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造血幹細胞移植 BMT Overview

造血幹細胞移植 BMT Overview. 台大醫院內科部 血液科主治醫師 姚 明. Hematopoietic Stem Cell Transplantation (HSCT). Hematopoietic Stem Cell Transfusion. Cell Therapy.

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造血幹細胞移植 BMT Overview

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  1. 造血幹細胞移植BMT Overview 台大醫院內科部 血液科主治醫師 姚 明

  2. Hematopoietic Stem Cell Transplantation(HSCT) Hematopoietic Stem Cell Transfusion Cell Therapy

  3. 骨髓暨血液幹細胞移植發展史1900年代 ※惡性貧血或骨髓疾患的病人接受口服骨髓細胞或肌肉或骨髓內注射，但未獲成功。1940年代 ※1945年，由日本廣島、長崎原子彈爆炸，骨髓被發現是最易受輻射傷害的器官，開啟了骨髓移植的研究。1950年代晚期 ※法國Mathé醫生成功以骨髓移植治療在南斯拉夫Vinca市遭受輻射意外病人。※美國Thomas醫生以同卵雙胞骨髓移植治療急性血癌以及重度再生不良性貧血。※法國Dausset醫生發現人類白血球抗原(HLA)系統。※美國McGovern醫生以高劑量輻射並自體骨髓移植治療急性血癌。

  4. 1960年代晚期 ※美國Good醫生完成首例異體親屬骨髓移植治療先天免疫不全病童。 ※美國Thomas醫生完成首例異體親屬骨髓移植治療末期血癌患者。 1970年代初期 ※美國Thomas醫生完成首例異體親屬骨髓移植治療再生不良性貧血患者。 ※美國紐約Memorial Sloan-Kettering 治癌中心 完成首例非親屬異體骨髓移植。 1970年代晚期 ※以異體骨髓移植治療急性血癌緩解期患者，治癒率超過55％ ，成為急性血癌標準療法。 1980年代初期 ※由於對高劑量治療的認識骨髓抗排斥藥及抗生素之進步，及骨髓冰凍技術之成熟，使異體及自體骨髓移植逐漸被廣泛運用在治療血液惡性疾病，固態腫瘤、其他骨髓疾病及先天代謝不全疾病。

  5. 1980年代中期 ※白血球生長刺激素 (G-CSF/GM-CSF) 進入臨床使用。 ※澳洲Juttner醫生完成以自體週邊血液幹細胞移植治療急性血癌患者。 1980年代晚期 ※美國Kessinger醫生進行親屬異體週邊血液幹細胞移植。 ※法國Gluckman醫生成功進行親屬臍帶血移植治療先天 Fanconi 氏貧血患者。 1990年 ※美國Thomas醫生因致力骨髓移植之研究而榮獲諾貝爾醫學獎。 1990年代初期 ※自體CD34純化之造血幹細胞移植 1990年代中期迄今 ※非親屬臍帶血移植 ※非親屬異體週邊血液幹細胞移植 ※發展迷你移植

  6. Hematopoietic Stem Cell Transplantation造血幹細胞移植 • 骨髓移植 (BMT) Bone marrow transplantation • 週邊血液幹細胞移植 (PBSCT) Peripheral blood stem cell transplantation • 血液暨骨髓移植 (BMT) Blood and marrow transplantation • 臍帶血移植 (CBT) Cord blood transplantation

  7. Type of BMT • Syngeneic同卵雙胞胎 • Allogeneic異體 • Related親屬 • Sibling兄弟姐妹 • Parent父母/Child子女 • Unrelated非親屬 • Autologous自體 • BMT • PBSCT • CBT

  8. Allogeneic BMT Indications: • Malignant hematological diseases • AML, ALL, CML, lymphoma, myeloma, MDS • Non- malignant hematological diseases • Severe aplastic anemia, thalassemia major • Malignant non-hematological diseases • breast ca, NPC • Non- malignant non-hematological diseases • Metabolic storage disease: eg. 黏多醣症 • severe combined immunodefficiency (SCID)

  9. Current Indication of Allo-BMT • Myeloma/ Lymphoma • SAA • Inherited diseases • Thalassemia major • SCID • Osteopetrosis • Storage diseases • Acute leukemia • High risk acute leukemia (AL) in CR1 • Good risk AL in > CR2 • Refractory AL • CML: TKI-resistant • high risk MDS

