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Nursing care of the blood cell transplant recipient
Nursing Care of the Blood Cell Transplant Recipient Patricia C. Buchsel, Ellen Leum, and Susan Rudder Randolph Objectives: To review the complications of blood cell transplantation (BCT) and their clinical and nursing management. Data sources: Review articles, research studies, book chapters pertaining to the complications of peripheral stem cell transplantation and the management of these complications. Conclusions: As the number of patients receiving BCT increases, complications related to stem cell mobilization, harvesting, dose-intensive conditioning therapy, in-
fusion, and engraftment are being documented with increasing accuracy. Implications for nursing practice: Oncology nurses will be caring for an increasing population of patients undergoing BCT. Although complications of both bone marrow transplantation and BCT are similar there are unique differences. Support and nursing interventions are of utmost importance for BCT patients and their family caregivers. Copyright © 1997 by W.B. Saunders Company
UTOLOGOUS blood cell transplantation (BCT) is increasingly replacing autologous bone marrow transplantation (BMT) as a treatment for numerous oncologic and hematologic diseases. Additionally, more than 250 allogeneic BCTs and more than 300 umbilical cord blood transplants have been documented. 1,2 The major difference between autologous BMT and BCT is stem cells from the marrow are used for BMT whereas BCT uses circulating stem cells collected from peripheral blood. Although complications of both BMT and BCT are similar, each has unique differences. The principles and concepts of BCT, which are similar to those of BMT, are reviewed by Kapustay elsewhere in this issue. The purpose of this article is to review the nursing care and complications as they relate to the BCT process.
ing regimens such as combination treatment with bulsulfan, and total body irradiation (TBI) may need to meet more stringent criteria than those receiving less toxic chemotherapy protocols before BCT. Additionally, pretransplant studies will be evaluated to determine the patient's eligibility and any modifications that may be necessary. For example, patients who had prior cranial radiation may require a brain scan to detect possible encephalopathies that would be exacerbated by TBI. Table 1 illustrates common patient eligibility criteria for BCT. In addition to the patient evaluation, family caregivers require special attention and education to prepare them for the responsibilities in managing the patient throughout the transplant trajectory. Stetz et al, 3 identified family caregiver needs so that transplant teams may provide optimal support to them during the transplant experience. Families identified the following four needs: (1) assistance to help select the most qualified transplant center, (2) accurate information about the patient's diagnosis and treatment, (3) strategies to manage patient care in the home, and (4) opportunities for them to obtain support. Thus, educational and supportive programs to assure the family caregiver of knowledge and respite care will allow family members to share in the care of the BCT recipient. Riveria, an oncology nurse and family caregiver of a BCT recipient, shares her personal experience elsewhere in this issue. Nursing responsibilities during the evaluation phase are to coordinate the implementation of procedures, explain their rationale, and monitor test
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NURSING CARE DURING THE PRETRANSPLANT PHASE
Eligibility criteria for BCT will vary depending on the patient's disease and its status, prior treatment, transplant protocol, age, economic resources, and the presence of a committed family member. Patients receiving highly toxic conditionFrom University of Washington, Issaquah, WA; and Coram Healthcare, Denver, CO. Patricia C. Buchsel, RN, MSN: Blood and Marrow Transplant Consultant, Issaquah, WA; Ellen Leum, RN, BSN, OCN®: Coram Healthcare, Denver, CO; Susan Rudder Randolph, RN, MSN, CS: Manager, Transplant Services, Caram Healthcare, Denver, CO. Address reprint requests to Patricia C. Buchsel, RN, MSN, 18503 SE 64th Way, Issaquah, WA 98027. Copyright © 1997 by W.B. Saunders Company 0749-2081/97/1303-000455.00 172
Seminars in OncologyNursing, Vo113, No 3 (August), 1997: pp 172-183
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Table 1. Patient Eligibility Criteria for Blood Cell Transplant Disease and status treatable with BCT Appropriate age, usually not over 65 Third-party coverage or ability to pay for BCT Available family or friend caregiver History and physical examination to determine organ function Performance status Battery of laboratory and radiographic tests Psychosocial evaluation Fertility counseling
results. In this time of high anxiety, nurses can alleviate patient and family stress by answering questions in a timely and patient manner. Once it is determined that a patient will proceed to BCT, informed consent is obtained and a central venous catheter (CVC) is inserted. CVC Placement
Patients presenting for BCT require placement of a CVC for stem cell collection and reinfusion, administration of medications, and drawing blood specimens. A large bore, permanent or temporary double lumen catheter such as the Perm Cath (Quinton Instrument Co, Bothell, WA) is inserted for stem cell collection to accommodate large and fluctuating circulating blood volumes. Adverse events such as perforation of the venous wall, pneumuothorax, and/or hemothorax, although rare, can result during placement. Patients should be monitored closely for signs and symptoms of hypotension, shortness of breath, decreased breath sounds, and/or tracheal shift during the immediate postoperative periods. Those presenting with risks for these complications may require evaluation for catheter placement in the femoral vein. Additionally, discomfort, contamination, and subsequent infection of the catheter insertion site may necessitate catheter removal following completion of apheresis. 4 Once the stem cell collection is completed, some clinicians will replace the apheresis catheter with a temporary small lumen or peripherally inserted central catheter. Nursing care of the patient with a CVC includes monitoring patient compliance in aseptic dressing changes, flushing techniques, and reportable signs and symptoms of infection. Bleeding at the catheter insertion site may occur and be prevented or alleviated through the application of ice packs and or sandbags. In some instances, substantial amounts of heparin (eg, 5,000 U/cc) may be required to
maintain the patency of these large bore catheters. In these cases, heparin must be removed before using the catheter to avoid the coagulopathies consistent with heparin therapy. 4 NURSING MANAGEMENT DURING STEM CELL MOBILIZATION
Mobilization is a method to stimulate production and release of progenitor marrow cells into the peripheral circulation to be collected, or apheresed, and subsequently reinfused. After a sufficient amount of cells are obtained, the cells are mixed with cryopreservatives, possibly purged for tumor cells, and cryopreserved until the time for reinfusion. In the case of allogeneic BCT, stem cells may be collected, processed, and immediately infused into the patient. 5,6 Mobilization is achieved with the administration of chemotherapy and recombinant growth factors either alone or in combination therapy. 7 The current belief is that a combination of these agents provide an optimal stem cell yield with the potential to assure durable engraftment and disease-free survival. Chemotherapy offers the additional benefit of decreasing tumor burden but immunosuppression, mucositis, hemorrhagic cystitis, and other doserelated complications can occur. Depending on the dose and duration of therapy, prophylactic antimicrobial agents such as ciprofloxacin (Cipro; Miles Elkhart, IN) and fluconazole (Diflucan; Roerig, New York, NY) may be ordered. 8 Nursing management of the patient receiving chemotherapy for mobilization focuses on patient preparation, assessment, and management of side effects from various agents. 9 Chemotherapy-related complications depend on the agent, dose, duration of administration and are similar to those manifested during and immediately after standard-dose conditioning therapy. Patients must be taught neutropenic precautions and signs and symptoms of infection. In the event of febrile episodes, cultures of blood, urine, stool, throat, and CVC exit sites are required. Uroprotectant therapy using mesna (Mesnex; Bristol Myers, Princeton, NJ) bladder irrigation, and forced diuresis are methods used to prevent hemorrhagic cystitis associated with cyclophosphamide and other alkylating agents. 8 Daily weights are required to determine nutritional status and fluid retention. Obtaining and monitoring complete blood counts (CBCs), serum electrolytes, and creatinine levels are necessary. Table 2
