HDB 30803 HSC Transplantation PDF

TOPIC 11 INSTITUTE OF MEDICAL SCIENCE TECHNOLOGY HEMATOPOIETIC STEM CELL TRANSPLANT DR. NORHAIDA CHE AZMI [email protected]...

TOPIC 11 INSTITUTE OF MEDICAL SCIENCE TECHNOLOGY HEMATOPOIETIC STEM CELL TRANSPLANT DR. NORHAIDA CHE AZMI [email protected] 03-87395894 ext:312 Universiti Kuala Lumpur (UniKL) | Where Knowledge Is Applied and Dreams Realised HDB 30803 ADVANCED HEMATOLOGY  COURSE LEARNING OUTCOME Upon completion of this course students should be able to: Discuss the causes, clinical features, laboratory investigation and management of the 1 disorders for different types of anemia, white blood cell disorders, disorders of hemoglobin and bleeding & coagulation disorders (C4). Analyze and solve cases with hematological findings given to identify the possible 2 condition or disease (C4, A4). Report hematological findings in written form to present case related diseases in class. 3 (A2) HDB 30803 ADVANCED HEMATOLOGY  TOPIC 11- HSCT TOPIC OUTLINES: 1. Definition of BM/HSCT 2. Origin and differentiation of HSC 3. Sources of HSC for transplantation 4. Type of stem cell transplant 5. Process of HSCT 6. Complications associated with SCT 1 HDB30803 ADVANCED HEMATOLOGY  1. BM / SC TRANSPLANT A bone marrow transplant (BMT) aka stem cell transplant or, more specifically, a hematopoietic stem cell transplant (HSCT). A BMT is a medical procedure that replaces your bone marrow that have been destroyed by drugs, radiation or disease (cancer- leukemia, lymphoma / non-cancerous- autoimmune disease, aplastic anemia, thalassemia) with healthy cells. The replacement cells can either come from your own body (autologous) or from a donor (allogeneic). 2 HDB 30803 ADVANCED HEMATOLOGY  1. BM / HSC TRANSPLANT ✓ The term BMT has been change to Hematopoietic Stem cell transplant (HSCT) since the introduction of peripheral blood and umbilical cord stem cells ✓ HSCTs become an established standard treatment for malignant and non- malignant blood disorders. ✓ >60,000 transplants performed yearly worldwide. 3 HDB 30803 ADVANCED HEMATOLOGY  can be derived from B cells or T cells and can arise in the lymph nodes as well as other organs presence of Reed-Sternberg cells (like owl eyes), which are mature B cells that have become malignant (Severe Combined Immune Deficiency) is a group of rare disorders caused by mutations in different genes involved in the development and function of infection-fighting immune cells. a group of cancers in which immature blood cells in the bone marrow do not mature, and as a result, do not develop into healthy blood cells - cancer of plasma cell 4 HDB 30803 ADVANCED HEMATOLOGY  2. ORIGIN OF HSC Stem cell – a class of unspecialized cells that can differentiate into specialized cells. They possess two key properties: a)Long term cell renewal - the cell can split off and make another cell b) cell differentiation, which means they can mature into cells for different parts of the body. 5 HDB 30803 ADVANCED HEMATOLOGY  3. SOURCES OF HSC FOR TRANSPLANT 1. 3. 2. 6 HDB 30803 ADVANCED HEMATOLOGY  PERIPHERAL BLOOD SCT Stem cell mobilization- using drugs to mobilize stem cells intothe peripheral blood Granulocyte Colony Stimulating Plerixafor [Mozobil] Factor ​ ommonly these drugs are given C "subcutaneously", right under the skin. 7 HDB 30803 ADVANCED HEMATOLOGY  UMBILICAL CORD BLOOD (CB) ❑ Cord blood – collected from the umbilical cord and placenta after a baby is born – CB is rich in hematopoietic stem cells (HSCs) that can differentiate into RBCs, WBCs and platelets. ❑ Cord tissue also contains mesenchymal stem cells (MSCs), which can differentiate into a variety of cells such as heart, cornea, kidney and fat. 8 HDB 30803 ADVANCED HEMATOLOGY  Blood stem cells are collected from the umbilical cord and can then be processed to be banked for public or private use. In Malaysia, there are several organizations which are involved in cord blood banking. i. The National Blood Bank in Ministry of Health handles cord blood banking for donation purposes. ii. There are several private companies which provide the service of cord blood banking. These include: CryoCord Sdn. Bhd. & StemLife Bhd-local company, laboratory/bank situated in Cyberjaya 9 HDB 30803 ADVANCED HEMATOLOGY  4. TYPES OF HSC FOR TRANSPLANT AUTOLOGOUS TRANSPLANTATION ALLOGENIC TRANSPLANTATION (stem cells are harvested from the (stem cells are harvested from a different patient's own body) person/Donor). The stem cell donor may be a family member, usually a sibling/relative or an unrelated person. 