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Pediatric Case Management - June 2010


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Pediatric Case Management - June 2010

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