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
General timeline for engraftment for Autologous and Allogenic transplants?
14-21 days
1-30 days when nonmyeloablative tx used
> 30 days for umbilical cord source
Major complication of HSCT?
GVHD
Graft vs Host Disease =
A complex immune reation between host (patient) and donor cells -> results in graft failure, disease relapse, fatal infection
Development of Graft Vs. Host disease is a __ step process
3
Step 1 in GVHD
Host tissue (mainly skin, GI tract, liver) is damaged by the conditioning regimen leading to inflammatory cytokines
Step 2 in GVHD
After a complex process, donor T cells activated, further enhancing inflammatory process
Step 3 in GVHD
Local tissue damage and death by donor T cells and continued cytokine simulation of T-cell activation
How do you diagnose GVHD?
By biopsy of affected organs
Risk factors for development of GVHD
Matched unrelated donor
Haploididentical transplants
Older patients
Peripheral stem collection
What organs are affected by GVHD?
Skin
GI tract
Liver
Skin effects of GVHD
Maculopapular rash with or without pruritis
First appears on palms, soles, neck, ears, shoulders
Erythoderma and bullous formation
GI tract effects of GVHD
N/V, anorexia, diarrhea (lower GI)
Liver effects of GVHD
Elevated bilirubin
Weight gain
Tx for GVHD
Corticosteroids*
Salvage therapies include photopheresis, monoclonal antibodies, antithymocyte globulin infusion
Types of HSCT complications (4)
Hematologic
Gastrointestinal
Renal, Hepatic
Cardiopulmonary
Hematologic complications (5)
The most common complication
Neutropenia Thrombocytopenia Anemia Engraftment Chimerism
Neutropenia
1) Induced by?
2) ANC of
3) Duration of neutropenia depends on
1) conditioning regimen
2) <100
3) conditioning regimen, # of CD34 cells per kilogram, use of growth factors, post transplant complications, hx of chemo and rt
Pre-engraftment is usually - days after transplantation
Primary risk factors for infection are (3)
0-15
Profound neutropenia
Alteration in skin integrity
Mucosal barrier toxicity
Types of infections that HSCT patients are prone to in pre-engraftment phase (3)
1) Bacterial
2) Fungal
3) Viral
Bacterial infections
1) 2 types
2) common sites
3) Prophylaxis medication
1) gram positive and negative
2) oral mucosa, cvc catheter
3) quilonlone
Fungal infections
1) 2 species
2) Reduce the risk by using
3) Prophylaxis medication
1) Candidia albicans (stomatitis), Aspergillus (pulmonary)
2) HEPA filter and positive pressure rooms
3) Fluconazole
Viral infections
1) 2 types
2) HSV usually presents itself in ____
3) Prophylaxis medication
1) Herpes simplex virus
2) stomatitis
3) Valacyclovir
Cytomegalovirus is more common in allogeneic transplant recipients
Which type of HSCT is at greater risk for infection?
Allogeneic > Autologous
Greater risk for what types of infections?
Nonbacterial (fungal and viral)
-Reactivation of latent viruses such as CMV and epstein barris common
Common infections
Streptococcus pneumoniae
Haemophilus influenzae
Sinusitis
Varicella zoster virus
-Reactivation of latent viruses such as CMV and epstein barris common
Why does thrombocytopenia persist post HSCT?
may indicate poor prognosis
Megakaryocytes are last to engraft for both types of transplants
- full platelet recovery usually 1-3 months post transplant
Cause of anemia post HSCT is from?
Conditioning regimen*
Other causative factors - bleeding, renal failure insufficiency dt therapies, hemolysis from ABO incompatibility
Engraftment is defined as an ANC and platelet count of?
> 500/mm3
>20,000/mm3
GI complications from HSCT (3)
N/V, Retching, Anorexia
Mucositis
Diarrhea
Causes of N/V, Retching, Anorexia post HSCT
- High dose chemo*
- GVHD
- Meds used for supportive therapy
- Electrolyte and nutritional imbalances
- Esophageal tears
- Decreased elimination of meds
- Aspiration PNA
Management of mucositis is important because?
because there is no treatment proven efficacious for prevention or symptoms
> 70% of patients experience it post HSCT
- can occur at any location along GI tract
- mucositis causes alteration in mucosal barrier can result in systemic infections
- reactivation of HSV
Melphalan =
A conditioning agent used for autologous transplantation that has a high incidence of causing mucositis
Nursing considerations for mucositis
Pain management is critical
Oral care and assessment
Causes of diarrhea post HSCT
Multifactorial
- conditioning regimens
- acute GVHD
- infections
Management of diarrhea post HSCT
Accurate I/O Fluid and Electrolyte replacement Monitor for s/s of dehydration Blood loss or hemorrhage Assess efficacy of pharmacologic interventions
The main Renal complication from HSCT
Acute Renal Toxicity
Renal Toxicity from HSCT
1) common adverse affect, primarily from which pre-regimen?
