Cancer Treatment Modalities: Hematopoietic Stem Cell Transplantation Flashcards
What is Hematopoietic stem cell transplatantation (HSCT)?
Hematopoietic stem cells (HSCs) to self renew, proliferate, and mature into functional blood cells and establish immunity
-provides constant levels of blood cells in peripheral blood needed for administration of high-dose therapy
Major maker of the HSC
CD34
Autologous stem cell transplantation =
Source of cells is self (patient)
Allogeneic stem cell transplantation =
Source of cells is human leukocyte antigen (HLA)- matched donor
Risks/Benefits of Autologous
No graft vs host disease
No benefit of graft vs tumor effect
Potential contamination of graft w cancer cells
Risks/Benefits of Allogeneic
Complications of infection or long term organ damage from tax regimens
Graft vs host disease
No malignant cells in graft
Length to time to locate compatibility donor
Synegenic stem cell transplant =
Source from identical twin
Rarely used bc of high relapse rate
What are HLAs?
Human Leukocyte Antigens are found on surface of white blood cells and other tissues in the body -> can differentiate from non self
What does two ppl sharing the same HLA mean?
Their white cells and tissues are immunologically and histiologically compatible with each other
Types of Cancers that use autologous stem cell transplants
1) Hematologic (3)
2) Solid (2)
1) Multiple Myeloma, Hodgkin lymphoma, Non-Hodgkins lymphoma
2) Neuroblastoma, Germ cell tumors
Types of Cancers that use Allogeneic stem cell transplants (6)
Hematologic
- Leukemias
- Non-Hodgkins Lymphoma
- Myelodyspastic syndrome
- Aplastic anemia
- Sickle cell disease
- Thalasemia
- Falconi anemia
The genes for HLAs are located on chromosome __ and are inherited as a single _____ from each ____
6, haplotype, parent
Surface proteins responsible for assisting the acquired immune response to recognize non-self molecules =
Major Histocompatibility complex (MHC)
The different classes of genes within the MHC (3)
Class I: HLA-A, HLA-B, HLA-C
Class II: HLA DR, HLA DP, HLA DQ
ex) individuals can have more than 20 varieties and more than 10,000 HLA types
Why is it important that the donors MHC sets match the patients?
Graft rejection, Graft vs. Host disease
If a T-lymphocyte recognizes a non-self MHC, it will rally immune cells to destroy the cell that bears it
HLAs vs. MHC?
HLA is the human body’s version of MHC
MHC’s are found in all vertebrates
Sources of stem cell collection (3)
Bone Marrow
Peripheral blood
Umbilical
Pluripotent =
(of an immature or stem cell) capable of giving rise to several different cell types
Characteristics of Bone Marrow stem cell collection
1) Rich in ____ stem cells
2) Harvested from what part of donors body?
3) Procedure is how long?
4) Total fluid obtained?
5) Adverse effects of procedure?
6) After collection how is the fluid processed?
7) How soon is the product infused into the patient?
8) Disadvantages?
1) pluripotent
2) posterior iliac crest
3) 1-2 hours
4) 500-1,000ml
5) postop pain, effects of anesthesia, infection, bleeding, hematoma
6) filtered to remove fat and bone particles, then further processing in stem cell lab
7) Ideally same day, but can be cryopreserved for a later date
8) surgery, longer duration for engraftment of stem cells
Characteristics of Peripheral stem cell collection
1) Stem cells ___ usually ___ in peripheral blood system
2) How do stem cells moved from marrow space to the periphery?
3) The cells are collected by what process?
1) not present
2) using high doses of granulocyte-colony stimulating factor administered 4-6 days before collection
3) Apheresis
Apheresis for peripheral stem cells
1) What machine is used?
2) Access of patient and donor?
3) Where is this procedure done?
4) Adverse effects?
5) When is it used?
6) Advantage?
7) Disadvantage?
1) Centrifuge (removes CD-34 stem cells from blood and returns blood back to donor)
2) Patient uses tunneled multi-lumen catheter, Donor has PIV, fem line if PIV not adequate
3) Outpatient, just 1 day
4) Hypocalcemia (bc sodium citrate in apheresis line to prevent clotting), Hypovolemia, Thrombocytopenia
5) Same day or cryopreserved
6) Shorter time for hematologic recovery and engraftment of cells
7) Risk for GVHD
Characteristics of Umbilical stem cell collection
1) When and from what is collected?
2) Where is it cryopreserved?
3) Advantage
4) Disadvantage
1) At birth, collected from umbilical cord and placenta
2) cord blood bank
3) Rich in stem cells, low risk for GVHD
4) Longer duration of myelosuppression and time of engraftment of cells
Minimum collection of stem cells from bone marrow vs peripheral sources
1-4 x 108cells/kg
2-10 x 108cells/kg
= more for peripheral
Prior to transplant, patient is clinically evaluated for what aspects of health and life? (5)
1) Labs
2) Organ function
3) Diseases
4) Psychosocial
5) Financial
What labs do we look at for a potential transplant recipient?
CBC BMP (liver and renal) Coags ABO/RH type Pregnancy test Full workup for infectious diseases HLA testing for allogenic recipients
Organ function tests for potential transplant recipient?
Cardiac
Electrocardiogram for EF
Pulmonary tests
Dental eval
Disease eval tests for potential transplant recipient?
Bone marrow biopsy/aspiration
Radiographic scans
Lumbar puncture
Immunoglobulins
Psychosocial eval for potential transplant recipient?
Comprehension of process, risk, adverse effects
Ability to comply
Social and spiritual issues
Family concerns
Financial eval for potential transplant recipient?
Reimbursement assessment
Personal financial resources
Impact of absence from work (pts and caregivers)
What treatment course is given to patient to prepare for transplant?
Single of combination chemotherapy with or without total body irradiation (TBI)
What is the purpose of giving chemo/radiation to prepare patient for transplant?
Used to eliminate disease or completely ablate the marrow
Myeloablative regimens =
The administration of lethal doses of therapy to eradicate cancer cells and produce severe immunosuppression before transplant
What is the benefit of a myeloablative regimen?
decreases ability of host to reject donor graft, enhance engraftment
Non-myeloablative regiments or reduced intensity (RIC regimens =
Uses reduced doses of chemo and TBI before transplant
When are non-myeloablative regimens used vs. myeloablative
Older patients
Comorbid conditions
Less toxic
Dimethyl Sulfoxide (DMSO)
A preservative present in processed stem cells that causes reactions during infusion -> pts given premeds and aggressive hydration
Adverse effects of infusion
1) Are the reactions intense?
2) Urine
3) Mouth
4) Cardiopulmonary
1) Minor, resolves in 1-2 days
2) Pink tinged/cherry red urine from breakdown of rbcs and stem cells
3) Garlic breath or taste in mouth bc of breakdown of DMSO
4) Hypo/Hypertension, Brady/Tachycardia, Chest tightness, Dyspnea, Cough, Flushing, hives, fever, N/V, diarrhea
How do we decrease the risk for adverse effects during infusion?
Less common with fresh cells transplantation (less time preserved)
What are the two signs of successful hematopoietic stem cell transplantation?
1) Engraftment
2) Chimerism (for allogenic pts)
What changes in the lab results to show successful engraftment?
ANC > 500/mm3
Platelets >20,000/mm3
Shows that stem cells are in the marrow space and reproducing