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Table 2. Complications of Stem Cell Mobilization and Harvest and High-Dose Conditioning Therapy Complications
Central Venous Catheter Exit site infection
Tunnel infection
Line infections
Catheter occlusion
Catheter-related venous thrombus
Catheter rupture
Phlebitis
Infection
Skin toxicity
Hemorrhagic cystis
Thrombocytopenia Most frequent sites of bleeding: mucous membranes, skin, GI, respiratory & GU systems, intracranial
Time of Onset
Duration of catheter placement
Symptoms
Cause
Clinical Management
Fever, skin breakdown, local erythema, pain, tenderness at catheter insertion site, possible purulent drainage, sepsis
Neutropenia secVancomycin 1 g IV every 2 h ondary to highor vancomycin 15 mg/kg dose conditioning IV every 12 h for gram+ regimens, poor organisms, ceftriazone catheter managesodium 1-2 g IV every 24 h merit techniques, commonly gram positive organisms As above Erythema, induration, As above Vancomycin 15 mg/kg every tenderness along 12 h for gram+ organisms, subcutaneous track ceftriazone sodium 1-2 g IV of catheter, posevery 24 h, possible cathesible purulent exuter removal date As above Cellulitis As above As above Colonization of infecting organism, ie, Staphylococcus epidermis, Staphy/ococcus aureus Asabove, particularly Ioability to aspirate G-CSF, G M - C S F Venogram, doppler study, during apheresis from, or flush cath- Thrombus, technical dye study, chest x-ray. procedure eter, arm swelling, or mechanical Urokinase 5,000 IU/mL (urokipain may be problems, blood nase not effective on drug asymptomatic clotting, drug preprecipitate) cipitate
Duration of catheter Arm swelling, pain placement, particumay be asymptomlarly during mobiliatic. Venous conzation and stem cell gestion in neck on collection side of catheter As above Pain, shortness of breath, air & blood emboli, leakage from catheter, inability to aspirate catheter 0-7 days after loserInflamed area in tion proximal upper extremity Chemotherapy inFever, shaking, chills, duced mobilization, hypotension high-dose conditioning regimens Mobilization, highIndurated skin, rash dose conditioning regimens Mobilization, highHematuria, blood dose eyclophosclots phamide
Venous collateral circulation
Venogram, doppler study, dye study, chest x-ray. Urokinase 5,000 iU/mL
Frequent catheter manipulation, forceful flushing against resistance
Replace catheter
Peripherally inserted central catheters
Heparin therapy
Chemotherapy, S aureus
Prophylactic antimicrobials
GM-CSF,G-CSF
Topical cortisones
Exposure of bladder lining to cyclophosphamide metabolites, adenovirus Chemotherapy inShortness of breath, Loss of platelets duced mobilization, headache, blurred during stem cell apheresis, highvision collection. dose conditioning Petechiae, ecchymoToxic effects of regimens sis, frank bleeding chemotherapy or oozing from any induced mobilizaorifice, or injection tion. site
Mesna, aggressive hydration, bladder irrigation may be necessary
Nursing Management
Blood and exit site cultures, administration of antibiotics if indTcated. Teach aseptic technique in dressing changes and catheter flushing, signs and symptoms of infection, and emergency instructions Blood cultures, culture exudate if present, administer appropriate antibiotics
As above
Gentle catheter flushing with heparin, reposition patient, possible catheter removal. Instill urokinase 5,000 IU/mL into lumen of catheter and let stand for 5 min Attempt to aspirate every 5 rain x 30 rain Wait 30-60 rain & attempt to aspirate again Reposition patient, gentle catheter flushing, possible catheter removal, monitor daily prothrombin time/ partial prothrombin time Turn patient on left side & call MD, clean and secure catheter, repair or exchange if possible, possible catheter removal Apply warm compresses to affected area; may necessitate catheter removal Teach neutropenic precautions, monitor prophylactic medications; acyclovir, ciprofloxacin, fluconazole Assess injection site daily
Strict I & O, administer meson and iV fluids
Monitor platelet count before Hematest urine, stool for apheresis occult blood, avoid invaVital signs before and during sive procedures, disconapheresis tinue drugs that interfere Platelet and/or red blood cell with platelets, institute transfusion bleeding precautions, Administer anovulatory maintain integrity of the therapy for menstruating skin and mucous memfemales. (Begin 1 week branes before starting chemoAvoid increased intracranial therapy, continue until pressure, administer blood recovery of platelets) products as indicated
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Table 2. Complications of Stem Cell Mobilization and Harvest and High-Dose Conditioning Therapy (Cont'd) Complications
33me of Onset
Citrate toxicity
Apheresis
Flu-like syndrome
Mobilization
Mucositis
Nausea, vomiting
VOD
Symptoms Perioral tingling, numbnessRingling in hands and feet, paresthesias, and muscle and/or abdominal cramps
Cause
Clinical Management
Mixing of blood and Calcium gluconate 1 g IV anticoagulant every 1 h as needed (ACD) in apheresis throughout duration of machine resulting procedure in hypocalcemis (free-floating calcium in the blood binds to citrate molecule) CSFs Acetaminophen 500 mg G-CSF orally every 4 h GM-CSF
Nursing Management Administer calcium gluconate, Turns (SmithKline Beecham, Philadelphia, PA) at least 6/d for 3-4 days before apheresis. Continue Turns throughout the apheresis procedure as needed, monitor vital signs
Administer analgesics, reassure patient that symptoms will resolve after medication is stopped Opioids, topical anesthetics, Frequent mouth care with Mobilization, highinfection prophylactic meause of toothbrush/floss/ dose conditioning toothette, bland rinses sures regimens Nystatin with 0.9 saline or saline/ Bleeding (GI) prophylaxis: sodium bicarbonate. carafate Mucosal coating agents, antacids, sodium alginate, cellulose film, ice bag applications. Assess mouth for signs and symptoms of herpes simplex and candidiasis. Teach patient to avoid irritants such as alcohol and tobacco, monitor nutritional status, avoid mouthwash containing alcohol Onda nsetron/decadron, Cold, small, bland, frequent Chemotherapy inMyriad of symptoms Conditioning regimens: bulsulfan, granisetron hydrochloride, liquid meals, decrease duced mobilization, resulting from a Iorazepam, diphenhydraexternal stimuli, hard high-dose condicomplex neuromelphalan, mints, sour candy. Sour tioning regimens physiologic phethiopeta. Constimine hydrochloride, stool pation/GI obstrucsoftner, milk of magnesia foods are sometimes tolernomenon ated. Administer medication, infection, for constipation with medications, ondansetron tion as ordered anxiety High-dose condition- Ascites, weight gain, High-dose condiSupportive care, diuretics Weigh patient 2x day, measure abdominal girth ing regimens confusion, jaundice tioning Fever, chills, arthralgins, myalgias, chills, headache, malaise Pain, facial and throat Cyclophosphamide swelling, airway Bulsulfan occlusion, anorexia, difficulty swallowing & talking, divided mucosal lining
Abbreviations: IV, intravenous; GI, gastrointestinal; GU, genital-urinary.
lists common complications and nursing interventions. Colony-stimulating factors (CSFs) are administered subcutaneously because of ease in administration and decreased costs as compared to intravenous administration. 10 Both patients and caregivers require instruction on the reconstitution, administration, storage, and disposal of these drugs. Additionally, patients and caregivers benefit from medication diaries to record their doses and sites of injection. 11 Patients receiving CSFs report bone pain, headaches, fevers, nausea, diarrhea, cough, nasal congestion and malaise, but are usually able to tolerate these side effects.a° Allergic reactions such as rash, erythema, dry skin, dyspnea, or hypotension are rare, but may occur. Monitoring blood counts and CD34+ cell assays are necessary to
determine the effects of CSFs on stem cell production. NURSING MANAGEMENT DURING APHERESIS
Stem cells are collected, or harvested, on an outpatient basis via an apheresis process through the patient's central venous access device using blood cell separators programmed to collect either lymphocytes or low-density leukocytes. Figure 1 illustrates a patient having a stem cell collection. The apheresis process takes approximately 2 to 4 hours and requires between 3 to 8 collections over a period of 3 to 5 days to obtain sufficient progenitor cells. 9 The collections are monitored by the total cumulative number of collected nucleated cells, colony-forming units-granulocyte macrophage or CD34+ cells. It is suggested that the minimal
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Fig 1. Stem cell harvest for blood cell transplantation. (Courtesy of Salick Health Care, Westlake Village, CA).
