Transcript The Role of Bone Marrow Transplant in Oncology

The Role of Bone Marrow
Transplant in Oncology
Diane Hill-Polerecky RN, BSN, MS
Leukemia Transplant Case Manager &
Transplant Clinical Projects Coordinator
Nebraska Medicine
Objectives
• Define and identify indication for
Hematopoietic Stem Cell Transplant
• Identify donor sources
• Identify sources of Hematopoietic Cells
• Describe the transplant process and
timeline
• Identify short-term and long-term
complications and follow up of the
Transplant patient
Transplant may be referred to as:
• BMT – Bone Marrow Transplant
• PBSCT – Peripheral Blood Stem Cell
Transplant
• UCBT – Umbilical Cord Blood Transplant
• ** HSCT/HCT – Hematopoietic (Stem) Cell
Transplant
Hematopoietic Cell Transplantation
Definition:
High doses of chemotherapy and/or radiation
are given to eradicate malignancies followed
by an infusion of hematopoietic cells to
reestablish marrow function.
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Hematopoietic Stem Cell
Cascade
A small number of transplanted cells can
replicate to repopulate a patient’s entire
hematopoietic system
Further defined by donor source
• Autologous
• Patient’s own hematopoietic stem cells
• Allogeneic
• Cells collected from a donor
• Related or unrelated
• Syngeneic
• Cells collected from an identical twin
Just a little history
• 1959 Dr. E Donnall Thomas 1st attempt at
treating leukemia with hi dose chemo and
syngeneic marrow transplant
• Mid 1960s before they figured out HLA
matching
• Late 1960s first successful (matched
sibling) allogeneic for leukemia
• 1973 first unrelated allogeneic transplant
• Mid 1970s success with autologous for
lymphoma, became widespread 1980s
• 1988 first successful UCB
Autologous Transplants
• Patient’s own cells are collected prior to
receiving myeloablative (hi dose)
chemotherapy
• Goal is to rescue the bone marrow after it
has been destroyed by this lethal therapy
• Chemotherapy is the treatment, stem cells
are the rescue.
• May be part of initial treatment plan or
reserved for relapse or persistent disease
states
Diseases treated with Autologous
Transplant
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Multiple Myeloma
Hodgkins Disease
Non Hodgkins Lymphoma
Acute Promyelocytic Leukemia
Germ Cell tumors
Neuroblastoma
Brain tumors
Sarcomas
Recurrent Wilms Tumors
Clinical Trials: other solid tumors, Crohns,
Juvenile Rheum Arthritis, autoimmune
disorders
Advantages of Autologous
Transplant
• Ready access to the stem cells
• Decreased incidence and severity of side
effects
• Earlier engraftment
• No risk of Graft VS Host Disease
Disadvantages of Autologous
Transplant
• Risk of potential tumor contamination in
the infused cell product
• Lack of Graft vs Tumor effect may
contribute to relapse
Allogeneic Transplants
• Treatment of choice for patients with
diseased bone marrow or patients with
genetic and immunologic disorders
• Myeloablative chemotherapy and/or
radiation are given to eradicate
malignancy AND to prepare recipient for
donor cells
• Donor cells repopulate the marrow and
provide GRAFT vs TUMOR effect
• Chemotherapy is the preparative regimen,
stem cells are the treatment
Malignant Diseases treated with
Allogeneic Transplant
• AML and ALL with intermediate and hi risk
prognostic factors
• Myelodysplastic Syndromes
• Chronic Myeloid Leukemia (blast phase)
• Myeloproliferative Disorders
• Non Hodgkin Lymphomas
• Multiple Myeloma / Hodgkins - rare
• Relapse after Autologous Transplant
Non Malignant Diseases treated
with Allogeneic Transplant
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Severe Aplastic Anemia
Fanconi Anemia
Thalassemia
Sickle Cell Disease
Diamond-Blackfan Anemia
Congenital Neutropenia
Severe Combined Immunodeficiency
(SCID)
• Hurler Syndrome
• Hunter Disease
Advantages of Allogeneic
Transplant
• Replacement of diseased or damaged
bone marrow/stem cells with healthy cells
• Graft vs Tumor effect – powerful immune
reaction wherein the newly transplanted
immune cells react against any residual
disease
Disadvantages of Allogeneic
Transplant
• Longer periods of immunosuppression
• Complex often long term medication
regimens
• Graft vs Host Disease (GVHD) both acute
and chronic
Syngeneic Transplant
• Stem cells are collected from identical twin
• Considered allogeneic as a donor is
involved. Acts more like autologous
rescue.
