Hodgkin disease

Section 4
Lymphomas
 Lymphomas
• Lymphomas are a group of diseases caused by
malignant lymphocytes that accumulate in lymph nodes
and cause the characteristic clinical features of
lymphadenopathy.
• Occasionally, they may spill over into blood (leukaemic
phase) or infiltrate organs outside the lymphoid tissue.
• The major subdivision of lymphomas is into Hodgkin
lymphoma and non - Hodgkin lymphoma and this is
based on the histological presence of Reed – Sternberg
(RS) cells in Hodgkin lymphoma.
 Hodgkin lymphoma
• The disease can present at any age but is rare
in children and has a peak incidence in young
adults.
• There is an almost 2 : 1 male predominance.
The following symptoms are common:
 Clinical features of Hodgkin
lymphoma
1. lymphadenopathy:
• Most patients present with painless, non-tender, asymmetrical, firm,
discrete and rubbery enlargement of superficial lymph nodes .
• The cervical nodes are involved in 60 – 70% of patients, axillary
nodes in approximately 10 – 15% and inguinal nodes in 6 – 12%.
• In some cases the size of the nodes decreases and increases
spontaneously. Typically, the disease is single peripheral lymph node
region and its subsequent progression is by contiguity within the
lymphatic system. Retroperitoneal nodes are also often involved but
usually only diagnosed by computed tomography (CT) scan.
localized, initially to
 Clinical features of Hodgkin
lymphoma
2. Modest splenomegaly
occurs during the course of the disease in 50% of patients.
The liver may also be enlarged because of liver involvement.

3. Mediastinal involvement is found in up to 10% of patients

at presentation. This is a feature of the nodular sclerosing
type, particularly in young women.

