Lymfom Mats Jerkeman

Lymfom Översikt Diffust storcelligt B-cellslymfom Follikulärt lymfom Burkittlymfom Mantelcellslymfom Hodgkinlymfom T-cellslymfom

Immunsystemet

B-cellens utveckling Antigen KLL Myelom Pre-B- ALL KLL Mantel cells Minnescell KLL Prekursor B-cell Naiv B-cell Centrocyt Centroblast Plasmacell Benmärg Blod Mantelzon Germinalcentrum Blod/benmärg Antigen Myelom Pre-B- ALL KLL Mantel cells lymfom Follikulärt lymfom Diffust Storcelligt B-cells lymfom

Lymfom - symptom Lymfkörtel svullnad Tumör i annat organ B-symptom Feber Svettningar Viktnedgång

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?

Nytillkommen förstorad lymfkörtel Primärvård Nytillkommen förstorad lymfkörtel Remiss för finnålspunktion, med frågeställning lymfom Labprover: Hb, V, diff, trc, LD

Om finnålspunktion bekräftar lymfommisstanke Remiss Onkolog – (Malmö/Lund) Hematolog(övriga sjukhus i regionen) Beställ samtidigt CT hals, thorax, buk(?)

Utredning hos onkolog/hematolog Röntgenologisk (CT thorax, buk, bäcken) Benmärg (biopsi, utstryk, flödescytometri) S-LD, urat Vid symptom: utredning av CNS, skelett

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)

Kvinna 45 år Finnålspunktion: kappamonoklonala celler, med hög Ig-täthet och CD19+/CD20+/CD5-/CD10+/CD23+ Remitteras till onkolog Lymfkörtelbiopsi: follikulärt lymfom, grad 1

Kadin, M. ASH Image Bank 2003;2003:100698 Diffust storcelligt B-cellslymfom Kadin, M. ASH Image Bank 2003;2003:100698

B-cellens utveckling Antigen DLBCL Memory B-cell Precursor B-cell Naive B-cell Centrocyte Centroblast Plasma cell Bone marrow Blood Germinal centre Generation of antibody diversity in mature B cells. The antigen binding site of antibodies are created in immature B cells by the random assembly of variable (V), diversity (D), and joining (J) segments into one coding exon by a process termed V(D)J rearrangement. This process creates a very large repertoire of antibodies with different specificities. Unfortunately, because these antibodies are created randomly, most antibodies that are generated bind to antigen with low affinity. In order to neutralize and clear pathogens and toxins from the circulation, B-cells must produce and secrete antibodies of higher affinity and of different classes. Following exposure to antigen, the V regions of the antibody genes acquire many base changes that result in antibodies that bind with higher affinities to their respective antigens. This phenomenon is achieved by the somatic hypermutation process in mice and humans and immunoglobulin gene conversion in chickens (Figure 1). The constant region of the antibody gene encodes the remaining part of the antibody molecule and is responsible for carrying out the effector functions of the antibody. Constant regions, which define the antibody class, can be replaced with other constant regions by the class switch recombination process (Figure 1), thereby changing the antibody effector functions without changing the antigen binding site. Blood/bone marrow Antigen DLBCL

Basala data Medianålder 70 år 5-års överlevnad DLBCL i Sverige 50% Kön 5-års överlevnad DLBCL i Sverige 50% Kv Män

Prognosfaktorer Ålder Performance Status Stadium Extranodala manifestationer S-LD

DLBCL - IPI 1 2 3 4 5

DLBCL - Ålder 0-40 år 40-60 år 60-70 år 70-80 år >80 år

Behandling DLBCL - historik 1976 CHOP Cyklofosfamid Doxorubicin Vincristin Prednison

Rituximab Antikropp mot CD20 CD20 alla B-celler (förutom prekursor B och plasmaceller) Ger apoptos, CDC, ADCC Sensitiserar för cytostatika