number of cells needed for successful engraftment is 2 to 5 × 106 mononuclear or 2 × 106 CD34+ cells per kg of recipient body weight, la
Complications Morbidity associated with stem cell apheresis is minimal. Complications are usually the result of problems with the CVC, citrate toxicities, and thrombocytopenia. Catheter occlusions are common and usually caused from a thrombus, kinked or malpositioned catheter secondary to the fluctuating flow rates of the apheresis machine, and the use of recombinant growth factors. 4 Goldberg et a113 reported that at least 60% of patients experienced at least one episode of CVC occlusion in a total of 412 collections. Stephens et all4 cite occlusion rates in a similar population to be 69%. Occlusions were cleared with mechanical clot aspiration and did not require thrombolytic agents. Nursing interventions to alleviate decreased blood flow include repositioning the patient, flushing the catheter with mild force or instilling urokinase to dissolve the clot. A venogram may be indicated to identify catheter obstruction. Citrate toxicities can arise as a result of the anticoagulant citrate dextrose (ACD) used to prevent the patient's blood from clotting during apheresis. Clinical manifestations include circumoral numbness or tingling and cramping in the hands and legs, paresthesias, and muscle and/or abdominal cramps. Administration of calcium
supplements by mouth or intravenous calcium gluconate may be necessary to manage persistent hypocalcemia. Hypovolemia caused by alterations in extracorporeal volume can result in lightheadedness, vertigo, tachycardia, hypotension, and dysrhythmias. These side effects can be minimized by reducing flow rates or administering blood products.4 Table 2 illustrates nursing management of the patient throughout stem cell collection. Thrombocytopenia has been noted as a complication of stem cell apheresis. 15 However, this phenomena is dependent on the type of cell separator used during apheresis. If apheresis is performed with a stem cell separator in which the patient's blood adheres to the surface of the bowl in the apheresis machine, a prophylactic platelet transfusion may be given before the apheresis procedure. Once the stem cells are collected, they are removed from the blood cell separator, isolated using a density gradient or other apheresis procedure to reduce contaminating red and white cells and other cellular debris inadvertently collected. To assure cell viability, the cells are mixed with cryoperservatives until time of reinfusion. Manipulation of cells for tumor reduction may be accomplished through purging techniques: pharmacologic (eg, mafosfamide), immunologic (eg, monoclonal antibodies) or physical methods (eg, density separation).16 The cells and their cryopreservatives, often referred to as the cell product, are
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taken to the cryopreservation laboratory and placed in liquid nitrogen (see Fig 2). NURSING MANAGEMENT DURING CONDITIONING REGIMEN
The doses of chemotherapeutic agents used alone or in combination with radiation therapy are substantially higher than conventional therapy and vary according to the underlying disease or the clinical trial. Table 3 lists common chemotherapeutic agents used in BCT, dosing, and dose-limiting toxicities. Most protocols involve 3 to 7 days of conditioning. The conditioning regimen can take place in the inpatient and outpatient ambulatory care settings, with supportive care provided in the hospital, local housing facilities, or in the home. Decisions regarding the location of therapy are based on availability of supportive care and types of conditioning regimens. 4 For example, one of the earliest studies assessing the feasibility of outpa-
Table 3. Common Dose-Intensive Conditioning Regimens and Dose-Limiting Toxicities Chemotherapy Agent BCNU Bulsulfan Carboplatin Cyclophosphamide Etoposide Melphalan Thiotepa TBI
Preparative Regimen Dose
Dose-LimitingToxicity
600 mg/m 2 16 mg/kg 200 mg/m 2 6 g/m 2 2,400 mg/m 2
Hepatic, pulmonary Hepatic, pulmonary Hepatic Cardiac, genitourinary Gastrointestinal, genitourinary 100-200 mg/m 2 Gastrointestinal, pulmonary 500 mg/m = Gastrointestinal, pulmonary 300-1,575 cGy Pulmonary
tient transplantation, selected patients receiving the conditioning regimen of cyclophosphamide/cisplatin/carmustine because of the minimal amount of mucositis associated with these agents as compared to regimens containing TBI, or highdose melphalan or thiotepa. The investigators showed that the regimen was well-tolerated, allowing 95% of eligible patients to be discharged soon after chemotherapy and followed by outpatient care. Of those patients, 70% required either no hospitalization or brief readmission of 1 to 4 days. 17 Bulsulfan is frequently administered in BCT conditioning regimens. Because the medication is taken orally, it is attractive for outpatient administration. Major disadvantages are the administration of a large number of pills and its highly emetic and seizure producing properties. Patients require detailed instruction and preparation to manage the protocol as an outpatient. Patients are taught to record the dose and time pills are taken and any resulting emesis. The emesis must be examined for pills and if any are vomited they must be replaced one for one. 18 Toxicities associated with TBI, eg, nausea, vomiting, dehydration, and mucositis, require antiemetic medications, intravenous hydration, and vigilant monitoring. 19 Several investigators have reported safe and cost-effective administration of TBI in the outpatient setting. 2°,21
Complications
Fig 2. Stem cell cryopreservation. (Courtesy of Salick Health Care, Westlake Village, CA).
The onset of complications from dose-intensive therapy are dependent on the type, dose, and duration of the agents used in the conditioning regimens. Most complications are related to pancytopenia and are similar to those encountered
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during the mobilization phase and preengraftment. The reader is referred to the discussion of complications related to engraftment and to Table 2 for a review of the complications and their management. Nursing interventions include astute physical assessment of the patient, frequent monitoring of vital signs, monitoring of laboratory tests, maintenance of fluid and electrolyte balance, daily weights, symptom management, and patient and family caregiver support. NURSING MANAGEMENT DURING STEM CELL TRANSPLANTATION/REINFUSION
BCT or stem cell reinfusion occurs several days after high-dose therapy. The cryopreserved stem cells are transported to the patient's room in dry ice, and thawed one at a time in a 37°C to 40°C water bath to prevent cell damage caused by premature thawing and to ensure a continuous infusion of cells. Some protocols require that the thawed stem cells be washed to remove dimethyl sulfoxide (DMSO) and cell lysis products before infusion to minimize side effects. Aggressive hydration is initiated before the infusion and for several hours after to prevent nephrotoxicity associated with the large amount of stem cells reinfused. In addition, premedications such as diphenhydramine, corticosteroids, acetaminophen, ondansetron, lorazepam, diuretics, or mannitol may be given before reinfusion. Unirradiated, unfiltered stem cells are infused IV piggyback over 15 to 20 minutes by gravity drip or through a large (60 cc) syringe into the patient's CVC. The infusion is often accompanied by a normal saline infusion to prime the tubing and to clear remaining stem cells from the IV tubing. It is important not to administer medications into the infusion line because of possible hemolytic reaction. Figure 3 shows a nurse drawing stem cells into 60 cc syringe in preparation for administration.
Complications Complications usually occur immediately and resolve in 24 to 48 hours. Common adverse effects include nausea, vomiting, facial flushing, hypertension, hypotension, bradycardia, tachycardia, cardiac arrhythmias, tachypnea, cough, chest tightness, fever, chills, and abdominal cramping. Patients typically report an unusual taste, emit a garlic-like breath, and urine or emesis may have an
Fig 3. Preparation by a nurse to administer stem cells. (Courtesy of Salick Health Care, Westlake Village, CA).
offensive smell, which may be attributed to the sulfur contained in DMSO. For patients with prolonged hypotension, increasing the rate of hydration while decreasing or stopping the stem cell administration may stabilize the patient. Vital signs should be monitored closely every 5 to 10 minutes until the patient is stable. Hypertension may be a delayed effect occurring 2 to 4 hours after infusion. Hemoglobinuria, hematuria, increased bilirubin or serum creatinine may occur immediately following infusion as a result of red cell contamination. However, this is not a serious problem and levels return to normal in a few days. Davis et al22 evaluated 37 adults who received 63 stem cell reinfusions. All patients were premedicared with dexamethasone, ondansetron, and lorazepam. Stem cell reinfusions were well-tolerated and most side effects resolved within 10 minutes after completion. The most frequent side effects during reinfusion were cough (46%), facial flushing (44%), nausea (23%), transient blood pressure changes (15%), hypotension (15%), bradycardia (11%), and chest pressure (12%). Hematuria was
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noted in 68% of patients after reinfusion and was significantly correlated with higher blood volumes. No cumulative adverse effects were noted. 22 Nursing research is important to characterize the scope and incidence of adverse effects during stem cell reinfusion. Nursing care during the reinfusion process combines clinical expertise and pychosocial skills to prevent or minimize complications and to prepare the patient and family for expected side effects that may occur. Nurses should administer prophylactic medications before reinfusion as ordered, monitor vital signs, fluid status, intake and output, provide comfort measures such as cool soaks for facial flushing, and assist in emotional support. Table 4 identifies the complications and interventions related to stem cell reinfusion. PRE-ENGRAFTMENT COMPLICATIONS The etiology of complications after BCT are the result of toxicities related to the preparative regimen and medications, graft failure, relapse, and in the allogeneic recipient, graft versus host disease (GVHD). Other factors that may contribute to the incidence of side effects include: age, performance status, disease, and infectious disease profile. Mucositis, hemorrhage cystitis, and hepatotoxicity are noted with cyclophosphamide, thiotepa, melphalan, and carmustine (BCNU). 23 High-dose treatment protocols consisting of cyclophosphamide (5,625 mg/m 2 total dose), cisplatin (165 mg/m 2 total dose), and BCNU (600 mg/m 2 total dose)
resulted in severe gut toxicity, pneumonitis, and significant neuro-physiological effects.23 Cutaneous toxicity is associated with high-dose carboplatin (1,500 to 2,000 mg/m 2) and ifosfamide (10 rag/m2). 24,25Cutaneous manifestations include pruritic maculopapular rash on the upper and lower extremities that progresses to a confluent rash with facial edema and swelling of the hands and feet. Gordon et a126 recently reported that the use of granulocyte-macrophage colony-stimulating factor was a significant factor in anticoagulant deficiency.
