Non-Hodgkin’s Lymphoma
Epidemiology, Disease and Staging
chronic myeloid
leukaemia
(CML)
Haematopoietic Malignancies
Polycythemia
vera
(PV)
Idiopathic
myelofibrosis
(MF)
Essential...
Non-
Hodgkin’s
Lymphom
a
Oliveros francis!!!!!!!!!!!!!!!!!
Haematopoietic Malignancies
 Family of chronic
neoplastic
diseases
 Due to a clonal
disorder arising
at the level of the...
The Lymphatic
System
Lymphatic Tissue
 Lymph nodes, spleen, liver, skin and the
respiratory, GI and GTU tract
 Lymphocytes undergo further pr...
Lymph Node - normal histology
afferent lymphatic vessel capsule
follicle (mainly B-
cells)
- germinal centre
- mantle zone...
Hodgkin’s Lymphoma
 15% of lymphomas
 First described by Thomas Hodgkin in 1832
 Originally had a very poor prognosis
(...
Non-Hodgkin’s Lymphoma (NHL):
Definition and Indication
A heterogeneous group of B- and T-cell
malignancies that are diver...
Non-Hodgkin’s Lymphoma (NHL)
 85% of lymphomas
 6th major cause of cancer deaths yearly
Heterogeneous group of malignant...
NHL Incidence
 Incidence of 13.3/100,000 per year (Aust)
 Predominates in the 40-70 years age group
– most common neopla...
 Increases with age
– implications
 Slight male predominance overall
 Striking male predominance for several subtypes
...
Estimated Incidence of NHL
in the Year 2000 (Worldwide)
0 10,000 20,000 30,000 40,000 50,000 60,000
Micronesia
Melanesia
C...
Adapted from Greenlee et al. CA Cancer J Clin. 2001;51:15.
EstimatedAnnualIncidence
Year
~4% compound annual
increase in i...
Revised European-American Lymphoma
(REAL) Classification: B-Cell Neoplasms
Hiddemann. Blood. 1996;88:4085.
Indolent Aggres...
World Health Organization (WHO)
Classification of Lymphoid Neoplasms: B-Cell
Neoplasms
Jaffe et al. Ann Oncol. 1998;9 (sup...
The Non-Hodgkin’s Lymphoma Pathologic Classification Project. Cancer. 1982;49:2112.
Modified Ann Arbor Staging of NHL
Stag...
Staging of NHL
Staging of NHL
Follicular non-Hodgkin’s Lymphoma
Classification and survival
Classification of Indolent NHL:
International Working Formulation (IWF)
A. Small lymphocytic 3.6 5.8
B. Follicular, predom...
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...
SWOG Finding: New treatment options have
changed the natural history of follicular
lymphoma1
0
25
50
75
100
1974-1978
CHOP...
Follicular Lymphoma:
Overall Survival
Adapted from Armitage and Weisenburger. J Clin Oncol. 1998;16:2780.
Year
8
IPI 0/1
I...
Aggressive non-Hodgkin’s
Lymphoma
Classification and Survival
National High-Priority Lymphoma Study:
Overall survival for aggressive lymphoma
Fisher et al. N Engl J Med. 1993;328:1002....
International Prognostic Index (IPI)
Patients of all ages Risk Factors
Age >60 years
PS 2-4
LDH level Elevated
Extranodal ...
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
H...
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...
non-hodgkin’s-lymphoma
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non-hodgkin’s-lymphoma

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non-hodgkin’s-lymphoma

  1. 1. Non-Hodgkin’s Lymphoma Epidemiology, Disease and Staging
  2. 2. chronic myeloid leukaemia (CML) Haematopoietic Malignancies Polycythemia vera (PV) Idiopathic myelofibrosis (MF) Essential thrombocythemia (ET) Acute myeloid leukaemia (AML) Chronic myeloid leukaemia (CML) Acute lymphatic leukaemia (ALL) Chronic lymphatic leukaemia (CLL) hairy cell leukaemia (HCL) Hodgkin’s lymphoma Burkitt's lymphoma cutaneous T-cell lymphoma (CTCL) Non-hodgkin’s lymphoma (NHL) Myeloproliferative diseases Leukaemias Malignant lymphomas
  3. 3. Non- Hodgkin’s Lymphom a Oliveros francis!!!!!!!!!!!!!!!!!
  4. 4. 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%) Myeloproliferative diseases Malignant lymphomas Leukaemias
  5. 5. The Lymphatic System
  6. 6. 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
  7. 7. 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
  8. 8. 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
  9. 9. 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
  10. 10. 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
  11. 11. 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
  12. 12.  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
  13. 13. 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
  14. 14. Adapted from Greenlee et al. CA Cancer J Clin. 2001;51:15. EstimatedAnnualIncidence 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
  15. 15. Revised European-American Lymphoma (REAL) Classification: B-Cell Neoplasms Hiddemann. Blood. 1996;88:4085. Indolent Aggressive Very Aggressive CLL/SLL Lymphoplasmacytic/ IMC/WM HCL Splenic marginal zone lymphoma MZL - Extranodal (MALT) - Nodal Follicle center lymphoma, follicular, grade I-II PLL Plasmacytoma/ Multiple myeloma MCL Follicle centre lymphoma, follicular, grade III DLCL Primary mediastinal large B-cell lymphoma High-grade B-cell lymphoma/Burkitt’s- like Precursor B-lymphoblastic lymphoma/ Leukemia Burkitt’s lymphoma/ B-cell acute leukemia Plasma cell leukemia
  16. 16. 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
  17. 17. 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
  18. 18. Staging of NHL
  19. 19. Staging of NHL
  20. 20. Follicular non-Hodgkin’s Lymphoma Classification and survival
  21. 21. 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)
  22. 22. 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
  23. 23. SWOG Finding: New treatment options have changed the natural history of follicular lymphoma1 0 25 50 75 100 1974-1978 CHOP + non-specific immunostimulants 1988-1994 ProMACE – MOPP + Interferon 1998-2000 CHOP + monoclonal antibody therapy 69% 79% 91%Overallsurvival(%) 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
  24. 24. 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 OverallSurvival(%) 0 2 5 6 73 41 P<0.001 60 40 20 0 80
  25. 25. Aggressive non-Hodgkin’s Lymphoma Classification and Survival
  26. 26. 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
  27. 27. 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.
  28. 28. 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 FactorsRisk Group Shipp. Blood. 1994;83:1165.
  29. 29. 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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