MDS. Marianne Bach Treppendahl Læge, PhD Hæmatologisk Klinik Rigshospitalet

Transkript

1 MDS Marianne Bach Treppendahl Læge, PhD Hæmatologisk Klinik Rigshospitalet

2 LT-HSC ST-HSC MPP Myelodysplastic syndrom (MDS) ~ 250 nye tilfælde per år Median alder ved diagnose~ år CMP CLP MEP GMP Megakaryocyte Monocyte B cell T cell NK cell Granulocytes Erythrocytes Platelets Macrophage

3 Immunsystemet Miljø i knoglemarv Stintzing et al. 2011, jour of biomedicine and biotechnology

4 Debut tidspunkt Register Median alder ved diagnose (år) Dusseldorf Pavia Spain 3 74 SW Thames 4 77 (77-78) Swedish INCA % >70 years Yorkshire Network UK** 75 ELN MDS Registry** (IPSS Low/INT-1 only) 74 ( ) 1. Germing et al, Leukemia Research, 2000, 24, Malcovati et al, Journal of Clinical Oncology, 2005, 23, Sanz et al, ASH 2008, 4. Phekoo et al, Haematologica 2006,91, 1400 **unpublished data

5 Køns fordeling Registry Mand / kvinde (%/ratio) Dusseldorf 1 56/44 (%) Pavia 1 61/39 (%) SW Thames (ratio) Swedish INCA 56/44 (%) Yorkshire Network UK** 69/31 (%) 1. Malcovati et al, Journal of Clinical Oncology, 2007, 25, Phekoo et al, Haematologica 2006,91, 1400 **unpublished data

6 Årsager Erhvervet Arvelige Alderdom Mutagen/genotoxic stress Tidligere kemoterapi Organiske opløsingmidler Rygning Neurofibromatosis Kongenital dyskeratosis Kongenital neutropeni Kostmann Schwachman-Diamond DNA repair defekter Fanconi, Bloom, AT Familiær MDS

7 Symptomer Blodmangel (anæmi) Svimmelhed, hovedpine, hjertebanken, åndenød, træthed. Hyppige infektioner Blødninger

8 DIAGNOSEN

9 MDS diagnose Blod prøver Udeluk andre årsager til dysplastiske ændringer B 12 mangel Folin syre mangel Inflammatoriske sygdomme Cancere HIV i Parvovirus B19 Bly and arsenik forgiftning Når MDS er diagnosticeret Serum erythropoietin Vævstype bestemmelse Ferritin koncentration

10 MDS diagnose Knoglemarvsundersøgelse Knoglespange» Imprint og snit Knoglemarvsaspirat» Udstryg og koagel Perifert blod» Udstryg Markørundersøgelse Kromosomundersøgelse

11 Patologi fund

12 WHO klassifikation 2008 Gruppe Dysplasi Blaster i blod Blaster knoglemarv Ringe sideroblaster Cytogenetik 5q syndrome RA, RN, RT, RCUD Mest DysE < 1% < 5% < 15% 5q isoleret DysE, N, T < 1% < 5% < 15% Forskellige RARS Mest DysE 0 < 5% > 15% Forskellige RCMD 2 3 linier Rare < 5% < 15% Forskellige RAEB linier < 5% 5 9% < 15% Forskellige RAEB linier 5 19% Auer rods 10 19% Auer rods < 15% Forskellige MDS-U 1 linier < 1% < 1% < 15% Forskellige DysE = dyserythropoiesis; N = neutropenia; RCUD = refractory cytopenia with unilineage dysplasia; RN = refractory neutropenia; RT = refractory thrombocytopenia; T = thrombocytopenia.

13 WHO klassifikation WHO Hyppighed 5q- syndrome RA RCMD MDS-U 7% 16% 17% 2% RARS RCMD-RS 7% 3% RAEB-1 RAEB-2 13% 15% Malcovati L, et al. J Clin Oncol. 2005;23:

14 Kromosom undersøgelser - analyseres mhp. genetiske abnomaliteter

15 Cytogenetiske afvigelser Afvigelse Hyppighed (%) de novo MDS (40 70%) -5/del 5q (del 5q 5%) /del 7q Y 10 17p- 7 del 20q 5 t(11q23) 5 6 Complex ( 3) Therpi relateret MDS (95%) -5/del 5q/ -7/del 7q t(11q23) 3 Complex 90 Olney HJ, Le Beau MM. Best Pract Res Clin Haematol. 2001;14:

16 Normal and dysplastic flow cytometric profiling Markør undersøgelser A-C-E: normal bone marrow; B-D-F: myelodysplastic bone marrow - til differentiering mellem celletyperne Normale KM A C E B D F MDS KM Adapted from Van de Loosdrecht AA and Westers TM. MDS Foundation News Letter 2013;19:2-4

17 PROGNOSE

18 Cumulative proportion surviving Cumulative proportion surviving WHO klassifikation overlevelse 467 patients Leukæmi fri overlevelse Overlevelse 1,0 0,9 0,8 0,7 1,0 0,9 0,8 0,7 RA/RARS RCMD/RCMD-RS RAEB-1 RAEB-2 AML 0,6 0,6 0,5 0,5 0,4 0,4 0,3 0,2 0,1 0,0 RA/RARS RCMD/RCMD-RS RAEB-1 RAEB ,3 0,2 0,1 0, Survival time (months) Survival time (months) Malcovati L, et al. J Clin Oncol. 2005;23:

19 IPSS score Score Prognostik variable Knoglemarv blaster (%) < Karyotype Good Int Poor Cytopenier Score Cytogenetics Cytopenias Low 0 Int Int High 2.5 Good Poor Int Normal: -Y del 5q 20q- Complex ( 3 abn) -7/del 7q Other abn Hb < 10 g/dl Neutrophils < 1.8 x 10 9 /L Platelets < 100 x 10 9 /L Int = intermediate. abn = chromosomal abnormalities Greenberg P, et al. Blood 1997;89:

20 MDS patients (%) MDS patients (%) IPSS score Number (%) Median overlevelse (år) 25% AML (år) Low (0 point) 267 (33) Int-1 ( ) 314 (38) Int-2 ( ) 176 (22) High ( 2.5) 59 (7) n = 171 n = 58 AML udvikling Time (years) n = 235 n = Low Int-1 Int-2 High n = 179 n = Overlevelse n = 267 n = Time (years) Greenberg P, et al. Blood 1997;89:

21 Lav risiko MDS IPSS Low IPSS Int-1 Høj risiko MDS IPSS Int-2 IPSS-HR

22 IPSS-revideret Blood 2012, Greenberg et al

23 MDS prognose - IPSS-R Risk group % of patients Median survial (yr) Median 25% AML (yr) Very low NR Low Intermediate High Very High Greenberg, Blood 2012

24 MDS prognose - IPSS-R