eha-tsh hematology tutorial on lymphoma · 2019-04-25 · any if bm, cns, liver, gi tract or lung 1...
TRANSCRIPT
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Self-assessment Case
DLBCL and Double Hit Lymphoma: Diagnosis and Treatment (First Line and Relapsed Disease)
Speaker: Burhan Ferhanoğlu, MD
İzmir, Turkey
April 6-7, 2019
EHA-TSH Hematology Tutorial on Lymphoma
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Introduction
‒ A 69-year-old woman presented in March 2015with fatigue, decreased urine output and leftinguinal pain
‒ PET/CT revealed generalised involvement of supra-and infra-diaphragmatic lymph nodes andincreased FDG in mesentery, retroperitoneum andendopelvic fascia.
‒ Bilateral urinary stent was placed to manageureteric obstruction
‒ Biopsy of the retro-peritoneal mass performed.
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- Immunohstochemical analysis showed DLBCL with a Kİ67 score of 80%
- The tumour cells were CD20,PAX5(+) bcl6, bcl2( 70%+), CD10 and, c-myc (>70%+)positive
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IHC
CD5 negativeTdT negative
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Bone marrow
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Q1) According to immunohistochemical data, our DLBCL case is of:
1. Germinal center B-cell origin
2. Non-germinal center B-cell origin
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Hans et al. Blood 2004
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The initial PET/CT scanMach 2015
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- Although our 69 year-old patient presented withfatigue, she was managing her daily activitieswithout difficulty.
- Involvement of the urinary bladder was biopsyproven
- The serum LDH level was above the upper limit of normal
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Q2) What is the correct IPI score?
1. IPI 1
2. IPI 2
3. IPI 3
4. IPI 4
5. IPI 5
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Bachy and Salles. Seminars in Hematology, 2015
IPI R-IPI NCCN-IPI
Age
>40 to ≤60
>60 to ≤75
>75
1 1
1
2
3
LDH
>1 to ≤3
>3
1 1 1
2
Ann Arbor Stage III-IV 1 1 1
Extranodal disease
>1 site
Any if BM, CNS, liver, GI tract or lung
1 1
1
Performance status ≥2 1 1 1
Score
Low
Low-intermediate
High-intermediate
High
0-1
2
3
4-5
0
1-2
≥3
0-1
2-3
4-5
≥6
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Q3) Which additional genetic test(s) would you recommend according to immunohistochemical results?
1. MYC rearrangement
2. BCL2 rearrangement
3. BCL6 rearrangment
4. p53
5. MYC rearrangment first, and if it positive, BCL-2and BCL-6 rearrangement
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All cases of DLBCL should be tested forMYC rearrangment
by FISH
further testing forBCL2 and BCL6
rearrangements
If the system has enough sources, evaluation of all three rearrangements is
recommended
Valera A. Mod Pathol.2016
Kluk MJ et al. Am J Surg Path 2016
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Q4) What is your diagnosis according to WHO 2016 classification?
1. DLBCL
2. Plasmablastic lymphoma
3. Intravascular lymphoma
4. EBV+ DLBCL
5. High grade B cell lymphoma with MYC, BCL2 and BCL6 re-arrangement
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Friedburg J.Blood 2017
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Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS)Germinal-centre B-cell-like (GCB)Activated B-cell-like (ABC)
DLBCL subtypesT-cell/histiocyte-rich large B-cell lymphomaPrimary DLBCL of the CNSPrimary cutaneous DLBCL, leg typeEpstein-Barr virus–positive DLBCL, NOS of the elderly
EBV+ mucocutaneous ulcer
Primary mediastinal (thymic) large B-cell lymphomaIntravascular large B-cell lymphomaDLBCL associated with chronic inflammationLymphomatoid granulomatosisALK-positive DLBCLPlasmablastic lymphomaPrimary effusion lymphoma
HHV8-positive, DLBCL, NOS
B-cell lymphoma, with features intermediate between DLBCL and classical Hodgkin Lym.B-cell lymphoma, with features intermediate between DLBCL and Burkitt lymphoma
H i g h g r a d e B - c e l l l y m p h o m a , w i t h M Y C a n d B C L 2 a n d / o r B C L 6 r e a r r a n g e m e n t s , N O S
DLBCL WHO Classification Update 2016
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Q5) Which regimen would you prefer to treat our patient?
1. R-CHOP
2. R-mini-CHOP
3. R-CHEOP
4. DA-EPOCH
5. Hyper CVAD
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Oki et al. BJH 2014
Median ageR-CHOP: 62DA-EPOCH-R: 65 RHCVAD/MA: 55
R-CHOP: 57 (%44)R-EPOCH: 28 (%22)R-HCVAD/MA: 34 (%26)Other 10 (%7)
P=0.004 P=0.057
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Q6) Regarding CNS involvement risk in this condition:
1. CNS prophylaxis should be offered for every DHL case
2. I would decide according to CNS-IPI
3. I would not offer intrathecal prophylaxis due to age
4. I would offer Hyper-CVAD which would provide required protection for CNS
5. I would offer intrathecal prophylaxis only
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Oki et al. BJH 2014
13%
IT prophylaxis; 3 year CNS involvementdecreased from 15% to 5% (p=0.017)
Bone marrow involvementECOG ≥2
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- After 2 courses of R-CHOP+ IT MTX, wereceived FISH analysis results, so then weswitched to DA-EPOCH
- Grade 4 neutropenia and related febrileepisode occured
- She had grade 4 mucositis and severe nutritional impairement
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-Interim PET after2 R-CHOP and
2 cycles of DA-EPOCH
-still there wasDeauville5
changes in areasinvolved in July
2015
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- She had severe pain and fatigue
- The PET scan before 6th cycles revealedprogressive disease
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InitialInterim
Before 6th cycle
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Q7) What is your next approach for this patient?
1. Refer for a clinical trial
2. Salvage regimen with stem cell support
3. R-Bendamustine
4. Venetoclax
5. Ibrutinib
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- We planned to administer 3 cycles of ICE; to collectperipheral stem cells following the first cycle and toevaluate the disease status after the second cycle andperform ASCT
- Before the ICE treatment, atypical cells were seen in thecerebrospinal fluid and CNS involvement wasdemonstrated
- The bone marrow was also infiltrated
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Bone Marrow
CSF
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- After 2 courses of R-ICE chemotherapy, weadministered 1.5 g/m2 methotrexate due to CNS involvement in addition to IT MTX which was given 4 times in the beginning.
- -The disease progressed and she died on November2015, 8 months after diagnosis.
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Self-assessment Case
DLBCL and Double Hit Lymphoma: Diagnosis and Treatment (First Line and Relapsed Disease)
Speaker: Burhan Ferhanoğlu, MD
İzmir, Turkey
April 6-7, 2019
EHA-TSH Hematology Tutorial on Lymphoma