Gaucherjeva bolezen v Sloveniji. Samo Zver Klinični oddelek za hematologijo UKC Ljubljana

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1 Gaucherjeva bolezen v Sloveniji Samo Zver Klinični oddelek za hematologijo UKC Ljubljana

2 . Gaucherjeve celice

3 View Notes

4 View Note

5 Mb. Gaucher: biopsija KM

6 View Notes

7 View Notes

8 View Note

9 Incidenca v zahodnem svetu 1 : Ashkenazi judje 1 : 850

10 View Notes

11 View Note

12 View Note

13 View Notes

14 View Notes

15 When to consider Gaucher disease (Type 1) (glucocerebrosidase/chitotriosidase? peripheral blood testing Lab. hem. odd. Pediatrične klinike, UKC Ljubljana) patients with otherwise unexplained (hepato)splenomely, especially when accompanied with some degree of anemia/thrombopenia less severe disease forms relatives check up of allready known patients? jewish ancestors?

16 Normocitna anemija

17 Biokemični bolezenski kazalci (sledenje bolezni) Hitotriozidaza CCL/PARC18

18 Zdravljenje encimsko nadomestno zdravljenje (imigluceraza; velagluceraza; taligluceraza) encim (glukocerobrozidaza) substrat (glukocerebrozid) reducirajoče zdravljenje (eliglustat, miglustat) simptomatsko ukrepanje

19 Kronologija zdravljenja Mb. Gaucher na KOH 2002: začetek zdravljenja z glukocerebrozidazo/imiglucerazo E/kg TT/14 dni 2004: zdravljenje z nižjim odmerkom zdravila 15 E/kg TT/14 dni 2006: spremljanje bolezni tudi s CCL18/PARC registrirano zdravilo miglustat (SRT) 2010: registracija zdravila velaglucerase s strani EMEA/FDA 2011: velagluceraza 2011: samozdravljenje doma z imiglucerazo 2015: eliglustat (SRT; oralna oblika zdravila ) 2015: 19 bolnikov/17 zdravljenih (13 C + 4V) 2 zdravljenje ni potrebno Incidenca

20

21 Mb. Gaucher: spremljanje bolezni OB DIAGNOZI 3M 12/24 M DOZE. Hgm KF, jetrni testi,feritin encim-ab + + Hitotriozidaza CCL18/PARC UZ/CT abd. + +/- + MRI: stegnenice RTG:s+hrbt. + DPX + +/ /- + QOL + + +

22 KLINIČNI PRIMER female, 1958 diagnosed in childhood with type I Gaucher disease genotype: N370S/recNci I 1998: skeletal pains (lumbal, hips), hepatosplenomegalia (6/11 cm) WBC 4,4x10 9 /L; Hb 105 g/l; Plt 36x10 9 /L 02/2003 started treatment with imiglucerase 60 U/kg BW/14 days 02/2004 reduced dose of imiglucerase 30 U/kg BW/14 days no treatment related symptoms/problems from that time point on

23 Chitotriosidase Hemoglobin Platelets liver and spleen size normalised after one year of therapy later on skeletal pains decreased also

24 Mogoči zapleti večja incidenca rakavih krvnih bolezni (MINP, MM) nagnjenost k krvavitvam okužbe pri bolnikih po splenektomiji krvne autoimunske bolezni Mb. Parkinson

25 kvantitativne in kvalitativne (funkcijske) motnje trombocitov kopičenje faktorjev strjevanja krvi v Gaucherjevih celicah sindrom DIK (blaga oblika)

26 Kaj se je dogajalo v zadnjih petih letih???

27 Pomanjkanje zdravila: junij 2009/imigluceraza Bolnik 1.: Hitotriozidaza

28 Bolnik 1.: Trombociti Pomanjkanje zdravila Bolnik 1.: Hemoglobin

29 Hitotriozidaza dinamika pri vseh bolnikih v obdobju pomanjkanja S 500 0

30 Series1 Hb: povprečje pri vseh bolnikih v obdobju pomanjkanja 133 okt.04 jan.05 apr.05 jul.05 okt.05 jan.06 apr.06 jul.06 okt.06 jan.07 apr.07 jul.07 Trombociti: povprečje pri vseh bolnikih v obdobju pomanjkanja okt.04 dec.04 feb.05 apr.05 jun.05 avg.05 okt.05 dec.05 feb.06 apr.06 jun.06 avg.06 okt.06 dec.06 feb.07 apr.07 jun.07 avg.07 Series1

31 Samozdravljenje na domu

32

33 priprava zdravila priprava/redčenje stekleničk Cerezyma s FR prenos vsebine stekleničk Cerezyma v infuzijsko vrečko ravnanje z infuzijskim sistemom vstavitev igle v periferno veno infuzija zdravila Samozdravi se 5/17 bolnikov Zdravljenje na domu omogočamo 12-tim bolnikom

34 Novi bolniki še prihajajo 2012: 1 nov bolnik (krvavitev v CŽS) 2013: 1 nov bolnik (dolgoletne stopnjujoče se bolečine po skeletu)

35 Autoimunski zaplet zdravljenja z imiglucerazo??

36 Sekundarni mlg??

37

38

39 Koncentracija trombocitov Tr (10^9/L) U/kg 15 U/kg bolnik 1 Bolnik 2 Bolnik 3 Bolnik 6 Bolnik 7 Bolnik Čas zdravljenja (meseci)

40 Koncentracija hemoglobina U/kg 15 U/kg Hb (g/l) Bolnik 1 Bolnik 2 Bolnik 3 Bolnik 6 Bolnik 7 Bolnik Čas zdravljenja (meseci)

41 Koncentracija serumske hitotriozidaze Hitotriozidaza (μmol/l) U/kg 15 U/kg B Bolnik 3 Bolnik 6 Bolnik 7 Bolnik Čas zdravljenja (meseci)

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