Non Hodgkins Lymphoma
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Non-Hodgkin’s Lymphoma Epidemiology, Disease and Staging
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chronic myeloid leukaemia(CML) Haematopoietic Malignancies Polycythemiavera(PV) Idiopathic myelofibrosis(MF) Essentialthrombocythemia(ET) Acute myeloidleukaemia(AML) Chronic myeloidleukaemia(CML) Acute lymphaticleukaemia(ALL) Chronic lymphaticleukaemia(CLL) hairy cellleukaemia(HCL) Hodgkin’slymphoma Burkitt's lymphoma cutaneous T-celllymphoma (CTCL) Non-hodgkin’slymphoma(NHL) Myeloproliferativediseases Leukaemias Malignant lymphomas
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Haematopoietic Malignancies Family of chronic neoplastic diseases Due to a clonal disorder arising at the level of the pluripotent stem cell Characterised by abnormal proliferation of 1 or more blood cell lines Neoplastic disease of a haematopoietic precursor cell Characterised by replacement of normal bone marrow Often infiltration into other organs Malignant clones suppress normal cell formation Neoplastic disease of lymphatic tissue Originates in lymph node or spleen Hodgkin’s (15%) non-Hodgkin’s (85%) Myeloproliferativediseases Malignantlymphomas Leukaemias
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The Lymphatic System
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Lymphatic Tissue Lymph nodes, spleen, liver, skin and the respiratory, GI and GTU tract Lymphocytes undergo further proliferation and differentiation in lymphoid tissue B-lymphocytes tend to reside in lymph nodes & spleen T-lymphocytes tend to circulate throughout the lymphatic system
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Lymph Node - normal histology afferent lymphatic vessel capsule follicle (mainly B-cells)- germinal centre- mantle zone C cortex medulla paracortex efferent lymphatic vessel artery vein
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Hodgkin’s Lymphoma 15% of lymphomas First described by Thomas Hodgkin in 1832 Originally had a very poor prognosis(<10% survival at 5 years) Improved staging techniques and understanding of the pattern of spread helps direct management Now curable in over 70% of cases through the use of radiotherapy and chemotherapy
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Non-Hodgkin’s Lymphoma (NHL):Definition and Indication A heterogeneous group of B- and T-cell malignancies that are diverse in cellular origin, morphology, cytogenetic abnormalities, response to treatment, and prognosis
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Non-Hodgkin’s Lymphoma (NHL) 85% of lymphomas 6th major cause of cancer deaths yearly Heterogeneous group of malignant diseases arising from lymphoid tissue lymph nodes, spleen Various immune cell types principally B-cells derivation (>85%) T-cells derivation Histiocytes (very rarely) Various stages of differentiation and maturation
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NHL Incidence Incidence of 13.3/100,000 per year (Aust) Predominates in the 40-70 years age group most common neoplasm in the 20-40 age group Incidence is rising 150% growth over the past 30 years increasing by 4% annually since 1970’s Mortality rate is also rising 2% rise per year third highest rise, exceeded only by lung cancer in women and malignant melanoma
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Increases with age implications Slight male predominance overall Striking male predominance for several subtypes Incidence of certain subtypes varies greatly around the world Burkitt’s Lymphoma in African children T-cell type more common in Japan NHL Incidence
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Estimated Incidence of NHL in the Year 2000 (Worldwide) 0 10,000 20,000 30,000 40,000 50,000 60,000 Micronesia Melanesia Caribbean Australia/New Zealand Northern Africa Western Africa Northern Europe Southeast Asia Eastern Europe South Central Asia North America
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Adapted from Greenlee et al. CA Cancer J Clin. 2001;51:15. Estimated Annual Incidence Year ~4% compound annual increase in incidence Estimated Incidence of NHL (US) 0 15,000 30,000 45,000 60,000 1980 1985 1990 1995 2000
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Revised European-American Lymphoma (REAL) Classification: B-Cell Neoplasms Hiddemann. Blood. 1996;88:4085.