Infection BCT recipients experience profound neutropenia resulting in viral and fungal infections. Infection prophylaxis with antibiotics (eg, ciprofloxan), antiviral medications (eg, acyclovir), and antifungal medications (eg, fluconazole) is common. Other measures to prevent infection include special dietary modifications (low bacterial diet). Despite rigorous infection control measures, many patients require empiric broad spectrum antibiotic treatment for neutropenic fever. 11 Kolb et a127 identified the type and incidence of infection in 66 BCT recipients. Sixty-two of the 66 (94%) patients experienced at least one febrile episode, 53% reported fever of unknown origin, and 39% had bacteremia caused by gram positive staphylococci. Lung filtrates were noted in 5% of recipients and one patient had herpes zoster virus infection. Severe organ infections were rarely observed. No mortalities due to infection were noted.
Table 4. Common Complications of Stem Cell Reinfusion Complication Renal compromise
Fluid overload
DMSO toxicity
Symptoms
Cause
Clinical Management
Hemoglobinuria, hematuria, increased bilirubin and creatinine Cough
Red cell contamination of stem cell product
IV hydration before and after infusion
Draw baseline serum bilirubin and creatinine levels
Large volume of stem cell product
Diuretics
Garlic-like odor, taste, cough, offensive odor to emesis and urine Arrhythmias, chest tightness
Cryopreservative
None
Monitor I & O and vital signs with infusion of each bag of stem cell product Offer citrus fruit, reassure patient that odor and smell will abate in 24-28 h Frequent monitoring of vital signs, administer medications as indicated Premedication with antiemetics
Nausea, vomiting
Facial flushing Allergic reaction, fever, chills
Cardiac monitors
Dexamethasone, ondansetron, Iorazepam
Nursing Management
Lorazepam-closely observe patient for somnolence, apply cool soaks
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Although BCT recipients have a shorter period of thrombocytopenia and anemia as compared to BMT recipients, packed red blood cells and platelet transfusions are required until engraftment stabilizes. Most protocols require that blood products be irradiated with 2,500 cGy to prevent transfusion related GVHD. Some protocols require that leukocyte-reduced or leukocyte filters be used to prevent cytomegalovirus (CMV) infection while others mandate that CMV negative blood products be administered to patients who are CMV seronegative. Clinical trials are underway to assess the efficacy of recombinant growth factor epoefin alpha and human megakaryocyte to stimulate rapid return of erythrocytes and thrombocytes.
Mucositis Mucositis usually begins at the time of stem cell reinfusion, peaks 7 to 14 days later, and resolves with neutrophil recovery. There are no mechanisms to prevent mucositis but supportive care can minimize infection, pain, anorexia, bleeding, and airway obstruction. Of particular concern is herpes simplex infection, which can further compromise the patient. Aggressive oral hygiene is imperative. Common mouth care protocols include combinations of saline and baking soda rinses several times a day and brushing with a soft toothbrush after any food or emesis. Chlorhexidine rinses and clotrimazole or nystatin troches may be appropriate for antifungal management. Topical anesthetics provide some pain relief and promote compliance with mouth care. IV narcotics may be necessary. 28
Skin Toxicities BCT recipients are at risk for alterations in skin integrity from chemotherapy, radiation, medications, or diarrhea, and in the case of aUogeneic BCT, GVHD. Because the skin is the primary barrier against infection, particular attention must be given to recipients during the period of profound neutropenia. Because thiotepa is excreted through perspiration, skin toxicities may be minimized by having the patient shower or bathe several times a day and wear loose clothing to allow perspiration to dry. Bulsulfan can cause painful erythematous macules on the hands, feet, axiUae, and groin. The lesions may progress to bullae formation followed by desquamation. Local treatment with ice packs may relieve discomfort but opioids may be
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required. Silver sulfadiazine may be applied as a topical antibiotic. 29
Veno-occlusive Disease (VOD) VOD, well-documented in BMT, is rarely seen in the BCT recipient. However, this life-threatening disorder is being reported with increasing regularity in BCT. Risk factors are high-dose therapy particularly TBI, cyclophosphamide, bulsulfan, and carmustine, preexisting hepatitis, and infection. It is caused by damage to the endothelial cells in the hepatic sinus as a result of high-dose chemotherapy and radiation. This disorder is characterized by hepatomegaly, jaundice, and fluid retention. There is great variation in severity, it affects several organ systems, requires close attention, and its treatment is diverse and controversial. Markers for severe VOD are onset of jaundice approximately 5 days after BCT, bilirubin >10 mg/dL before day 10 after BCT or >20 mg/dL 20 days after BCT, weight gain >5% within 10 days of BCT, doubling of baseline creatinine, decrease in urine sodium excretion, and abdominal ascites. Encephalopathy can occur due to shunting of blood from the liver and inadequate metabolism of waste products and drugs. Common timings are lethargy, confusion, and disorientation. 3° Death in patients with severe VOD is usually caused by cardiopulmonary and renal compromise and occurs between 30 and 60 days after BCT. Treatments under investigation for VOD include the use of anticoagulants, fibrinolytics, fluid restriction, and intense supportive c a r e . 31 Careful patient selection and identification of appropriate conditioning regimens may be the most effective defense against VOD until an effective prophylaxis or treatment is found. Nursing assessment includes identification of agents used in the patient's conditioning regimen, baseline liver function studies, history, assessing the abdomen twice daily, assessment of the skin, eyes, and urine for evidence of jaundice, twice daily weights, measuring abdominal girth, monitoring postural blood pressure, intake and output, liver function tests, coagulation studies, and the administration of therapies.
