lisa Lowry a, Peter Hoskin b, David Linch

Biggest take aways:

1) PET & CT/PET scans used pre-treatment result in a change in staging in 4 out of 10 patients, with a change in the treatment plan for 2 of those patients but more care & scrutiny over all.

2) PET & CT/PET scans given mid-course in treatment can predict outcome and treatment plans can be modified earlier. How treatment modification on the basis of such scans affects outcome is still being studied, for example http://clinicaltrials.gov/ct2/show/NCT00433433 .

3) Nodular lymphocyte-predominant Hodgkin's lymphoma pts (a rare and somewhat indolent subtype) respond well to Rituxan and for many of these patients, surgery to remove affected nodes and low dose IFRT (involved-field radiotherapy) may be sufficient treatment resulting in 80% achieving long-term progression free survival (PFS). For those NL-P HL patients, chemo may only be necessary in relapse.

4) Current controversy over treatment recommendations for first timers: Treat with ABDV and accept 20% relapse and then treat the relapsers with heavier chemo vs. offer more aggressive treatment at the outset to all and reduce relapse rates?

5) Small field radiation (IFRT) targeted to specific nodes and immediate area (with complex planning and delivery techniques) controls disease as well as other forms of higher-dose and wider field radiation, but with fewer side effects.

6) Combined modalities (chemo + radiation) enable a reduction of the number of cycles of chemo, which can reduce long term side effects such as heart damage (cardio-toxicity).

7) Patients with clinical stage I or IIA disease without bulk or other adverse risk factors who achieve complete remission from chemo do not derive additional benefit from radiation according to findings. Progression Free Survival is not increased.

8) Patents who are still PET positive after salvage treatment chemo are predicted to do poorly with an autologous stem cell transplant & may wish to consider a reduced-intensity-conditioning allograft (allogeneic BMT or SCT). More research & further studies are needed.

9) As the cure rate for Hodgkin's lymphoma has increased, keeping late effects to a minimum (without decreasing cure rate) has become an important factor in initial management decisions.

10) In one notable trial, escalated BEACOPP showed significant improvement in freedom from treatment failure and overall survival versus a hybrid regimen of COPP-ABVD.

~ PAL editors (Lay summary - as always, discuss with your doctors.)

Hodgkin's treatment destroys tumors with antibody linked to radioactive particle - CHT25 http://bit.ly/CHT25

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 

Results of Conventional Therapy  medscape.com 

Articles on Refractory HD  PubMed

Allogeneic stem cell transplantation in children and adolescents with recurrent and refractory Hodgkin's lymphoma  Blood. 2009 Jun PMID: 19498021

SGN-35 targeting CD30, in patients with relapsed or refractory Hodgkin lymphoma. ASCO 2007 

SGN-35, a novel ADC targeting CD30, was generally well tolerated at doses up to 2.7 mg/kg, and induced multiple objective responses in heavily pretreated pts. These encouraging results indicate SGN-35 should be further evaluated in phase II studies for pts with HL.

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 chemo-responsive 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