Download - Caz Leucemie Acuta
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Caz clinic 10Caz clinic 10
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Anamneza (I)Anamneza (I)• Pacienta ET, in varsta de 52 ani este spitalizata in
urgenta, pe data de 15.03.2004, prin transfer de la Spitalul jud Bacau pentru investigarea unui sdr anemic si hemoragipar.
• APF – PM 14 ani, UM 45 ani, S=2, A=0, N=2, C=2.
• APP – diagnosticata in 1994 cu gusa nodulara pt care a urmat tratament cu Eutyrox
• AHC - Tata cu arteriopatie mb inf (decedat). Mama cu hernie inghinala operata (decedata). Nu are frati sau surori. Un copil cu sdr Raynaud
• Nefumatoare, consuma ocazional alcool. Pensionara. A lucrat in mediu cu praf (fabrica postav).
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Anamneza (II)Anamneza (II)• Debut insidios, in urma cu 2 luni, prin astenie fizica,
adinamie, inapetenta si scadere in greutate, aproximativ 6 kg. Pe acest fond survin episoade infectioase repetate.
• Pe 20.02.2004 este spitalizata la Spit Buhusi pentru sdr febril si este dg cu pneumonie interstitiala si sdr anemic. Persistenta sdr febril sub antibioterapie determina transferul in Spit jud Bacau.
• Se constata anemie severa (Hb 5,5 g/dl) si Trombocitopenie severa (10.000/mmc). Se instituie antibioterapie (Gentamicin + Penicilina) si substitutie cu ME. Aparitia de echimoze si sangerari gingivale determina transferul in serviciul nostru.
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Examen clinicExamen clinic
• Starea generala discret influentata, astenie, fatigabilitate, PS=2. Subfebrilitate 37,6C
• Tegumente usor palide cu multiple echimoze si petesii diseminate pe membrele.
• Mucoase – hipertrofie gingivala moderata cu sangerari.
• Adenopatii - absente.• Respirator – normal. Cardiovasular – tahicardie.• Abdomen suplu, depresibil, moderat sensibil in
epigastru. Polul inferior al splinei palpabil in inspir profund
• Diureza diminuata
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InvestigatiiInvestigatii
• Hemograma : – Hb 9 g/dl, – Tr 12.500/mmc – GA 9.300/mmc cu 41% celule blastice cu corpi Auer,
PN 40%, L15%, M 4%.
• Hemostaza : TQ 19,5”, IQ 59%, aPTT 24,8”, fibrinogen 1.70g/l, PDF absent.
• VSH 45 mm/1h, LDH 681 UI/l, glicemie 117 mg/dl, uree 52, cre atinina0,65, restul bliantului este corect
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Sangele perifericSangele periferic
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Problematica• Pacienta in varsta de 52 ani• Clinic
– Sdr anemic – paloare– Sdr infectios – febra, inf respiratorii repetate– Sdr hemoragipar – purpura, hemoragii gingivale– Sdr tumoral (+/-) – hipertrofie gingivala
• Biologic– Anemie– Trombocitopenie– Prezenta de blasti
examenul medular
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Examen medular
• Examen morfologic
• Examen citochimic
• Examen imunofenotipic
• Examen citogenetic
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Examen Morfologic• Acest prim abord investigational ramane
fundamental in orientarea diagnosticului in cadrul primei etape de diagnostic la un pacient nou.
» Permite :
• Clasificarea leucemiilor acute (LA), - clasificarea FAB - bazata initial pe descrieri citologice, ramane, inca, dependenta de analiza morfologica traditionala, realizata pe frotiurile sanguine si medulare, colorate cu May-Grunwald-Giemsa (MGG), la care se asociaza cateva reactii citochimice.
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Examen Morfologic
• Examenul microscopic al frotiurilor de sange periferic si medular (in special) – ramane investigatia de baza a diagnosticului de LA si trebuie sa fie cunoscut de orice medic de laborator, si de orice clinician hematolog.– Simplu– Rapid– Utilizabil in orice serviciu medical chiar in
absenta unor dotari deosebite.
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Mielograma (ET)Mielograma (ET)
• Examenul medular evidentiaza o maduva bogata, hiperplazica, infiltrata in proportie de 70% cu celule blastice hipergranulare cu prexenta de copri Auer numerosi, uneori asezati in “snopi”. Hematopoieza reziduala are morfologie normala.
