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![Page 1: Lymfom](https://reader030.fdocuments.net/reader030/viewer/2022012822/56812f93550346895d951109/html5/thumbnails/1.jpg)
Lymfom
Mats Jerkeman
![Page 2: Lymfom](https://reader030.fdocuments.net/reader030/viewer/2022012822/56812f93550346895d951109/html5/thumbnails/2.jpg)
Lymfom
• Översikt
• Diffust storcelligt B-cellslymfom
• Follikulärt lymfom
• Burkittlymfom
• Mantelcellslymfom
• Hodgkinlymfom
• T-cellslymfom
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Immunsystemet
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B-cellens utveckling
Benmärg Blod Mantelzon Germinalcentrum
Blod/benmärg
Prekursor B-cell Naiv B-cellCentrocyt Centroblast
Plasmacell
Minnescell
Antigen
Pre-B-ALL KLL
Mantelcells
lymfom
Follikulärt lymfom
DiffustStorcelligt
B-cellslymfom
KLL
Myelom
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Lymfom - symptom
• Lymfkörtel svullnad
• Tumör i annat organ
• B-symptom– Feber– Svettningar– Viktnedgång
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Kvinna, 45 år
• Sedan 1 år 1 cm stor knuta vä ljumske
• Sedan 1 månad 2 till, ökar snabbt i storlek
• Trött, viktnedgång 8 kg
• Blodstatus normalt
• Åtgärd?
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Primärvård
• Remiss för finnålspunktion, med frågeställning lymfom• Labprover: Hb, V, diff, trc, LD
Nytillkommen förstorad lymfkörtel
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Om finnålspunktion bekräftar lymfommisstanke
• Remiss– Onkolog – (Malmö/Lund)
– Hematolog(övriga sjukhus i regionen)
– Beställ samtidigt CT hals, thorax, buk(?)
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Utredning hos onkolog/hematolog
• Röntgenologisk (CT thorax, buk, bäcken)
• Benmärg (biopsi, utstryk, flödescytometri)
• S-LD, urat
• Vid symptom: utredning av CNS, skelett
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Stadieindelning - Ann Arbor
• Stadium I en lymfkörtelstation
• Stadium II >1 lymfkörtelstation, samma sida av diafragma
• Stadium III >1 lymfkörtelstation, bägge sidor om diafragma
• Stadium IV Utbrett extranodalt engagemang (ex benmärg, lever)
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Kvinna 45 år
• Finnålspunktion: kappamonoklonala celler, med hög Ig-täthet och CD19+/CD20+/CD5-/CD10+/CD23+
• Remitteras till onkolog
• Lymfkörtelbiopsi: follikulärt lymfom, grad 1
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Kadin, M. ASH Image Bank 2003;2003:100698
Diffust storcelligt B-cellslymfom
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B-cellens utveckling
Bone marrow Blood Germinal centre
Blood/bone marrow
Precursor B-cell Naive B-cell Centrocyte Centroblast
Plasma cell
Memory B-cell
Antigen
DLBCL
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Basala dataÅlder
Kön
MänKv
5-års överlevnad DLBCL i Sverige
50%
Medianålder
70 år
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Prognosfaktorer
• Ålder • Performance Status • Stadium • Extranodala manifestationer• S-LD
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DLBCL - IPI
0
1
2
34
5
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DLBCL - Ålder
0-40 år
40-60 år
60-70 år
70-80 år
>80 år
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Behandling DLBCL - historik
• 1976 CHOP– Cyklofosfamid– Doxorubicin– Vincristin– Prednison
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Rituximab
• Antikropp mot CD20
• CD20 alla B-celler (förutom prekursor B och plasmaceller)
• Ger apoptos, CDC, ADCC
• Sensitiserar för cytostatika
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R-CHOP > CHOP
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Recidivbehandling
• Kurativt syfte: annan kemoterapi, ex DHAP, GDP
• Mål: respons konsolidering med högdosbehandling med autologt stamcellsstöd (<70 år) – 20% bot
• Palliativt syfte: klorambucil, rituximab, XRT
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Follikulärt lymfom
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Follikulärt lymfomt(14;18)
Överuttryck av BCL2- hämmare av apoptos
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B-cellens utveckling
Bone marrow Blood Germinal centre
Blood/bone marrow
Precursor B-cell Naive B-cell Centrocyte Centroblast
Plasma cell
Memory B-cell
Antigen
FL
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Klinik
• Stillsam, kronisk sjukdom
• Ej botbar
• Behandling endast vid symptom
• Kan transformera till DLBCL (ca 10%)
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FL Överlevnad
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Behandling
• Rituximab
• R-Bendamustin
• R-CHOP
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Burkittlymfom
• Denis Burkitt
• Uganda 1958
Michael Epstein, Yvonne Barr
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Burkittlymfom• Endemisk
– EBV + malaria
• HIV-relaterad• Spontan
– Ofta engagemang i buk, benmärg, CNS (1/6)
Sverige: ca 15 patienter/år, B-ALL 2-5/år
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Burkittlymfom - Behandling
• Extremt känslig för alkylerare (ctx)– Tidiga stadier 80% bot singel-dos ctx
• Tumörlyssyndrom!
