20 C GROUP
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Transcript of 20 C GROUP
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8/12/2019 20 C GROUP
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Lo 1
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Physiology & Anatomy
Lymphatic system
Open circulatory system
Part of immune system
Includes: lymph, lymphatic vessels, lymph
nodes, spleen, tonsils, adenoids, Peyer
patches, thymus Body has 600 lymph nodes
Lymph drains through nodes as it heads to
right lymphatic duct and thoracic duct
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LymphaticSystem
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Physiology & Anatomy
Lymph nodes are populated by:
Macrophages, dendritic cells, B and T
lymphocytes B Lymphocytes
Located in follicles and perfollicular area of
lymph nodes
T Lymphocytes
Interfollicular or paracortical area of lymph
nodes
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Approach to Patient
Lymphadenopathyrefers to lymph nodes
that are abnormal in size, number or
consistency Consider:
Age of Patient
Size of Nodes
Location of Nodes
Quality of Nodes
Localized or generalized
Time course of the lymphadenopathy
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Patient Age
Not palpable in newborn
Palpable nodes are the norm in the
cervical, axillary, and inguinal regionsthroughout early childhood
Children < 5 years old
44% palpable nodes at check up
64% palpable nodes at sick visits
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Patient Age
The differential diagnosis is huge! But
consider age as you narrow it down.
For example: Preschool and early school age:
URI, AOM, Conjunctivitis
Teenagers Hodgkin lymphoma
STDs
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Size of Lymph Nodes
Rules of thumb:
Axillary and cervical nodes < 1 cm
Inguinal
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Location of Lymph NodesNode Groups
Occipital
Postauriclular Preauricular
Parotid
Submandibular
Submental
Superficial cervical Deep cervical
Supraclavicular
Deltopectoral
Axillary
Epitrochlear Inguinal
Popliteal
Region Drained
Posterior Scalp
Temporal & parietal scalp Scalp, ear canal, conjunctiva
Scalp, midface, ear canal and ear, parotid
Cheek, nose, lips, tongue, subman. gland
Lower lip, floor of mouth
Lower larynx, lower ear canal, parotid Tonsils, adenoids, scalp, larynx, sinuses
Mediastinum, lungs, abdomen
Arm
Arm, breast, thorax, neck
Medial arm below elbow Lower extremities, genitalia, abdomen
Lower leg
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Quality of Lymph Nodes
Painful Usually infection, especially if erythema, warmth, or
fluctance
Malignancy can cause node tenderness because ofhemorrhage into node and stretching of capsule
Hard Found in cancers because of fibrosis
Nonmobile
Become fixed from invasive cancers of inflammation intissue surrounding nodes (ie TB or sarcoidosis)
SOFT, COMPRESSIBLE = NORMAL
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Localized vs. Generalized
Lymphadenopathy Localized
Most commonly cervical then inguinal
Can be infection/inflammation in the areadrained by that node or infection of node
itself
Generalized Systemic disease
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Localized Lymphadenopathy
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Differential Diagnosis - Infection Bacterial
Localized: Staph aureus, GAS, cat-scratch, tularemia, diphtheria
Generalized : Brucellosis, leptospirosis, typhoid
Viral EBV, CMV, HSV, HIV, Hep B, Measles, Mumps, Rubella,
Dengue Fever
Myocobacterial TB, Atypical mycobacteria
Fungal Coccidiomycosis, Cryptococcosis, Histoplasmosis
Protozoal Toxoplamosis, Leishmaniasis Spirochetal
Lyme disease, symphilis
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Differential Diagnosis - Other
Malignancy leukemia, lymphoma, metastasis from solid tumor
Immunologic SLE, serum sickness, Langerhans cellhistiocytosis, RA, Drug Reaction, dermatomyositis,CGD
Endocrine Addison disease, hypothyroidism
Other Amyloidosis, Kawasaki disease, Sarcoidosis,
Churg-Strauss syndrome, Kikuchi disease,Castleman disease
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Time Course of Lymphadenopathy
When to biopsy Many advocate biopsy of concerning nodes that
have not decreased after 4-6 weeks or have not
normalized in 8-12 weeks Lymph nodes present for long time are not likely to
be malignant except for Hodgkins
Exposure medications, animals, uncooked meats,
unpasteurized milk Associated constitutional symptoms
Fever, night sweats, weight loss, pruritus,arthralgias, fatigue
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Specific Causes of
Lymphadenopathy
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Lymphadenitis
Lymphadenitisenlarged, inflamed, tender lymph nodes
Organisms: Staph aureus, GAS (80%)
Usually submandibular
Southwest US Yersinia pestis = Bubonic plague
Bartonella henselae = cat scratch
TB and atypical mycobacteria (M. avium and M. scrofulaceum)
Management Culture drainage or of pharyngeal exudate
Treatment 1st/2ndgeneration cephalosporin or dicloxacillin
Clindamycin or Augmentin if anaerobe suspected (oral)
Ultrasound to determine if abscess
I&D indicated if abscess present
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Infectious Mononucleosis
Symptoms fever, pharyngitis, lymphadenopathy (symmetric
involvement of posterior cervical nodes)
EBV, CMV, toxoplasmosis, Streptococcus,hep B, HIV
Testing
Monospot test (heterophile antibody) High false negative in < 4 YO and early illness
Specific serologic tests Elevated immunoglobulin M titer to viral capsid antigen
(Igm-VCA) indicates acute infection
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Diagnostic Testing to Consider
Blood
CBC, ESR, LDH
