NHL: DLBCL + aggressive NHL Flashcards
1
Q
What is the most common type of aggressive NHL?
A
DLBCL
2
Q
What is the ball park figure for survival in non treated aggressive NHL?
A
Months
3
Q
What is the brief treatment paradigm for limited stage DLBCL?
A
R-CHOP for 3 cycles followed by
ISRT to 30-36Gy for CR
40-50Gy for PR
or
R-CHOP for 6 cycles
4
Q
What is the brief treatment paradigm for advanced stage DLBCL?
A
R-CHOP 6-8 cycles with consideration of consolidate ISRT 30-36Gy
5
Q
What risk factors favour treatment with consolidate RT?
A
- bulk >7.5cm
- skeletal involvement
- inability to tolerate full CHT
- residual disease after CHT on PET
- genetic factors
6
Q
What options are there for relapsed or refractory DLBCL?
A
Initially:
Chemoimmunotherapy followed by autologous stem cell transplant
+- RT pre or post transplant
Further relapse can be managed with Car-T cell therapy or allogenic stem cell transplant
7
Q
Epi of aggressive NHL
A
- 7th most common noncutaneous cancer
- M >F (slightly)
- 50-60% of NHL is aggressive
- more common in low and middle income countries
8
Q
What are the most common types of NHL (not just aggressive types)
A
- DLBCL 30%
- follicular 25%
- SLL/CLL 7%
- MZL/MALT 9%
- mantle cell 8%
- MZL/nodal 3%
- primary mediastinal DLBCL 2%
9
Q
What proportion of NHL is DLBCL?
A
30%
10
Q
What are risk factors for (any) NHL?
A
- older age
- race
- family hx
- geographic region
- some types of viral and bacterial infection are assoc with specific types of NHL
- auto-immune disease
- immune suppression (HIV, organ transplant)
- medication (immunosuppressants, alkylating agents)
- chemicals (hair dye, pesticides)
- previous CLL/hairy cell leukaemia (Richter’s transformation into DLBCL in 5-10%)
11
Q
What type of lymphoma is EBV infection a/w?
A
NK-T cell
Burkitt
12
Q
What type of lymphoma is Hep C a/w?
A
DLBCL
Splenic MZL
13
Q
What type of lymphoma is HTLV-1, HHV8 a/w?
A
Kaposi sarcoma
Various lymphomas in HIV+
14
Q
What type of lymphoma is H Pylori infection a/w?
A
Gastric MALT
15
Q
What type of lymphoma is chlamydia psittaci a/w
A
orbital MALT
16
Q
What type of lymphoma is campylobacter jejuna a/w?
A
intestinal MALT
17
Q
How many nodal groups are used in staging?
A
13
18
Q
Are Waldeyer’s ring and the spleen considered nodal or extra nodal for staging?
A
extra nodal
19
Q
Do NHL arise from cells that differentiate into T or B cells?
A
Both
20
Q
What proportion of NHL arise from B-cell origins?
A
85-90%
21
Q
Do NHL arise from cells originating from bone marrow or peripheral nodal tissue?
A
both
22
Q
What “indolent” NHL is treated the same as DLBCL?
A
grade 3B follicular lymphoma
23
Q
What is the double hit subtype of DLBCL?
A
Has a rearrangement of MYC and BCL2 or BCL6 genes.
Poor prognosis
24
Q
What is the triple hit subtype of DLBCL?
A
Rearrangement of MYC, BCL2 and BCL6 genes.
Dismal prognosis
25
What is the classic IHC of DLBCL?
CD19+
CD20+
CD45+
26
What are the classic genetic alterations in DLBCL
t(14:18)
BCL-2, BCL-6
ALK
many others
27
What are the classic genetic alterations in primary mediastinal DLBCL?
No classic translocations
28
What is the IHC for primary mediastinal DLBCL?
CD19+
CD20+
CD5-
29
What type of patient is primary mediastinal DLBCL most common in?
Young female
30
What does primary mediastinal DLBCL present as?
Anterior mediastinal (thymic) mass
31
Is the treatment for DLBCL and primary mediastinal DLBCL the same or diff?
Diff
32
What are the classic genetic alterations in Mantle cell lymphoma?
t(11:14)
Cyclin D1
33
What is the classic IHC for mantle cell lymphoma?
