Objectives BMT Preparative Phase:

Objectives BMT Preparative Phase: Finding The Way Pat Groff, RN, BMTCM 10/30/17 Discuss the patient experience prior to deciding to proceed to BMT Describe the patient and donor medical evaluation prior to BMT Discuss patient and caregiver education during the preparative phase Identify significance of HLA typing and Donor selection Before Arrival to SCCA. Identify the SCCA/FHCRC as their transplant center, often after visiting other places (Consult) Access the SCCA system (Intake) Obtain Financial Clearance for the workup (but not the transplant) Preparing For Transplant manual sent to help plan their time in Seattle Allogeneic patients must have a suitable donor identified Autologous transplant patients may have collected and stored their cells OR arrive ready to collect 4 1/17/2018 More Concerns Identify caregivers, one or many Non-local patients leave home, job, family, school, children, pets, aged parents Locate temporary housing for 2-6 months within a 30 minute radius Local patients try to juggle it all Worry of life-threatening illness and treatment Commitment to Stay Allogeneic (donor other than self) expect a 4 month stay 2-4 weeks prior to transplant, 3 months after transplant 100 days Autologous (self donor) can be up to 6 months Two weeks for Collect on Arrival Can have multiple rounds of chemo prior to collection and transplant One month for mobilization of cells & recovery 2 weeks assessment/conditioning One month for post-transplant care After all this, there is no guarantee of success 1

Intake Choosing Treatment Plan Communicates with Home MD Talks with Patient & Caregiver Time commitment, housing, finances, plan of care Talks with Donor Time commitment, two trips to donate, what to expect from both types of donation if plan is unknown Gathers all pertinent medical data & records Sends information and schedule to patient Attending physician chooses Treatment via CCO Book Based on diagnose, age, inclusion criteria, priority protocol 7 1/17/2018 8 Leaving Home Coming Here Yakima, WA 2016 Pop. 91,067, 142 miles to.. the Mercer Mess Seattle 2016 Pop. 704,352 The Preparative Phase at SCCA Two to three week period Patient evaluated for Transplant Blood and Marrow Transplant Clinic BMT clinic is open 365 days a year; Lab and Infusion room Triage Area short term care for acute issues, prelude to hospital admission or stabilize for home care Learning about Caregiving Insurance approval Daily Team Rounds 2

Transplant Teams Team Members Attending: Physician-Scientist Transplant Specialist rotates Provider: (APRN or PA-C) rotates Q 1-3 months RN: consistent 4 days, one day regular sub Allogeneic Adult Teams Autologous Adult Teams Pediatric Teams Ongoing Care BMT Teams Adult TTC Transplant Transition Clinic (too sick to be handled completely by local MD can share the patient) Adult LTFU Long Term Follow-Up returning for assessment and treating chronic problems (years) Pediatric CC Continuing Care including LTFU (55 and growing yearly) returning for assessment and treating chronic problems (years) It Takes a Village to do an Outpatient Transplant Patient, family and caregivers form the core Clinical Pharmacist Transplant specialists cover 2-3 teams Team coordinators responsible for ALL scheduling Dietitians researchers specializing in Transplant Social Worker assess every Transplant patient/family Transition RN s insurance, discharges from hospital and to hospice, home care needs, education for home care More Villagers Child Life for Peds and children of adult patients Chaplaincy Palliative Care & Pain Team Physical Therapy Shuttle Driver Staff at Pete Gross and SCCA House Volunteers Arrival Visit First Time in clinic for Patient, Family, and Caregivers Patient Registration--register and consented for care/blood draw Alliance Lab--Adult blood draw; pediatric patients clinic first (weight and EMLA) Outpatient Primary provider (APP) completes H & P--at least an hour) Team Nurse--at least an hour+ for Adults, 2 for kids & translator Orient to the system names, numbers, people Transplant Resource Manual Consent packet (binder) Tour the building (time permitting) Arrival Conference the following day + Consent signing Work-up and More Extensive work-up over the next several days to weeks (shuttling between SCCA, UWMC, SCH) Multiple Blood Draws additional labs Chest X-Ray follow-up CT and Pulmonary Consult delay Bone Marrow Aspirate & Biopsy (if indicated) relapse or remission? Decision time Lumbar Puncture (disease specific) Positive treatment delay Oral Medicine Exam dental issues delay Gynecologic Exam (if indicated) hormone control/fertility issues 3