• Lack of Graft vs Tumor effect
• Rare Graft vs Host Disease
• Recovery is more like an Autologous
Transplant
Sources of Hematopoietic Cells
• Bone Marrow
• Peripheral Stem Cell
• Umbilical Cord Blood
Bone Marrow Harvest
Multiple needle aspirations of marrow from iliac crests
Advantages
• Completed in several
hours
Disadvantages
• May still require multiple
trips to donor center
• No mobilization required
• Need for general or
epidural anesthesia
• Decreased risk of GVHD
• Preferred in nonmalignant
disorders
• Risk of bleeding,
increased pain, infection,
bone, soft tissue or nerve
damage
• Slower Engraftment
Bone Marrow Harvest
Peripheral Blood Stem Cell
Collection
• Autologous and Allogeneic Donors
• Stem Cells are mobilized out of the bone
marrow into the peripheral blood in larger
quantities with the use of growth factors
and sometimes chemotherapy (auto
donors)
• Stem cells then collected via apheresis
process and remaining blood components
returned to the donor
Peripheral Blood Stem Cell Collection
Advantages
• Outpatient, no anesthesia
• Generally well tolerated
• Cells obtained are more
mature and engraft earlier
– improved outcomes for
recipient
• Can be utilized in patients
that have received pelvis
irradiation
Disadvantages
• Side effects of growth
factor (bone pain, flu like
sx)
• Low blood counts with
chemomobilization
• Requires apheresis
catheter or large bore IVs
• Hypocalcemia
• Hypovolemia
Peripheral Stem Cell Collection
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Umbilical Cord Blood Transplant
• Rich source of stem cells collected at time
of childbirth. No risk to mother/child
• UCB cells have not matured
immunologically, naïve, allows for greater
degree of mismatch
• Can be frozen and stored
• Limited and finite number of cells. Can not
go back to donor if additional cells are
needed
• Slow engraftment, decreased graft vs
tumor, increased graft failure
Transplant Timeline
Eligibility Considerations for
Transplant
• The malignancy is sensitive to therapy
• The disease is in an early stage
• Low tumor burden
• Marrow toxicity is the only dose-limiting
effect of the treatment - Comorbidities
• Age
• Psychosocial well-being
• Compliance
• Caregiver availability
Care Partner Responsibilities
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Assist with daily living activities
Participate in educational sessions
Collect data (VS, I/O, Wt)
Assist patient with self-medication
Ensure compliance with treatment
and care schedule
Care for central venous catheter
Assist with oral care
Encourage use of incentive
spirometer
Transportation
Observe for therapy-related side
effects and symptoms
Contact the transplant team to report
new symptoms or emergencies
Transplant Timeline
Allogeneic Donors and HLA
Matching
• Human Leukocyte Antigens (HLA)
are proteins found on the surface of
most cells in the body
• The immune system uses HLA to
verify that a given cell is part of the
body and not foreign
• There are many different HLA proteins
(HLA-A, -B, -C, -DRB1, -DQ, -DP) and
there are many varieties of each one
Why is HLA Matching Important?
• If donor cells are not the same HLA type as
the recipient the Tcells will recognize the
recipient as being different and attack – and
vice versa
• If the recipient cells win, you get graft rejection
• If the donor cells win, you get graft-versus-host
disease (GVHD)
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HLA Inheritance
Mother
Father
A
1
2
A
9
10
B
3
4
B
11
12
C
5
6
C
13
14
7
8
DR
15
16
DR
Child 1
Child 3
Child 2
Child 4
A
1
9
A
1
10
A
2
9
A
2
10
B
3
11
B
3
12
B
4
11
B
4
12
C
5
13
C
5
14
C
6
13
C
6
14
DR
7
15
DR
7
16
DR
8
15
DR
8
16
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What If No Family Members Match?
• >17,000,000 people around the world have signed up to
be volunteer donors for unrelated patients in need
• NMDP’s Be The Match Registry
• World’s largest pool of donors
• Domestic and International donors and cord blood
units
• The transplant center is responsible for initiating a donor
search
What if no NMDP match?