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Mielograma (ET)Mielograma (ET)
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Examenul citochimic (I)
• Reactiile citochimice pun în evidenta prezenta unor enzime intracelulare si permit astfel, diferentierea între LA limfoblastice si mieloblastice cat si precizarea subtipului, atunci cand examenul morfologic se dovedeste insuficient.
• Reactii utilizate : Mieloperoxidaza Negru Sudan B Esterazele nespecifice Cloroacetat-esteraza Acidul periodic Schiff (PAS) Fosfataza acida
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Mieloperoxidaza
• Este o enzima prezenta in granulatiile azurofile (primitive) ale celulelor din seriile granulocitara si monocitara.
• Reactia este intens pozitiva în granulocite, slab pozitiva în monocite si absenta în limfocite.
• Reactia este mult mai intensa in linia granulocitara decat in cea monocitara.
Pozitivitatea reactiei în cel putin 3% din celulele blastice permite diagnosticul de LA nonlimfoblastica
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Mieloperoxidaza
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Esterazele
• Reactia esterazica este utila in diferentierea seriilor granulocitara si monocitara.
• Tipuri :• Esteraza specifica
– Naftol-ASD-cloroacetat esteraza - este prezenta in precursorii granulocitari si slaba sau negativa in precursorii monocitari
• Esterazele nespecifice– Reactia este intensa si inhibata de florura de sodiu in
monocite si megakariocite, in timp ce reactia este slaba, si rezistenta la florura de sodiu in linia granulocitara
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Esteraza nespecifica/Dubla esteraza
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Acidul periodic Schiff
• Reactia PAS este intens pozitiva cu aspect de granule mari sau blocuri în limfoblasti.
• Reactia PAS este negativa sau pozitiva cu aspect fin granular, difuz în mieloblasti.
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Citochimie (ET)Citochimie (ET)
• Reactia peroxidazica este intens pozitiva, acoperind practic atat aria citoplasmatica cat si cea nucleara.
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ANTICORPII MONOCLONALI UTILIZA}I IN DG LA
Antigen Specificitate
CD13 Mieloida
CD33 Mieloida
CD65 Mieloida
Anti-mieloperoxidaza Mieloida
CD41, CD42 Megakariocit
CD61 Megakariocit
Antiglicoforin Eritrocitara
CD19 Limfocitara B
CD79a Limfocitara B
CD10 Limfocitara B
CD3 Limfocitara T
CD7 Limfocitara T
Anti-TdT Limfocitara T si B
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LAM – subtipuri imunologice
CAR ACT ER I ZAR EA FENOT I P I C| A LAM Marker Tip M0 M1 M2 M3 M4 M5 M6 M7 CD34 + + +/- - +/- +/- +/- +/- CD11c + + +/- +/- + + + + CD13 + + + + + + + + CD14 - - - - + + - - CD15 +/- - +/- +/- +/- +/- +/- - CD16 - - + - - - - - CD33 + + + + + + + +/- CD36 - - - - + + + + CD41 - - - - - - - + CD42 - - - - - - - + Glicoforina A - - - - - - + - HLA-DR + + + - + + + +
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Fenotipare (ET)Fenotipare (ET)
• Imunofenotip: – CD13+, CD33+, HLA DR-, CD34+
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Examenul citogeneticCor ela]i i pr ognostice ale anomali i lor cr omozomiale n L AL
(dup\ Wetzler ) Grupa de risc Anomalia
citogenetic\ Probabilitate de
remisiune complet\ continu\ la 5 ani
Favorabil del(12p) sau t(12p) t(14q11-q13)
75-80%
Intermediar
Cariotip normal +21 del(9p) sau t(9p) Hiperdiploidie del(6q)
30-45%
Nefavorabil
t(9;22)(q34;q11) t(4;11)(q21;q23) t(1;19)(q23;p13) +8 -7 Hipodiploidie
8-25%
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Examenul citogenetic (ET)
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Concluzie diagnostica
• Leucemie acuta promielocitara – LAM3 (forma clasica)
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LEUCEMII ACUTE – INVESTIGA}II
bilantul hemostazei pentru cautarea unei CIVD sau alte coagulopatii (mai ales in LAM3, 4, 5);
dozarea LDH, B12, transcobalamina - sunt crescute datorita turnover-ului crescut al celulelor leucemice;
ionograma, ureea, creatinina (functia renala poate fi alterata la diagnostic sau survine in cursul tratamentului),
calcemia, fosforemia si magnezemia (hiperfosforemia si hipocalcemia sunt semnalate in distructiile celulare crescute si impun compensarea terapeutica);
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LEUCEMII ACUTE – INVESTIGA}II
uricemia si uricuria (pot fi crescute in cazurile cu volum tumoral mare, sau in cursul tratamentului citostatic, antrenand un risc crescut pentru nefropatia urica);
bilantul bacteriologic – prelevari umori; bilant viral (HIV, HTLV-I, CMV, EBV, Hepatita) punctia lombara sistematica (este obligatorie in toate
cazurile de LAL pentru depistarea unei eventuale infiltrari neuro-meningee);
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LEUCEMII ACUTE – INVESTIGA}II
radiografia toracica în cautarea unei mase tumorale in mediastinul anterior. Este semnalata in 5 – 10 % din cazuri, in special in formele cu celula T.
