PowerPoint Sunusu

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APLASTIK ANEMI
Dr. Yahya Büyükasik
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I. HEMATOPOEZ
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PLURIPOTENT STEM CELLS
COMMITTED PROGENITORS
HEMATOPOIETIC PRECURSORS
MATURE CELLS
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Proliferasyon Maturasyon
Maturasyon
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HÜCRE ÇOGALMASI için GEREKLI HAM MADDELER

• UYGUN MIKROÇEVRE
• Anatomik çevre
• Hormon sitokinler

YETERLI KÖK HÜCRE
Vit B12
Fe
HEMOGLOBINIZASYON için GEREKLI HAM MADDELER
Folat
Dogal Ölüm
Hemoliz
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II. EDINSEL KÖK HÜCRE BOZUKLUKLARI
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AKUT LÖSEMI
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• Akut Lösemi

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MIYELOPROLIFERATIF HASTALIK (ET ve AMM)
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• MPH

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APLASTIK ANEMI
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• Aplastik Anemi

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PNH ve MDS (?)
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II. APLASTIK ANEMI PATOGENEZI
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Insidans 2/milyon/yil
(Dogu Asyada 2-3 kat daha) sik
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SITOTOKSIK AJANLAR
RADYASYON
?
KÖK HÜCRE
ilaç
otoimmün hastalik
virüs
OTOIMMÜNITE
KONSTITÜSYONEL Fanconi AA Dyskeratosis
Congenita Schwachman-Diamond
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Br J Haematol 2003123782
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Br J Haematol 2003123782
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Relationship of PNH to Aplastic Anemia and
Myelodysplasia
Immün Hasar
Aplazi
Klonal kaçis
Schwartz, R. S. N Engl J Med 2004350537-538
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GPI ÇIPASINA BAGLANAN YÜZEY ANTIJENLERI
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PNH Klonu Normal Hematopoez
PNHNIN SEYRI
Asikar PNH
Remisyon
Seyirde Akut L, MDS Gelisebilir
Hipoplastik PNH AA/PNH
Hipoplastik PNH AA/PNH
AA (/- PNH Klonu)
AA (/- PNH Klonu)
PNHyi Baslatan Olay Aplastik Anemideki gibi
Otoimmün Ataktir (Hedef Antijen GPI ile Ilgili ?)
Immün Ataktan Korundugu için Büyüme Avantaji Elde
Eden PNH Klonunun Proliferasyon Derecesine Göre
Asikar PNH ile AA Arasinda bir Spektrumda Klinik
Tablo Ortaya Çikar. PNH Klonu (Malin
Transformasyon Olmazsa) Genellikle Yillar Sonra
Tükenir. Bu Arada Normal Hematopoezin Toparlanma
Derecesine Göre Remisyon ile AA Arasinda bir
Klinik Tablo Gelisir. Aradaki Dönemlerde de Kemik
Iligi Yetmezligi ile PNH Klinigi Arasinda Klinik
Tablolar Izlenir .
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HIPOSELLÜLER MDS
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Br J Haematol 2004126176
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Br J Haematol 2004126176
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III. NASIL TANI KONUR ?
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ERITROSITLERIN MORFOLOJIK ÖZELLIKLERI (CBC ve PY)

• ANEMI
• ?
• Diger sitopeni

ÖYKÜ ve FM


TANI
YAPIM-YIKIM DENGESINI GÖSTEREN PARAMETRE (RETIKÜLO
SIT)
PERIFERIK KAN INCELEMELERI Serum Fe
Parametreleri B12, folat Hb elektroforezi /
oraklasma Coombs testleri Ozmotik fragilite Asit
ham-sukroz hemoliz / akim sitometri Eritrosit
enzimleri Idrarda hemosiderin ...

TANI
KEMIK ILIGI INCELEMELERI Aspirasyon / Biopsi /
Hemosiderin / Sitogenetik incelemeler

TANI
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• Kanama
• egilimi

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• Infeksiyon
• egilimi

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• Solukluk

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Fanconi Aplastik Anemisi

• APLASTIK ANEMI
• SOMATIK BOZUKLUKLAR
• Büyüme geriligi
• Hiperpigmentasyon
• Iskelet bozukluklari
• Kalp-böbrek-göz defektleri
• Mikrosefali
• Hipogonadizm
• ARTMIS KANSER RISKI

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TANI KRITERLERI
1. Pansitopeni

• Hblt 10 g/dL
• Nötrofillt 1500/mL
• Trombosit 50 000/mL

2. lt 20-30 sellülerite
3. Diger Hastalik Isaretleri Yok
Retikülin fibrozis ? Displazi ? Infiltrasyon ?
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KLASIK ASOSIYASYONLAR

• TA-GVHD
• Hemofagositik Sendrom/Aplazi
• Hepatitis/Aplazi

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APLASTIK ANEMI SIDDETININ TANIMLANMASI
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DEB (diepoksibütan) testi
Br J Haematol 2003123782
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IV. AYIRICI TANI
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AYIRICI TANI
Ann Intern Med 2002136534