CD19+
CD20+
CD5+ (as opposed to PM DLBCL which is CD5-)
34
What appearance microscopically is classic for Burkitt lymphoma?
Starry sky
35
What is the most common type of NHL in children?
Burkitt lymphoma
36
What is the classic genetic alteration in Burkitt lymphoma?
t(8:14) -> C-MYC {transcription factor}
37
What is the IHC for Burkitt lymphoma?
CD19+
CD20+
CD10+
CD5-
38
Why is grade 3B follicular lymphoma treated as DLBCL?
Genetically distinct from lower grades of FL
more aggressive
39
What is the IHC for follicular lymphoma grade 3B
CD19+
CD20+
40
Mantle, Burkitt, Follicular, DLCBL and PM DLBCL are what lineage of cells derived?
B cell
41
Anapaestic large cell, Angioimmunoblastic, Peripheral- T cell, extra nodal NK- T cell, are derived from what cell lineage?
T cell
42
lymphoblastic lymphoma/leukaemia arise from B or T cells
Either
43
genetics of Peripheral T cell lymphoma NOS
t(7:14)
t(11:14)
t (14:14)
44
IHC of peripheral T cell lymphoma NOS
Variable T-cell
+- CD 2, 3,4, 5, 7
45
Anapastic large cell lymphoma genetics
t (2:5) -> ALK
46
Anapaestic large cell IHC
CD30+
EMA+
46
IHC of angioimmunoblastic
CD4+
47
genetics of angioimmunoblastic
no classic translocations
48
genetics of extra nodal NK-T cell lymphoma, nasal type
loss of heterozygosity 6q
49
IHC extra nodal NK T cell, nasal type
CD2+
CD56+
50
genetics of lymphoblastic lymphoma/leukaemia
t(1:19)
t (9:22)
51
IHC of lymphoblastic lymphoma/leukaemia
TdT+
52
Common clinical presentation of NHL
Painless enlarging LN
B symptoms or other symptoms e.g fatigue, anaemia, pain, cord comp, SVCO) may be present depending on location and burden of disease
53
Definition of B symptoms
fever >38C
drenching night sweats
weight loss >10% in 6 months
54
Work up of aggressive NHL
H/P and Labs
H&P
*constitutional symptoms
* enlarged LN
*hepatosplenomegaly
Labs
*FBC
*LFTS, Use, electrolytes
*B2 microglobulin
*LDH
*uric acid
*Hep B serology (reactivation with ritux)
*pregnancy test
55
Who should have a lumbar puncture with flow cytometry as part of their workup?
symptomatic
testicular
double hit
HIV associated
epidural lymphoma
56
Work up of aggressive NHL
imaging
FDG PET standard
CT contrast
ECHO or MUGA for CHT
57
What feature on PET suggests transformation in low grade lymphoma?
uptake >10 SUV in low grade lymphoma
58
For what types of lymphoma is PET not helpful in
Low grade, indolent histologies e.g extranodal MZL and SLL
59
What is the preferred type of biopsy for lymphoma?
excision biopsy for adequate pathological evaluation including morphology, nodal architecture, genomic profiling, and immunoprofiling.
Core biopsy at least if excision not possible
60
What type of biopsy is insufficient for lymphoma?
FNA
61
What is the risk of bone marrow involvement in DLBCL compared with other types of lymphoma?
20% risk in aggressive NHL compared with 50-80% in indolent NHL
62
Is a negative PET sufficient in ruling out bone marrow involvement in DLBCL? what about in indolent NHL?
sufficient to rule out BM involvement in DLBCL.
Not sufficient in non aggressive NHL- bone marrow biopsy is standard
63
What factors make up the IPI prognostic system?
LEAPS
LDH (high)
Extra nodal site (equal or more than 2)
Age (>60)
Performance status (ecog greater or equal to 2)
Stage (Ann arbor III or IV)
Each scores 1 point
64
What are prognostic factors for DLBCL?
Age (older worse)
Bulk (>= 7.5cm)
Stage
Germinal centre subtype >non germinal centre subtype
Deauville score on post treatment PET
65
Describe the 5 Deauville scores
Level 1: no uptake above background
Level 2: less than or equal to mediastinal blood pool
Level 3: uptake above mediastinal blood pool, less than or equal to liver
Level 4: moderately above liver
Level 5: markedly greater than liver or new lesions
66
What is the natural history of DBCL/aggressive NHL
survival measured in months if untreated
Compared to HL, pattern of spread is less predictable and can skip nodal levels/sites
67
What is 3Yr OS and PFS for IPI 0-1 in ritux era?
