pediatric case management by richard lirio,md 16 th june 2010
TRANSCRIPT
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Pediatric Case ManagementBy
Richard Lirio,MD16th June 2010
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History
14 y/o Caucasian Female h/o seizure disorder, autism,
developmental delay Referred to Hem-Onc clinic for:
Progressively worsening cough Neck swelling Abnormal chest x-ray
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History Over the past 3 mos
Increasing cough Initially treated with Abx improved Exacerbated by lying supine Associated with respiratory distress
Axillary lymphadenopathy ~ 2 mos prior 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
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Past Medical History No prior hospitalizations No surgical hx + seizure disorder
Levetiracetam Clonazepam Lamotrigine
+ autism + developmental delay
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Physical Examination
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
Large, firm, 5x8cm each, NT
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Physical Examination
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
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Labs
15.3
9.4
30.3
695
6 B, 66 N, 12 L, 10 M
ESR 94
3.7
99
27
12
.72
138
84
10.5
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
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Differential Diagnosis
Non-Hodgkin lymphoma Metastatic adenopathy from other
primary tumors Toxoplasmosis Mycobacterium EBV SLE
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Pathology
Biopsy Classical Hodgkin Lymphoma
Nodular sclerosis subtype
Bone marrow aspirates Active tri-lineage haematopoiesis No evidence of malignancy
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Objectives 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
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History Highly curable malignant disease First cancer to be cured with radiation or
with a combination of several chemotherapy agents
Therapeutic success long-term toxicities 30-year survivor is more likely to die of
therapy-related complications than from HL current risk-adapted, response-based
approach to treatment
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Pathophysiology
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
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Pathophysiology 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
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Pathophysiology
Findings from several epidemiologic studies suggest links between HL and certain viral illnesses
The strongest case to date is a relationship to EBV EBV viral DNA can be found in
Hodgkin-Reed-Sternberg (HRS) cells 25-50% of cases of classical HL in
developed countries are EBV +
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Incidence Age-adjusted standardized rate (ASR) in
North America, western Europe, and Oceania is usually just below 7 cases per million 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
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Incidence In the US, the incidence among
whites and blacks is essentially the same. 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 In older children and adults, the male-
to-female ratio is about 1:1
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Incidence 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. However, in developing countries, the first
peak is shifted into childhood, usually before adolescence
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History
Persistent painless adenopathy 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
at risk for respiratory failure, especially if they undergo sedation or anesthesia for diagnostic procedures
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History
Patients with HL may present with symptoms associated with advanced disease & adverse prognosis (B – designation) 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
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Diagnostic Evaluation In addition to stage and male sex,
certain laboratory findings suggest poor prognostic factors 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
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Imaging Chest XR – AP and lateral
Mediastinal mass with a thoracic ratio of 33% or greater is of prognostic importance
CT or MRI of neck, chest, abdomen, and/or pelvis to assess sites of disease (nodal and
extranodal) as well as to assess liver and spleen involvement
PET scans to identify the extent of disease at diagnosis
and for follow up
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Staging The most widely used staging system is the
Ann Arbor staging system. 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
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Treatment
Hodgkin lymphoma can be cured with radiation therapy, chemotherapy, or a combination of both.
Acute and late toxicities vary depending on treatment Balance between reducing late effects
of therapy vs. maintaining cure rates
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Treatment based on Stage Standard treatment regimens for pediatric Hodgkin lymphoma
are as follows: Early or favorable disease (stage IA or IIA with <3 nodal sites)
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.
Intermediate-risk disease (stage IA, IIA, or IIA bulky disease with extension or >3 nodal sites):
4-6 chemotherapy cycles (OPPA and COPP, Stanford V) plus low-dose, involved-field 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): 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.
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Acute Effects of Treatment Radiation
Erythema +/- hyperpigmentation
Transient hair thinning
GI sx Dry mouth or
altered taste
Chemotherapy N/V Alopecia Myelosuppression Immunosuppressi
on
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Late Complications Impaired growth of soft tissue and
bones Thyroid dysfunction Gonadal dysfunction Cardiopulmonary toxicity Second malignancies Functional impairment and
reduced overall general health
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Steidl et al. New England Journal of Medicine
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"
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
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Tumor-Associated Macrophages
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 Possibly by increasing blood-vessel
formation through the secretion of vascular endothelial growth factorSteidl et al.. N Engl J Med. 2010; Vol 362, No 10:875-85
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Implications of CD68 marker
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 toxicitiesSteidl et al.. N Engl J Med. 2010; Vol 362, No 10:875-85
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References 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)