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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. 4 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 • • • • • • • • • • 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 • • • • • • • 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 24 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 • • • • • • • • • • • 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) 32 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 34 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: • • • • 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 • • • • • • 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 +100 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