OS 91%
PFS 87%
68
What is 3yr OS and PFS for IPI 2 in ritux era?
OS 81%
PFS 75%
69
What is the 3yrs OS and PFS for IPI 3 in ritux era?
OS 65%
PFS59%
70
What is the 3yrs OS and PFS for IPI 4-5 in ritux era?
OS 59%
PFS 56%
71
In the Ann arbor (Lugano) staging, what dose stage I denote?
one node or a group of adjacent nodes
OR
single extra nodal lesion without nodal involvement (IE)
72
In the Ann arbor (Lugano) staging, what dose stage II denote?
>= 2 nodal groups on same side of diaphragm
73
In the Ann arbor (Lugano) staging, what dose stage III denote?
Nodes on both side of diaphragm; nodes above diaphragm with spleen involvement
74
In the Ann arbor (Lugano) staging, what dose stage IV denote?
Additional noncontiguous extra lymphatic involvement
75
In the Ann arbor (Lugano) staging, what dose A denote?
No systemic symptoms
2014 Lugano update doesn't use
76
In the Ann arbor (Lugano) staging, what does B denote?
B symptoms present
2014 Lugano update doesn't use for NHL
77
In the Ann arbor (Lugano) staging, what does E denote?
extra nodal involvement
2014 Lugano update doesn't use for NHL
78
In the Ann arbor (Lugano) staging, what does X denote?
Bulky
2014 Lugano update doesn't use
79
Is observation an appropriate treatment option for aggressive NHL
No,
notable exception is mantle cell with a low tumour burden
80
What is the role of surgery for aggressive NHL?
generally limited to excision biopsy
81
What is 10yr OS for IPI 0-1?
80%
82
What is 10yr OS for IPI 2-3?
70%
83
What is 10yr OS for IPI 4-5?
40%
84
What is the role of CHT in treatment for aggressive NHL?
backbone of therapy
85
What is rituximab?
anti-CD20 antibody
Improves 5year OS for DLBCL by approx 10% with minimal increase in toxicity
86
What is R-CHOP
rituximab, cyclophosphamide, doxorubicin, vincristine
87
What is the common treatment regime for DLBCL , favourable type?
non bulky <7.5cm, IPI 0-1
R-CHOP x3C + ISRT 30-36Gy
or
R-CHOP x4 for IPI 0
R-CHOP x 6 for IPI >0
then PET at 4C
if CR then consider RT
if PR then complete 6Cycles and ISRT
88
What is the common treatment regime for DLBCL , activated B cell type?
R-CHOP x 6-8C +- RT
R-ACVBP + MTX/Leukovorin
R-CHOP + Lenalidomide
Studies suggest inferior outcomes with standard R-CHOP so some intensify CHT
89
What is the common treatment regime for DLBCL double hit or triple hit
R- EPOCH (R-CHOP + etoposide)
R-Hyper-CVAD
Consider CNS prophylaxis
Consider consolidation with autologous Stem cell transplant
90
How can CNS prophylaxis be given in high risk patients?
Systemic MTX
intrathecal MTX
cytarabine
91
What is the common treatment regime for DLBCL transformed follicular?
R-CHOP x 6C +- RT
92
What is the common treatment regime for Follicular lymphoma grade 3B
Same as DLBCL paradigm
R-CHOP +- RT
93
What is the common treatment regime for primary mediastinal DLBCL?
R-EPOCH x 6C +-RT
R-CHOP x 6C + RT
94
What chemo/treatment options are there for mantle cell?
R-CHOP + autologous stem cell transplant
R-Hyper-CVAD/Cytarabine/MTX
R-CHOP + RT for selected stages I-II
Bendamusitne + ritux
R-chop not curative
95
What chemo options are there for Burkitt lymphoma?
CODOX-M
CALGB regimen
R-EPOCH
Hyper-CVAD
96
What chemo options are there for extra nodal NK -T-cell nasal type?
SMILE +RT
DeVIC + concurrent RT
GELOX + sandwich RT
97
What is the treatment paradigm for unfavourable early stage DLBCL?
R-CHOP x 6 + ISRT 30-36Gy
98
What is early stage in DLBCL
stage I and II
99