4. Cutaneous Hodgkin lymphoma occurs as a late

complication in approximately 10% of patients. Other organs
(e.g. bone marrow, gastrointestinal tract, bone, lung, spinal
cord or brain) may also be involved, even at presentation, but
this is unusual.
 Clinical features of Hodgkin
lymphoma
5. Constitutional symptoms are prominent in
patients with widespread disease. The following
may be seen:
• Fever,
• Drenching night sweats and
• weight loss more than 10% of body mass over 6
months
 Diagnosis of Hodgkin disease
• Diagnosis requires the presence of Reed–Sternberg cells in the
lymph node biopsy.
• Clinical staging is based on :
o Noninvasive procedures such as history, physical examination,
laboratory tests(CBC with differential , LFTs ,renal fuctions ,LDH and
ESR), and radiography, including positron emission tomography (PET)
and CT to neck, chest, abdomen, and pelvis.
• Pathologic staging is based on:
o Biopsy findings of strategic sites (eg, bone marrow, spleen, and
abdominal nodes) using an invasive procedure.
Hodgkin disease
Classical Hodgkin disease
Nodular lymphocyte predominant
Hodgkin disease
 Haematological and biochemical
findings of HL
1. anaemia is most common.
Bone marrow involvement is unusual in early disease but if it
occurs bone marrow failure may develop with a leucoerythroblastic
anaemia.
2. One - third of patients have a neutrophilia; eosinophilia
is frequent.
3. Advanced disease is associated with lymphopenia and loss
of cell - mediated immunity.
4. The platelet count is normal or increased during early
disease and reduced in later stages.
5. The ESR and C-reactive protein are usually raised and are
useful in monitoring disease progress.
6. Serum LDH is raised initially in 30 – 40% of cases
Hodgkin disease
 Histological classification of Hodgkin
disease
• Histological classification is into four classic types(RS-
cells) and nodular lymphocyte predominant
disease(popcorn cells).
• each type of HL implies a different prognosis.
• Nodular sclerosis and mixed cellularity are most
frequent.
• Patients with lymphocyte rich histology have the most
favourable prognosis of classic Hodgkin lymphoma.
• Nodular lymphocyte predominant does not show RS
cells and has many features of NHL and may be treated
as such.
Histological classification of Hodgkin
disease
Subtype Characteristics
•Accounts for 70 percent of classical Hodgkin lymphoma cases
•Most common type in young adults .
•Involved lymph nodes contain elements of fibrous tissues (sclerosis)
Nodular Sclerosis •Incidence similar in males and females
•Highly curable
•B symptoms in approximately 40 percent of cases
•Worst prognosis , similar to NHL
•Accounts for 20-25 percent of classical Hodgkin lymphoma cases
•Most common in older adults
•Most common in males
•More prevalent in patients with HIV (human immunodeficiency virus)
Mixed Cellularity
infection
•Involved lymph nodes contain Reed-Sternberg cells and several other
cell types
•B symptoms common
•Accounts for approximately 5 percent of classical Hodgkin lymphoma
cases
•Involved lymph nodes contain numerous normal
appearing lymphocytes and Reed-Sternberg cells
Lymphocyte-rich
•Usually diagnosed at an early stage
•More common in males
•B symptoms are rare
•Most favarable prognosis
•Rarest classical Hodgkin lymphoma subtype
•Involved lymph nodes contain few normal lymphocytes and numerous
Reed-Sternberg cells
Lymphocyte-depleted •Median age range 30-37 years
•More prevalent in patients with HIV infection
•Usually diagnosed at an advance stage
 Staging of Hodgkin disease
• The selection of appropriate treatment depends on
accurate staging of the extent of disease.
• Staging is performed by thorough clinical examination
together with chest X - ray and CT scan to detect
intrathoracic, intra - abdominal or pelvic disease.
• It is also used to monitor response to therapy.
• Magnetic resonance imaging (MRI) scanning may be
needed for particular sites.
• Bone marrow trephine is sometimes carried out and
liver biopsy may be needed in difficult cases. Positron
emission tomography (PET) scanning is also useful in
staging and is combine.
Staging of Hodgkin disease
Staging of Hodgkin disease
 Prognosis of Hodgkin disease
• At diagnosis, approximately half of patients have
localized disease (stages I, II, and IIE) and the others
have advanced disease, of which 10%–15% is stage
IV.
• Prognosis predominantly depends on age and amount
of disease;
o patients older than 65–70 years have a lower cure rate than
younger patients.
o Patients with limited stage disease (stages I and II) have a
90%–95% cure rate, whereas those with advanced disease
(stages III and IV) have a 60%–80% cure rate.
 Hodgkin disease
Hodgkin lymphoma (HL) cases are generally classified
into the three subgroups described below:
• Early-stage favorable: stage I to II with no
unfavorable risk factors
• Early-stage unfavorable: stage I to II with one or
more of the following unfavorable risk factors.
• Advanced stage: stage III to IV
 Hodgkin disease
• Unfavorable risk factors:
 Hodgkin disease
The International Prognostic Factors Project Score for Advanced Hodgkin
Lymphoma(Seven factors provide a basis for recommending either aggressive or
less-intensive treatment options
Risk Factors):

Risk Factors
Serum albumin (<4 g/dL [40 g/L])
Hemoglobin (<10.5 g/dL [105 g/L; 6.52 mmol/L])
Male gender
Stage IV disease
Age (≥45 years)
3
White blood cell (WBC) count (≥15,000 cells/mm [15 ×
9
10 /L])
3 9
Lymphocytopenia (<600 cells/mm [0.6 × 10 /L] or <8%
of WBC count)
 The International Prognostic Factors Project Score for
Advanced Hodgkin Lymphoma

• The prognosis depends on age, stage and

histology.
• The International Prognostic Score (Hansclever
Index) is useful for patients with advanced
disease.
– It includes seven factors and each of these is
associated with an 8% reduction in the predicted
5 year disease - free progression rate.
 Hodgkin disease

• the initial treatment goal for all stages of Hodgkin

lymphoma is cure plus minimizing short- and
long-term treatment-related complications.
 Hodgkin disease
• Treatment options include radiation therapy (RT),
chemotherapy, or both (combined-modality
therapy). The therapeutic role of surgery is
limited, regardless of stage.