Specific Serologic testing (EBV, CMV,Bartonella)
Tuberculin Skin Testing
Chest X-ray Biopsy
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LO 2
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ALL MMCLL Lymphomas
Hematopoietic
stem cellNeutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloid
progenitor
Myeloproliferative disordersAML
Lymphoid
progenitor T-lymphocytes
Plasma
cells
B-lymphocytes
nave
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B-cell development
stem
cell
lymphoid
progenitor
progenitor-B
pre-B
immature
B-cell
memoryB-cell
plasma cellDLBCL,FL, HL
ALL
CLL
MM
germinal
center
B-cell
mature
naive
B-cell
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Clinically useful
classification
Diseases that have distinct
clinical features
natural history
prognosis
treatment
Biologically rational
classification
Diseases that have distinct
morphology
immunophenotype
genetic features
clinical features
Classification
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Lymphoma classification
(2001 WHO) B-cell neoplasms
precursor
mature
T-cell & NK-cell neoplasms
precursor
mature
Hodgkin lymphoma
Non-Hodgkin
Lymphomas
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A practical way to think of lymphoma
Category Survival of
untreatedpatients
Curability To treat or
not to treat
Non-
Hodgkin
lymphoma
Indolent Years Generally
not curable
Generally
defer Rx if
asymptomaticAggressive Months Curable in
some
Treat
Very
aggressive
Weeks Curable in
some
Treat
Hodgkin
lymphoma
All types Variable
months to
years
Curable in
most
Treat
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Epidemiology of lymphomas
5thmost frequently diagnosed cancer in
both sexes
males > females
incidence
NHL increasing
Hodgkin lymphoma stable
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Incidence of lymphomas in comparisonwith other cancers in Canada
Year
1985 1990 1995 2000ageadjustedincidence
/100,000/yr
0
10
20
30
40
50
60
70
Hodgkinlymphoma
NHL
breast
colorectallung
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Age distribution of new NHL cases inCanada
Age (years)
0-11-45-9
10-14
15-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75-79
80-84
85+
In
cidence/100,000/annum
0
20
40
60
80
100
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Age distribution of new Hodgkinlymphoma cases in Canada
Age (years)
0-11-45-9
10-14
15-19
20-24
25-29
30-34
35-39
40-44
45-49
50-54
55-59
60-64
65-69
70-74
75-79
80-84
85+
inc
idence/100,000
/annum
0
1
2
3
4
5
6
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Risk factors for NHL
immunosuppression or immunodeficiency
connective tissue disease
family history of lymphoma
infectious agents
ionizing radiation
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Clinical manifestations
Variable severity: asymptomatic to extremely ill
time course: evolution over weeks, months, or
years Systemic manifestations
fever, night sweats, weight loss, anorexia, pruritis
Local manifestations lymphadenopathy, splenomegaly most common any tissue potentially can be infiltrated
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Other complications of
lymphoma bone marrow failure (infiltration)
CNS infiltration
immune hemolysis or thrombocytopenia
compression of structures (eg spinal
cord, ureters)
pleural/pericardial effusions, ascites
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Diagnosis requires an
adequate biopsy Diagnosis should be biopsy-proven
before treatment is initiated
Need enough tissue to assess cells andarchitecture
open bx vscore needle bx vsFNA
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Stage I Stage II Stage III Stage IV
Staging of lymphoma
A: absence of B symptoms
B: fever, night sweats, weight loss
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Three common lymphomas
Follicular lymphoma
Diffuse large B-cell lymphoma Hodgkin lymphoma
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Relative frequencies of different
lymphomas
Hodgkin
lymphomaNHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~85% of NHL are B-lineage
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Follicular lymphoma
most common type of indolentlymphoma
usually widespread at presentation often asymptomatic
not curable (some exceptions)
associated with BCL-2 generearrangement [t(14;18)]
cell of origin: germinal center B-cell
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defer treatment if asymptomatic
(watch-and-wait) several chemotherapy options if
symptomatic
median survival: years
despite indolent label, morbidity and
mortality can be considerable
transformation to aggressive lymphomacan occur
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Diffuse large B-cell lymphoma
most common type of aggressive
lymphoma
usually symptomatic
extranodal involvement is common
cell of origin: germinal center B-cell
treatment should be offered
curable in ~ 40%
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Hodgkin lymphoma
Thomas Hodgkin
(1798-1866)
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Classical Hodgkin Lymphoma
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Hodgkin lymphoma
cell of origin: germinal centre B-cell
Reed-Sternberg cells (or RS variants) in
the affected tissues
most cells in affected lymph node are
polyclonal reactive lymphoid cells, not
neoplastic cells
Reed Sternberg cell
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Reed-Sternberg cell
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RS cell and variants
popcorn celllacunar cellclassic RS cell
(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of
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A possible model ofpathogenesis
germinalcentre
B cell
transforming
event(s)
loss of apoptosis
RS cellinflammatory
response
EBV?
