Transcript Pediatric Case Management By Richard Lirio,MD 16th June 2010 History  14 y/o Caucasian Female   h/o seizure disorder, autism, developmental delay Referred to Hem-Onc clinic for:    Progressively worsening cough Neck.

Pediatric Case Management
By
Richard Lirio,MD
16th June 2010
History
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14 y/o Caucasian Female
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h/o seizure disorder, autism, developmental
delay
Referred to Hem-Onc clinic for:
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Progressively worsening cough
Neck swelling
Abnormal chest x-ray
History
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Over the past 3 mos
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Increasing cough
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Axillary lymphadenopathy ~ 2 mos prior
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Initially treated with Abx  improved
Exacerbated by lying supine
Associated with respiratory distress
Also treated with Abx  improved
Past few weeks b/l neck swelling
Swelling of face
5-6 lbs weight loss
No fevers, N/V/D, bone pain, or neuro changes
Past Medical History
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No prior hospitalizations
No surgical hx
+ seizure disorder
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Levetiracetam
Clonazepam
Lamotrigine
+ autism
+ developmental delay
Physical Examination
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NAD, slightly anxious, slightly thin
female, interactive, leaning forward
T = 35.8, RR 22, HR 133, BP 102/69,
O2 sats 98% on RA
HEENT - WNL
B/L supraclavicular adenopathy
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Large, firm, 5x8cm each, NT
Physical Examination
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Some swelling noted on anterior chest
wall with increased prominence of
anterior chest wall veins
No breath sounds on the left; clear on
the right
PMI shifted to the midline; no m/r/g
Abdo soft, NT, ND, No HSM
Labs
9.4
138
695
15.3
3.7
99
12
84
27
.72
10.5
30.3
6 B, 66 N, 12 L, 10 M
ESR 94
Phos 7.7, Mg 2.3
Alb 3.9 , TP 7.7
LDH 686, AP 91
AST 24, ALT 8, TB 0.3
Uric Acid 5.2
Differential Diagnosis
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Non-Hodgkin lymphoma
Metastatic adenopathy from other
primary tumors
Toxoplasmosis
Mycobacterium
EBV
SLE
Pathology
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Biopsy
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Classical Hodgkin Lymphoma
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Nodular sclerosis subtype
Bone marrow aspirates
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Active tri-lineage haematopoiesis
No evidence of malignancy
Objectives
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To discuss the epidemiology, presentation, &
diagnostic evaluation for Hodgkin’s
Lymphoma
To discuss the differential diagnosis for
anterior mediastinal masses
To discuss the treatment for Hodgkin’s
Lymphoma
To discuss new development regarding
prognostic indicators for Hodgkin’s Lymphoma
History
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Highly curable malignant disease
First cancer to be cured with radiation or with
a combination of several chemotherapy
agents
Therapeutic success  long-term toxicities
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30-year survivor is more likely to die of therapyrelated complications than from HL
current risk-adapted, response-based approach to
treatment
Pathophysiology
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B-cell malignant disorder that affects
the reticuloendothelial and lymphatic
systems
Can affect other organs and systems,
predominantly the lungs, bone, bone
marrow, liver parenchyma, and, rarely,
the CNS
Pathophysiology
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Epidemiologic data suggest environmental,
genetic, and immunologic factors are involved
Clustering of cases in families or racial groups
supports the idea of a genetic predisposition
or a common environmental factor
In identical twins of patients with HL, the risk
of developing HL is higher than that of other
first-degree relatives
Subjects with acquired or congenital
immunodeficiency disorders also have an
increased risk of developing HL
Pathophysiology
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Findings from several epidemiologic
studies suggest links between HL and
certain viral illnesses
The strongest case to date is a
relationship to EBV
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EBV viral DNA can be found in HodgkinReed-Sternberg (HRS) cells
25-50% of cases of classical HL in
developed countries are EBV +
Incidence
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Age-adjusted standardized rate (ASR) in
North America, western Europe, and Oceania
is usually just below 7 cases per million
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For children and adolescents younger than 15
years, the incidence is 5.5 cases per million
For individuals aged 15-20 years, the incidence is
12.1 cases per million
Western Asia (from the Mediterranean to
northwest India), the ASR is consistently
higher than 7 cases per million
Incidence
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In the US, the incidence among whites
and blacks is essentially the same.
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However, the ratio is 1.4:1 in children older
than 10 years
A significant male-to-female
predominance of 3:1 is observed in
children younger than 10 years
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In older children and adults, the male-tofemale ratio is about 1:1
Incidence
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The incidences by age show a bimodal
distribution
In developed nations, the first peak occurs at
approximately age 20, and the second peak is
observed in patients aged 55 years or older
HL is uncommon before age 5 years.
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However, in developing countries, the first peak is
shifted into childhood, usually before adolescence
History
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Persistent painless adenopathy
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More than 70% of patients with HL present
with cervical lymphadenopathy
Patients with mediastinal adenopathy may
present with respiratory symptoms such as
shortness of breath, chest pain, or cough
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at risk for respiratory failure, especially if they
undergo sedation or anesthesia for diagnostic
procedures
History
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Patients with HL may present with
symptoms associated with advanced
disease & adverse prognosis (B –
designation)
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Unexplained fever with temperatures
above 38°C for 3 consecutive days
Unexplained weight loss of 10% or more in
the previous 6 months
Drenching night sweats
Diagnostic Evaluation
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In addition to stage and male sex,
certain laboratory findings suggest poor
prognostic factors
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Hemoglobin < 10.5 g/dL
WBC count of 15,000/μL or less
Absolute lymphocyte count < 800/μL
Albumin level < 4 g/dL
ESR > 50
Imaging
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Chest XR – AP and lateral
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CT or MRI of neck, chest, abdomen, and/or
pelvis
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Mediastinal mass with a thoracic ratio of 33% or
greater is of prognostic importance
to assess sites of disease (nodal and extranodal)
as well as to assess liver and spleen involvement
PET scans
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to identify the extent of disease at diagnosis and
for follow up
Staging
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The most widely used staging system is the Ann
Arbor staging system.