Nursing Management Nursing care during the engraftment recovery phase is directed at early detection of multiple complications and prompt intervention. The etiology of symptoms are often confounding and the
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patient's condition can change rapidly. Nurses must be skilled in assessing and managing toxic effects and provide psychosocial support. The engraftment phase of transplant is an intense time for the patient and family. Until techniques are significantly improved, professional health care teams need to support recipients with the use of prophylactic measures and astute patient assessment. 3°
Relapse Relapse is a significant problem after BCT and may be attributed to the reinfusion of malignant cells contained in the stem cell product or residual cancer cells not eradicated by the preconditioning regimen. 32 A number of investigational approaches are being employed to diminish recurrent disease. Posttransplant immunotherapy using active immunization is one approach that might eliminate any remaining tumor cells. Other options for treatment of recurrent disease after BCT include salvage chemotherapy, second transplants, withdrawal of immunosuppressive medications (in allogeneic BCT), cytokine therapy, donor leukocyte infusions, and monoclonal antibody therapy. 32,33 DISCHARGE CRITERIA
Discharge criteria for the BCT recipient, either from the hospital or to return to their referring physician, is highly variable and dependent on the condition of the recipient, 24-hour availability of the transplant team, the geographic proximity to the transplant facility, the availability of transportation to outpatient and emergency facilities, and the availability of a competent caregiver. Typically patients must be free of overwhelming clinical problems, be afebrile, and have a strong family caregiver to manage their c a r e . 4 LONG-TERM COMPLICATIONS The identification of long-term effects of BCT will be forthcoming as more BCT recipients become long-term survivors. Prolonged abnormalities in humoral and cell mediated immunity have been reported after BCT, and secondary complications such as varicella zoster infection, CMV infection, and others are not uncommon. Delayed engraftment and graft failure have also been documented. 13Although it is tempting to superimpose the long-term complications of BMT to BCT, one must carefully review the BMT literature to identify those complications related to TBI before
assigning these problems to BCT recipients who receive only chemotherapy. For example, in describing growth and development problems in pediatric BMT recipients, Sanders 34 found that complications were dependent on the child's age at time of transplant, prior cranial irradiation, and type, dose and duration of high-dose therapy. Children who received cyclophosphamide only in conditioning regimens had normal growth rates whereas children receiving TBI showed decreased growth rates. Cataract formation after BMT is caused by TBI or steroids to decrease the impact of GVHD. 35 Consequently, it is not likely that cataracts will be a notable complication in patients receiving chemotherapy only in conditioning regimens. Care and management of the BCT recipient does not end with successful engraftment and resolution of all complications. The outcome of transplantation is not always successful, and for patients with disease recurrence, palliative care, and bereavement support for families becomes an important focus. For patients who survive transplantation, there are numerous physical, psychological, quality of life, family caregiver burden, and economic issues to address. The BCT patient should be routinely monitored for potential late complications, relapse, and graft failure. ALLOGENEIC BCT
More than 250 allogeneic BCTs have been documented and this number is growing rapidly. The process, and patient and donor eligibility for allogeneic BCT are similar to allogeneic BMT. If the donor has adequate venous access, stem cells are collected through bilateral large bore catheters inserted in the antecubital fossas. Long-term, indwelling catheters are avoided to prevent risks of infection, pneumothorax, and the inconvenience of a catheter. The amount of stern cells collected are based on the recipient's size. If an ABO incompatibility exists between the patient and donor, the cells are processed to accommodate ABO incompatibility. Allogeneic BCT recipients receive prophylaxis and treatment for GVHD with cyclosporine and corticosteroids. Initial data report the incidence and severity of acute GHVD after allogeneic BCT not to be significantly different from that after marrow transplant. In a small cohort of 73 patients receiving HLA identical BCT and GVHD prophy-
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laxis, 56% of 23 evaluable patients developed some form of chronic GVHD. 36 Manifestations of chronic GVHD in allogeneic BCT recipients are being studied closely. Initial fears that chronic GVHD would present with even greater morbidity and mortality than in B M T recipients was based on the knowledge that peripheral blood contains approximately 20 times the number of T cells compared to marrow. Because donor T cells cause GVHD, it is postulated that chronic GVHD would be a major limitation to successful BCT. Early research is encouraging, but conflicting. Milfin et al, 37 reported that of 44 allogeneic BCTs, chronic GVHD occurred in 17 out of the 37 evaluable patients, but more long-term follow-up is needed. Another study of 21 patients reported that more than half presented with liver and skin chronic GVHD. 38 Donor safety is a major concern during cytokine mobilization.39 Transplant teams must assess the risks of subjecting healthy donors to the complications of cytokine therapy, the expense and compli-
cations of surgical catheter placement, and possible u n k n o w n late complications of therapy. Current studies do not confirm long-term effects of growth factors in healthy donors, but more research is needed in this area. 4° CONCLUSION
Although it is believed that BCT is less expensive, less toxic, and as beneficial as BMT, research is needed to document these potential advantages and predictions that BCT will replace B M T within the next 5 years. Currently, several randomized clinical trials are comparing BCT with BMT. Only the results of long-term trials will determine the optimal treatment based on decreased morbidity, mortality, disease-free survival, quality of life, and cost of care. Oncology nurses working with transplant recipients will need to keep abreast of changing technology as more patients receive hematologic transplants from new cell sources such as blood and umbilical cord.
REFERENCES 1. GratwohlA, SchmitzN: First internationalsymposiumon allogeneic peripheral blood precursor cell transplants. Bone Marrow Transplant17:S1-$3, 1996 (suppl 1) 2. www.hhpt:CBRstore@aolCordBloodRegistry 3. Stetz M, McDonald JC, Comptom K: Needs and experience of family caregiver during marrow transplantation. OncolNurs Forum 23:1422-1427, 1996 4. BuchselPC, KapostayPM: Peripheral stem cell transplantation, in HubbardSM, GoodmanM, KnobtTK (eds): Oncology Nursing Update: Patient Treatmentand Support. Philadelphia, PA, Lippincott, 1995,pp 1-14 5. GorinNC: Cryopreservationand storage of stem cells, in Areman EM, Deeg HJ (eds): Bone Marrow and Stern Cell Processing:A Manualof CurrentTechniques.Philadelphia,PA, Davis, 1992pp 171-184 6. BensingerW: Peripheral blood stem cell transplantation, in Buchner CD (ed): Technical and Biological Comments of Marrow Transplantation.Boston,MA, KluwerAcademic, 1995, pp 216-254 7. Burns JM, TierneyDK, Long GD, et al: Criticalpathway for administeringhigh-dose chemotherapy followedby peripheral blood stem cell rescue in the outpatientsetting. OncolNurs Forum 22:1219-1224, 1995 8. KhimppTR: Complicationsof peripheral blood stem cell transplantation.SeminOnco122:263-270,1995 9. KingC: Peripheral sterncell transplantation:Past, present, and future, in Buchsel PC, Whedon MB (eds): Bone Marrow Transplantation:Administrativeand ClinicalStrategies. Boston, MA, Jones and Bartlett, 1995, pp 187-211 10. KessingerA, BishopM, AndersonJ, et al: Comparisonof subcutaneous and intravenous administrationof recombinant human granul0cyte macrophage colony stimulating factor for
peripheral blood stem cell mobilization.Hematology 4:81-84, 1995 11. Walker F, Roethke S, Martin G: An overview of the rationale, process, and nursing implicationsof peripheral stem cell transplantation.CancerNurs 17:141-148, 1994 12. Rowe JM, Ciobanu N, Ascensao J: Recommended guidelines for the managementof autologous and allogeneic bone marrow transplantation. A report from the eastern cooperative oncologygroup (ECOG).Ann Intern Med 120:143158, 1994 13. GoldbergSL, ManganKF, KlumppTR, et al: Complications of peripheral blood stem cell (BCT) collections. Blood 82:631, 1993 (abstr, suppl 1) 14. Stephens LC, Haire WD, Schmit-PokornyK: Granulocyte macrophage colony stimulatingfactor: High incidence of apheresis catheter thrombosis during peripheral stem cell collection.Bone MarrowTransplant11:51-54, 1993 15. Hooper PJ, Santas EJ: Peripheral blood stem cell transplantation.OncolNuts Forum20:1215-1221, 1993 16. Shpall EJ, Jones RB: Mobilization and collection of peripheralbloodprogenitorcells for supportof high dose cancer therapy, in Forman S, Blume K, Thomas ED (eds): Bone Marrow Transplantation.Boston, MA, Blackwell Scientific, 1994, pp 913-918 17. Peters WP, Ross M, Vredenburg JJ, et aI: The use of intensive clinic support to permit outpatient autologous bone marrow transplantationfor breast cancer. Semin Oncol 21:2531, 1994 (suppl7) 18. Phillips GL: Conditioning regimens, in Deeg HJ, KlingemannHG, Phillips GL (eds): A Guide to Bone Marrow Transplantation(ed 2). Berlin,Germany,Springer-Verlag,1992, pp 67-88