Work-up Scans (CT, MRI, PET) more extensive disease delay Additional Consults: o ID infectious issues- delay o Immunology supportive services o GI + guaiac w/u delay o Fertility uncommon o Psych long delays for assessment o Pain management Cardiac Studies r/o additional problems Pulmonary Function Test may not meet standards and yet MORE Work-up Nutrition malnourishment may need treatment Physical Therapy rehab Spiritual Assessment lack of support Social Work Inadequate Caregiver plan means delay or denial if Competency is in question Financial Insurance must be adequate. Transplants are not charity care eligible--family may also need assistance for daily living expenses What s happening with the Donor during delay? Education for Caregivers/Patients Medication Teach Food Safety Managing Care at Home Caregiver 101 hands on with line Review of Caregiver Manual Preparative Phase Ends Data Review Conference Attending discusses the findings of the work-up and the plan for transplant They may not be a transplant candidate (don t usually wait this long) The plan for treatment may change better transplant prep Insurance issues could delay or deny Donor confirmation Patient signs treatment consents/assents (for their protocol and many others) Line placement the following day Team nurse chemotherapy teach for outpatient or inpatient conditioning Line Placement Prior to transplant patients will have a double-lumen, tunneled Central Venous Catheter placed Adults will have their line placed in the SCCA Procedure Suite or at UWMC PICC or other lines (not ports) will be removed Pediatric patients will have their lines placed at SCH Patients and caregivers will have individual nursing instruction about how to care for the line Not all patients will change the dressing or flush lines, but do need shower protection teach Caregivers Non-Patient Care Activities Navigate the system Communicate with family and friends Provide transportation Manage finances Grocery shop and prepare food Clean apartment and do laundry daily Manage their home life from afar BE AN ADVOCATE for patient and themselves 4

Taking Care of the Patient Learn how to care for their loved one (or not so loved one) Can be a role reversal & stressful Independent person can become dependent Adult children and older parents Teens trying to make their way in the world Learn how to make, track, and change appointments Study the Caregiver Manual English not their language only Spanish guide available* Central Line Care Shower care Line flush Daily cleaning There s More to Do Manage medications both IV and PO, and their frequent changes Give IV fluids Give antibiotics and antivirals Track pain, anti-nausea meds Change Cyclosporine/Tacrolimus/Sirolimus dosing Track oral intake Provided multiple small meals throughout the day Provide for daily hygiene Daily shower, towel and bedding wash Track symptoms Monitor temperature Call clinic or after-hours Be cheerleader, task-master and manager of all Allogeneic Donor Complexity of finding the Best Donor The Best Donor Increases likelihood of successful Transplant Improves Engraftment rates Less Graft vs Host Disease Provides Better Long Term Survival Finding the Best Donor #1: Matched sibling 25% chance of matching #2: Matched unrelated donor depends on ethnicity #3: Mismatched unrelated donor (9 out of 10) #4: Cord Blood--UCB #5: Haploidentical (related half match) 5

How is a Donor Chosen? HLA Basics HLA = Human Leukocyte Antigen Located on Chromosome 6 Protein or marker that the immune system uses to identify self from non-self Inherit half from your mother and your father Chromosomes are inherited in groups Ethnic groups share common chromosome markers Inherited as a group *most of the time Matching and Mismatching HLA sites identified as: A, B, C, DRB1, DQB1, and DP 4/6 sites = A, B, C (cord blood standard) 8 sites = A, B, C + DRB1 (majority standard) 10 sites = A, B, C, DRB1 + DQB1 (FH minimum) 12 sites = A, B, C, DRB1, DQB1 + DP (preferred at FH) Human Leukocyte Antigens Segregation of HLA Haplotypes in Families A1 B8 DR3 DQ2 Father Mother a b c d A2 B44 DR7 DQ2 A3 B7 DR2 DQ1 A11 B60 DR4 DQ4 A1 B8 DR3 DQ2 a Patient A3 B7 DR2 DQ1 c b d a d With parents Haploidentical b c With patient A1 B8 DR3 DQ2 a A3 B7 DR2 DQ1 c Identical Factors Affecting Donor Choice Age prefer younger than older - less risk, better collection Gender Sex matched less GVHD UNLESS donor is Multiparous woman Blood Type Mismatch takes longer to be red cell independent Anti-HLA Crossmatch screening--not just mismatched but can have antibodies to different HLA type Degree of Mismatch risk of too high for GVHD with < 9/10 match (except cords) Donor Choice Considerations Size of patient/cord blood units: difference can delay or cause lack of engraftment Disease Status: aggressive disease may risk mismatch PBSC or BM: donor center ability, donor preference, disease status BM less Chronic GVHD CMV status donor/patient: prefer CMV neg donor for CMV neg recipient 6