R-CHOP > CHOP

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

Follikulärt lymfom

Follikulärt lymfom t(14;18) Överuttryck av BCL2 - hämmare av apoptos

B-cellens utveckling Antigen FL Memory B-cell Precursor B-cell Naive B-cell Centrocyte Centroblast Plasma cell Bone marrow Blood Germinal centre Generation of antibody diversity in mature B cells. The antigen binding site of antibodies are created in immature B cells by the random assembly of variable (V), diversity (D), and joining (J) segments into one coding exon by a process termed V(D)J rearrangement. This process creates a very large repertoire of antibodies with different specificities. Unfortunately, because these antibodies are created randomly, most antibodies that are generated bind to antigen with low affinity. In order to neutralize and clear pathogens and toxins from the circulation, B-cells must produce and secrete antibodies of higher affinity and of different classes. Following exposure to antigen, the V regions of the antibody genes acquire many base changes that result in antibodies that bind with higher affinities to their respective antigens. This phenomenon is achieved by the somatic hypermutation process in mice and humans and immunoglobulin gene conversion in chickens (Figure 1). The constant region of the antibody gene encodes the remaining part of the antibody molecule and is responsible for carrying out the effector functions of the antibody. Constant regions, which define the antibody class, can be replaced with other constant regions by the class switch recombination process (Figure 1), thereby changing the antibody effector functions without changing the antigen binding site. Blood/bone marrow Antigen FL

Klinik Stillsam, kronisk sjukdom Ej botbar Behandling endast vid symptom Kan transformera till DLBCL (ca 10%)

FL Överlevnad

Behandling Rituximab R-Bendamustin R-CHOP

Burkittlymfom Denis Burkitt Uganda 1958 Michael Epstein, Yvonne Barr

Burkittlymfom Sverige: ca 15 patienter/år, B-ALL 2-5/år Endemisk EBV + malaria HIV-relaterad Spontan Ofta engagemang i buk, benmärg, CNS (1/6) Sverige: ca 15 patienter/år, B-ALL 2-5/år

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

Burkittlymfom - överlevnad

Mantelcellslymfom Äldre män (75% >65 år, 70% män) Vanliga extranodala lokaler: Gastrointestinalkanalen (lymfomatoid polypos) ca 30% Benmärg Waldeyer, mjälte

Mantelcellslymfom t(11;14) Immunhistokemi cyklin-D1 FISH FCM: CD5+

R R RR MCL-1 TRIAL 1996-2000 MCL-2 TRIAL 2000-2006 B E A M/C B E A M/C INDUCTION RE- STAGE STEM-CELL HARVEST REINFUSION B E A M/C Maxi C H O P Maxi C H O P Maxi C H O P Maxi C H O P Week: 1 4 7 10 13 14 MCL-2 TRIAL 2000-2006 INDUCTION RE- STAGE STEM-CELL HARVEST REINFUSION R R RR B E A M/C Maxi C H O P A r a C Maxi C H O P A r a C Maxi C H O P A r a C Week: 1 4 7 10 13 16 19 20 AraC: 4 Infusions: < 60 years 3g/m2, > 60 years 2g/m2

Nordic MCL2

Hodgkinlymfom Incidenstopp i 20 års åldern, samt i 60 årsåldern.

Hodgkinlymfom -historik 50-talet Strålbehandling – mantelbehandling God behandlingseffekt Långtidsbiverkningar Sekundära maligniteter Klaffstenoser Coronarstenoser Muskelatrofi

HL - behandling Stadium I-IIA Stadium IIB-IV ABVD x 2-4 + strålbehandling 30 Gy Stadium IIB-IV ABVD x 6-8 BEACOPP

HL Överlevnad

PET PET is the most important event in HL management in last decades. In other lymph PET has est for assess resp after compl therapy, but has turned out to be more probl in detect of early response (false positives). In HL repeatedly reliable, usually after 2 cycles.

PET för Hodgkinlymfom Responsutvärdering Standard Tidig prediktion (efter 2 cykler) Experimentellt

Responsstyrd behandling PET efter 2 cykler Positiv – eskalering Negativ – kortare behandling

T-cellslymfom Nodala Extranodala Leukemiska Kutana 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)

Lymfom Stort antal skilda sjukdomar Många olika presentationer Finnålspunktion ger vägledning Remiss onkolog/hematolog