再障 2010.5.13

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再障 2010.5.13

  1. 1. Aplastic anemia( AA) 再生障碍性贫血 中山大学附属第一医院
  2. 2. <ul><li>understand the etiological factors and mechanism of aplastic anemia </li></ul><ul><li>master the clinical features </li></ul><ul><li>master the diagnosis of AA </li></ul><ul><li>know the common diseases associated with pancytopenia </li></ul><ul><li>master the treatment of AA </li></ul>Content
  3. 3. A case <ul><li>man , 24 year old , he had symptoms of skin and mucosal bleeding ,weakness 、 fatigue 、 dizziness, palpitation, fever in December ,2002 </li></ul>
  4. 4. He looked pallor and had Bilateral legs bleeding spots X-ras showed sever pneumonia
  5. 5. blood chang <ul><li>Hb 87g/L , RBC 2.91× 10 12 / L </li></ul><ul><li>Plt 3.0 ×10 9 / L </li></ul><ul><li>WBC 0.5 ×10 9 / L </li></ul><ul><li>the smear may contain 90% lymphocytes, neutrophil 10% </li></ul><ul><li>absolute reticulocyte rate is less than 0.1% </li></ul>
  6. 6. <ul><li>Initial diagonsis :pancytopenia </li></ul><ul><ul><ul><li>aplastic anemia ? </li></ul></ul></ul><ul><ul><ul><li>acute leukemia ? </li></ul></ul></ul><ul><li>How to diagnosis ? </li></ul><ul><li>How to treat ? </li></ul><ul><li>What is Prognosis ? </li></ul>
  7. 7. Definition <ul><li>AA is defined as pancytopenia with hypocellularity of the bone marrow; there are no leukemic, cancerous or other abnormal cells in peripheral blood or bone marrow </li></ul>
  8. 8. Two kinds of AA <ul><li>Severe A A </li></ul><ul><li>non-severe AA( moderately AA) </li></ul>
  9. 9. Etiology (Classes) <ul><li>congenital ( fanconi’s anemia):is rare </li></ul><ul><li>Idiopathic(probably autoimmune):is common </li></ul><ul><li>secondary </li></ul><ul><li>1. drugs: chloramphenicol </li></ul><ul><li>2. toxins: benzene 、 insecticides </li></ul><ul><li>3. chemotherapy: cytotoxic drugs </li></ul><ul><li>4. radiation </li></ul><ul><li>5. infections: hepatitis. </li></ul><ul><li>6. other: SLE 、 PNH </li></ul>
  10. 10. fanconi’s anemia
  11. 11. Normal blood cell source <ul><li>All hematopoietic cells are derived from a pluripotent stem cell that gives rise to precursors of erythroid, myeloid, and platelet forms </li></ul>
  12. 12. 造血干细胞 多向祖细胞 单向祖细胞 淋巴系祖细胞 巨核系祖细胞 粒 - 单核系祖细胞 红系祖细胞 单核系祖细胞 粒系祖细胞 定向干细胞 CD38+ 1.CD34-/CD38+ 。 2. 对称分裂方式。 3. 无自我更新能力,只有增殖分化能力。 <ul><li>precursors </li></ul><ul><li>stem cell </li></ul>form erythroid, myeloid, and platelet precursors
  13. 13. What is pathogenesis of AA? <ul><li>The most common pathogenesis of AA is </li></ul><ul><li>autoimmune suppression of hematopoiesis by a T cell-mediated cellular mechanism </li></ul>
  14. 14. Many factors activate T-cell,manly CD4CD8cells which injure stem cell and secrete inhibitor factors like INFTNF-a inhibiting bone marrow hematopoietic function pancytopenia infection, bleeding, anemia Mechanisms hypocellularity of the bone marrow T cell APLASTIC ANEMIA
  15. 15. Young NS, et al. N Engl J Med 1997;336:1365–1372
  16. 16. anemia infection <ul><li>bleeding </li></ul>四、 clinical features
  17. 17. clinical features <ul><li>Anemia leads to symptoms of weakness 、 fatigue 、 dizziness, palpitation </li></ul><ul><li>bleeding: caused by thrombocytopenia, when blood platelet count is less than 50 ×10 9 / L , can have skin and mucosal bleeding, when count is less than 20 ×10 9 / L , can have visceral bleeding </li></ul><ul><li>infection: caused by neutropenia, when the neutrophil count is less than 0.5 ×10 9 / L , there is a 90% chance of infection </li></ul>