• Tbc
• Hiposellüler HCL
• Hiposellüler ALL
• AMM
• Diger KI Yetmezlik Sendromlari

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HIPOTEZ AA, PNH ve MDS ILISKILI HASTALIKLARDIR
IPUÇLARI
APLASTIK ANEMI
IST
IST
8-13/7 yil
8-15/7 yil (lösemi dahil)
MDS
PNH

• IST üçünde de basarili sonuçlar verebilmektedir
• AA ve MDS hastalarinin ? 20sinde tanida PNH
  klonu vardir
• 10 yilda AA hastalarinin 21 kadarinda (ilik
  morfolojisinden bagimsiz) karyotipik bozukluklar
  gelisebilmektedir

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Ann Intern Med 1999131401
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V. TEDAVI TRANSPLANTASYON ? IMMÜN SÜPRESIF
TEDAVI ?
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Effect of patient age on actuarial survival by
treatment group
Doney, K. et. al. Ann Intern Med 1997126107-115
Figure 3. Effect of patient age on actuarial
survival by treatment group. Tick marks denote
censoring times of surviving patients. A. Patient
age, younger than 6 years 12 patients had
transplantation and 25 patients received
immunosuppressive therapy (P 0.006). B. Patient
age, 6 to 19 years 63 patients had
transplantation and 62 patients received
immunosuppressive therapy (P 0.001). C. Patient
age, 20 to 39 years 82 patients had
transplantation and 73 patients received
immunosuppressive therapy (P 0.04). D. Patient
age, 40 years or older 11 patients had
transplantation and 67 patients received
immunosuppressive therapy (P gt 0.2).
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Cumulative Incidence of Observed Cancers in 860
Patients with Aplastic Anemia Who Received
Immunosuppressive Therapy and 748 Patients Who
Underwent Bone Marrow Transplantation
ST insidansi esit, MDS ve AL IST ile daha sik
Socie, G. et al. N Engl J Med 19933291152-1157
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Cumulative incidence of long-term complications
Doney, K. et. al. Ann Intern Med 1997126107-115
Figure 1. Cumulative incidence of long-term
complications. Top. Cumulative incidence of
rejection or evolution of a secondary malignant
condition in patients having bone marrow
transplantation. Bottom. Cumulative incidence of
evolution of a myelodysplastic syndrome or acute
leukemia, paroxysmal nocturnal hemoglobinuria
(PNH) or recurrent aplasia after
immunosuppressive therapy.
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IS TEDAVI ile YANIT ELDE EDILEN HASTALARDA CyA
KESILEBILME ORANI
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ISLEMIN YAPILDIGI TARIHE GÖRE TRANSPLANT
SONUÇLARI (IBMTR)
Daha etkin GVHD Px (CsAMtx gt Mtx) Daha uygun
hazirlama rejimleri (CyATG gt Cy I)
Blood 199790858
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Effect of transfusion status on actuarial
survival by treatment group
Doney, K. et. al. Ann Intern Med 1997126107-115
Figure 4. Effect of transfusion status on
actuarial survival by treatment group. Top.
Survival of 53 transplant recipients who did not
receive transfusion and 115 transplant recipients
who received transfusion (P 0.04 log-rank
test). Bottom. Survival of 41 patients who
received immunosuppressive therapy and did not
receive transfusion and 174 patients who received
immunosuppressive therapy and transfusion (P
0.11 log-rank test). Tick marks denote censoring
times of surviving patients.
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DEGISIK IS TEDAVI REJIMLERININ SONUÇLARI
Blood Rev 200014157
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Effect of the absolute neutrophil count (ANC)
before therapy on actuarial survival by treatment
group
Doney, K. et. al. Ann Intern Med 1997126107-115
Figure 5. Effect of the absolute neutrophil count
(ANC) before therapy on actuarial survival by
treatment group. Tick marks denote censoring
times of surviving patients. P gt 0.2 for the bone
marrow transplantation group and P 0.002 for
the immunosuppressive therapy group. In the bone
marrow transplantation group, 98 patients had an
absolute neutrophil count greater than 2.0 x
109/L and 70 had a count less than 2.0 x 109/L.
In the immunosuppressive therapy group, 133
patients had an absolute neutrophil count greater
than 2.0 x 109/L and 94 had a count less than 2.0
x 109/L.
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TEDAVI AGIR AA
Br J Haematol 2003123782
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TEDAVI AGIR OLMAYAN
Br J Haematol 2003123782
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IS TEDAVIYE YANIT KRITERLERI
Acta Haematologica 200010316
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VI. PROGNOZ
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• TRANSPLANTASYON ve IST ÖNCESI

ILK 4 AYDA 25, ILK YIL IÇINDE 50 MORTALITE
IST
NÜKSLER, KLONAL HASTALIKLAR, SOLID Tm
60-80 TOTAL YANIT (CR ve PR)
TRANSPLANTASYON
TRANSFÜZYON ? ? 80 KÜR
KRONIK GVHD, SOLID Tm
gtgt TRANSFÜZYON ? 55-60 KÜR