cytokines
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Hodgkin lymphomaHistologic subtypes
Classical Hodgkin lymphoma
nodular sclerosis (most common subtype)
mixed cellularity lymphocyte-rich
lymphocyte depleted
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Epidemiology
less frequent than non-Hodgkin
lymphoma
overall M>F peak incidence in 3rd decade
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Associated (etiological?)
factors EBV infection
smaller family size
higher socio-economic status
caucasian > non-caucasian
possible genetic predisposition
other: HIV? occupation? herbicides?
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Clinical manifestations:
lymphadenopathy
contiguous spread
extranodal sites relatively uncommonexcept in advanced disease
B symptoms
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Treatment and Prognosis
Stage Treatment Failure-
free
survival
Overall 5
year
survival
I,II ABVD x 4
& radiation
70-80% 80-90%
III,IV ABVD x 6 60-70% 70-80%
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Long term complications of
treatment infertility
MOPP > ABVD; males > females
sperm banking should be discussed premature menopause
secondary malignancy
skin, AML, lung, MDS, NHL, thyroid,breast...
cardiac disease
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Overview
Concepts, classification, biology
Epidemiology
Clinical presentation
Diagnosis
Staging
Three important types of lymphoma
d ki l h
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Non-Hodgkins lymphomas-definition
and epidemiology
1. Definition: malignant disease of the lymphoid
system, highly heterogeneous, both histologically
and clinically.2. Epidemiology:
- annual incidence: 5-10 new cases per 100 000persons,
- age distribution: middle-age patients and the elderly,
- males are affected more often than females (1.5:1.0).
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Non-Hodgkins lymphomas-Clinicalfeatures
1. Constitutional symptoms (fever, night sweats,
weight loss)
2. Lymphadenopathy
(cervical, supraclavicular, axillary, inguinal,
mediastinal, retroperitoneal, mesenteric, pelvic).
3. Mediastinal adenopathy (T cell lymphoma)
4. Extralymphatic involvement (gastrointestinal,
testicular masses, solitary bone lesions, CNS).
5. Unexplained anemia and thrombocytopenia (
bone marrow infiltration).
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Histologic classification of non-Hodgkins lymphomas
1. Rappaport - 1966
2. Lukes and Collins - 1974
3. Dorfman - 1974
4. Bennet et al., - 19745. Lennert - 1974
6. WHO - 1976
7. Working Formulation - 1982
8. REAL - 1994
9. WHO - 1999
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Histologic classification of non-Hodgkins lymphomas - Working
Formulation (WF)
1. Low grade
2. Intermediate grade
3. High grade
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Histologic classification of non-Hodgkins lymphomas - Working
Formulation (WF)Low grade
A. - Small lymphocytic cell.
B. - Follicular, predominantly small
cleaved cell
C. - Follicular mixed, small cleaved and
large cell.
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Histologic classification of non-Hodgkins lymphomas - Working
Formulation (WF)
Intermediate grade
D. - Follicular, predominantly largecell.
E. - Diffuse small cleaved cell.
F. - Diffuse mixed, small and large
cell.
G. - Diffuse large cell.
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Non-Hodgkins lymphomas
/NHL/
- clinical features
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For the diagnosis of non-Hodgkins lymphomas the
histological examination of alymph node is necessary!
