Term
| 3 Components of Hemopoietic Stem Cell Transplantations |
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Definition
1. Bone marrow transplantation
2. Peripheral blood stem cell transplantation
3. Cord blood transplantation |
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Term
| Allogeneic Hematopoietic Stem Cell Transplant (HSCT) |
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Definition
| Transfer stem cells from a donor to an immunologically matched recipient |
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Term
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Definition
1. Treat patient with chemotherapy/radiation/immunotherapy to ablate patient's marrow and destroy malignancy
2. Rescue with autologous or normal allogeneic product |
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Term
| Name the 3 types of stem cell donors |
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Definition
1. Autologous - self
2. Syngeneic - identical twin
3. Allogenic - another person (not identical twin) |
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Term
| Name the 4 Types of allogeneic donors |
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Definition
1. Matched sibling (25% chance for 6/6 HLA match)
2. Closely matched unrelated donor (80% chance for match...if caucasian)
3. Haploidentical family member (50% match by parent)
4. Cord blood |
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Term
| Rationale for autologous transplant |
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Definition
| Allow dose intensification of chemotherapy |
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Term
| Rationale for allogeneic transplant (3) |
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Definition
1. Replace defective marrow with normal marrow
2. Graft vs. tumor effect
3. Marrow source won't be good under any circumstance |
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Term
| Treatment for Hematologic Malignancy |
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Definition
| Allogeneic Stem Cell Transplant |
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Term
| Examples of hematologic malignancies |
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Definition
Acute lymphoblastic leukemia
Acute myeloid leukemia
Chronic myeloid leukemia
Myeloma
Lymphoma
Chronic lymphoid leukemia |
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Term
| Non-malignant disorders treated with allogeneic stem cell transplantation |
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Definition
Aplastic Anemia
Metabolic Storage Disease
Immunodeficiency
Hemoglobinopathy
Auto-immune disease |
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Term
| Malignant diseases treated with AUTOLOGOUS stem cell transplantation |
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Definition
**Hodgkin disease
**Multiple Myeloma
**Neuroblastoma
**Other cancers
Acute leukemia
**Lymphoma
Autoimmune disease |
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Term
| Goals of Conditioning Regimens |
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Definition
1. Ablate host immune system to ensure engulfment
2. Eradicate malignancy to prevent relapse
3. Minimize toxicity |
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Term
| Components of Conditioning Regimens |
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Definition
1. Chemotherapy
2. Radiation
3. Immunosuppressants - ATG, monoclonal antibodies |
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Term
| What is different about a "mini" transplant? |
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Definition
| Has reduced conditioning procedures |
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Term
| Describe "mini" transplants. |
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Definition
| Initial mixed chimerism followed by conversion to full chimerism allowing graft vs tumor affect |
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Term
| What are the benefits of mini transplants? |
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Definition
Less toxicity to older patients
Different sensitivity of different tumors |
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Term
| What was the first common type of transplant? |
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Definition
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Term
| What 2 types of transplants are becoming more popular in recent years? |
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Definition
**Peripheral blood stem cells
Cord blood |
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Term
| From where in the donor is the bone marrow removed? |
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Definition
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Term
| What happens after the bone marrow is harvested? |
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Definition
Passed through a series of filters to remove bone fragments and platelet clots
Collected into a bag - if a syngeneic donor - can be transfused directly into the recipient |
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Term
| Define the function of GCSF. |
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Definition
Granulocyte colony stimulating factor
Increases CD34+ stem cells in periphery |
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Term
| How do the hemopoietic stem cell graft get to its final location? |
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Definition
| HSCs home to marrow and engraft over 10-30 days. |
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Term
| Features of Bone Marrow Harvest |
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Definition
1. Typically only one collection
2. Contains more "accessory" cells that may aid engraftment
3. Believed to contain more primitive cells that PBPC
4. Donor under general anesthesia |
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Term
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Definition
1. Can have multiple collections
2. Produces about twice as many nucleated cells as bone marrow