• 9/10 Unrelated Donor – some mismatches
are better than others
• Haploidentical Related Matches
• Data supporting similar outcomes to
unrelated10/10 match
• Further testing for antibodies
• More flexibility with scheduling – move
to Transplant faster
• Post Transplant Cytoxan to reduce
GVHD
Transplant Timeline
Preparative Regimens:
Myeloblative Full Intensity
• Higher doses of chemo/radiation with goal
of killing ALL the patient’s diseased cells
and stem cells
• Generally more side effects – healthy cells
are killed as well
• Auto conditioning vs Allo conditioning
• Allo patients begin receiving
immunosupressive meds to prevent GVHD
and graft rejection
Preparative Regimens:
Nonmyeloablative - Reduced
Intensity
• Allogeneic Transplants only
• Lower doses of chemo/radiation
• Main goal to suppress recipient immune system
to allow donor cells to engraft
• Primary benefit Graft vs Tumor Effect
• Patients less likely to tolerate side effects
of high dose
• Age, Comorbidities, Lower Performance Status,
Prior Therapies
• Blood Counts depressed for shorter time
• Most effective with very minimal residual
disease
Transplant Timeline
Day 0 – Cell Infusion:
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Hydration
Premedication
Monitoring
Cell infusion
• Cryo preserved vs non cryopreserved
**Cells ability to find their way to the marrow
after IV infusion
Transplant Timeline
Inpatient Recovery
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Inpatient 2-3 weeks post cell infusion
Monitor for fever/infection
Blood product support
Nutrition support
Activity - PT
Manage toxicities
• Mouth sores, electrolyte imbalances,
nausea/vomiting
Length of Stay in Omaha
(Average Time)
Autologous Transplant
Allogeneic Transplant
• Evaluation/Work-up: 1-2
days
• Collection: 1 week
outpatient
• Inpatient: 3-4 weeks
• Outpatient: 1-2 weeks
• Evaluation/Work-up: 1-2
days
• Collection from donor: 1
week outpatient
• Inpatient: 3.5 - 4 weeks
• Outpatient: Until day
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Why 100 Days ? … or Allogeneic
Transplants are a big deal!
• Balancing act : Graft vs Tumor and Graft
vs Host Disease
• Acute Graft vs Host can happen fast and
can be deadly: Skin, Liver, GI Tract
• Management of Acute GVHD is very
specialized
• Complex medication management with
multiple side effects
• Immunosuppressant medications increase
risk of infections
• Patients not allowed to drive, require 24hr
caregiver and must be within 30min of
NMC
Long Term Follow Up
Autologous
• Immunizations: 3,6,9,12
months and 2 years
• Irradiated Blood Products
• Day 100 Restaging
• Annual Follow Up
• Managing Long Term
Side Effects
Allogeneic
• Frequent follow up at
NMC during 1st year
• Immunizations: 3,6,9,12
months and 2 years
• Irradiated Blood Products
• Annual Follow Up
• Collaborate with referring
Oncologist
• Managing Long Term
Side Effects
• Treating Chronic GVHD
High Dose Therapy
Side Effects - Long Term
• Fatigue/Depression
• Shingles
• Infertility
• Slow or Failure to Engraft
• Lung Scarring
• Heart Damage
• Secondary Cancer / Leukemia
• Cataracts
• Low Thyroid Function
Chronic GVHD – Trading one bad
disease for another?
• Despite having good HLA match,
undergoing preparative regimen and
compliance with immunosuppressant
meds – GVHD can still occur
• Months to years later
• Skin, Eyes, Mouth, Pulmonary
• Early identification and treatment are key
• May require long term immunosuppression
and steroids
• Greatly impacts Quality of Life
What’s new – What’s next?
• CAR T cells
• Alternate Donor Sources: Haplo Related
and Unrelated
• Preventing and Treating GVHD: Clinical
Trials and Multidisciplinary Clinics
• Improving Long Term Quality of Life and
Survivorship
• Selected Stem Cells/Cells for immune
reconstitution
• Targeted Therapies (antibodies)
Questions?
Additional Resources
• NMC Transplant Education Videos –
http://www.nebraskamed.com/cancer/bloo
d-marrow/patient-education
• Be the Match – www.bethematch.org
• Leukemia and Lymphoma Society –
www.lls.org