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Stage I - Single lymph node region or single extranodal site
Stage II - Two or more lymph node regions on the same
side of the diaphragm
Stage III - Lymph node regions on both sides of the
diaphragm
Stage IV - Diffuse or disseminated involvement of one or
more extralymphatic organs (liver, bone marrow, lung) or
tissues with or without associated lymph node involvement
(The spleen is considered a nodal site.)
A vs B
Treatment
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Hodgkin lymphoma can be cured with
radiation therapy, chemotherapy, or a
combination of both.
Acute and late toxicities vary depending
on treatment
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Balance between reducing late effects of
therapy vs. maintaining cure rates
Treatment based on Stage
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Standard treatment regimens for pediatric Hodgkin lymphoma are as
follows:
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Early or favorable disease (stage IA or IIA with <3 nodal sites)
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Intermediate-risk disease (stage IA, IIA, or IIA bulky disease with
extension or >3 nodal sites):
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2-4 chemotherapy cycles without alkylators (VAMP; etoposide, bleomycin,
vinblastine, and prednisone [EBVP]; OEPA; or ABVE) plus low-dose, involved-field
radiation of 15-30 Gy or 6 chemotherapy cycles (alternating COPP and ABVD or
derivatives of these regimens) and no irradiation. The use of very limited doses of
chemotherapy (2-3 cycles) should be administered only as part of a clinical trial.
4-6 chemotherapy cycles (OPPA and COPP, Stanford V) plus low-dose, involvedfield radiation of 15-30 Gy or 6 chemotherapy cycles (alternating COPP and ABVD
or their derivatives) or a dose-intense, hybrid regimen (eg, Stanford V, ABVE-PC,
or BEACOPP) and no irradiation.
Advanced or unfavorable disease (stages IIB, IIIB, or IV):
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6-8 chemotherapy cycles (OPPA and/or COPP, ABVE-PC, BEACOPP) plus low-dose
involved-field radiation of 15-30 Gy or 6-8 chemotherapy cycles (alternating
COPP and ABVD or their derivatives) or a dose-intense, hybrid regimen (ABVE-PC
or BEACOPP) and no irradiation.
Acute Effects of Treatment
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Radiation
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Erythema +/hyperpigmentation
Transient hair
thinning
GI sx
Dry mouth or altered
taste
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Chemotherapy
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N/V
Alopecia
Myelosuppression
Immunosuppression
Late Complications
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Impaired growth of soft tissue and
bones
Thyroid dysfunction
Gonadal dysfunction
Cardiopulmonary toxicity
Second malignancies
Functional impairment and reduced
overall general health
Steidl et al.
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New England Journal of Medicine
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About 20% of HL patients cannot be cured
About 20% of HL patients are over-treated
"An increased number of tumor-associated
macrophages was strongly associated with
shortened survival in patients with classic
Hodgkin's lymphoma, and provides a new
biomarker for risk stratification"
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The tumor-associated macrophages were identified by a
single marker of CD68+ cells
Steidl et al. Tumor-Associated Macrophages and Survival in Classic Hodgkin’s Lymphoma. N
Engl J Med. 2010; Vol 362, No 10:875-85
Tumor-Associated
Macrophages
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Previously, thought that macrophages
were a manifestation of an immune
response against the tumor
Currently, Lewis et al (2006) link the
presence of tumor-associated
macrophages with a poor prognosis
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Possibly by increasing blood-vessel
formation through the secretion of vascular
endothelial growth factor
Steidl et al.. N Engl J Med. 2010; Vol 362, No 10:875-85
Implications of CD68 marker
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Identify the subgroup of patients with
HL who have a poor prognosis and
prescribe aggressive treatment with
both radiotherapy and combination
chemotherapy
Would spare majority of the patients
from over treatment and associated
toxicities
Steidl et al.. N Engl J Med. 2010; Vol 362, No 10:875-85
References
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Jemal et al. Cancer statistics, 2009. CA Cancer J Clin 2009;59:225
Alexander et al. Risk factors for Hodgkin’s disease by EBV antibodies –
a prospective study. Br J Cancer 2000; 82:1117
Steidl et al. Tumor-Associated Macrophages and Survival in Classic
Hodgkin’s Lymphoma. N Engl J Med. 2010;Vol 362; No 10: 875-85
Lewis et al. Distinct role of macrophages in different tumor
microenvironments. Cancer Res 2006;66:605-12
Pollard et al. Trophic macrophages in development and disease. Nat
Rev Immuno 2009;9:259-70
Montovani et al. The origin and function of tumor-associated
macrophages. Immunol Today 1992;13:265-70
DeVita et al. A selective history of the therapy of Hodgkin’s disese. Br J
Haematol 2003;122:718-27
www.instantanatomy.net (figure)