  18. 18. <ul><li>clinical features of bleeding and infection is more severe in patients with severe AA than moderately AA </li></ul>
  19. 19. <ul><li>no lymphadenopathy, </li></ul><ul><li>no hepatosplenomegaly </li></ul><ul><li>physical examination </li></ul>
  20. 20. 1 blood change 五、 laboratory examination <ul><li>Pancytopenia: red cells 、 neutrophils and platelets decrease , reticulocytes decrease </li></ul>
  21. 21. blood change <ul><li>Hb may be as low as 70g/L </li></ul><ul><li>Leukocyte count may be as low as 1.5 ×10 9 / L or even 0.5 ×10 9 / L ,the smear may contain as many as 70 to 90% lymphocytes </li></ul><ul><li>platelets count may be as low as 2 ×10 9 / L ,or more lower </li></ul><ul><li>absolute reticulocyte rate is less than 1.5% </li></ul>
  22. 22. Bone marrow aspirate <ul><li>Diagnosis of AA is mainly based on bone marrow aspirate ,we have to aspirate from different </li></ul><ul><li>Spots to confirm diagnosis </li></ul><ul><li>bone marrow ; hypocellularity </li></ul><ul><li>erythroid, myeloid 、 megakaryocyte ↓ </li></ul><ul><li>lymphocyte↑ plasmocyte↑ </li></ul><ul><li>  </li></ul><ul><li>  </li></ul>
  23. 23. 检验 2 骨髓涂片外观 There are a lot of fat drops on the smear of AA
  24. 24. 2 Bone marrow hypocellularity 骨髓小粒空虚,成空网状结构,其中造血细胞减少 normal bone marrow
  25. 25. Bone marrow biopsy 骨髓造血组织面积减少( <10%) ,主要组分由脂肪细胞所构成,可见灶性出血。 骨髓造血活跃 Normal AA
  26. 26. diagnosis standards for AA <ul><li>pancytopenia, decrease of absolute value of reticulocyte </li></ul><ul><li>no lymphadenopathy, no hepatosplenomegaly </li></ul><ul><li>hypocellularity in bone marrow and bone marrow biopsy </li></ul><ul><li>discard other diseases : PNH ( paroxysmal nocturnal hemoglobinuria) 、 acute leukemia 、 MDS ( myelodysplastic syndrome) 、 SLE ( systemic lupus erythematosus) </li></ul>
  27. 27. 七、 severe 、 non-severe AA PLT ﹥20×10 9 / L PLT <20×10 9 / L moderate hypocellularity severe hypocellularity bone marrow NEC﹥0.5×10 9 / L NEC<0.5×10 9 / L RET ﹥1% -<1.5% RET<1% blood non-severe AA severe AA
  28. 28. Differentital diagnosis 与全血细胞减少疾病鉴别 <ul><li>PNH </li></ul><ul><ul><li>haemoglobinuria </li></ul></ul><ul><ul><li>CD55 - 、 CD59 - ↑ </li></ul></ul><ul><li>MDS </li></ul><ul><ul><li>Morphologic abnormalities or increased blasts (5- 19%) </li></ul></ul><ul><ul><li>Abnormal cytogenetics in bone marrow </li></ul></ul>
  29. 29. <ul><li>Acute leukemia </li></ul><ul><li>Increased blasts in bone marrow ≥30% </li></ul><ul><li>Abnormal cytogenetics in bone marrow </li></ul><ul><li>Acute hematopoiesis detention </li></ul><ul><li>in one month time,CBC will reture into normal value </li></ul>
  30. 30. treatment <ul><li>supportive treatment </li></ul><ul><li>ALLO HSCT ( allogeneous hemopoietic stem cell transplantation) </li></ul><ul><li>immuno-suppressive treatment( ALG/ATG) </li></ul><ul><li>androgen </li></ul>
  31. 31. supportive treatment <ul><li>Hb<60g/L, red blood cell transfusions are given as necessary </li></ul><ul><li>when Plt<20×109/L , platelets transfusion is necessary </li></ul><ul><li>GCSF ( granulocyte colony stimulating factor) </li></ul><ul><li>antibiotics are used to treat infection </li></ul>
  32. 32. allogeneous hemopoietic stem cell transplantation <ul><li>Allo-HSCT is used in <50 years severe AA who has a HLA-identical donor. </li></ul>
  33. 33. Reconstruction Hematopoiesis Principle of All0-HSCT is by using immune suppression to inhibit the receptor immune function , allo dornor stem cells start normal hematopoiesis T cell IST IST Allo HSC