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19. Buchsel PC, Kelleher J: Bone marrow transplantation. Nurs Clin North Am 24:907-938, 1989 20. Algara M, Valls A, Vivancos P, et al: Outpatient total body irradiation for bone marrow transplantation. Bone Marrow Transplant 14:381-382, 1994 21. Dager R, Robertson KA, Lucas KG, et al: Outpatient total body irradiation for pediatric patients undergoing stem cell transplant. Blood 88:413a, 1996 (abstr, suppl 1) 22. Davis ME, Klemm I, Wiest D: Side effect associated with peripheral blood stem cell PBSC reinfusion. Proceedings Bone Marrow Transplant Conference, Dallas, TX, March 1997 23. Williams SF, Meyers SE: The University of Chicago experience with high-dose chemotherapy intensification and autologous stem cell rescue. Bone Marrow Transplant 10:38, 1992 (abstr) 24. Pittman KB, To KB, Bayly JL, et al: Cutaneous toxicity of high dose carboplatin, etoposide, and ifosfamide followed by autologous stem cell infusion. Bone Marrow Transplant 10:535-540, 1992 25. Beyer J, Grabbe K, Lenz V, et al: Cutaneous toxicity of high dose carboplatin, etoposide, and ifosfamide followed by autologous stem cell infusion. Bone Marrow Transplant 10:491-494, 1992 26. Gordon B, Haire W, Ruby E, et al: Factors predicting morbidity following hematopoietic stem cell transplantation. Bone Marrow Transplant 19:497-501, 1997 27. Kolb HJ: For the European group for blood and marrow transplantation working party for chronic leukemia. Blood 86:2041-2050, 1994 28. Lloid M: Oral medicine concerns of the BMT patient, in Buchsel PC, Whedon MB (eds): Bone Marrow Transplantation: Administrative and Clinical Strategies. Boston, MA, Jones and Bartlett, 1995, pp 257-276 29. Tenenbaum L, Leshin D: Alterations in the integumentary system, in Tenenbaum L (ed): Cancer Chemotherapy and Biotherapy: A Reference Guide (ed 2). Philadelphia, PA, Saunders, 1994, pp 287-302
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30. Ballard B: Renal and hepatic complications, in Whedon MB (ed): Bone Marrow Transplantation: Nursing Principles, Practices and Insights. Boston, MA, Jones and Bartlett, 1991, pp 240-261 31. McDonald GV: Venoocclusive disease of the liver following marrow transplantation, in Sullivan KM, Koppa S (eds): Marrow Transplant Review. Charlottesville, VA, Kluge Carden Jennings, 1994, pp 169-134 32. Lilleby K: Breast and ovarian cancer vaccine study: New hope for patients posttransplant. Puget Sound Oncol Nurs Soc 19:8-9, 1996 33. Arcse W, Iori AE Nucci G, et al: What does one do for the CML patient in relapse after allogeneic bone marrow transplantation? Leuk Lymphoma 12:231-219, 1993 34. Sanders J: Growth and development after bone marrow transplantation, in Forman S, Bhime K, Thomas ED (eds): Bone Marrow Transplantation. Boston, MA, Blackwell Scientific, 1994, pp 527-537 35. Deeg H: Delayed complications after bone marrow transplantation, in Forman S, Blume K, Thomas ED (eds): Bone Marrow Transplantation. Boston, MA, Blackwell Scientific, 1994, pp 376-403 36. Bensinger WI, Longin K, Applebanm E et al: Transplantation of allogeneic peripheral blood progenitor cells mobilized by human granulocyte colony-stimulating factor. Blood 85:16551658, 1995 37. Milfin G, Russell Nit, Hutchinson R, et al: Allogeneic peripheral blood stern cell transplantation for hematological malignancies--an analysis of kinetics of engraftment and GVHD risk. Bone Marrow Transplant 19:9-13, 1996 38. Urbam-Ispizua, Garcia-Conde J, Brunet F, et al: High incidence of chronic graft versus host disease (GVHD) after allogeneic peripheral blood progenitor cell transplantation. (PBPCT 1996 Abstr 2455) Blood 88:617a, 1996 (abstr, suppl 1) 39. Korbling M, Champlin R: Peripheral blood progenitor cell transplantation: A replacement for marrow auto- or allo-grafts. Stem Cells 14:185-195, 1996
fusion, and engraftment are being documented with increasing accuracy. Implications for nursing practice: Oncology nurses will be caring for an increasing population of patients undergoing BCT. Although complications of both bone marrow transplantation and BCT are similar there are unique differences. Support and nursing interventions are of utmost importance for BCT patients and their family caregivers. Copyright © 1997 by W.B. Saunders Company
UTOLOGOUS blood cell transplantation (BCT) is increasingly replacing autologous bone marrow transplantation (BMT) as a treatment for numerous oncologic and hematologic diseases. Additionally, more than 250 allogeneic BCTs and more than 300 umbilical cord blood transplants have been documented. 1,2 The major difference between autologous BMT and BCT is stem cells from the marrow are used for BMT whereas BCT uses circulating stem cells collected from peripheral blood. Although complications of both BMT and BCT are similar, each has unique differences. The principles and concepts of BCT, which are similar to those of BMT, are reviewed by Kapustay elsewhere in this issue. The purpose of this article is to review the nursing care and complications as they relate to the BCT process.
ing regimens such as combination treatment with bulsulfan, and total body irradiation (TBI) may need to meet more stringent criteria than those receiving less toxic chemotherapy protocols before BCT. Additionally, pretransplant studies will be evaluated to determine the patient's eligibility and any modifications that may be necessary. For example, patients who had prior cranial radiation may require a brain scan to detect possible encephalopathies that would be exacerbated by TBI. Table 1 illustrates common patient eligibility criteria for BCT. In addition to the patient evaluation, family caregivers require special attention and education to prepare them for the responsibilities in managing the patient throughout the transplant trajectory. Stetz et al, 3 identified family caregiver needs so that transplant teams may provide optimal support to them during the transplant experience. Families identified the following four needs: (1) assistance to help select the most qualified transplant center, (2) accurate information about the patient's diagnosis and treatment, (3) strategies to manage patient care in the home, and (4) opportunities for them to obtain support. Thus, educational and supportive programs to assure the family caregiver of knowledge and respite care will allow family members to share in the care of the BCT recipient. Riveria, an oncology nurse and family caregiver of a BCT recipient, shares her personal experience elsewhere in this issue. Nursing responsibilities during the evaluation phase are to coordinate the implementation of procedures, explain their rationale, and monitor test
A
NURSING CARE DURING THE PRETRANSPLANT PHASE
Eligibility criteria for BCT will vary depending on the patient's disease and its status, prior treatment, transplant protocol, age, economic resources, and the presence of a committed family member. Patients receiving highly toxic conditionFrom University of Washington, Issaquah, WA; and Coram Healthcare, Denver, CO. Patricia C. Buchsel, RN, MSN: Blood and Marrow Transplant Consultant, Issaquah, WA; Ellen Leum, RN, BSN, OCN®: Coram Healthcare, Denver, CO; Susan Rudder Randolph, RN, MSN, CS: Manager, Transplant Services, Caram Healthcare, Denver, CO. Address reprint requests to Patricia C. Buchsel, RN, MSN, 18503 SE 64th Way, Issaquah, WA 98027. Copyright © 1997 by W.B. Saunders Company 0749-2081/97/1303-000455.00 172
Seminars in OncologyNursing, Vo113, No 3 (August), 1997: pp 172-183
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Table 1. Patient Eligibility Criteria for Blood Cell Transplant Disease and status treatable with BCT Appropriate age, usually not over 65 Third-party coverage or ability to pay for BCT Available family or friend caregiver History and physical examination to determine organ function Performance status Battery of laboratory and radiographic tests Psychosocial evaluation Fertility counseling
results. In this time of high anxiety, nurses can alleviate patient and family stress by answering questions in a timely and patient manner. Once it is determined that a patient will proceed to BCT, informed consent is obtained and a central venous catheter (CVC) is inserted. CVC Placement
Patients presenting for BCT require placement of a CVC for stem cell collection and reinfusion, administration of medications, and drawing blood specimens. A large bore, permanent or temporary double lumen catheter such as the Perm Cath (Quinton Instrument Co, Bothell, WA) is inserted for stem cell collection to accommodate large and fluctuating circulating blood volumes. Adverse events such as perforation of the venous wall, pneumuothorax, and/or hemothorax, although rare, can result during placement. Patients should be monitored closely for signs and symptoms of hypotension, shortness of breath, decreased breath sounds, and/or tracheal shift during the immediate postoperative periods. Those presenting with risks for these complications may require evaluation for catheter placement in the femoral vein. Additionally, discomfort, contamination, and subsequent infection of the catheter insertion site may necessitate catheter removal following completion of apheresis. 4 Once the stem cell collection is completed, some clinicians will replace the apheresis catheter with a temporary small lumen or peripherally inserted central catheter. Nursing care of the patient with a CVC includes monitoring patient compliance in aseptic dressing changes, flushing techniques, and reportable signs and symptoms of infection. Bleeding at the catheter insertion site may occur and be prevented or alleviated through the application of ice packs and or sandbags. In some instances, substantial amounts of heparin (eg, 5,000 U/cc) may be required to
