Download - Boli mieloproliferative cronice
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SINDROAME (BOLI) MIELOPROLIFERATIVE CRONICE
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Sindroame
(boli) mieloproliferative cronice
Definţie: boli
clonale
ale celulei
stem pluri-sau multipotente
hematopoietice
caracterizate
prin
proliferarea
uneia
sau
mai
multor
linii
celulare mieloide.
SMC include:-
leucemia
granulocitară
cronică
(LGC),
-
metaplazia
mieloidă
cu mieloscleroză
(MMM), -
policitemia
vera
(PV)
-
Trombocitemia esentiala (TE)
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Clasificarea
OMS a bolilor
cronice
mieloide
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Sindroame
mieloproliferative
cronice (SMC)
Caracteristici comune:-
proces de maturare si diferentiere cvasinormal
-
la inceputul evolutiei proliferare multilineara si metaplazie mieloida (ficat,splina).
-
la sfarsitul evolutiei mielofibroza, evolutie spre LA-
tratamentul nu are scop curativ
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Leucemia granulocitară cronică (LGC)
Definitie: boala a celulei stem hematopoietice a seriei granulocitare, caracterizata prin cresterea masei granulocitare totale si a masei granulocitare circulante.
•
In 90% din cazuri prezenta cromozomului Philadelphia prezenta anomalie citogenetica T 9 / 22 implicata in etiopatogenia bolii.
Epidemiologieincidenta 1,6 /100 000frecv. maxima 30-50ani,sex masculin
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Etiologie (necunoscuta)radiatii ionizante (in vitro radiatii X )chimici( solventi organici ,insecticide )predispozitie genetica
PatogenieCromozom Philadelphia (Cr Ph+):-
Translocatie reciproca intre bratul lung al Cromozom 9 si brat lung al cromozom 22
-
Avantaj de crestere, aderenta scazuta la matricea stromala, autonomie (nu raspunde la mec. reglatoare
-
Prezent si la indivizii sanatosi, confera un teren pe care o alta modificare duce la aparitia si dezvoltarea clonei leucemice.
Leucemia granulocitară cronică
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Tablou clinic
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Tablou clinic
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Examen
obiectiv
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Examen
de laborator
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Examen
de laborator hematologie
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Examen
de laborator biochimie
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Medulograma-
Maduva
osoasa
hierplazica,
-
75-90% din volum
medular
tesut
hematopoetic
-
Tesut
grasos
redus
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Analiza
citogenetica
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Diagnostic pozitiv
SplenomegalieLeucocitozaFormula leucocitara deviata la stangaFAL = OCr. Ph pozitivAnomalii genetice
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Diagnostic diferenţial
BCR=blackpoint
cluster region=regiune
constituita
din 5-6 perechi
baze
brat Cromozom
22
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Factori de prognostic negativ in faza cronica
Varsta > de 60 aniSplina > 10 cm. sub rebordBlasti > 3 % in SP sau MOBazofilie > 7 %Trombocitoza > 700 000/mmc.Anomalii cromozomiale aditionale
Cr Ph dublutrisomia 8
Stadializarea prognostica a LGC:Stadiul 1 –
0 sau 1 factor de prognostic prezent
Stadiul 2 –
2 factori de prognostic prezentStadiul 3 –
3 factori de prognostic prezent
Stadiul 4 –
faza accelerata
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FAZA ACCELERATA
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CRITERII DE FAZA ACCELERATA
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FAZA ACUTA (PUSEU BLASTIC)
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FAZA ACUTA (PUSEU BLASTIC)
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TRATAMENT
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TRATAMENT
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TRATAMENT
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TRATAMENT
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TRATAMENT
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TRATAMENT
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TRATAMENT
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TRATAMENT
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TRATAMENT-
GLIVEC
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TRATAMENT-
GLIVEC
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TRATAMENT-
GLIVEC
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TRATAMENT-
GLIVEC
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TRATAMENT
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TRATAMENT
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TRATAMENTUL FAZEI ACCELERATE
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•
Tratamentul
fazei
blastice
limfoide
•
Tratamentul
fazei
blastice
mieloide
TRATAMENTUL FAZEI BLASTICE
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Policitemia vera
Definiţie: boala a celulei stem hematopoietice caracterizata prin proliferarea celulelor eritroide, granulocitare si megacariocitare.
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Manifestari clinice-
Debut insidios
-
SNC cefalee, ameteli, acufene, insomnii, confuzie, tulburari vizuale
-
Aparat cardiovascular: angina pectorala,claudicatie intermitenta, sindrom Raynaud, eritromelalgie, HTA, tromboze arteriale, venoaseTegumente
–
mucoase: facies
pletoric, prurit, urticarie,
sdr.hemoragipar-
Aparat digestive: UD, HDS, splenomegalie
-
Aparat respirator: dispnee, ↓
capacitatea de difuziune O2
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Manifestari paraclinice
-
Poliglobulie Hb 18-24g%, Ht >/= 47 % F (52 B ), Vol. masei eritrocitare >
-
Leucocitoza moderata cu bazofilie, fara deviere la stg. a formulei eritrocitare
-
Trombocitoza > 400 000/mmc cu anomalii morfologice / functionale,
-
FAL normal/crescut-
MO hiperplazica pe toate seriile, predominent eritroida, fibroza reticulinica
-
Vit. B12
>, hiperuricemie
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Evoluţie, prognostic, complicatii
Evoluţie, prognosticDurata de supravietuire sub tratament 10-15 aniPrognostic negativ:
-
varsta -
hepatomegalia
-
nleucocitoza-
anomalii citogenetice aditionale
Complicaţii:-
Tromboembolii
-
Hemoragii -
MM (evolutie “naturala”),LAM, SMD
-
Alte neoplazii
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TratamentRecomandări
pentru
tratament
1.
