Hodgkin's Lymphoma

MaryKate Janita
Epidemiology

 Roughly 10,000 new cases every year, and about a quarter of

those will relapse
 Greatest chance of diagnosis is ages 20-34 years old
 Occurrence in children under 5 is extremely rare
 More prevalent in males than females
 Whites and non-Hispanics of both genders have slightly higher
rates of occurrence compared to other races
Etiology

 Presence of Reed Sternberg cells

 Genetic makeup, environmental exposures, and
infectious agents
 Previous infection with Epstein Barr virus
 Family history
 HIV
Presenting Signs & Symptoms
 Painless mass
 Shortness of breath, cough, chest discomfort
 B symptoms
 Unexplained weightloss of more than 10% of body
weight in 6 months, frequent night sweats, and
unexplained fever higher than 100.4°F
 Pruritus and pain with alcohol ingestion
 Advanced lymphoma: enlarged spleen, tender abdomen,
achy bones, and pleural effusion
Anatomy & Physiology
 Lymphatic system: lymph fluid, lymph nodes, and lymphatic organs
(spleen, thymus, tonsils, adenoids, bone marrow)
 Lymph fluid travels thru the body via nodes and vessels
 Carries antibodies, nutrients, and lymphocytes throughout the
body and provides protection while filtering particles that may
give rise to infection or disease
 Reed Sternberg cell is a giant connective tissue cell that is
characterized by one or two large nuclei
Lymph Node Drainage
 Waldeyers Ring
 Occipital
 Cervical
 Preauricular
 Supraclav
 Infraclavicular
 Axillary
 Epitrochlear
 Mediastinal
 Rt. & Lt. Hilar
 Para Aortic
 Splenic
 Mesenteric
 Iliac
 Inguinal/femoral
 Popliteal
Staging
 Ann Arbor staging system
 A: Patient does not have B symptoms
 B:The patient has B symptoms
 E: Extranodal disease is present
 S: Disease is found in the spleen
 Stage I: involvement of a single Lymphnode region or localized involvement of a
single extralymphatic organ or site in the absence of any lymph node
involvement
 Stage II: Involvement of two or more lymph node regions on the same side of the
diaphragm, or localized involvement of a single extralymphatic organ or site in
association with regional lymph node involvement with or without involvement of
other lymph node regions on the same side of the diaphragm.
 Stage III: Involvement of lymph node regions on both sides of the diaphragm,
which also may be accompanied by an extralymphatic extension in association
with adjacent lymph node involvement or by involvement of the spleen
 Stage IV: Diffuse or disseminated involvement of one or more extralymphatic
organs with or without associated lymph node involvement or isolated
extralymphatic organ involvement in the absence of adjacent regional lymph
node involvement, but in conjunction with disease in distant sites.
Common Site for Distant Metastasis
 Spread of disease mimics the route of the
lymphatic system
 Can also be spread thru direct extension from the
lymphatic system to areas such as the viscera,
spleen, liver, bone marrow, or other organs.
Treatment for Hodgkin’s Lymphoma
 Best treatment modality for early stage HL is
chemotherapy
Stages I and II
 Four cycles of ABVD
 Use MOPP for patients at risk of heart failure
 Standford V (8 weeks)
 nitrogen mustard, Adriamycin, oncovin, prednisone,
bleomycin, vinblastine, etoposide
 Radiation may be used with early stage HL if bulky/local
disease
Treatment for Hodgkin’s Lymphoma
Stages III and IV with bulky disease or B symptoms
 Chemotherapy and adjuvant radiation therapy
In cases of reoccurrence, chemotherapy can be used for areas
that have already been treated with radiation, this is known as
salvage therapy
If both chemo and radiation fail, patients can receive allogenic
bone marrow and peripheral blood stem cell transplant
 Monoclonal Antibody Therapy
 Developed in a laboratory and are designed to attach to
specific cancer causing growths that either kill or prevent
cancer cells from growing.
 Brentuximab vedotin and Rituximab are currently used
 Clinical Trails on effectiveness
Radiation Therapy Treatment Techniques
 Neck, chest, axilla, or para-aortic lymph nodes and spleen
 Due to predictable spread, prophylactic treatment to
subsequent nodes surrounding the disease
 Mantle Field: neck, chest and axilla
 Inverted Y: pelvis and para-aortic
 These field together: total nodal radiation
 Radiation alone: 35 to 44 Gy with 6-10MV to areas free of
disease and 25 to 30Gy to areas of initial nodal involvement
 Radiation and Chemo: 20Gy with 6-10MV
 Mantle Field
 Cervical, submandibular, axillary, supraclavicular, infraclavicular, mediastinal, and hilar lymph nodes
 Patients are treated supine, with hands above head or akimbo, with chin extended.
 AP/PA with lung, humeral head, occipital, anterior larynx, and spinal cord blocks
 Borders: superior-lower mandible and mastoid tips, inferior-t9/t10 interspace, lateral- flash beyond
the axillary nodes
Para-aortic Field
 Spleen, para-aortics, and retroperitoneal nodes are treated AP/PA
 Setup same as mantle field just incase more fields are added
 Spinal block and kidney block if spleen is to be treated
 Borders: Superior- mid T10/T11, inferior- L4/L5, lateral- 9cm to 10cm wide of
midline.
Pelvic Field
 Blocks are used to protect bone marrow, bowel, and the bladder
 Preserving fertility is especially important
 May use blocks to shield ovaries/testes or females can undergo an oophoropexy
 Borders: Superior-L5, inferior-2cm below ischial tuberosity, lateral- 2cm
beyond pelvic inlet
New Treatment #1
 To reduce intensity without minimizing effectiveness of ABVD by omitting
Bleomycin and Decarbazine from the regimen
 HL has become one of the most curable malignant diseases, therefore severity
of side effects to treatment is very important for long term survival
 1502 patients randomized into four groups, ABVD, ABV, AVD, and AV.
 All patients were newly diagnosed stage I or II with classical or nodular HL, median
age of 39 years old, 60% being men
 All four regimens were given on days 1 and 15 of 4 week cycles at standard doses
 Each patients also received 30Gy of RT in 4-6 weeks 180-200 cGy 5 days a week
Overall at 5 years, freedom from treatment failure (FFTF) for ABVD=93.1%,
ABV=89.2%, AVD=89.2%, and AV=77.1%
 Leukopenia was the most common side effect
 Alopecia, nausea & vomiting, pain, infections
 Patients who had WHO grade III or IV toxicity: ABVD=33%, ABV=28%, AVD=26%,
AV=26%
New Treatment #1 continued
 Important to note that both groups where Decarbazine
was omitted from the regimen had to be stopped early
because most patients had progressive disease/early
relapse
 However overall survival did not have significant
difference between each of the treatment groups
 AV with FFTF of 77.1% still had five year survival of
98.1%