maintain the patency of these large bore catheters. In these cases, heparin must be removed before using the catheter to avoid the coagulopathies consistent with heparin therapy. 4 NURSING MANAGEMENT DURING STEM CELL MOBILIZATION
Mobilization is a method to stimulate production and release of progenitor marrow cells into the peripheral circulation to be collected, or apheresed, and subsequently reinfused. After a sufficient amount of cells are obtained, the cells are mixed with cryopreservatives, possibly purged for tumor cells, and cryopreserved until the time for reinfusion. In the case of allogeneic BCT, stem cells may be collected, processed, and immediately infused into the patient. 5,6 Mobilization is achieved with the administration of chemotherapy and recombinant growth factors either alone or in combination therapy. 7 The current belief is that a combination of these agents provide an optimal stem cell yield with the potential to assure durable engraftment and disease-free survival. Chemotherapy offers the additional benefit of decreasing tumor burden but immunosuppression, mucositis, hemorrhagic cystitis, and other doserelated complications can occur. Depending on the dose and duration of therapy, prophylactic antimicrobial agents such as ciprofloxacin (Cipro; Miles Elkhart, IN) and fluconazole (Diflucan; Roerig, New York, NY) may be ordered. 8 Nursing management of the patient receiving chemotherapy for mobilization focuses on patient preparation, assessment, and management of side effects from various agents. 9 Chemotherapy-related complications depend on the agent, dose, duration of administration and are similar to those manifested during and immediately after standard-dose conditioning therapy. Patients must be taught neutropenic precautions and signs and symptoms of infection. In the event of febrile episodes, cultures of blood, urine, stool, throat, and CVC exit sites are required. Uroprotectant therapy using mesna (Mesnex; Bristol Myers, Princeton, NJ) bladder irrigation, and forced diuresis are methods used to prevent hemorrhagic cystitis associated with cyclophosphamide and other alkylating agents. 8 Daily weights are required to determine nutritional status and fluid retention. Obtaining and monitoring complete blood counts (CBCs), serum electrolytes, and creatinine levels are necessary. Table 2
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Table 2. Complications of Stem Cell Mobilization and Harvest and High-Dose Conditioning Therapy Complications
Central Venous Catheter Exit site infection
Tunnel infection
Line infections
Catheter occlusion
Catheter-related venous thrombus
Catheter rupture
Phlebitis
Infection
Skin toxicity
Hemorrhagic cystis
Thrombocytopenia Most frequent sites of bleeding: mucous membranes, skin, GI, respiratory & GU systems, intracranial
Time of Onset
Duration of catheter placement
Symptoms
Cause
Clinical Management
Fever, skin breakdown, local erythema, pain, tenderness at catheter insertion site, possible purulent drainage, sepsis
Neutropenia secVancomycin 1 g IV every 2 h ondary to highor vancomycin 15 mg/kg dose conditioning IV every 12 h for gram+ regimens, poor organisms, ceftriazone catheter managesodium 1-2 g IV every 24 h merit techniques, commonly gram positive organisms As above Erythema, induration, As above Vancomycin 15 mg/kg every tenderness along 12 h for gram+ organisms, subcutaneous track ceftriazone sodium 1-2 g IV of catheter, posevery 24 h, possible cathesible purulent exuter removal date As above Cellulitis As above As above Colonization of infecting organism, ie, Staphylococcus epidermis, Staphy/ococcus aureus Asabove, particularly Ioability to aspirate G-CSF, G M - C S F Venogram, doppler study, during apheresis from, or flush cath- Thrombus, technical dye study, chest x-ray. procedure eter, arm swelling, or mechanical Urokinase 5,000 IU/mL (urokipain may be problems, blood nase not effective on drug asymptomatic clotting, drug preprecipitate) cipitate
Duration of catheter Arm swelling, pain placement, particumay be asymptomlarly during mobiliatic. Venous conzation and stem cell gestion in neck on collection side of catheter As above Pain, shortness of breath, air & blood emboli, leakage from catheter, inability to aspirate catheter 0-7 days after loserInflamed area in tion proximal upper extremity Chemotherapy inFever, shaking, chills, duced mobilization, hypotension high-dose conditioning regimens Mobilization, highIndurated skin, rash dose conditioning regimens Mobilization, highHematuria, blood dose eyclophosclots phamide
Venous collateral circulation
Venogram, doppler study, dye study, chest x-ray. Urokinase 5,000 iU/mL
Frequent catheter manipulation, forceful flushing against resistance
Replace catheter
Peripherally inserted central catheters
Heparin therapy
Chemotherapy, S aureus
Prophylactic antimicrobials
GM-CSF,G-CSF
Topical cortisones
Exposure of bladder lining to cyclophosphamide metabolites, adenovirus Chemotherapy inShortness of breath, Loss of platelets duced mobilization, headache, blurred during stem cell apheresis, highvision collection. dose conditioning Petechiae, ecchymoToxic effects of regimens sis, frank bleeding chemotherapy or oozing from any induced mobilizaorifice, or injection tion. site
Mesna, aggressive hydration, bladder irrigation may be necessary
Nursing Management
Blood and exit site cultures, administration of antibiotics if indTcated. Teach aseptic technique in dressing changes and catheter flushing, signs and symptoms of infection, and emergency instructions Blood cultures, culture exudate if present, administer appropriate antibiotics
As above
Gentle catheter flushing with heparin, reposition patient, possible catheter removal. Instill urokinase 5,000 IU/mL into lumen of catheter and let stand for 5 min Attempt to aspirate every 5 rain x 30 rain Wait 30-60 rain & attempt to aspirate again Reposition patient, gentle catheter flushing, possible catheter removal, monitor daily prothrombin time/ partial prothrombin time Turn patient on left side & call MD, clean and secure catheter, repair or exchange if possible, possible catheter removal Apply warm compresses to affected area; may necessitate catheter removal Teach neutropenic precautions, monitor prophylactic medications; acyclovir, ciprofloxacin, fluconazole Assess injection site daily
Strict I & O, administer meson and iV fluids
Monitor platelet count before Hematest urine, stool for apheresis occult blood, avoid invaVital signs before and during sive procedures, disconapheresis tinue drugs that interfere Platelet and/or red blood cell with platelets, institute transfusion bleeding precautions, Administer anovulatory maintain integrity of the therapy for menstruating skin and mucous memfemales. (Begin 1 week branes before starting chemoAvoid increased intracranial therapy, continue until pressure, administer blood recovery of platelets) products as indicated
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Table 2. Complications of Stem Cell Mobilization and Harvest and High-Dose Conditioning Therapy (Cont'd) Complications
33me of Onset
Citrate toxicity
Apheresis
Flu-like syndrome
Mobilization
Mucositis
Nausea, vomiting
VOD
Symptoms Perioral tingling, numbnessRingling in hands and feet, paresthesias, and muscle and/or abdominal cramps
Cause
Clinical Management
Mixing of blood and Calcium gluconate 1 g IV anticoagulant every 1 h as needed (ACD) in apheresis throughout duration of machine resulting procedure in hypocalcemis (free-floating calcium in the blood binds to citrate molecule) CSFs Acetaminophen 500 mg G-CSF orally every 4 h GM-CSF
Nursing Management Administer calcium gluconate, Turns (SmithKline Beecham, Philadelphia, PA) at least 6/d for 3-4 days before apheresis. Continue Turns throughout the apheresis procedure as needed, monitor vital signs
Administer analgesics, reassure patient that symptoms will resolve after medication is stopped Opioids, topical anesthetics, Frequent mouth care with Mobilization, highinfection prophylactic meause of toothbrush/floss/ dose conditioning toothette, bland rinses sures regimens Nystatin with 0.9 saline or saline/ Bleeding (GI) prophylaxis: sodium bicarbonate. carafate Mucosal coating agents, antacids, sodium alginate, cellulose film, ice bag applications. Assess mouth for signs and symptoms of herpes simplex and candidiasis. Teach patient to avoid irritants such as alcohol and tobacco, monitor nutritional status, avoid mouthwash containing alcohol Onda nsetron/decadron, Cold, small, bland, frequent Chemotherapy inMyriad of symptoms Conditioning regimens: bulsulfan, granisetron hydrochloride, liquid meals, decrease duced mobilization, resulting from a Iorazepam, diphenhydraexternal stimuli, hard high-dose condicomplex neuromelphalan, mints, sour candy. Sour tioning regimens physiologic phethiopeta. Constimine hydrochloride, stool pation/GI obstrucsoftner, milk of magnesia foods are sometimes tolernomenon ated. Administer medication, infection, for constipation with medications, ondansetron tion as ordered anxiety High-dose condition- Ascites, weight gain, High-dose condiSupportive care, diuretics Weigh patient 2x day, measure abdominal girth ing regimens confusion, jaundice tioning Fever, chills, arthralgins, myalgias, chills, headache, malaise Pain, facial and throat Cyclophosphamide swelling, airway Bulsulfan occlusion, anorexia, difficulty swallowing & talking, divided mucosal lining
Abbreviations: IV, intravenous; GI, gastrointestinal; GU, genital-urinary.
