Infusion Of T H C Hematopoetic (Pbsc) Stem Cells

INFUSION OFHEMATOPOETICSTEM CELLSBYKARLA BELL BSN, CPHON TYPES OF HEMATOPOIETIC CELLS Peripheral(PBSC) Fresh or cryopreserved Cord THINGS TO CONSIDER Fresh cells are generally given within 24-48 hours ofharvesting Institutional policy (UW 3 policies, SCH 1 policy)Cryopreserved vs. NON-CryopreservedPre-hydration, pre-meds, infusion length, start timeTubing If delayed, cells can be stored at room temp for a few hours or 4degrees Celsius overnight Discuss with Attending firstCryopreserved cells (Cord blood or PBSC) can bestored in DMSO for years, but are usually givenwithin 1-4 monthsMarrowUsually freshSTORAGE BloodAlways cryopreserved Bone Blood Stem Cells Filtered vs. non filtered, Pumped vs. gravity Venous Access ABO Compatibility and Processing CVC preferred, required for Cryopreserved***HPCs are NEVER irradiated***CONSIDERATIONSCONT Signed consent?Do you have an order to infuse? Has it been 36 hours since the completion ofchemotherapy/conditioning? (protocol dependent) Has the patient received 24 hours (or 3 doses) ofTacrolimus or Cyclosporine doses for an allogenictransplant? (protocol dependent) Teaching and Support 1

CONSIDER THE MEDICATION SCHEDULE:CONCOMITANT INFUSIONS No medications or fluids piggybackedDiscuss Meds/TPN to be given through otherlumen with the team Amphotericin, antibodies, investigationalmedications or blood products should not be givenconcomitantly Keep fluid max in mindPRODUCT TRACKING INVOICEStays with the cells at all timesDocuments chain of custody Donor information Recipient information ABO information Documents start and end infusion times High risk of anaphylaxis or reactionHPCs cannot be infused during plasmapheresisor hemodialysisDAY “0” The day cell infusion is completeThere can be 2 days Itacts as a reference point for the pre/posttransplant timeline Eg.: when to give day 1 MTX, immunosuppressiveagents, and pre-transplant chemotherapy Day AUDIENCE RESPONSE CRYO-PRESERVED CELLSWhich type of HPCs are typically used inautologous transplants? 0 can be inpatient or outpatientDepends on cell type, conditioningregimen, supportive care needed,patient clinical status, reimbursement.A: Cord Blood cellsB: Peripheral blood stem cellsC: Bone marrowD: All of the aboveTRUE or FALSE? The nurse can run IV fluidsthrough the same lumen as the HPC infusion2

PATIENT POPULATIONS What NeuroblastomaMedulloblastoma, astrocytomaRelapsed Ewings, Hodgkins Lymphoma Why Non-Hodgkins Lymphoma, Hodgkins Lymphoma,Multiple Myeloma,Multiple Sclerosisare we doing this:Alternate to bone marrow or PBSCsVery rich in stem cellsLower incidence of GVHD AdultsCORD BLOODDonated umbilical cord and placenta blood collectedafter a baby is born and the cord is cutCryopreserved and saved for a matched patient Pediatricsit is:Cryopreserved products are autologous or cordblood transplants What Pt receives 2 (3 for adults) UCB (Umbilical CordBlood) infusions DMSO 1st (2nd): Standard UCB2nd (3rd): Expanded/Manipulated UCB given 4 hrs post 1stinfusion Why EXPANDED CORD BLOODit is:DiMethylSulfOxide Preservative for stored cells are we doing this:Decrease pt infection risk - by decreasing the waittime until engraftment How: When the UCB cells are expanded, they have ahigher number of bone marrow progenitor cells,which engraft more quicklyExpanded cells are T cell depleted - thus die morequickly Anti-coagulant added to cells to prevent clumpingduring apheresis and storageBinds ionized calcium - patient can have acute dropsin calcium levels Hypocalcemia: tingling, numbness, restlessness, nauseaIV Calcium or TumsStop/slow the infusion to allow time to recover.May need to monitor baseline calcium if multiple bags expectedHistamine release S/S: hypotension, abdominalcramps, dyspnea, nausea, diarrheaDue to dose related toxicity: total cell volume notto exceed10mL/kg/day ACID CITRATE DEXTROSE (ACD) Can cause histamine release and allergicreactions: pre-medicate regardless ofh/o transfusion reaction.Sometimes resulting in multiple infusion days.*Cells are DMSO preserved and then frozenPATIENT PREP FOR INFUSION Baseline Assessment Hydration, Decrease to TKO during infusion of cells Including AM weight and abdominal girthPre: 2 hoursPost: 4 hoursPre-medications Benadryl, Tylenol, HydrocortisoneConsider anti-emetics Emergency medications available and oxygen ready Orange wedges/hard candy/lollipops 3

