造血干細(xì)胞移植Hematopoietic Stem Cell Transplantation

1、Hematopoietic Stem Cell Transplantation, PhD, MDDepartment of Hematology Nanfang Hospital123Q & A BMT is a Surgery? What kind of pts need BMT? AIDS? How BMT cure leukemia? Post-BMT need immuosuppression? What is GVHD & GVL? How to find a matching donor? Cost of BMT? What can U do?4Outline of the Sli

2、des Background of stem cell & HSCT Definition & Classification & Eligibility Step by step of Procedure Acute Chronic Complications of HSCT 5Key words Stem cell, Hematopoietic stem cell MHC, HLA HSCT, PBSCT, CBT, BMT, NST, RIST GVHD, aGVHD, cGVHD, GVL, GVT OS EFS TRM QoL6 Stem cell a generalized moth

3、er cell that has pluripotency descendants may specialize in different directions Hematopoeitic Stem cell pluripotent stem cells that give rise to all the blood celltypes including myeloid (monocytes and macrophages, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes/platelets, dendrit

4、ic cells), and lymphoid lineages (T-cells, B-cells, NK-cells).7HLA Human leukocyte antigena key part of the human immune systemMHC Major histocompatibility complex a highly polymorphic region on chromosome 6 with genes particularly involved in immune functionsMHC HLA engraftment-related8 HSCT Hemato

5、poietic stem cell transplantation PBSCT Peripheral blood stem celltransplantation CBT Core blood transplantation BMT Bone marrow transplantation NST Non-myeloblative Stem cell Transplantation RIST Reduced Intensifying Stem cell Transplantation 9 GVHD Graft-Versus-Host Disease aGVHD acute GVHD cGVHD

6、chronic GVHD GVL Graft-Versus-Leukemia GVT Graft-Versus-Tumor DLI Donor Lymphocyte Infusion TRM Transplantation-Related Morbidity QoL Quality of Life 10Part 1 Background Stem Cell11SMART: Unique Feature of HSCT Cheng. SMART stem cells, Gene Therapy 2008; 15, 677312S elf-renewal of SMART stem cell Se

7、lf-renewal -asymmetrical: 1 daughter SC & 1 differentiated cell after division -symmetrical, 2 daughter SC after division -HSCs, asymmetrical self-renewing division 13S elf-renewal of SMART Stem cell Blastomere-Like Stem Cells 14Mature of SMART stem cell Differentiation is the most direct cellular b

8、asis for using stem cells in regenerative medicine. All stem cells are able to differentiate into specified cell types underspecific conditions.15M ature of Stem Cell16A poptosis of SMART Stem cellAsymmetrical divisions to maintain number of stem cells, apoptosis may be less frequent. symmetrical se

9、lf-renewing division occurs, stem cell pool size is increased, apoptosis is likely to maintain the stem cell pool at its proper size. Stem cells must have the capability to die in order to prevent the overgrowth that may lead to cancer.17Resting Mode of SMART stem cellAdult stem cells resistant to m

10、any physiological stimuli and pathophysiological insults. HSCs do not respond to many hematopoietic growth factors.HSCs are relatively quiescent in cell cycle.18Quiescence of Stem cell19T rafficking of SMART Stem CellThe ability of stem cells to traffic or migrate is best described with HSCs. HSCs h

11、ave an active motility.They constantly move in and out of their bone marrow niche and even circulate in the blood under homeostatic conditions.20Mobilizing and Homing of Stem cell21Part 2 Definition of HSCT Hematopoietic stem cell transplantation HSCT, a transplantation of blood stem cells Derived f

12、rom bone marrow /peripheral/cord. a medical procedure in the fields of hematology and oncology22Objective of HSCTDisease Eradication HD-CT/RT Hematological Malignancy: Leukemia/Lymphoma/MM Some types of solid tumor: Breast cancerHematopoietic Reconstitution Leukemia Lymphoma: Replace of hematopoieti

13、c Function Aplastic anemia:Hematopoietic Failure Immunology Reconstitution: GVL/GVT Malignancy disease: GVL/GVT effect Autoimmune disease: Rebalance of immune system 23Part 2 Classification Source of Stem cell BMT PBSCT CBTSource of Donor Matched Unrelated Donor: CMDP Buddhist Tzu Chi Stem Cells Cen

14、ter Matched sibling donor: family donor24Part 2 Classification Genetic Difference: Autologous HSCT Allogeneic HSCTConditioning Intensify Myeloblative Transplants Non-myelobaltive Conditioning NST 25Part 33.1 Indications For HSCT Hematological Malignancy acute myeloid leukemia AML Auto/Allo acute lym

15、phoblastic leukemia ALL Allo myelodysplasia disorders MDS Allo chronic myeloid leukemia CML Allo multiple myeloma MM Auto-Allo Non-Hodgkins lymphoma NHL Auto/Allo Hodgkins lymphoma HL Auto 26 non-malignancy hematological disease Aplastic Anemia, AA Solid Tumor Germ cell tumors, Breast cancer Autoimm

16、une diseases AD SLE systemic lupus erythematosus 27 Auto-HSCT for autoimmune disease28 Auto-HSCT for autoimmune disease29Part 33.2 Procedure of HSCT Screening for HLA matched Donor Mobilizing & Collecting PBSC/BM Conditioning of Patient Reinfusion of PBSC/BM Reconstitution of hematopoietic and immun

17、e Control of complication 30Autologous Stem Cell Transplants31Allogeneic Stem Cell TransplantsNEXT32 Laminar air flow Ward33Step one of HSCT Screening Donor Induction Therapy for Leukemia Patient HLA typing for patient HLA-A, B, DR Screening for matched donor, Family or MUD Preparative Examination o

18、f Donor 34HLA typing of HLA-A, B, DR35HLA-typing of Family Donor 36Step two of HSCTMobilizing of HSC Activating and mobilizing stem cell Drugs: G-CSF, GM-CSF, CTX, etcCollecting HSC BM PBSC37 Mobilizing and Collecting of PBSC38 Collecting of BM stem cell 39STEP Three of HSCT Condition Regimen of Pat

19、ient Principles of Conditioning Conditioning Regimens NST: Tumor eradication TRM Vs Engraft GVL Immuno Vs Bone-marrow suppression 40Principles of Conditioning Creation of space: Still Controversial concept Immunosuppression prevent Host-versus-Host reaction Disease Eradication Bone-Marrow suppressio

20、n Get rid of tumor load41Conditioning Regimens BuCy TBI/Cy FBC, etc BU: Busufan myeloablation Cy: cyclophosphamide Immunoablation TBI/Cy: Total Body Irradiation42 Immunoablation Vs MyeloablationMyeloablation Relapse TRM Immunoablation Relapse TRM NST Immunoablation outweigh Myeloablation TRM DLI GVL

21、 Relapse 43 Schematic Diagram of NST44STEP FOUR OF HSCTReinfusion of HSC 45STEP 5 ReconstitutionHematopoietic Reconstitution 2-3 weeksImmunology Reconstitution: GVL/GVT Less than 1 ys for B-cell Imunology M ore than 1-3 ys for T-cell Immunology 46Part 4Complications of HSCT Early Complications: HC, VOD, aGVHD Late complications: PTLD, cGVHD Infection 47Mechanism of G