造血幹細胞移植 bmt overview
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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. - PowerPoint PPT PresentationTRANSCRIPT
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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
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Hematopoietic Stem Cell Transplantation(HSCT)
Cell Therapy
Hematopoietic Stem Cell Transfusion
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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。
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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。
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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
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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
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Type of BMT
• BMT
• PBSCT
• CBT
• 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
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Allogeneic BMTIndications:• 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)
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Current Indication of Allo-BMT
• Acute leukemia
– High risk acute
leukemia (AL) in CR1
– Good risk AL in > CR2
– Refractory AL
• CML: TKI-resistant
• high risk MDS
• Myeloma/ Lymphoma
• SAA
• Inherited diseases– Thalassemia major
– SCID
– Osteopetrosis
– Storage diseases
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Procedures of Allo-HSCT
• 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
Donor Recipient
Donor Selection:HLA-A,B,DR matching
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Ex: An AMLPatient
D-6 D-5 D-4 D-3 D-2 D-1 D0 D+1 D+2 D+3
TBI TBI TBI Cy Cy BMT
Donor BM Harvest
Conditioning Regimen
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Conditioning Regimen• Myeloablative vs Non-myeloablative (RIST)• Reduced Intensity
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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
G G G G G
L L
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BMT vs PBSCT
• BMT– Donor
• 全身麻醉• 住院
– Recipient• 血液相恢復較慢• cGvHD 機率較低
• PBSCT– Donor
• G-CSF injection• 一般不需住院
– Recipient• 血液相恢復較快• cGvHD 機率較高
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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
RBC A B AB O
Plasma Anti-B Anti-A - Anti-APLT - Anti-B
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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
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Current Indication of High dose therapy plus Auto-BMT
• Chemotherapy sensitive relapse
Lymphoma (NHL or HD)
• Myeloma
• AML (purged graft)
• Neuroblastoma etc.
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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
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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
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ESHAP
G-CSF
5ug/kg/d from D+7
B-NHL in 2nd CR
WBC
Nadir
HPCP+
Leukapheresis
PBSC collection
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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
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Skin Stage Skin involvement0 01 0~25%2 25%~50%3 >50%4 >50% with blisters
Gut Stage Stool volume0 <7 (ml/kg)1 7~142 14~213 21~284 >28
Liver Stage Bilirubin (mg/dL)0 <21 2~32 3~63 6~154 >15
Acute Graft versus Host Disease
aGvHD
移植物抗宿主疾病Overall Grade Organ stage
0 01 S1-2
2S3 or S<3 andG1or L1
3 S>3 and G2 or L24 S4 or G4 or L4
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Chronic Graft versus Host Disease
cGvHDLimited Localized skin involvement
Liver dysfunction , or both
Extensive Generalized skin involementLiver dysfunction, or any of the following: Chronic active hepatitis, bridging necrosis or cirrhosis Eye involvement (Schirmer's test <5mm) Mucosal involvement Salivary gland involvement*Scleroderma*Bronchiolitis obliterant (BO)
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PNEUMONIA
VIRAL
FUNGAL
BACTERIAL
RISKFACTOR
BACTERIAL
---
marrow infusion
0 50 100 12
NONBACTERIAL(INTERSTITAL)
DAYS AFTER TRANSPLANT MONTHS
HSV CMV ADENO VZV
CANDIADA ASPERGILLUS
GRAM POSGRAM NEG
ENCAPSULATED
neutropenia ACUTE GVHD + Rx CHRONIC GVHD
PCP
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Post BMT : Fungal Infection
ASPERGILLUS
CANDIADA
Risk Factors
---
marrow infusion
0 30 100 12
DAYS AFTER TRANSPLANT MONTHS
neutropenia ACUTE GVHD + Rx CHRONIC GVHD
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VIRAL
HSV
CMV
VZV
Post BMT : Viral InfectionHerpes Viruses
RISKFACTOR
---
marrow infusion
0 50 100
DAYS AFTER TRANSPLANT MONTHS
neutropenia ACUTE GVHD + Rx CHRONIC GVHD