• RT is an integral part of treatment and can be used

alone for select patients with early-stage disease,
although most patients will receive chemotherapy
and radiation.
 Hodgkin disease

• Initial treatment of classical Hodgkin lymphoma:

ABVD, Stanford V, and some version of BEACOPP..
• For patients with refractory or recurrent disease,
salvage therapy consists of multi-agent chemotherapy
with or without high-dose chemotherapy and
autologous hematopoietic stem cell transplantation
(HSCT).
Hodgkin disease
 Hodgkin disease
• Early stage favorable disease can be treated with two cycles
of ABVD alone or plus ISRT or two to four cycles of the
Stanford V regimen followed by a restaging PET-CT scan.
• Depending on the response to the initial chemotherapy,
consolidative ISRT is recommended if anything less than a
complete response is achieved. (radiation is optional)
• With this approach, 5-year progression-free and overall
survival rates of more than 90% can be achieved in early stage
favorable disease.
 Hodgkin disease
• Early stage unfavorable disease can be treated with
the standard ABVD plus ISRT, but the Stanford V
regimen plus radiation or BEACOPP for two cycles
followed by ABVD for two cycles are both
alternatives in select patients.(radiation is essential)
 Hodgkin disease
• There are several approaches to the initial treatment of stages
III and IV Hodgkin lymphoma.
• A standard treatment of advanced stage Hodgkin lymphoma is
to administer two cycles of ABVD chemotherapy followed by
a restaging PET-CT.
o If minimal disease is found (Deauville score 1-3), four additional
courses of ABVD should be given (total of six cycles).
o If residual disease is suspected (Deauville score 4-5), a switch to
escalated-BEACOPP for four cycles should be considered.
Hodgkin disease
 Hodgkin disease
• No further treatment is needed for patients who achieve a
complete remission (Deauville 1-2) with chemotherapy alone.
• Patients who achieve a partial remission (Deauville 3-5)
should be considered for consolidative radiation to residual
sites of disease.
• As with all stages and risk-groups of Hodgkin lymphoma, if a
Deauville score of 5 remains after completion of initial
chemotherapy, a biopsy is recommended to determine if
refractory disease is present.
 Hodgkin disease
Treatment of Refractory or Relapsed Disease:
• Autologous HSCT
• Brentuximab vedotin
 Hodgkin disease
Long-Term Complications
o Gonadal dysfunction (including sterility and
hypothyroidism),
o Secondary malignancies(leukemia, Solid tumors, including
breast cancers, gastrointestinal cancers, and lung cancers),
and
o Cardiopulmonary diseases
o Almost all men and up to 50% of premenopausal women
treated with six cycles of regimens containing alkylating
agents become sterile.
 Hodgkin disease
• Regular mammograms and breast MRI are recommended
starting 10 years following the completion of therapy or at age
40 (whichever is earlier) for females.
• Patients are at increased risk of lung cancer if they have a
smoking history, chest irradiation, and/or alkylating agent
exposure.
• These patients should be considered for low-dose screening
chest CT.
 Hodgkin disease
• For cardiovascular monitoring, annual blood pressure
monitoring and aggressive management of cardiovascular risk
factors are strongly encouraged.
• Hypothyroidism is reported in about 50% of long-term
survivors who received irradiation to this area. Thyroid
function tests should be performed annually.
• Monitoring and follow-up should be personalized and patient-
specific, after assessing a patient’s risks for long-term
complications.
 Follow-up of HL
• Typically, follow-up visits are scheduled every 3 months
during the initial 2 years, followed by a reduction to every 6
months for the subsequent 3 years. Afterward, the frequency is
further reduced to annual visits.
• In addition, a CBC, metabolic panel, and serum lactate
dehydrogenase are recommended. Surveillance scans after
remission are discouraged, especially for DLBCL and HL and
only ordered by clinical indications because the false-positive
rate with PET scans is greater than 20%, leading to
unnecessary investigations, radiation exposure, biopsies,
expense, and patient anxiety
 Hodgkin disease
HPI
• E.J. is a 28-year-old woman who presents with 2
months of swollen lymph nodes in her neck and right
axilla. She states that the nodes in her neck “come