10 HDB 30803 ADVANCED HEMATOLOGY  4. TYPES OF HSC FOR TRANSPLANT AUTOLOGOUS HSCT 1. Collection of stem cells-Stem cell mobilization- PBSCT 2. Processing 3. Cryopreservation 4. Conditioning & treatment 5. Reinfusion into patient 11 HDB 30803 ADVANCED HEMATOLOGY  4. TYPES OF HSC FOR TRANSPLANT ALLOGENIC TRANSPLANT 1. Collection of donor cells 2. Processing 3. Cryopreservation 4. Conditioning & treatment 5. Reinfusion into patient 12 HDB 30803 ADVANCED HEMATOLOGY  ALLOGENIC STEM CELL TRANSPLANT & HLA MATCHING ❖ Human Leukocyte Antigen (HLA) matching is needed for allogenic transplant to find the best suitable donor. ❖ The genes for HLA proteins are clustered in the major histocompatibility complex (MHC) ❖ located on the short arm of chromosome 6 ❖ MHC Class 1 (HLA-A, HLA-B, HLA-C), MHC Class II (HLA-DR, HLA- DQ, HLA-DP) ❖ Matched related donor (siblings): 1:4 chance a sibling will be full Matching for the HLA-A, -B,- C,- DRB1 and -DQB1 loci is match. referred to as a 10/10 match, when HLA-DPB1 is included, it ❖ If no matched, search for matched unrelated donors (MUD) becomes a 12/12 match. Matching for HLA-A, -B, -C, and - DRB1 loci is an 8/8 match. through bone marrow registry databases such as Malaysian Stem There is still no international standard for reporting DRB3/4/5 Cell Registry (MSCR). as well as DQA1 and DPA1 mismatches ❖ Ethnicity is an important factor for HLA matching. The best HLA match? 'Twin>Sibling>Parent>Unrelated donor'. MHC Class II MHC Class I 13 HDB 30803 ADVANCED HEMATOLOGY  5. PROCESS OF SCT PBSC collection 14 HDB 30803 ADVANCED HEMATOLOGY  5. PROCESS OF SCT ▪ Maintain collected stem cell products in liquid nitrogen until the time of the patient’s transplantation. ▪ Cryopreservative used is dimethylsulfoxide (DMSO). ▪ DMSO maintains cell viability by preventing ice crystal formation within the cells during storage. ▪ Maintain temperature of – 80 ⁰ C to – 180⁰ Storage of stem cells in liquid C. nitrogen tank Cryopreserved / Frozen Stem Cells 15 HDB 30803 ADVANCED HEMATOLOGY  5. PROCESS OF SCT CONDITIONING REGIMENS AGENTS USED PRIMARILY FOR IMMUNOSUPRESSION: Anti-thymocyte globulin Fludarabine AGENTS USED PRIMARILY FOR ANTI-NEOPLASTIC EFFECTS: Busulfan Melphalan Caboplatin Thiotepa 16 HDB 30803 ADVANCED HEMATOLOGY  5. PROCESS OF SCT 17 HDB 30803 ADVANCED HEMATOLOGY  5. PROCESS OF SCT 18 HDB 30803 ADVANCED HEMATOLOGY  5. PROCESS OF SCT 19 HDB 30803 ADVANCED HEMATOLOGY  6. COMPLICATIONS ASSOCIATED WITH HSC TRANSPLANTATION Hepatic sinusoidal obstruction syndrome GVHD remain the Acute GVHD occurs before day 100 of post-transplant major cause of mortality 20 HDB 30803 ADVANCED HEMATOLOGY  GRAFT VERSUS HOST DISEASE (GVHD) ✓ Graft-versus-host disease (GVHD) is a potentially Treatment for GVHD serious complication of allogeneic stem cell transplantation. Some common medications that are given to prevent GVHD include: ✓ During allogeneic SCT, a patient receives stem cells from a donor or donated umbilical cord Methotrexate (Trexall®) blood. Cyclosporine Tacrolimus (Prograf®) ✓ GVHD occurs when the donor’s T cells (the graft) Mycophenolate mofetil (CellCept®) view the patient’s healthy cells (the host) as Sirolimus (Rapamune®) foreign, and attack and damage them. Corticosteroids (methylprednisolone or prednisone) ✓ Graft-versus-host disease can be mild, moderate Antithymocyte globulin (ATG) or severe. In some cases, it can be life- Alemtuzumab (Campath®) threatening. Cyclophosphamide (Cytoxan®) ✓ GVHD can usually be treated with steroids or other immunosuppressive agents. 21 HDB 30803 ADVANCED HEMATOLOGY  GVHD – Sign and Symptom Nausea, vomiting, abdominal cramps, loss of appetite and diarrhea indicate involvement of the gastrointestinal tract. Jaundice (yellowing of the skin or eyes) may indicate that GVHD has injured the liver Poikiloderma (Skin become discolored and break down) Lichen planus like lesion - skin, mouth & genitalia (a condition that causes a rash to develop on one area or several parts of your body at the same time) Esophageal stricture (an abnormal tightening or narrowing of the esophagus) Bronchiolitis obliterans- obstruction of the smallest airways of the lungs (bronchioles) due to inflammation Joint contracture & fasciitis (inflammation of the fascia, which is the connective tissue surrounding muscles, blood vessels and nerves) 22 HDB 30803 ADVANCED HEMATOLOGY  WHAT IS THE BEST CELL SOURCE FOR ME? The doctors will choose the best cell source based on the following factors; ✓ Your disease ✓ Overall health ✓ How quickly transplant is needed ✓ Number of blood-forming cells you need. 23 HDB 30803 ADVANCED HEMATOLOGY THANK YOU UNIVERSITI KUALA LUMPUR © Copyright of Universiti Teknikal MARA Sdn. Bhd. 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