echografie abdominala - mase tumorale echocardiografie
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LAM– Prognostic
• varsta de peste 45 ani si sub 2 ani • formele secundare • formele citologice M0, M5, M6, M7, M3 varianta
microgranulara; • imunofenotipaj : prezenta CD34, CD15 sau absenta
CD13, CD14 • cariotipul medular • hiperleucocitoza (peste 40.000/mm3) in momentul
diagnosticului • sdr tumoral la diagnostic• obtinerea sau nu a remisiunii complete si durata pana la
instalarea acesteia
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LAM - Tratament
• Tratementul de inductie
• Tratamentul postinductie– Tratamentul de intretinere
• Tratamentul de sustinere– Tratamentul complicatiilor bolii– Tratamentul complicatiilor terapiei
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Tratament de inductie (ET)
• S-a aplicat schema standard "3+7," cuprinzand : – 3 zile cu antraciclina `n perfuzie de 15-30
minute : • Farmorubicin 35 mg/m2(50 mg)/zi sau
– 7 zile cu Citosar-arabinosid 100 mg/m2 (300 mg)/zi in perfuzie de 24 ore
• Continuat cu Acid transretinoic (ATRA) (Diamalin®) 3 cp/zi
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Aplazia medulara (ET)
• Perioada de aplazie a durat 20 zile avand la nadir Hb 4 g/dl, GA 50/mmc, Tr 2.500/mmc
• Complicatii – Sdr emetogen– Sdr anemic – Sdr hemoragipar– Infectii – febra a debutat in ziua 5 si a cedat in
ziua 19
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Tratamentul de sustinere
• Tratamentul anemiei – – se realizeaza prin transfuzii cu masa eritrocitara
atunci cand Hb scade sub 7 g/dl. – Initierea transfuziilor eritrocitare va tine seama
si de toleranta clinica a anemiei, existenta unor tare organice asociate.
– Pacienta a primit 7 unitati ME.
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Tratamentul de sustinere
• Tratamentul hemoragiilor :– în caz de trombopenie : concentrat
plachetar multi sau monodonor sub contol al anticorpilor antiplachetari, pentru mentinerea trombocitelor peste 10.000/mm3 sau peste 3-50.000/mm3 la cei cu tare ce favorizeaz\ hemoragiile.