and go” but are always somewhat swollen; she relates
this to a sore throat. The node in the axilla has been
consistently swollen and painless during this time.
She also complains of new-onset fatigue and general
back pain for the last 4–5 months. She denies any
shortness of breath but has experienced fever, night
sweats, and weight loss for the past few months.
 Hodgkin disease
PMH
• She has been suffering from GERD for the last 7 years.
SH
• The patient’s parents and five siblings are all in good
health. There is a history of breast cancer and colon
cancer in her family. The patient is recently married and
wishes to have a family. She drinks socially about two
glasses of wine per week. She began smoking at the age
of 18 and smoked socially, two cigarettes a week, until
the age of 24. She has not smoked since. She does not use
street drugs.
 Hodgkin disease
Medications:
• Ranitidine: 300 mg PO once daily.
• She has no known drug allergies.
Physical examination:
• Gen: Young, healthy-appearing woman in no
apparent distress.
• VS: T 36.8 (36.5–37.5) °C, BP 130/80 (120/80–
140/90), HR 80 (60– 100), RR 17 (12–20).
• Wt: 68 kg.
• Ht: 165 cm.
 Hodgkin disease
• Skin: Soft, diffusely enlarged soft tissue swelling
around neck and right axilla; no erythema or warmth;
no rashes.
• HEENT: PERRLA, EOMI.
• Lymph nodes: Anterior cervical lymph nodes on the
right side are enlarged. Right axillary nodes are
palpable.
• Cor: RRR, normal
 Hodgkin disease
• Chest: Respirations with normal rhythm; clear
to auscultation.
• Abd: Soft and nontender with no masses;
bowel sounds are normoactive.
• Ext: Warm, no C/C/E.
• Neuro: A&O × 3, CN II–XII intact.
 Hodgkin disease
Laboratory findings:
• WBCs 10.9 (4–10) ×109 /L
• Lymphs 13.2 (25–35) %
• Hct 37.8 (36–44) %
• Hgb 12.5 (12–15) g/dL
• Plts 390 (140–440) ×109 /L
• SCr 0.7 (0.6–1.1) mg/dL
• BUN 14 (8–25) mg/dL
• AST 19 (11–47) IU/L
• ALT 22 (7–53) IU/L
• T. bili 0.4 (0.3–1.1) mg/dL
• Alb 4 (3.5–5.0) g/dL
• LDH 290 (100–250) IU/L
 Hodgkin disease
• Other investigations:
An ultrasound of the neck and right axilla
showed a number of enlarged lymph nodes
ranging from 1.5 to 3 cm. As a result, a lymph
node excisional biopsy was performed that
demonstrated Reed-Sternberg cells classifying
this as Hodgkin’s disease , nodular sclerosis type.
 Hodgkin disease
• CT and PET scans showed involvement of the
superior mediastinal and hilar nodal chains within the
chest. There are multiple, enlarged para-aortic and
right iliac lymph nodes in the abdomen and pelvis.
• Bone Marrow Biopsy is negative.
• The bilateral lungs and myocardium are negative for
disease.
• Normal physiologic liver, GI, and urinary activity is
noted.
 Hodgkin disease
1)According to Ann Arbor staging system, what is the
stage of this case? Why?
3B
2) The subscript “B” following the stage designation of a
Hodgkin’s disease indicates that:
a. The patient has a mediastinal disease.
b. The disease is relapsed following initial therapy or was
refractory to initial therapy.
c. The patient has constitutional symptoms, including fever,
night sweats, and weight loss.
d. The disease is bulk
 Hodgkin disease
3) Adverse prognostic signs for advanced Hodgkin's disease
include (according to International Prognostic Score):
a. Age over 45, male gender, more than one extranodal site of
disease.
b. Age over 60, more than one extranodal site of disease,
lymphocytic count greater than 8%.
c. More than one extranodal site of disease, serum creatinine
greater than 1.5.
d. Age under 45, poor performance status
 Hodgkin disease
4) What is the goal of therapy for E.J.’s advanced
disease?
Curable disease with high survival rate
 Hodgkin disease
5) ABVD has replaced MOPP as the standard
regimen for advanced Hodgkin lymphoma
because:
a. It has less acute toxicities and long-term
complications.
b. It is cheaper.
c. It provides better outcomes.
d. a & c.
 Hodgkin disease
• 6) What is appropriate initial therapy for E.J.?
• A standard treatment of advanced stage Hodgkin lymphoma
is to administer two cycles of ABVD chemotherapy followed
by a restaging PET-CT.
o If minimal disease is found (Deauville score 1-3), four additional
courses of ABVD should be given (total of six cycles).
o If residual disease is suspected (Deauville score 4-5), a switch to
escalated-BEACOPP for four cycles should be considered.
Thank you