Longer follow up would be needed to wage survival and side

effects with effectiveness of different regimens.
New Treatment #2
 Reed-Sternberg cells exploit programmed cell death (PD-1) pathway
to evade immune detection.
 Nivolumab (Opdivo) which is a monoclonal antibody can inhibit
disease evasion safely and effectively in cases of relapsed HL.
 23 patients with relapse or refractory (resistant to other treatments)
 At least 18 years of age (median age of 35), Previous treatment
with at least one chemo regimen, already received an average of
3+ treatments, One lesion measuring at least 1.5cm, and No
autologous stem cell transplant within the last 100 days
 Received dose of 3mg per kg of body weight every two weeks until
complete response, tumor progression, or excessive toxic effects for a
maximum of up to two years
 Patients were assessed throughout the study and for around 100
days after the last dose
 CT/PET imaging
New Treatment #2 Continued:
 SAFETY
 Safety: 78% (18 patients) had low grade
reaction to the drug most commonly rash and
decrease platelet count
 5% (5 patients) of patients had grade 3 adverse
events such as myelodysplastic syndrome,
pancreatitis, pneumonitis, stomatitis, colitis,
etc.
 There were no grade 4-5 reactions
 3 patients with grade three side effects
received extensive treatments prior to this
study
 EFFECTIVENESS
 Some type of response in 87% (20 patients) (95% confidence
interval) while 13% had stable disease (no change)
 17% (4 pts) had complete response while 70% (16 patients) had
partial response
 60% of these patients had response within the first 8 weeks
 Progression free survival at 24 weeks was 86%

 12 patients chose to discontinue treatment

 2 had toxic effects
 Were reversible
 4 had progressive disease during treatment
 6 elected to undergo an allogenic stem-cell transplant
 11 patients continued to participate in the study, therefore
median overall survival has not been reached.
Side Effects of Different Treatments
 Chemotherapy
 Cardiotoxicity, fatigue, nausea and vomiting, alopecia, leukopenia,
infection, difficulties with GI tract, difficulties with respiratory
tract
 Radiation
 Fatigue, alopecia, akin erythema, esophagitis, altered tastes,
dysphagia, dry cough, nausea, vomiting, and diarrhea
 Hypothyroidism, cardiac disease, radiation pneumonitis, increased
dental caries, xerostomia, secondary malignancy
 Nivolumab
 Thrombocytopenia and rash
 Myelodysplastic syndrome, pancreatitis, pneumonitis, stomatitis,
colitis, gastrointestinal inflammation, and thrombocytopenia
Prognosis & Survival of Treatments
Stage Five Year Survival %
I 90%-95%
II 90%-95%
III 85%-90%
IV 65%

Regimen Five Year Survival %

ABVD 97%
ABV 94%
AVD 97.6%
AV 98%

Worse prognosis if: B symptoms, bulky disease, older than 45, male, etc.
The "Best" Treatment Option
 ABVD chemo regimen proves to be the best treatment for patients
with early onset disease
 Due to many different prognostic factors effecting survival
rates/treatments, it is very difficult to say which treatment is the
“best” treatment.
 For patients who have tried chemotherapy, radiation, and stem-cell
transplants and continue to relapse, target therapy such as Nivolumab
could be a potential treatment to help slow progression.
 More research needs to be done of the effect of using Nivolumab
with a history of past treatments and how those may effect this
new targeted therapy. For example, two of the patients who
received toxic effects had extensive chemo and radiation prior to
using Nivolumab. Why?
References
 Ansell SM, Lesokhin AM, et al. Pd-1 Blockade with Nivolumab in Relapsed or
Refractory Hodgkin's Lymphoma. The New England Journal of Medicine. 2015;
372(2), 311-319.
 Behringer K, Goergen H. Omission of dacarbazine or bleomycin, or both, from
the ABVD regimen in treatment of early-stage favourable Hodgkin's
lymphoma. Lancet (london, England). 2015; 385(9976), 1371-1373.
 Nivolumab shows promise for Hodgkin's lymphoma. Mayo Clinic Cancer
Center's Online Magazine. 2015; 4(1).
 Trad ML. : Washington CM, Leaver DT, eds. Lymphoreticular System Tumors.
Principles and Practice of Radiation Therapy. 4th edition. St. Louis, MI:
Elsevier Health Sciences; 2016.