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Non-Hodgkins lymphomas -
histological classification
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REAL /R i d E A i
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REAL /Revised European-AmericanLymphoma/-WHO classification of
non-Hodgkins lymphomas
Precursor B cell lymphomas
- acute lymphoblastic
leukemia
- lymphoblastic lymphoma
REAL /Revised European-American
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REAL /Revised European-AmericanLymphoma/-WHO classification of
non-Hodgkins lymphomas
Peripheral B cell lymphomas
- Chronic lymphocytic leukemia/lymphocyticlymphoma
- Chronic prolymphocytic leukemia
- Immunocytoma/lymphoplasmocytic lymphoma
- Mantle cell lumphoma- Marginal zone lymphoma /MALT-type/
- Hairy cell leukemia
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REAL /R i d E A i
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REAL /Revised European-AmericanLymphoma/-WHO classification of
non-Hodgkins lymphomas
Peripheral T cell lymphomas
T cell chronic lymphocytic leukemia T cell chronic prolymphocytic leukemia
Large granular lymphocyte leukemia
/LGL/ Mycosis fungoides /Szary syndrome
Peripheral T cell lymphomas,
unspecified
REAL /R i d E A i
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REAL /Revised European-AmericanLymphoma/-WHO classification of
non-Hodgkins lymphomas
Peripheral T cell
lymphomas/continued/Angioimmunoblastic T cell lymphoma
Angiocentric lymphoma
Intestinal T cell lymphomaAdult T cell lymphoma/leukemia
Anaplastic large cell lymphoma
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Very aggressive non-Hodgkinslymphomas
B-, T-cell acute lymphoblastic
leukemia B-, T-cell lymphoblastic lymphomas
Burkitts lymphoma
Adult T cell lymphoma/leukemia
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High risk aggressive non-
Hodgkins lymphomas
1. Age abowe 60 years.
2. Disease stage III and IV.3. Extranodal involvement of more
than 1 site.
4. Serum LDH concentration >1 xnormal.
5. Performance status < 80%.
Treatment results of aggressive non-
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Treatment results of aggressive nonHodgkins lymphomas according to the
risk group
Risk group No of risk CR 5-yearsurvival
__________________factors
________%______________%______
Low 0,1 87 73
Low intermediate 2 67 50
High intermediate 3 55 43
High 4,5 44 26
Treatment results of patients under age
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Treatment results of patients under age60 with aggressive non-Hodgkins
lymphomas according to the risk group
Risk group No of risk CR 5-yearsurvival
factors________%_______________%_________
Low 0 92 87
Low intermediate 1 78 69
High intermediate 2 57 46High 3 46 32
Treatment results of aggressive
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advancednon-Hodgkins lymphomas using
different chemotherapy programs
1. First-generation: CHOP
- CR: 50-55%. Long-term survival: 35-50 %.
2. Second-generation: mBACOD, ProMACO-MOPP
- CR: 70-80%. Long-term survival: 50-60%.
3. Third-generation: MACOP-B
- CR: 84%. Long-term survival: 75%
- CR: 52-57%. Long-term survival: 47-56%
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Treatment results in patients over 60
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pyears with aggressive advanced non-
Hodgkins lymphomas
______Program_____________________5-year
survival %
CHOP 45
mBACOD 39
ProMACE-CytoBOM 41
MACOP-B 23
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Therapy of aggressive non-Hodgkins lymphomas
1. Chemotherapy: CHOP
complete remission: 60-
80%
permanent cure: 40-60%
refractory/recurrent disease 30-50%
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Treatment results of refractory/
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Treatment results of refractory/recurrent aggressive non-Hodgkins
lymphomas
1. Chemotherapy programs: DHAP, IMVP16,
MINE, ESHAP
2. Complete remission: 20 - 30%
3. 2-3-year survival: 10%
Hematopoietic stem cell transplantation
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Hematopoietic stem cell transplantationin aggressive non-Hodgkins lymphomas
- Indications
1. Refractory disease2. Relapse
3. High risk in CR
4. Lymphoblastic and Burkittslymphomas
Treatment results of aggressive
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Treatment results of aggressivenon-Hodgkins lymphomas with
high risk
1. Ablative therapy and hematopoietic stem cell
transplantation - 5 year survival (DFS):70-90%
2. Consolidation chemotherapy (DHAP)
- 5-year survival (DFS):25-50%
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Results of radiotherapy in pathologic
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Results of radiotherapy in pathologicstage I/IE aggressive non-Hodgkins
lymphomas1. Complete remission -
90%
2. 10-year survival - 54%
- patients under 60 years - 75%
3. Chemotherapy - if one of the
following symptoms are present:
- bulk of disease (lymph node > 7 cm),- high serum LDH concentration,
- localization in gastrointestinal track,testicles
Therapy of very aggressive non-
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py y ggHodgkins lymphomas (lymphoblastic,
Burkitts lymphomas)
1. Previous results: 2-3 year survival:15%
2. At present
- remission induction treatment as in ALL (High risk),
- consolidation:
a/ ablative therapy and hematopoietic stem celltransplantation (allogeneic or autologous)
- CR: 80-100%
- 3-5 year survival (DFS) 50-70%
b/ high - dose cytarabine
Age-adjasted prognostic index in
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Age adjasted prognostic index inaggressive non-Hodgkins
lymphomas
1. Disease stage (I, II vs. III, IV).
2. Serum LDH concentration (< 1x normal vs >1 xnormal).
3. Performance status (80% vs < 80%).
Age-adjasted International PrognosticIndex
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