  10. Physical examination HBV;HCV;HIV checkup Autodonation 2-4 wk prior to BM harvest Admission one day prior to BM harvest Bone marrow harvest Physical examination HBV;HCV;HIV checkup Conditioning High dose therapy/NST C/T + total body irradiation (TBI) BMT-BM cells infusion GvHD prophylaxis Cyclosporin A/ FK-506 Methotrexate Procedures of Allo-HSCT Donor Selection:HLA-A,B,DR matching Recipient Donor

  11. Ex: An AMLPatient Conditioning Regimen Donor BM Harvest

  12. Conditioning Regimen • Myeloablative vs Non-myeloablative (RIST) • Reduced Intensity

  13. Allo-PBSC collection • G-CSF adminerstration to donor for PBSC mobilization • G-CSF 10 ug/Kg/d for 5 days • Leukapheresis to collect PBSC • Leukapheresis • aim :CD34+cell > 2x106/Kg patient BW D-4, D-3, D-2, D-1, D0, D+1 s/p PBSCT GGGGG LL

  14. BMT Donor 全身麻醉 住院 Recipient 血液相恢復較慢 cGvHD機率較低 BMT vs PBSCT • PBSCT • Donor • G-CSF injection • 一般不需住院 • Recipient • 血液相恢復較快 • cGvHD機率較高

  15. Blood component therapy post Allo-BMT BMT輸血對照表〈舉例 〉 Donor R pRBC Platelet, Plasma wRBC (FFP, Cryoprecipitate) O A O A, AB A B O AB A AB A, O AB AB O O A, B, AB All blood product must be irradiated 自preconditioning起至病人血型改變為止 => 改為donor type PRBC 自preconditioning起至血清抗體改變為止 => 改為donor type Platelets

  16. Autologous BMT • Concepts: • High dose therapy is beneficial for controlling underlying dx • Auto-BMT is served as rescue for hematopoietic recovery • Indications: • High dose therapy sensitive malignancies • Acute leukemia, Lymphoma, Myeloma • Breast ca, Ovarian ca, NPC, Germ cell tumor, Neuroblastoma, etc. • Autoimmune diseases

  17. Current Indication of High dose therapy plus Auto-BMT • Chemotherapy sensitive relapse Lymphoma (NHL or HD) • Myeloma • AML (purged graft) • Neuroblastoma etc.

  18. Procedures of Auto-BMT • Auto-BM harvest in remission state • Patient received high dose therapy • BEAM for Lymphoma; HD Mel for Myeloma • Auto-BMT • thawing of DMSO-containing Auto-BM • transfusion of Auto-BM

  19. Auto –PBSC Collection • G-CSF injection after chemotherapy • Leukapheresis when hematopoietic progenitor cells (HPC) present in PB • Target: CD34+cell > 2 x 106/kg • Cryopreservation

  20. B-NHL in 2nd CR ESHAP G-CSF              5ug/kg/d from D+7 HPCP+ WBC Leukapheresis PBSC collection Nadir

  21. Complications of BMT • High dose therapy effect • Veno-occlusive disease of liver (VOD) • Jaundice, hepatomegaly, ascites, RUQ pain • Hemorrhagic cystitis • Interstitial pneumonitis • Graft versus host disease (GvHD) in Allo-BMT • Infection

  22. Acute Graft versus Host Disease aGvHD 移植物抗宿主疾病

  23. ChronicGraft versus Host Disease cGvHD

  24. NONBACTERIAL (INTERSTITAL) PNEUMONIA BACTERIAL PCP VIRAL HSV CMV ADENO VZV CANDIADA ASPERGILLUS FUNGAL GRAM POS GRAM NEG ENCAPSULATED BACTERIAL RISK FACTOR neutropenia ACUTE GVHD + Rx CHRONIC GVHD --- 0 50 100 12 DAYS AFTER TRANSPLANT MONTHS marrow infusion

  25. Post BMT : Fungal Infection ASPERGILLUS CANDIADA Risk Factors neutropenia ACUTE GVHD + Rx CHRONIC GVHD --- 0 30 100 12 DAYS AFTER TRANSPLANT MONTHS marrow infusion

  26. Post BMT : Viral Infection Herpes Viruses VIRAL HSV CMV VZV RISK FACTOR neutropenia ACUTE GVHD + Rx CHRONIC GVHD --- 0 50 100 DAYS AFTER TRANSPLANT MONTHS marrow infusion

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