CRYOPRESERVED HPC SEQUENCE(CONT.)CRYOPRESERVED HPC INFUSION SEQUENCE Review Policy and Procedure1.8.2. Review Patient Roadmap for correct date of infusion anddetermination of cell type3. Ensure patient has signed Hematopoietic Progenitor Cell InfusionConsent and orders for Infusion Infusion start time is discussed with Cellular Therapy Lab and RN4. Let the MD/Charge RN/RN buddy know when you are starting aninfusion5. RN pre-medicates the patient 30 minutes prior6. Obtain correct tubing for infusion and validate correct venousaccess7.9.10.11.1213.14Cord blood: Infuse at 2x maintenance rate. Maintenance will bedefined in the physician CIS order.If a product needs to be infused greater than 2xmaintenance in order to meet product expiration timean Attending order will be required.On average 30-60 minutes per cord blood.Calculate Drip rate to infuse via gravity (use unitresources)Non- Cord blood: Start slowly at 3-5 ml/min for 1st 4 minIf tolerated increase to wide open Receipt of transfer is signed by RN and technician CTL tech thaws initial bag of HPC (for cords, it may come alreadythawed) Infuse HPC by gravity Each bag is spiked and infused by the RN after thawing by CTL tech Vital signs After infusion is completed hydration and side effect monitoringcontinue (4-24 hours)CORD BLOOD ADMINISTRATION:STAGGERED DELIVERIESCORD BLOOD ADMINISTRATION: RATES RN and Cellular therapy tech check patient ID and product ID onProduct Tracking InvoiceThis will allow for slower infusion rates withoutgoing past product expiration times. The thaw of the cord will be staggered by aboutan hour. The second unit will arrive about anhour after the first. You will have a separate Monitoring form foreach cord blood unit. If there is a delay in infusing bags back to back(traffic, processing, etc ) resume hydration untilthe next bag is started. Each product will have it’s own expiration time. MONITORINGTROUBLE SHOOTING Cells may run too slowly or stop dripping Attach tubing “hub to hub”Elevate poleUn-spike the bag (open to air to eliminate vacuumeffect)Technician may use “stripper”Flush lumen with NSUse 3-way stopcock and 20cc syringe to draw cellsfrom the tubing and inject into patient Sideeffectsand support Cryopreserved monitoring: 4 hours aftercompletion of HPC Cord Blood monitoring: 24 hours aftercompletion of last bag Mandated documentation of how infusion istolerated Teaching4

SIDE EFFECTS:NAUSEA AND VOMITING Why: Why: What can help:Can be caused by DMSO or granulocytes SIDE EFFECTS:COUGH OR DRY TICKLE IN THROATMay be immediate and can occur suddenlyWhat can you do: Have PRN anti-emetics already ordered Temporarily slow rate Why: should be done:Stop InfusionCheck O2 sat, give oxygen if neededNotify MDIncrease hydration/fluid bolus Nursing Why: DMSO preserves stem cells well, but not red cells As the product thaws red cell death/hemolysisAssessment:CV changes may occur up to 6 hours post infusion Nursing What Ensure adequate UOP Record Q2 hr I/OFollow renal function for next few days 2-3mL/kg/hour Educate: Regardingpink/red urineSIDE EFFECTS:TAKOTSUBO (STUNNED OR BROKEN HEART)CORD BLOOD ONLY Related to the volume of DMSOCan occur despite premedsCan be immediate or delayedMay have increased potential in Cord Blood asalso preserved with DextranhydrationAssessment “Slime” can clog kidneys Prevention: Pre and Post Why: Slow infusionDeep breathingSucking on oranges/candy/lollipopSipping on water or juiceSIDE EFFECTS:RENAL DYSFUNCTIONSIDE EFFECTS:ALLERGIC / HYPERSENSITIVITYREACTIONS Caused by DMSObuild of DNA “slime”Usually a response to histamine release What Remember to use a separate lumen for all medsSIDE EFFECTS:HYPOTENSION, HYPERTENSION,BRADYCARDIA Mimics acute coronary syndrome – reversible leftventricular apical ballooning Also called “stress cardiomyopathy”Transient and usually precipitated by acutestress Treatment would involve usual treatment forcardiomyopathy. to do:Stop infusion and notify MDAdminister anaphylaxis meds as needed 1st line drug EpinephrineBenadryl, hydrocort given as pre-meds5