• CNS-profylax (HDMTX)
• Hög dosintensitet, kort behandling (3 mån)
• God prognos
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Burkittlymfom - överlevnad
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Mantelcellslymfom
• Äldre män (75% >65 år, 70% män)
• Vanliga extranodala lokaler:– Gastrointestinalkanalen (lymfomatoid
polypos) ca 30%– Benmärg– Waldeyer, mjälte
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Mantelcellslymfom
• t(11;14)• Immunhistokemi
cyklin-D1• FISH• FCM:
– CD5+– CD23-– CD10-
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BEAM/C
RE-STAGE
Maxi
CHOP
STEM-CELLHARVEST REINFUSION
Maxi
CHOP
Maxi
CHOP
Maxi
CHOP
Week: 1 4 7 10 13 16 19 20
Week: 1 4 7 10 13 14
RRRRAraC
AraC
AraC
Maxi
CHOP
Maxi
CHOP
Maxi
CHOP
BEAM/C
RE-STAGE
STEM-CELLHARVEST REINFUSION
INDUCTION
INDUCTION
MCL-1 TRIAL 1996-2000
MCL-2 TRIAL 2000-2006
AraC: 4 Infusions: < 60 years 3g/m2, > 60 years 2g/m2
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Nordic MCL2
0 2 4 6 8 100
20
40
60
80
100
P < 0.0001
A
Years
Per
cen
t S
urv
ival
MCL2: n= 169
Event-Free Survival
MCL1=42
0.0 2.5 5.0 7.5 10.00
20
40
60
80
100
Overall survival
P = 0.003
MCL2
MCL1B
Legend
Years
Per
cen
t S
urv
ival
0.0 2.5 5.0 7.5 10.00
20
40
60
80
100
C
Protocol
P < 0.02
Response Duration
MCL2 n= 159
MCL1 n= 28
Years
Per
cen
t S
urv
ival
Median obs. time 2.3 years
45 pts beyond 3 years
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Hodgkinlymfom
• Incidenstopp i 20 års åldern, samt i 60 årsåldern.
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Hodgkinlymfom -historik
• 50-talet– Strålbehandling – mantelbehandling
• God behandlingseffekt
• Långtidsbiverkningar– Sekundära maligniteter– Klaffstenoser– Coronarstenoser– Muskelatrofi
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HL - behandling
• Stadium I-IIA– ABVD x 2-4 + strålbehandling 30 Gy
• Stadium IIB-IV– ABVD x 6-8– BEACOPP
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HL Överlevnad
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PET
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PET för Hodgkinlymfom
• Responsutvärdering– Standard
• Tidig prediktion (efter 2 cykler)– Experimentellt
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Responsstyrd behandling
• PET efter 2 cykler
• Positiv – eskalering
• Negativ – kortare behandling
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T-cellslymfom• Nodala
– Anaplastiskt storcelligt lymfom (ALCL – Angioimmunoblastiskt T-cellslymfom– Perifert T-cells lymfom, ej närmare specificerat
• Extranodala– NK/T-cellslymfom av nasal typ– T-cellslymfom, enteropatityp– Hepatospleniskt T-cellslymfom– Subkutant pannikulit-liknande T-cellslymfom
• Leukemiska– Prekursor T-lymfoblastiskt lymfom (T-LBL) – T-cell prolymfocytleukemi (T-PLL)– Granulär lymfatisk leukemi (LGL) – Adult T-cellsleukemi /lymfom
• Kutana– Blastiskt NK-cellslymfom– Mycosis fungoides (MF) och Sezarys syndrom (SS)– Primärt kutant storcelligt anaplastiskt lymfom (C-ALCL)– Lymfomatoid papulos (LyP)
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Lymfom
• Stort antal skilda sjukdomar
• Många olika presentationer
• Finnålspunktion ger vägledning
• Remiss onkolog/hematolog