3. No anesthesia necessary
4. Collection procedure typically about 4 hours |
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Term
| Marrow Vs. Peripheral Blood |
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Definition
Peripheral Blood - faster engraftment
- No increase in acute GVHD
- Better DFS in poor risk patients
- Increased incidence chronic GVHD |
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Term
| Cord Blood As a Source of Stem Cells |
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Definition
Available immediately
May induce less GVHD
Limiting cell number for larger patients
No longer term data (promising so far) |
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Term
Major Risks of Hemopoietic Stem CEll Transplant
*Autologous & Allogeneic* |
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Definition
Relapse of Primary Disease
Regimen related toxicity
Infection |
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Term
| Major Risks of Hemopoietic Stem Cell Transplant - Allogeneic Only |
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Definition
Graft vs host disease
graft rejection |
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Term
| What are the symptoms of regimen related toxicity? |
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Definition
Veno-occlusive disease
pneumonitis
hemorrhagic cystitis
mucositis
cardiac damage |
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Term
| How long does T cell recovery take after transplant? |
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Definition
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Term
| What makes immune system recovery slower after transplant? |
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Definition
Allogeneic transplant
GVHD and immunosuppression |
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Term
| Why are patients susceptibile to viral and fungal infections after transplant? |
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Definition
| Extremely lymphopenic (100-200 cells) |
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Term
| What is the most polymorphic of all genes? |
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Definition
| Human Leukocyte Antigen (HLA) for the MHC |
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Term
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Definition
| Some HLA haplotypes are more common within certain populations |
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Term
| Haplotypes shared via blood line (parent->child) |
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Definition
completely identical
Genes are inherited together
useful when selecting best mismatches |
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Term
| What types of transplants have a higher rate of rejection? |
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Definition
| Cord blood and mini transplants (b/c there is more of the host immune system left over) |
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Term
| Describe Graft Vs. Host Disease |
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Definition
| Immune competent cells from the donor recognize alloantigen in the recipient (MHC and minor histocompatibility antigens) |
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Term
| Describe the pathophysiology of GVHD. |
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Definition
1. Activation of T cells by alloantigen
2. Expansion of alloreactive T cell clones
3. Release of cytokines: TNF, IL1
4. Recruitment of other immune system effectors
5. Tissue Damage |
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Term
| What cytokine is involved in *A*cute Graft vs. host disease? |
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Definition
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Term
| What are the target organs for acute GVHD? |
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Definition
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Term
| Effects of acute GVHD on skin |
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Definition
| macular papular rash over entire body |
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Term
| EFfect of acute GVHD on GI |
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Definition
| terrible diarrhea and necrosis of bowel |
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Term
| What is the prophylactic treatment of GVHD? |
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Definition
Block activation and expansion of T cells
- Steroids: lympholytic (BEST)
- Methotrexate: prevent division and expansion
- Cyclosporin/FK506, block synthesis cytokines and prevent activation |
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Term
| Describe a prophylactic technique to prevent GVHD |
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Definition
Select stem cells (CD34+)
Deplete T cells through T cell monoclonal antibodies |
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Term
| What are two ways to deplete T cells in vivo? |
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Definition
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Term
| Compare effectiveness of therapy vs. prophylaxis for GVHD. |
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Definition
| Prophylaxis is much more effective than treatment. |
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Term
| Describe the therapies for GVHD. |
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Definition
1. Steroids - BEST
2. T cell Antibodies - Dacluximab
3. Anti-cytokine Antibodies - Infliximab
4. MMF |
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Term
| What is the pathophysiology of chronic GVHD? |
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Definition
Shares features with auto-immune disease
Epithelial injury
Autoantibodies
FIBROSIS |
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Term
| What is balance you have to strike with HSC transplants? |
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Definition
Graft vs. Host
Graft vs. Leukemia |
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