PATIENT AND FAMILY EDUCATIONDMSO is excreted through all body orifices andfluids Garlic-like odor may last up to 36 hours Urine may be dark red or even black due tohemolyzed red cells AUDIENCE RESPONSE DMSO can cause which of the following sideeffects: A: an unpleasant odorB: an allergic reactionC: renal damageD: all of the aboveFRESH HEMATOPOETIC CELLSPROCESSING Asfresh HPC are allogeneic, processingmay be required for ABO incompatibletransplants Know your donor and recipient bloodtypes Be aware of any planned or possibleprocessingVOLUME Usual total 10-15ml/kg (URD marrow may beup to 2 liters)For pediatric patients, notify MD if marrowvolume exceeds 15ml/kgTIMING AND PREPARATION Lesscontrol over time of infusionpre-hydration necessary Tubing No Inspect bag prior to spiking for clumps or visiblefat droplets: return to lab Fresh: Always pumpedNon-filtered (standard tubing): whole HPCmarrow, plasma reduced HPC marrowFiltered: PBSC, RBC Reduced Bone Marrow,donor lymphocytes, CD34 or T cell depletedmarrow, fresh NK cells6

FRESH HPC INFUSION SEQUENCEPATIENT PREP FOR INFUSION1. Baseline Assessment 2. Review Patient Roadmap for correct date of infusion and determinationof HPC type3. Ensure patient has signed Hematopoietic Progenitor Cell InfusionConsent and orders for Infusion4. Let the MD/Charge RN/RN buddy know when you are starting aninfusionIncluding AM weight and abdominal girthPremedicationNone, unless history of blood reactionsIf required, then follow platelet transfusionguidelines Review Policy and Procedure5.6.7. RN pre-medicates the patient only if history of reaction to blood products Obtain correct tubing for infusion and validate correct venous access RN and Cellular therapy tech check patient ID and product ID onProduct Tracking InvoiceFRESH HPC SEQUENCE (CONT.)INFUSION8.9.10.11.12.13. Receipt of transfer is signed by RN and technician Infuse HPC by pump Each bag is spiked and infused by the RN Vital signs Document rate increases with vitals and patient tolerance After infusion is completed hydration and side effect monitoringcontinue.REACTIONS: VOLUME OVERLOAD Signs and Symptoms: Respiratory: Dyspnea or tachypnea, rales, chest tightness,dry cough Cyanosis Decreased O2 Saturation CVS: HypertensionJugular Venous DistentionNeuro: Restlessness(major indicator with pediatrics)What can be done: Product reduction may be required if 20ml/kg adult weight;15 ml/kg pediatric weight Administer lasix OFMARROW AND PBSCSAdults (PBSCs Only): begin at ½ maintenance for 15 minutes, thenincrease to 2x maintenance 20kg/Adults: begin at ½ maintenance for 15 minutes, thenincrease to 1.5x maintenance 20kg: begin at 1ml/kg/hr for 30 minutes, thenincrease to by 25% of fluid maximum q15 untilmax; 1.5x maintenance Marrow infusion often take 4-8 hoursREACTIONS: HEMOLYTIC TRANSFUSION Why: May be secondary to ABO incompatibletransplants Signs and Symptoms:Sudden onset nausea or vomiting“Sense of doom”/AnxietyFever 1 or chillsSevere lower back or flank painAnuria Prevention: Red cell depletion or plasma exchange canprevent reactions7