2) 1/3 of pts will require _____
1) Myeloablative regimen
2) dialysis
Renal Toxicity causes (5)
1) ______ regimen
2) Nephrotoxic _____ therapy
3) S____
4) Infusion of ____ ____
5) _______ immunosuppresive agents (3)
1) Conditioning
2) Antibiotic
3) Sepsis
4) Stem cells
5) Calcineurin
Tacrolimus
Cyclosporine
Volume depletion
Effect of Calcineurin agents on the kidneys?
Vasoconstriction and decreases vasodilators -> decreased renal blood flow and GFR -> interstitial fibrosis and tubular atrophy
Increased incidence of acute renal toxicity with patients that have (2)
TBI (total body irradiation)
High trough levels
Tx of acute renal toxicity post HSCT
Vigorous hydration
Close monitoring of trough levels
High-dose cyclophosphamide therapy usually causes what and how?
Hemorrhagic cystitis
The metabolite acrolein binds to wall of bladder -> bleeding and severe clot formation
Sx of hemorrhagic cystitis
Dysuria
Frequency
Urgency
Tx of hemorrhagic cystitis
1) what drug?
2) vigorous ______
Mesna (neuroprotectant)
hydration
Hemorrhagic cystitis that occurs at later point of transplant process usually occurs from what viruses?
Cytomegalovirus
BK virus
Adenovirus
Main Hepatic complication of HSCT
Hepatotoxicity
Causes of hepatotoxicity from HSCT
1) _V_D
2) HSOS
3) F___ and V____ infections
1) GVHD
2) Hepatic sinusoidal obstructive syndrome (venous occlusive disease)
3 Fungal, Viral
Hepatic aGVHD
1) Usually occurs - weeks after transplantation but may occur up to the ____ day mark
2) Risk factors (2)
3) Severe symptoms (3)
4) Treatment (1)
1) 2-4, 100
2) Old age, mismatched donor (matched unrelated donor)
3) Jaundice, severe upper quadrant pain, hepatomegaly
4) high-dose corticosteroids
HSOS (Hepatic Sinusoidal obstructive syndrome)
1) Total _ _ and conditioning regimens containing (3)
2) Effects of these drugs on the liver
3) Occurs in the first _ weeks after transplant
4) Triad of symptoms
5) Two systems used to diagnose
6) Treatment
7) Preventative drugs (3)
1) TBI; Busulfan, melphalan, cyclophosphamide
2) injury to endothelial tissue -> thrombosis within sinusoids and venules -> decreased blood flow
3) 4
4) Rapid weight gain, elevated bilirubin, painful hepatomegaly
5) Seattle and Baltimore
6) Diuretics, Symptom management
7) Urodeoxycholic acid (Ursodiol), Antithrombin III, Glutamine
Neurologic complications from HSCT causes
1) B____ use (can produce seizures; requires use of prophylactic anti-seizure meds)
2) C_____ use
3) Severe a_ _ _
4) Prior hx of intrathecal _____
5) Prolonged ______
6) Conditioning regimens that include _ _ _
1) Busulfan
2) Carmustine
3) aGVHD
4) Methotrexate
5) Immunosuppression
6) TBI
Cardiac complications of HSCT are uncommon and usually occur as a result of cardiotoxic effects of what 2 drugs?
Cyclophosphamide
Anthracyclines
Cyclophasphamide and Anthracyclines cause what cardiac effects (2)
Cardiomyopathy
Sx of CHF
High doses of cyclophosphamide cause what severe cardiac effects (2)
Pericardial effusion
Tamponade
Infusion of stem cells may cause what cardiac effect?
Bacterial and fungal infections may cause what cardiac effect?
Arrhythmia (SVT)
Endocarditis
Pulmonary complications of HSCT
1) Classified as either (2)
1) Infectious or Noninfectious
Infectious causes of pulmonary complications
Viral (CMV, varicella, zoster, community acquired respiratory, adenovirus)
Protozoans
Myocobacterial organisms
Non-infectious causes of pulmonary complications
Interstitial pneumonitis Diffuse alveolar hemorrhage Postengraftment respiratory syndrome Bronchiolitis obliterans syndrome Bronchiolitis obliterans pneumonia
Diagnosis of pulmonary complications made by what tests?
Chest Xray, CT scan
Bronchoscopy with lavage for indentification of infectious agent
Treatment of pulmonary complications
Infectious =
Noninfectious =
Antimicrobials
Corticosteroids
Late effect of HSCT
Risk for secondary malignancy (3)
AML, MDS
PTLD
Solid tumors (radiation induced: melanoma, oral cavity bone, thyroid, breast)