Emisia
de sânge
pentru
a menţine
Ht<0,452. Doze mici
de aspirina
(cand
nu
sunt
contraindicate)
3. Controlul
agresiv
al factorilor
reversibili
de risc
trombotic (fumat, HTA, Obezitate)
4. Citoreducţie
dacă:-
pacientul
nu
tolereaza
emisiile
de sange
-
trombocitoza
creste-
splenomegalia
este simptomatica
sau
progresiva5. Alegerea
terapiei
de citoreductie:
< 40 ani -
interferon-α> 40 ani –
hidroxiuree
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Obiectivreducerea
masei
eritrocitare
1) Flebotomiiemisii
300ml la doua
zile
Ht =45-47%
in manifestari
clinice
severe,inter.chir.emisii
masive
cu reinfuzie
de plasma sau
inlocuitori
de plasma
administrare
de fiernu
influenteaza
trombocitoza,pruritul,HSM
2) Agenti alchilantiFosfor radioactivHidroxiuree la tineri
3) Alfa interferon -
scade pruritul,CoTE
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Metaplazia
mieloidă
cu mieloscleroză
(MMM)
Definitie: boala a celulei stem caracterizata prin1) mieloproliferare clonala cu pancitoza2) proces de mataplazie mieloida (F,S) responsabil de aparitia in periferie a precursorilor serici E,G si a fragmentelor de megacariocite3) proces
de mielofibroza
reactiva datorat
prezentei
megacariocitelor
displaziceMetaplazie
cu pancitoza
insuficienţă
medulară
cu pancitopenie
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Manifestări cliniceSimptomatologie (std. avansate )
-
astenie,fatigabilitate-
transpiratii,scadere ponderala
-
disconfort abdominalExamen fizic:
-
splenomegalie-
hepatomegalie, HTPortala
-
paloare, subicter-
sindrom hemoragipar
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Examene paraclinice
-
anemie normocroma, normocitara, anizocitoza, poikilocitoza, dacriocite, eritroblasti
-
leucocitoza moderata, deviere la stanga a formulei leucocitare, bazofilie; leucopenie
-
trombocitoza, trombocite gigante; trombocitopenie-
FAL crescuta, Cr Ph -
- Puncţie sternală - alba- Biopsie măduvă osoasă: osteofibroza,hiperplazia seriei G
si Meg cu semne de displazie-
Rx. osoase -osteoscleroza
-
Biochimie: a uric, histamina, LDH
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Diagnostic•
Diagnostic pozitiv:
•
Clinic: paloare, splenomegalie•
Paraclinic: anemie, tablou leucoeritroblastic, dacriocite, fibroza medulara
•
Diagnostic diferenţial:•
- SMPC-PV, LGC
•
- LAM 7•
-
HCL
•
-
SMD(maduva hiperplazica)•
-
carcinomul metastatic
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Evoluţie, prognostic, complicaţii
-
supravietuire 1 -
15 ani-
prognosticul coreleaza cu
severitatea anemiei,tronbocitopeniei si hepatomegaliei
AHAI semnificaţie
prognostică
defavorabilă
-
complicaţii: infectii severe, hemoragii AHAI, LA(25%), IRA
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Tratament•
Pacientii asimptomatici pot prezenta o boala stabila ani de zile,fara tratament
•
Androgenii amelioreaza partial anemia(Danazol)•
Corticoizi
in AHAI
•
Transfuzii
de masa
eritrocitara, masa trombocitara
•
Radioterapie
pe
splina
-infarcte,S
masive, AHAI refractare
•
Chimioterapia-controlul L,T, HSM•
Splenectomie
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Trombocitemia esentialaDefiniţie:
boala mieloproliferativa cronica
caracterizata printr-o proliferaremieloida globala, in principal pe seria trombocitara (T>600 000/mmc)
Nu exista semne clinice si de laborator specifice, diagnosticul stabilindu-se prin excluderea celorlalte boli mieloproliferative cronice si a altor afectiuni cauzatoare de hiperplachetoza
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Manifestări clinice
-
manifestari hemoragice la varstnici-
manifestari vasoocluzive circulatorii
-
accidente trombotice arteriale si venoase
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Manifestări paracliniceT trombocitoza
>600 000/mmc(1-4mil), anizotrombocitoza,
forme bizare -
functii plachetare alterate (agg. spontana, agg
scazuta la ADP,A)L leucocitoza(de
obicei
pana la 40 000/mmc),deviere la
stanga putin importanta+/-
bazofilie,eozinofilie
E variabileMO -
hiperplazie
megacariocitaracu
megacariocite
mari,polilobateModificari
biochimice
- acid
uric >-
hiperpotasemie
- histamina >-
vit. B12
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Diagnostic
Diagnostic
pozitiv:-
Trombocite
450000-1000000/mmc
-
Hiperplazie
megacariocitara, -
Anizocitaza
trombocitara
-
Absenta cromozomului
Ph-
Absenta
cresterii
ME
-
Absenta unei
afectiuni
cu tombocitoza
reactiva
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Recomandări pentru tratament:Toti pacientii-tratamentul agresiv al factorilor de risc
cardiovascular(fumat,HTA,hipercolesterolemie,obezitate)
1. Pacienti cu risc inalt (tromboza,varsta>60 ani,T>1500x109/l)
-doze mici de aspirina plus hidroxiuree-anagrelid sau interferon ca a doua linie
2. Risc intermediar(40-60 ani,absenta factorilor de risc)-doze reduse de aspirina(citoreductie cand exista
factori de risc cv)3. Risc scazut (<40 ani,absenta factorilor de risc inalt)
-doze reduse de aspirina
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FROTIU PERIFERIC –ASPECT NORMAL
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LMC-ASPECT PERIFERIC