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異體造血幹細胞移植簡介 (Allogeneic hematopoietic stem cell transplantation)

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Presentation on theme: "異體造血幹細胞移植簡介 (Allogeneic hematopoietic stem cell transplantation)"— Presentation transcript:

1 異體造血幹細胞移植簡介 (Allogeneic hematopoietic stem cell transplantation)
李 啟 誠 醫 師

2 E. DONNALL THOMAS, M.D. Nobel Prize in Physiology or Medicine, 1990
for his pioneering work on bone marrow transplantation

3 造血幹細胞移植的歷史 1957: Thomas ED et.al.: st attempt of BMT in human beings (failure; HLA was identified in 1960+) 1959: Thomas ED et.al.: nd attempt of BMT in identical twin (hematological recovery occurred in 2 weeks, but leukemia recurred months later)

4 Allogeneic HSCT, for What?
To replace incorrigible hematopoietic defects: Quantitative defect: 再生不良性貧血/Fanconi’s anemia Qualitative defect: 惡性疾病: 各種急性或慢性,骨髓性或淋巴球性白血病,淋巴癌,多發性骨髓瘤 非惡性疾病: 骨髓造血幹細胞缺陷疾病:重度免疫不全症候 造血細胞基因缺損: 嚴重型地中海型貧血 酵素相關基因缺陷: 大理石症,高雪氏症,黏寶寶

5 造血幹細胞移植的種類 自體移植 (Autologous) 異體移植 (Allogeneic) 同卵雙胞胎移植 (Syngeneic)

6 異體移植 (Allogeneic Transplantation)

7 異體移植:捐贈者免疫基因須與病人相符 淋巴球 MHC Major HLA (MHC)
Class I: A, B, C, E, H, G, F Class II: DR, DQ, DP, DM, Class III: not so important Minor HLA (mHC) Non-MHC KIR NOD

8

9 Resolution Low resolution Serologically antigen (ex. A01)
CREG (cross-reactive groups) Intermediate resolution (ex. A0101/ 0102/ 0105) High resolution (ex. *A0101)

10 異體移植 親屬間異體移植 (sibling or other family donors)
非親屬間異體移植 (unrelated donor; MUD: HLA-matched unrelated donor)

11 造血幹細胞的來源 骨髓幹細胞 (Bone marrow; BMT)
週邊血液幹細胞 (Peripheral blood stem cell; PBSCT) 臍帶血幹細胞 (Cord blood stem cell; CBT)

12 異體造血幹細胞移植之步驟

13 正常骨髓

14 急性血癌

15 殲滅療法

16 死傷殆盡

17 造血幹細胞移植

18 FHCRC 大廳服務中心

19 Allogeneic HSCT TBI + Cy: Total body irradiation + Cyclophosphamide
Conditioning therapy (殲滅療法): 高劑量化學治療或放射治療 TBI + Cy: Total body irradiation + Cyclophosphamide BuCy: Busulfan + Cyclophosphamide Stem cell transplantation: Day 0 Evaluate engraftment Evaluate GVHD Control infection

20 四個階段 Conditioning to engraftment: D-7 to D30
Early stage after engraftment: D30-D100 Late stage after engraftment: D100 – 1yr Chronic stage after engraftment: > 1yr

21 Chimera

22 Tests for chimerism Erythrocyte Ag (ABO, Rh, MN…)
Cytogenetics of metaphase for sex chromosome FISH STR(microsatellite)/VNTR(minisatellite) of nuclear cells—even lineage-specific STR analysis (after FACS with sorting)

23 西雅圖華盛頓大學

24 Three major complications after allo-HSCT
Infection Acute GVHD Chronic GVHD

25 Dilemma post allogeneic HSCT
Immunosuppressant GVHD (GVT) Life-threatening GVHD (GVT) Disease relapse Immunosuppressant Infection: bacteria, fungus, virus

26 Infection complications after allogeneic HSCT
Day 0 Day 100 1 year (or more) Bacterial Fungal HSV CMV PCP Day 30 Day 0 Day 100 1 year (or more)

27 Life-threatening infection
Invasive fungal infection CMV infection

28 Aspergillus pneumonia

29 CMV pneumonia

30 CMV colitis: edema, congestion and multiple ulcers in the sigmoid colon
Inclusion body

31 GVHD Mechanism PB BM CD34 cells 3-4X 1X T-cells 10X To prevent aGVHD:
↓conditioning intensity ↓cytokine storm To prevent aGVHD: Suppress T T-depletion Later DLI

32 Changing Concepts: GVHD Syndrome After AlloHCT
Acute GVHD: rash, GI, liver Chronic GVHD: skin, eyes, mouth, GI liver, musculoskeletal, lungs, GU Alloreactivity Autoimmunity Immunodeficiency - Classic acute Late acute - Classic chronic - Chronic overlap All Images Are Copyright Protected Day y 2 y y y Activity Damage (inflammation) i n j u r y r e p a i r (fibrosis)

33 Acute GVHD Engraftment to D+100
Alloreactive T-cells against HLA-bearing host tissue General performance decreased Skin rash Oral mucositis Gastritis Colitis Hepatobiliary: hepatitis, jaundice Cytopenia, thrombocytopenia Impaired immunity

34 Skin GVHD

35

36 Severe oral GVHD: multiple ulcers

37 Chronic GVHD After D+100 Appear as auto-immune phenomenon
Sicca syndrome: dry eye, dry mouth Scleroderma Esophageal dysmotility Lung: obstructive lung disease (BO, BOOP) Hepatobiliary Cytopenia, thrombocytopenia Impaired immunity

38 Chronic GVHD of Skin: Day 170

39 Infections Disability Quality of life Endocrine Metabolism Nutrition
Bronchiolitis obliterans Ocular sicca Loss of bile ducts Oral ulcers Nail dystrophy Fasciitis Infections Disability Quality of life Endocrine Metabolism Nutrition Pain Skin sclerosis Skin ulcers Spectrum of manifestations in chronic GVHD All Images Are Copyright Protected Deep sclerosis

40 Dilemma post allogeneic HSCT
Immunosuppressant GVHD (GVT) Life-threatening GVHD (GVT) Disease relapse Immunosuppressant Infection: bacteria, fungus, virus

41 Tulip

42 Patient evaluation toward medical staff
Competence Courtesy Compassion Neutral Satisfied Very satisfied

43 Thank You!


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