This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
癌症診療準則與核心測量 -淋巴瘤
彰化基督教醫院 內科部血液腫瘤科
張正雄
Agenda
• Lymphocyte differentiation
• Classification of lymphomas
• Disease definitions and symptoms
• Tests that identify specific lymphoid histologies
Historical Classification Systems for Non‐Hodgkin Lymphoma
• Working Formulation • Low grade
∙ A. Small lymphocytic, consistent with chronic lymphocytic leukemia ∙ B. Follicular, predominantly small‐cleaved cell ∙ C. Follicular, mixed small‐cleaved, and large cell
• Intermediate grade∙ D. Follicular, predominantly large cell ∙ E. Diffuse, small‐cleaved cell ∙ F. Diffuse mixed, small and large cell ∙ G. Diffuse, large cell, cleaved, or noncleaved cell
• High grade∙ H. Immunoblastic, large cell ∙ I. Lymphoblastic, convoluted, or nonconvoluted cell ∙ J. Small noncleaved‐cell, Burkitt, or non‐Burkitt
Table B11: Histiocytic and Dendritic Cell Neoplasm
WHO Preferred Term ICD-O-3
Disseminated juvenile xsanthogranuloma No Code
Fibroblastic reticular cell tumor 9759/3
Follicular dendritic cell sarcoma 9758/3
Histiocytic sarcoma 9755/3
Indeterminate dendritic cell tumor 9757/3
Langerhans cell histiocytosis 9751/3
Langerhans cell sarcoma 9756/3
Histiocytic Cell Neoplasms
20
Table 14.01 True histiocytic malignancy, a vanishing diagnosis.
Original diagnosis Currently considered
Histiocytic lymphoma, nodular and diffuse Diffuse large B‐cell lymphomaFollicular lymphoma, grade 3Peripheral T‐cell lymphomaHistiocyte‐rich variants of B‐cell, T‐cell, and Hodgkin lymphomaAnaplastic large cell lymphoma
Not specific to diseaseSwollen lymph nodesChest pain/breathing problemsUnexplained weight lostRecurring fevers/night sweatsRashesLower back painSore LN after alcohol consumption
24
Tests That Identify Specific Lymphoid Histologies
25
2008 WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues
Basic principle: Classification for all neoplasms based on:
• Morphology and biologic features
• Genetic• Immunophenotype
• Clinical features
26
Genetic Testing
Laboratory studies of blood, bone marrow, or tissue to analyze DNA to identify chromosome abnormalities which diagnose specific neoplasms
27
Normal Chromosomes
46 in each cellEach chromosome has a specific number
Example: (1;2)
Short arm “p” and a long arm “q”
Example: (p13;q22)
28
Genetic Abnormalities
1. Translocation: t(1;2)
2. Inversion: inv16
3. Deletion: ‐7 or 7‐
4. Addition: +8 or 8+
29
Gene Translocation
30Courtesy: National Human Genome Research Institute
Gene Inversion
31Diego Diez, Ph, Bioinformatics Center, Institute for Chemical Research, Kyoto University.Gokasho, Uji, Kyoto 611-0011 JAPAN [email protected]
Gene Deletion
32
Courtesy: National Human Genome Research Institute
Gene Addition
33
Walters L, Palmer JG. “The Ethics of Human Gene Therapy.” Oxford University Press. 1997.
Genetic Testing
FISH: Identifies genetic changes and translocations.
Polymerase chain reaction (PCR): Measures cancer cells that cannot be detected by FISH.
Karyotyping: To arrange and classify chromosomes based on number, size, shape, and other characteristics.
34
FISH to Identify NPM/ALK Fusion Gene
35http://www.pathologyoutlines.com
Genetic Testing/Cytogenetics
36Appelbaum, MD, Frederick R. Leukemia [Internet]. Version 5. Knol. 2008 Jul 28. Available from: http://knol.google.com/k/frederick-r-appelbaum-md/leukemia/pOIC0j0O/gRxHJw
Karyotype
37http://www.pathologyoutlines.com
Immunophenotyping
Cells from blood, BM, tissue used to determine types of antigens or markers on surface of cell. Referred to as CD
CD; cluster of differentiation: Used to define the findings in immunophenotyping .
38
Additional Immunophenotyping
Flow cytometry: Cells from blood, BM, tissue are treated with antibodies and passed in front of a laser beam.
Immunocytochemistry (IHC): Shows specific antigens in cells from blood, BM, by using either fluorescent dyes or enzymes as markers
• Stage IStage I NHL means involvement of a single lymph node region (I) or localized involvement of a single extralymphatic organ or site (IE).
• Stage IIStage II NHL means involvement of two or more lymph node regions on the same side of the diaphragm (II) or localized involvement of a single associated extralymphatic organ or site and its regional lymph nodes with or without other lymph node regions on the same side of the diaphragm (IIE). [Note: The number of lymph node regions involved may be indicated by a subscript (e.g., II3).]