– Se poate asocia plasma proaspata congelata sau crioprecipitat
– Pacienta a primit 33 unitati CP multidonor si 18 unitati de plasma
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Sindromul hemoragipar- Tratamentul adjuvant -
• Tratament hemostatic :– Vitamina K 1f + Etamsilat 2f + Vitamina C 1f administrate la
12 – 8 – 6 – 4 ore interval in functie de severitatea hemoragiilor
– Calciu gluconic 1 - 2 f/24 ore/1/2 f la fiecare unitate de produs transfuzat (combatere EDTA)
– NOVOSEVEN® - factor 7 activat• Tratament antifibrinolitic
– Acid epsilon amino-caproic (AEAC) – bolus 5-10 g apoi continuu 2-4 g/ora
– Acidul Tranexamic 1-2 g la 8-12 ore• Tratament protector al peretelui vascular
– Rutosid 3 cp/zi
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Complicatii infectioaseStrategii de preventie
• Masuri generale– Izolarea– Decontaminarea corecta a anturajului (personal/familie)– Reducerea manevrelor invazive– Buna ingrijire a cailor de acces venos– ingrijire in conditii de asepsie si antisepsie– Atentie in prepararea alimentelor, apa de baut– Curatenia spatilui de izolare– Supravegherea temperaturii la 4 ore
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Complicatii infectioaseStrategii de preventie
• Masuri specifice– Profilaxia intestinala prin antibiotice nonrezorbabile– Decontaminare selectiva
• Biseptol• Chinolone (Norfloxacin, Ciprofloxacin)
– Gargarisme si bai de gura cu solutii antiseptice si bicarbonat
– Decontaminarea tegumentelor
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Complicatii infectioaseStrategii terapeutice
• Majoritatea infectiilor severe, bacteriene sau fungice, la pacientii cu afectiuni hemato-oncologice sunt determinate de germeni cu virulenta scazuta, componente ale florei normale de contaminare.
• Aparitia febrei la acesti pacienti este considerata de origine infectioasa pana la demonstrarea contrariului.
• Neutropenia (PN sub 1.000/mm3) reprezinta un factor de risc major pentru infectile cu germeni oportunisti.
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Complicatii infectioaseStrategii terapeutice
• La pacientii neutropenici se impune tratament antibiotic cu spectru larg pana cand episodul infectios este rezolvat sau PN revin in limite normale.
• Antibioterapia trebuie demarata intravenos si in doze maximale.
• Expunerea la mediul spitalicesc creste riscul infectiilor cu Staphylococcus aureus meticilin-rezistent sau cu bacili gram-negativi polirezistenti.
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Complicatii infectioaseStrategii terapeutice
• Aplazie PN 500 – 1.000/mm3 (gradul 3 OMS)
PN < 500/mm3 (gradul 4 OMS) • Aplazie scurta – < 7 zile• Aplazie lunga - > 7 zile Aplazie tardiva – survine
la 5-10 zile post-chimioterapie (LMNH)• Aplazie febrila – evidentierea unei temperaturi >
3805 C la o determinare sau > 380C la doua determinari la 12 ore interval – impune– Bilant bacteriologic
– Demarare antibioterapie empirica cu spectru larg
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Complicatii infectioaseStrategii terapeutice
• Sdr febril la pacient hemato-oncologic• Bilant bacteriologic• Tratament : • beta-lactamina/cefalosporina (a treia generatie) +
aminoglicozid +/- antistafilococic (Vancomicina, Fosfomicina).
• persistenta a febrei dupa 48 de ore se asociaza antistafilococicul, iar ulterior un antifungic (Amfotericina B in doze de 1 – 2 mg/kg/zi sau Fluconazol (Diflucan) in doze de 200 mg/zi).
• Eventual, se asociaza tratament antiviral (Aciclovir pentru Herpes sau Ganciclovir pentru Cytomegalovirus).
• +/- factor de crestere
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Evolutie (ET)
• 15.03.-18.04.2004 – internarea initiala : diagnostic si cura de inductie
• 25.04.-3.05.2004 – control medular (Raspuns partial – persistenta a 7% blasti) I cura de consolidare (Cytosar 4 g/zi + Etoposid 100 mg/zi x 3 zile)
• 11.05-16.052004 – aplazie post consolidare
• 30.05.-3.06.2004 – II-a cura de consolidare (Cytosar 3 g/zi + Etoposid 100 mg/zi x 3 zile)
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Evolutie (ET)
• Ulterior se aplica cure de consolidare lunar pana in ianuarie 2005 apoi la 2 luni interval pana in martie 2006.
• Curele aplicate sunt de tip Cytosar + Etoposid alternand cu Cytosar + Antraciclina (Farmorubicin v Idarubicin v Mitoxantron)
• Controlul medular efectuat in 2005 arata 4% blasti iar cel din martie 2006 0% blasti (Remisiune completa)
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Evolutie (ET)
• Ultimul control : 25.04.2007 RC
• Supraveghere pana la 5 ani de la diagnostic