Donor Issues URD located, asked, agrees but not evaluated until patient arrives for evaluation URD Donor fails evaluation two or more donors are prepped Family Donor fails evaluation d/t unforeseen circumstances Donor backs out often have second URD donor ready Related donors-- demand money or backs out Family members alienated from each other Donor Evaluation Similar Exclusions to Blood Donation Basic Medical Evaluation Heart, Lungs, Liver OK? Normal CBC Lab values No Active viral or bacterial infections Exclusions for travel Zika, recent Malaria exposure Disqualifications can be Justified donor approved based on need, identified problem, approved by recipient and/or recipient medical team Donor Evaluation Similar Exclusions to Blood Donation Medical evaluation more liberal for related donors URD: >18 and < 60 age less concern for related donors Negative for HIV, Hep B, exposure to Hep B good for a Hep B Positive patient Pregnant? surgery in second trimester if no other donor NO to most autoimmune diseases Does NOT have to match blood type Peripheral Blood Stem Cell-PBSC or Bone Marrow-BM? Disease status more aggressive PBSC causes more AGvHD Protocol specific non-myeloablative require PBSC Degree of Mismatch may not engraft with BM fewer cells Haplotidentical tested with BM first, now PBSC Risk of Graft vs Host Disease worse Chronic GVHD PBSC Donor preference terrified of needles or surgery Unrelated Donor Center practice fewer centers can do BM Unrelated Donor Selection 70% of patients will not have a related match Extended Family Search Unrelated Donor Search Cord Blood Unit Search 66-97% of all patients will find a match through the NMDP Registry Depends on ethnic background 10% matched donors unavailable for donation 80-99% will have at least one mis-matched UCB unit HLA Match Likelihoods for Hematopoietic Stem-Cell Grafts in the U.S. Registry N Engl J Med 2014; 371:339-348July 24, 2014DOI: 10.1056/NEJMsa1311707 Unrelated Donor Providers National Marrow Donor Program (NMDP) 16 million U.S. donors and 238,000 cord blood units Facilitated more than 68,000 transplants since 1987 In 2016, facilitated approximately 6200 transplants Over 25 million world wide donors (488 centers) Timeframe for finding URD match Approximately 3 months Donors only partially tissue typed (HLA-A, B) 7

Likelihood of Finding 8/8 HLA Match *10/10 match preferred 44 1/17/2018 Role of Cord Blood in Transplants by Patient Ethnic Background Role of Cord Blood in Transplants by Patient Ethnic Background AVERAGE COST OF URD SEARCH US Donor up to $40,000 Foreign Donor up to $55,000 Stem Cell Procurement $43-68,000 Cord Blood Procurement $25-60,000 URD PROGRAM CONFIDENTIALITY Transplant recipient only informed of donor s age, sex, vague geographic location, ABO compatibility, CMV status URD Donor informed only of recipient s diagnosis, age (child/adult), chance of survival with & without transplant One year must past before contact can be made only if donor center allows The Next Phase Begins There is no break for the patient and caregiver. The preparatory phase ends when conditioning begins. Patients may begin conditioning as early as the next day. 8

Key Points Uncertainty permeates the Preparative Phase Successful Caregivers require both basic and ongoing teaching Donor Selection is complex Questions? pgroff@seattlecca.org 206-288-7731 9