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HIV RELATED LYMPHOMA Dr Martin Rowlands North Manchester General Hospital PowerPoint Presentation
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HIV RELATED LYMPHOMA Dr Martin Rowlands North Manchester General Hospital

HIV RELATED LYMPHOMA Dr Martin Rowlands North Manchester General Hospital

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HIV RELATED LYMPHOMA Dr Martin Rowlands North Manchester General Hospital

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  1. HIV RELATED LYMPHOMADr Martin RowlandsNorth Manchester General Hospital

  2. First description of high grade NHL in 90 homosexual men with AIDS in 1984. • Aggressive B cell lymphoma classified as AIDS defining illness in 1985. • Lymphoma second most common cancer associated with HIV infection. • Relative risk of developing lymphoma within 3 years of HIV diagnosis is increased by 165 fold compared with people without HIV infection.

  3. Risk 652 fold for diffuse immunoblastic lymphomas. • 3600 fold for primary CNS lymphomas. • 1000 fold for Burkitt lymphomas. • 113 fold for intermediate grade Non Hodgkins lymphomas. • 14 fold for low grade Non Hodgkins lymphomas. • Risk of Hodgkins Disease increased 5 to 15 fold (x10).

  4. SPECTRUM OF HIV ASSOCIATED LYMPHOMAS 1.Lymphomas also occurring in immunocompetent: • Burkitt lymphoma: Classical Plasmacytoid differentiation. • Diffuse large B cell lymphoma: Centroblastic Immunoblastic • Extranodal marginal zone lymphomas • Peripheral T cell lymphomas :Anaplastic NOS • Classical Hodgkins lymphoma.

  5. LYMPHOMAS SPECIFIC TO HIV INFECTION. • Primary effusion lymphomas : Effusion only Solid extracavitatory • Plasmablastic lymphomas : Oral cavity Systemic OTHER: • Multicentric Castlemans Disease (plasma cell variant).

  6. CD4 ( T helper ) cell is specifically infected and lysed by HIV. • CD4 count is used as a measure of immunocompetence. • Normal CD4 count 500-1500 x 106 / L. • HAART usually started when CD4 < 350 • Increasing opportunistic infections and malignancies as CD4 count falls ( particularly <100) HIV viral load measure ( PCR) of HIV viraemia. Usual aim of HAART is undetectable viral load and increase in CD4 count.

  7. OVERVIEW OF LYMPHOMAGENESIS • Defect of immune surveillance i.e reduced CD4 count. This is a particular feature of DLBC and Primary CNS lymphomas whose incidence increases as CD4 count falls. • The incidence of Burkitt lymphoma and Hodgkins disease is little affected by CD4 count. • Chronic immune stimulation either by HIV or other pathogens. • B cell dysregulation (Igs,cytokines) • Other viruses: EBV in DLBC,HD,Plasmablastic lymphoma,Hodgkins disease. HHV-8 in Primary effusion lymphoma and Castlemans disease. (Lymphomas seen with particularly low CD4 counts).

  8. THE EFFECT OF HAART • Significant reduction in the incidence of DLBC (immunoblastic) and Primary CNS lymphoma since the introduction of effective HAART. • No change / proportional increase in incidence of Burkitt lymphoma and Hodgkins disease which are largely unrelated to CD4 count.

  9. Differential Diagnoses: • Tuberculosis. • Other malignancies. • Immune reconstitution syndromes. • Toxoplasmosis.

  10. Features of clinical presentation in HIV lymphoma. • Usually present at advanced stage with B symptoms. • Extranodal disease common i.e. G.I.tract • Marrow and meningeal involvement more common. • Both Hodgkins and Non Hodgkins lymphomas behave with more aggressive course.

  11. PRETREATMENT INVESTIGATIONS: • FBC, Renal and liver function, LDH, urate, IgGS. • Histology review. • Marrow aspirate+trephine (cytogenetics, immunology) • CD4 , HIV viral load. • CT Scans. (MR Brain) • (PET scan ) • Echo / LVEF • CMV,Hep B+C,Toxoplasma serology • MAI screen. • LP for CSF cytology +/- intrathecal Rx. (DLBC , Burkitt,Plasmablastic).

  12. TREATMENT (general) • HAART (avoid AZT,didanosine) • Hydration • Allopurinol / Rasburicase. • Septrin / Dapsone • Aciclovir • Fluconazole • Azithromycin ( CD4 count <100) • Nutrition • CMV PCR monitoring. ( CD4 count <100) • Growth factor support.

  13. Complicating Factors: Co-Infections: Hepatitis B Hepatitis C Tuberculosis Mycobacterium avium intracellulare (MAI) Pneumocystis. Psychological / Social “Double diagnosis” at presentation Family issues Drug abuse.

  14. DLBC NHL • Pre HAART poor outcomes .Median survival 5-6mnths. • HAART era : • CHOP+Rituximab CR 58% CDE-R CR 70% DA-EPOCH-R CR 73% Caution in use Rituximab at CD4 counts <50. CNS prophylaxis required. • In good performance relapsed patients HDT + PBSC is a viable option.

  15. PRIMARY CNS LYMPHOMA • Typically occurs with marked immunosuppression CD4<50. • Marked reduction in incidence post HAART. • Always EBV positive DLBC NHL. • Commonly multifocal brain lesions. • High dose methotrexate iv • Followed by brain XRT. • Poor prognosis survival months to 1-2 years.

  16. BURKITT LYMPHOMA • Poor response to CHOP type chemotherapy. • Very good results with : • R-CODOX-M / R-IVAC x 4 Courses. • (R-HyperCVAD / R-HDMTX/Cytarabine x 6) • DA-EPOCH-R • CNS disease potentially curable.

  17. HODGKINS DISEASE. • More aggressive histologies common. • Usually advanced disease at presentation. • Bone marrow involvement approx.40% • Localised disease ( 1A ) ABVD x3 + XRT. • Advanced Disease ABVD X 6-8 • Favourable outcome in Post HAART era.

  18. PLASMABLASTIC LYMPHOMA • Aggressive disease. • Characteristically presents with oral cavity mass. Systemic forms occur • No standard treatment • Poor responses to CHOP like treatments. • Increasing evidence of good responses to more intensive treatments such as: HyperCVAD / HD MTX / Cytarabine CODOX-M / IVAC EPOCH

  19. PRIMARY EFFUSION LYMPHOMA • Associated with HHV8 +/- EBV • Usually presents with pleural,pericardial effusions or ascites without mass lesions. • May relapse with extrcavitatory form. • No standard treatment. • CHOP type therapies +/- Rituximab if CD20 +ve. • Prognosis generally poor.Median survival <6mnths.

  20. MULTICENTRIC CASTLEMAN’S DISEASE. • Commonly presents with lymphadenopathy,effusions and marked constitutional symptoms +/- haemolysis. • Standard treatment now Rituximab X 4 • Prone to relapse / progression to NHL. • Commonly ( approx 30%) occur with Kaposi sarcoma • Use HHV-8 PCR to monitor for early relapse.