  34. 34. <ul><li>Allo-HSCT gives a 75%-90% chance of long-team survival and restoring the blood count to normal </li></ul>
  35. 35. immunosuppressive therapy(IST)- ALG or ATG <ul><li>ALG or ATG is used in severe AA without available HLA-identical donor or over age 50 years. </li></ul><ul><li>treatment efficacy of 50-60% </li></ul><ul><li>Dosage : generally for 5 days </li></ul><ul><li>Rabbit ALG: 2.5-4 mg·kg-1·d-1 </li></ul>
  36. 36. Restore Hematopoiesis patients only use immunosuppressive therapy(IST) , The time of restoring hematopoiesis will be long because of no dornor stem cell T cell IST IST
  37. 37. cyclosporine A(CSA ) <ul><li>Dosage : 4mg/Kg/d, 200~400μg/L, each 1-2 weeks should check for the concentration of CSA in the blood. </li></ul><ul><li>Course of treatment: should not be less than 6 mths </li></ul><ul><li>Efficacy : reaches 50%~60% </li></ul><ul><li>Side effects : hyperplasia of gum , injury to hepato-renal function, hirsutis, muscle fremitus, hypertension </li></ul>
  38. 38. <ul><li>hyperplasia of gum </li></ul>
  39. 39. androgen <ul><li>Androgen is used in patients moderately AA </li></ul><ul><li>oxymetholone : 2-3 mg/kg.d </li></ul><ul><li>Course of treatment : not less than 3 months </li></ul><ul><li>Side –effects : pay attention to hepatic function damage, at the same time apply protective hepatic therapy </li></ul>
  40. 40. The treatment of choice of AA <ul><li>In different types of AA ,the choice of treatment is also different </li></ul><ul><li>severe AA : </li></ul><ul><li>● <50 years 、 HLA-identical donor: Allo-SCT </li></ul><ul><li>● over age 50 years orwithout HLA-identical donor : </li></ul><ul><li>ALG/ATG+ CSA </li></ul><ul><li>moderately AA (non-severe AA) : </li></ul><ul><li>androgens + CSA </li></ul>
  41. 41. British Journal of Haematology, 2009,147, 43–70 再障的治疗选择 英国血液学标准委员会 2009
  42. 42. Prognosis <ul><li>it is related with the type of AA </li></ul><ul><li>Around 70-80% of patients with chronic AA who have received active treatment have benefited from different degrees of improvement, with a relatively good prognosis. </li></ul>
  43. 43. Diagnosis base <ul><li>he had symptoms of skin and mucosal bleeding ,weakness 、 fatigue 、 dizziness, palpitation, fever </li></ul><ul><li>Pancytopenia </li></ul><ul><li>hypocellularity of the bone marrow </li></ul><ul><li>discard other diseases </li></ul><ul><li>NEC<0.5×10 9 / L </li></ul>
  44. 44. Diagnosis and treatmemt <ul><li>Diagnosis : severe AA </li></ul><ul><li>choice of severe AA </li></ul><ul><li>allogeneous hemopoietic stem cell transplantation was used for him </li></ul><ul><li>Dornor : his sister , HLA-matched, blood group A </li></ul><ul><li>Patient blood group O </li></ul>
  45. 45. result <ul><li>41days after Allo-HSCT,Bone marrow hematpoiesis retured to normal value, </li></ul><ul><li>before HSCT,his blood group was O group, </li></ul><ul><li>41days after Allo-HSCT ,his blood group changed into A group </li></ul>Before Allo-SCT 41 days after Allo-SCT
  46. 46. He is still alive up to now (8 years) patient donor
  47. 47. QUESTIONS <ul><li>diagnosis of AA? </li></ul><ul><li>differential diagnosis of severe and non-severe AA? </li></ul><ul><li>etiology of pancytopenia, and its differential diagnosis? </li></ul><ul><li>Treatment of choice of AA? </li></ul>
  48. 48. 谢谢

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