Diane HillPolerecky RN BSN MS Leukemia Transplant Case Manager amp Transplant Clinical Projects Coordinator Nebraska Medicine Objectives Define and identify indication for Hematopoietic Stem Cell Transplant ID: 915215
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Slide1
The Role of Bone Marrow Transplant in Oncology
Diane Hill-Polerecky RN, BSN, MS
Leukemia Transplant Case Manager & Transplant Clinical Projects Coordinator
Nebraska Medicine
Slide2Objectives
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
Slide3Transplant 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
Slide4Hematopoietic 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.
4
Slide5Hematopoietic Stem Cell Cascade
Slide6A small number of transplanted cells can replicate to repopulate a patient’s entire hematopoietic system
Slide7Further 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
Slide8Just a little history
1959 Dr. E
Donnall
Thomas 1
st
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 leukemia1973 first unrelated allogeneic transplantMid 1970s success with autologous for lymphoma, became widespread 1980s1988 first successful UCB
Slide9Autologous 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
Slide10Diseases treated with Autologous Transplant
Multiple Myeloma
Hodgkins
Disease
Non
Hodgkins
Lymphoma
Acute Promyelocytic LeukemiaGerm Cell tumorsNeuroblastomaBrain tumorsSarcomasRecurrent Wilms TumorsClinical Trials: other solid tumors, Crohns, Juvenile Rheum Arthritis, autoimmune disorders
Slide11Advantages 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
Slide12Disadvantages of Autologous Transplant
Risk of potential tumor contamination in the infused cell product
Lack of Graft
vs
Tumor effect may contribute to relapse
Slide13Allogeneic 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
Slide14Malignant 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 LymphomasMultiple Myeloma / Hodgkins - rareRelapse after Autologous Transplant
Slide15Non Malignant Diseases treated with Allogeneic Transplant
Severe Aplastic Anemia
Fanconi
Anemia
Thalassemia
Sickle Cell Disease
Diamond-
Blackfan AnemiaCongenital NeutropeniaSevere Combined Immunodeficiency (SCID)Hurler SyndromeHunter Disease
Slide16Advantages 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
Slide17Disadvantages of Allogeneic Transplant
Longer periods of immunosuppression
Complex often long term medication regimens
Graft
vs
Host Disease (GVHD) both acute and chronic
Slide18Syngeneic 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 DiseaseRecovery is more like an Autologous Transplant
Slide19Sources of Hematopoietic Cells
Bone Marrow
Peripheral Stem Cell
Umbilical Cord Blood
Slide20Bone Marrow HarvestMultiple needle aspirations of marrow from iliac crests
Advantages
Completed in several hours
No mobilization required
Decreased risk of
GVHD
Preferred in nonmalignant disorders
DisadvantagesMay still require multiple trips to donor centerNeed for general or epidural anesthesia
Risk of bleeding, increased pain, infection, bone, soft tissue or nerve damage
Slower Engraftment
Slide21Bone Marrow Harvest
Slide22Peripheral 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
Slide23Peripheral 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 chemomobilizationRequires apheresis catheter or large bore IVsHypocalcemia
Hypovolemia
Slide24Peripheral Stem Cell Collection
24
Slide25Slide26Umbilical 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
Slide27Transplant Timeline
Preparative Therapy
Transplant Day 0
Consultation
Chemotherapy
?
Evaluation
Ascertain Donor Harvest
Cells
Recovery
Slide28Eligibility Considerations for
Transplant
The malignancy is sensitive to
therapy
The disease is in an early
stage
Low tumor
burdenMarrow toxicity is the only dose-limiting
effect of the
treatment - Comorbidities
Age
Psychosocial well-
being
Compliance
Caregiver
availability
Slide29Care Partner Responsibilities
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 scheduleCare for central venous catheterAssist with oral careEncourage use of incentive spirometerTransportation
Observe for therapy-related side effects and symptoms
Contact the transplant team to report new symptoms or emergencies
Slide30Transplant Timeline
Preparative Therapy
Transplant Day 0
Consultation
Chemotherapy
?
Evaluation
Ascertain Donor
Harvest
Cells
Recovery
Slide31Allogeneic Donors and HLA Matching
H
uman
L
eukocyte
A
ntigens (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
Slide32Why 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)
32
Slide33Slide34HLA Inheritance
Mother
Father
A
9
10
B
11
12
C
13
14
DR
15
16
A
B
C
DR
2
1
3
4
5
6
7
8
Child 1
Child 2
Child 3
Child 4
1
3
5
7
9
11
13
15
1
3
5
7
10
12
14
16
16
2
4
6
9
A
B
C
DR
A
B
C
DR
8
11
13
15
A
B
C
DR
2
4
6
8
14
12
10
DR
C
B
A
34
Slide35What If N
o
F
amily
M
embers
Match?
>17,000,000 people around the world have signed up to be volunteer donors for unrelated patients in needNMDP’s Be The Match RegistryWorld’s largest pool of donorsDomestic and International donors and cord blood unitsThe transplant center is responsible for initiating a donor search
Slide36What 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
Slide37Transplant Timeline
Preparative Therapy
Transplant Day 0
Consultation
Chemotherapy
?
Evaluation
Ascertain Donor Harvest
Cells
Recovery
Slide38Preparative 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
conditioningAllo patients begin receiving immunosupressive meds to prevent GVHD and graft rejection
Slide39Preparative 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 EffectPatients less likely to tolerate side effects of high doseAge, Comorbidities, Lower Performance Status, Prior TherapiesBlood Counts depressed for shorter timeMost effective with very minimal residual disease
Slide40Transplant Timeline
Preparative Therapy
Transplant Day 0
Consultation
Chemotherapy
?
Evaluation
Ascertain Donor Harvest
Cells
Recovery
Slide41Day 0 – Cell Infusion:
Hydration
Premedication
Monitoring
Cell
infusion
Cryo
preserved vs non
cryopreserved
**Cells ability to find their way to the marrow after IV infusion
Slide42Transplant Timeline
Preparative Therapy
Transplant Day 0
Consultation
Chemotherapy
?
Evaluation
Ascertain Donor Harvest
Cells
Recovery
Slide43Inpatient Recovery
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
Slide44Length 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 weeksEvaluation/Work-up: 1-2 days Collection from donor: 1 week outpatient
Inpatient: 3.5 - 4 weeks
Outpatient: Until day +100
Slide45Why 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 TractManagement of Acute GVHD is very specializedComplex medication management with multiple side effectsImmunosuppressant medications increase risk of infections Patients not allowed to drive, require 24hr caregiver and must be within 30min of NMC
Slide46Long Term Follow Up
Autologous
Immunizations: 3,6,9,12
months and 2
years
Irradiated Blood Products
Day 100 Restaging
Annual Follow UpManaging Long Term Side EffectsAllogeneicFrequent follow up at NMC during 1st yearImmunizations: 3,6,9,12 months and 2 yearsIrradiated Blood ProductsAnnual Follow Up
Collaborate with referring Oncologist
Managing Long Term Side Effects
Treating Chronic GVHD
Slide47High Dose TherapySide Effects - Long Term
Fatigue/Depression
Shingles
Infertility
Slow or Failure to Engraft
Lung Scarring
Heart Damage
Secondary Cancer / Leukemia
Cataracts
Low Thyroid Function
Slide48Chronic 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
Slide49What’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 reconstitutionTargeted Therapies (antibodies)
Slide50Questions?
Slide51Additional Resources
NMC Transplant Education Videos –
http://www.nebraskamed.com/cancer/blood-marrow/patient-education
Be
the Match –
www.bethematch.org
Leukemia and Lymphoma Society –
www.lls.org