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World Health Organization (WHO) Classification of Lymphoid Neoplasms: B-Cell Neoplasms Jaffe et al. Ann Oncol. 1998;9 (suppl 5):S25. Precursor B-cell neoplasm Precursor B-lymphoblastic leukemia/lymphoma (precursor B-cell acute lymphoblastic leukemia) Mature (peripheral) B-cell neoplasms B-cell CLL/SLL B-cell PLL Lymphoplasmacytic lymphoma Plasmacytoma, plasma cell myeloma HCL Marginal zone B-cell lymphoma Marginal zone B-cell lymphoma of MALT Nodal marginal zone lymphoma(+/- monocytoid B-cells) Splenic marginal zone B-cell lymphoma FL Grade 1, 0-5 centroblasts/hpf Grade 2, 6-15 centroblasts/hpf Grade 3, >15 centroblasts/hpf 3a, >15 centroblasts, but centrocytes still present 3b, centroblasts from solid sheets with no residual centrocytes Variants Cutaneous follicle center MCL DLCL Mediastinal (thymic) large B-cell lymphoma Intravascular lymphoma Primary effusion lymphoma Burkitt’s lymphoma/Burkitt cell leukemia
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The Non-Hodgkin’s Lymphoma Pathologic Classification Project. Cancer. 1982;49:2112. Modified Ann Arbor Staging of NHL Stage I Involvement of a single lymph node region Stage II Involvement of ?2 lymph node regions on the same side of the diaphragm Stage III Involvement of lymph node regions on both sides of the diaphragm Stage IV Multifocal involvement of ?1 extralymphatic sites ± associated lymph nodes or isolated extralymphatic organ involvement with distant nodal involvement
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Staging of NHL
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Staging of NHL
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Follicular non-Hodgkin’s Lymphoma Classification and survival
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Classification of Indolent NHL:International Working Formulation (IWF) A. Small lymphocytic 3.6 5.8 B. Follicular, predominantly small cleaved cell 22.5 7.2 C. Follicular, mixed small and large cell 7.7 5.1 D. Follicular, predominantly large cell 3.8 3.0 The Non-Hodgkin’s Lymphoma Pathologic Classification Project. Cancer. 1982;49:2112. % of NHL Median Class Patients Survival (y)
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Adapted from Horning. Semin Oncol. 1993;20(5 suppl 5):75. Patients (%) Year 1987-1996 1976-1986 1960-1975 100 60 40 20 0 80 0 5 10 15 20 25 30 Survival of Patients with Indolent Lymphoma:The Stanford Experience, 1960-1996
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SWOG Finding: New treatment options have changed the natural history of follicular lymphoma1 1974-1978CHOP +non-specificimmunostimulants 1988-1994ProMACE – MOPP+ Interferon 1998-2000CHOP + monoclonalantibody therapy 69% 79% 91% Overall survival (%) Impact of new treatment options on the natural history of follicular lymphoma determined by SWOG via retrospective analysis of three sequential treatment approaches. 1:Fisher et al Blood 2004;104 Abstract 583 Adapted from ref 1
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Follicular Lymphoma: Overall Survival Adapted from Armitage and Weisenburger. J Clin Oncol. 1998;16:2780. Year 8 IPI 0/1 IPI 2/3 IPI 4/5 100 Overall Survival (%) 0 2 5 6 7 3 4 1 P<0.001 60 40 20 0 80
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Aggressive non-Hodgkin’s Lymphoma Classification and Survival
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National High-Priority Lymphoma Study: Overall survival for aggressive lymphoma Fisher et al. N Engl J Med. 1993;328:1002. Patients (%) Years After Radomization 100 80 60 40 20 0 0 1 2 3 4 5 6 CHOP m-BACOD ProMACE-CytaBOM MACOP-B
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International Prognostic Index (IPI) Patients of all ages Risk Factors Age >60 years PS 2-4 LDH level Elevated Extranodal involvement >1 site Stage (Ann Arbor) III-IV Patients ?60 years (age-adjusted) PS 2-4 LDH Elevated Stage III-IV Shipp. N Engl J Med. 1993;329:987.
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IPI Risk Strata All ages Low (L) 0-1 Low-intermediate (LI) 2 High-intermediate (HI) 3 High (H) 4-5 Age-adjusted L 0 LI 1 HI 2 H 3 Risk Factors Risk Group Shipp. Blood. 1994;83:1165.
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IPI: Overall Survival by Risk Strata Adapted from Shipp. N Engl J Med. 1993;329:987. 100 75 50 25 0 0 2 4 6 8 10 H HI LI L Patients (%) Year
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Age-Adjusted IPI: Overall Survival by Risk Strata HI H LI L 100 75 50 25 0 0 2 4 6 8 10 Patients (%) Year Adapted from Shipp. N Engl J Med. 1993;329:987.
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DLCL: Overall Survival Year Adapted from Armitage and Weisenburger. J Clin Oncol. 1998;16:2780. Patients (%) 100 60 40 20 0 0 2 5 6 7 8 3 4 1 80 IPI 0-1 IPI 2-3 IPI 4-5 P<0.001
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chronic myeloid leukaemia (CML) Haematopoietic Malignancies . Polycythemia vera (PV) Idiopathic mye
chronic myeloid leukaemia (CML) Haematopoietic Malignancies . Polycythemia vera (PV) Idiopathic myelofibrosis (MF) Essential thrombocythemia