Stage
• Stage IIIStage III NHL means involvement of lymph node regions on both sides of the diaphragm (III) that may also be accompanied by localized involvement of an extralymphatic organ or site (IIIE), by involvement of the spleen (IIIS), or both (IIIS+E).
• Stage IVStage IV NHL means disseminated (multifocal) involvement ofone or more extralymphatic sites with or without associated lymph node involvement or isolated extralymphatic organ involvement with distant (nonregional) nodal involvement.
Stage
• adult NHL can be subclassified into A and B categories :
A for those without such symptoms
B for those with well‐defined generalized symptoms
B symptom
• B designation is given to patients with any of the following symptoms:
I. Unexplained loss of more than 10% of body weight in the 6 months before diagnosis.
II. Unexplained fever with temperatures above 38°C.
III. Drenching night sweats.
Stage I & II
Stage IIE & III
Stage IV & Bone marrow aspiration
Stage I lymphoma‐ PET
Upstaged from stage II to stage IIIs
Stage IV lymphoma
Cancer registry
52
Most Common Lymphomas
Armitage JO, et al. J Clin Oncol. 1998;16:2780-2795.
Diffuse large B cell: 31%
Follicular: 22%Marginal zone, extranodal: 8%
Peripheral T cell: 7%
Small lymphocytic/CLL: 7%
Mantle cell: 6%
Mediastinal large B cell: 2%
Anaplastic large cell: 2%
Burkitt: 2%
Marginal zone, nodal: 2%
T lymphoblastic: 2%Other: 9%
Cancer registry
• USA
• New cases: 63,190.
• Deaths: 18,660.
• Taiwan
• New cases: 1,902
• Deaths: 1,298
非何杰金氏淋巴瘤
非何杰金氏淋巴瘤
年齡別發生率 , 96年 年齡別死亡率, 96年
組織形態
首次療程
何杰金氏淋巴瘤
何杰金氏淋巴瘤
年齡別發生率 , 96年 年齡別死亡率, 96年
組織形態
首次療程
Treatment and prognosis
63
Indolent lymphomas
• Relatively good prognosis with a median survival as long as 10 years
• Usually are not curable in advanced clinical stages
• Early stage (stage I and stage II) can be effectively treated with radiation therapy alone
Aggressive lymphomas
• Shorter natural history
• Significant number of these patients can be cured with intensive combination chemotherapy
Treatment Option Overview
• Radiation therapy : varies from 25 Gy to 50 Gy
• Combination chemotherapy
• Aggressive consolidation with marrow or stem cell support
Treatment Options for Advanced Low‐Grade Lymphoma
• Observation (watch and wait)
• Radiation
• Single‐agent therapy
• Combination chemotherapy
• Interferon
• Monoclonal antibodies
• Hematopoietic transplantation
• Antisense molecules
• Vaccines
• Targeted agents
Treatment Option Overview
• Treatment of non‐Hodgkin lymphoma (NHL) depends on the histologic type and stage.
• Late effects of treatment of NHL :permanent sterility elevated risk for second primary cancers Left ventricular dysfunction Myelodysplastic syndrome and acute myelogenous leukemia
Evolving Standards of Care in Non-Hodgkin’s Lymphomaclinicaloptions.com/oncology
CHOP ± Rituximab in DLBCL: 7-Yr Survival Results (GELA LNH-98.5 Study)
Coiffier B, et al. ASCO 2007. Abstract 8009.
OS (N = 399) Parameter, % Low Risk
High Risk
Age, < 70 vs ≥ 70 yrs 58.0 49.0
LDH, NI vs > NI 69.0 45.0*
Stage, I/II vs III/IV 67.0 50.0
Bone marrow, yes vs no 60.0 34.5*
Tumor size, < 10 vs ≥ 10 cm 60.0 36.5
β2-microglobulin, NI vs > NI 64.5 39.0*
Serum albumin, ≥ 35 vs < 35 g/L 60.0 40.0
*P < .05 (multivariate analysis).
Surv
ival
Pro
babi
lity
Yrs
0
0.2
0.4
0.6
0.8
1
0 1 3 5 7 82 4 6
CHOPR-CHOP
P = .0004
Prognosis
• Overall survival at 5 years is approximately 50% to 60%
• Aggressive NHL, 30% to 60% can be cured
• Vast majority of relapses occur in the first 2 years after therapy
• Asymptomatic patients with indolent forms of advanced NHL, treatment may be deferred until the patient becomes symptomatic as the disease progresses
The Follicular Lymphoma International Prognostic Index (FLIPI)
• FLIPI score used to predict outcomes of therapy based on adding number of risk factors (each factor = 1 point)– Older than 60 yrs of age– Ann Arbor stage III/IV disease