lists common complications and nursing interventions. Colony-stimulating factors (CSFs) are administered subcutaneously because of ease in administration and decreased costs as compared to intravenous administration. 10 Both patients and caregivers require instruction on the reconstitution, administration, storage, and disposal of these drugs. Additionally, patients and caregivers benefit from medication diaries to record their doses and sites of injection. 11 Patients receiving CSFs report bone pain, headaches, fevers, nausea, diarrhea, cough, nasal congestion and malaise, but are usually able to tolerate these side effects.a° Allergic reactions such as rash, erythema, dry skin, dyspnea, or hypotension are rare, but may occur. Monitoring blood counts and CD34+ cell assays are necessary to
determine the effects of CSFs on stem cell production. NURSING MANAGEMENT DURING APHERESIS
Stem cells are collected, or harvested, on an outpatient basis via an apheresis process through the patient's central venous access device using blood cell separators programmed to collect either lymphocytes or low-density leukocytes. Figure 1 illustrates a patient having a stem cell collection. The apheresis process takes approximately 2 to 4 hours and requires between 3 to 8 collections over a period of 3 to 5 days to obtain sufficient progenitor cells. 9 The collections are monitored by the total cumulative number of collected nucleated cells, colony-forming units-granulocyte macrophage or CD34+ cells. It is suggested that the minimal
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Fig 1. Stem cell harvest for blood cell transplantation. (Courtesy of Salick Health Care, Westlake Village, CA).
number of cells needed for successful engraftment is 2 to 5 × 106 mononuclear or 2 × 106 CD34+ cells per kg of recipient body weight, la
Complications Morbidity associated with stem cell apheresis is minimal. Complications are usually the result of problems with the CVC, citrate toxicities, and thrombocytopenia. Catheter occlusions are common and usually caused from a thrombus, kinked or malpositioned catheter secondary to the fluctuating flow rates of the apheresis machine, and the use of recombinant growth factors. 4 Goldberg et a113 reported that at least 60% of patients experienced at least one episode of CVC occlusion in a total of 412 collections. Stephens et all4 cite occlusion rates in a similar population to be 69%. Occlusions were cleared with mechanical clot aspiration and did not require thrombolytic agents. Nursing interventions to alleviate decreased blood flow include repositioning the patient, flushing the catheter with mild force or instilling urokinase to dissolve the clot. A venogram may be indicated to identify catheter obstruction. Citrate toxicities can arise as a result of the anticoagulant citrate dextrose (ACD) used to prevent the patient's blood from clotting during apheresis. Clinical manifestations include circumoral numbness or tingling and cramping in the hands and legs, paresthesias, and muscle and/or abdominal cramps. Administration of calcium
supplements by mouth or intravenous calcium gluconate may be necessary to manage persistent hypocalcemia. Hypovolemia caused by alterations in extracorporeal volume can result in lightheadedness, vertigo, tachycardia, hypotension, and dysrhythmias. These side effects can be minimized by reducing flow rates or administering blood products.4 Table 2 illustrates nursing management of the patient throughout stem cell collection. Thrombocytopenia has been noted as a complication of stem cell apheresis. 15 However, this phenomena is dependent on the type of cell separator used during apheresis. If apheresis is performed with a stem cell separator in which the patient's blood adheres to the surface of the bowl in the apheresis machine, a prophylactic platelet transfusion may be given before the apheresis procedure. Once the stem cells are collected, they are removed from the blood cell separator, isolated using a density gradient or other apheresis procedure to reduce contaminating red and white cells and other cellular debris inadvertently collected. To assure cell viability, the cells are mixed with cryoperservatives until time of reinfusion. Manipulation of cells for tumor reduction may be accomplished through purging techniques: pharmacologic (eg, mafosfamide), immunologic (eg, monoclonal antibodies) or physical methods (eg, density separation).16 The cells and their cryopreservatives, often referred to as the cell product, are
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taken to the cryopreservation laboratory and placed in liquid nitrogen (see Fig 2). NURSING MANAGEMENT DURING CONDITIONING REGIMEN
The doses of chemotherapeutic agents used alone or in combination with radiation therapy are substantially higher than conventional therapy and vary according to the underlying disease or the clinical trial. Table 3 lists common chemotherapeutic agents used in BCT, dosing, and dose-limiting toxicities. Most protocols involve 3 to 7 days of conditioning. The conditioning regimen can take place in the inpatient and outpatient ambulatory care settings, with supportive care provided in the hospital, local housing facilities, or in the home. Decisions regarding the location of therapy are based on availability of supportive care and types of conditioning regimens. 4 For example, one of the earliest studies assessing the feasibility of outpa-
Table 3. Common Dose-Intensive Conditioning Regimens and Dose-Limiting Toxicities Chemotherapy Agent BCNU Bulsulfan Carboplatin Cyclophosphamide Etoposide Melphalan Thiotepa TBI
Preparative Regimen Dose
Dose-LimitingToxicity
600 mg/m 2 16 mg/kg 200 mg/m 2 6 g/m 2 2,400 mg/m 2
Hepatic, pulmonary Hepatic, pulmonary Hepatic Cardiac, genitourinary Gastrointestinal, genitourinary 100-200 mg/m 2 Gastrointestinal, pulmonary 500 mg/m = Gastrointestinal, pulmonary 300-1,575 cGy Pulmonary
tient transplantation, selected patients receiving the conditioning regimen of cyclophosphamide/cisplatin/carmustine because of the minimal amount of mucositis associated with these agents as compared to regimens containing TBI, or highdose melphalan or thiotepa. The investigators showed that the regimen was well-tolerated, allowing 95% of eligible patients to be discharged soon after chemotherapy and followed by outpatient care. Of those patients, 70% required either no hospitalization or brief readmission of 1 to 4 days. 17 Bulsulfan is frequently administered in BCT conditioning regimens. Because the medication is taken orally, it is attractive for outpatient administration. Major disadvantages are the administration of a large number of pills and its highly emetic and seizure producing properties. Patients require detailed instruction and preparation to manage the protocol as an outpatient. Patients are taught to record the dose and time pills are taken and any resulting emesis. The emesis must be examined for pills and if any are vomited they must be replaced one for one. 18 Toxicities associated with TBI, eg, nausea, vomiting, dehydration, and mucositis, require antiemetic medications, intravenous hydration, and vigilant monitoring. 19 Several investigators have reported safe and cost-effective administration of TBI in the outpatient setting. 2°,21
Complications
Fig 2. Stem cell cryopreservation. (Courtesy of Salick Health Care, Westlake Village, CA).
The onset of complications from dose-intensive therapy are dependent on the type, dose, and duration of the agents used in the conditioning regimens. Most complications are related to pancytopenia and are similar to those encountered
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during the mobilization phase and preengraftment. The reader is referred to the discussion of complications related to engraftment and to Table 2 for a review of the complications and their management. Nursing interventions include astute physical assessment of the patient, frequent monitoring of vital signs, monitoring of laboratory tests, maintenance of fluid and electrolyte balance, daily weights, symptom management, and patient and family caregiver support. NURSING MANAGEMENT DURING STEM CELL TRANSPLANTATION/REINFUSION
BCT or stem cell reinfusion occurs several days after high-dose therapy. The cryopreserved stem cells are transported to the patient's room in dry ice, and thawed one at a time in a 37°C to 40°C water bath to prevent cell damage caused by premature thawing and to ensure a continuous infusion of cells. Some protocols require that the thawed stem cells be washed to remove dimethyl sulfoxide (DMSO) and cell lysis products before infusion to minimize side effects. Aggressive hydration is initiated before the infusion and for several hours after to prevent nephrotoxicity associated with the large amount of stem cells reinfused. In addition, premedications such as diphenhydramine, corticosteroids, acetaminophen, ondansetron, lorazepam, diuretics, or mannitol may be given before reinfusion. Unirradiated, unfiltered stem cells are infused IV piggyback over 15 to 20 minutes by gravity drip or through a large (60 cc) syringe into the patient's CVC. The infusion is often accompanied by a normal saline infusion to prime the tubing and to clear remaining stem cells from the IV tubing. It is important not to administer medications into the infusion line because of possible hemolytic reaction. Figure 3 shows a nurse drawing stem cells into 60 cc syringe in preparation for administration.
Complications Complications usually occur immediately and resolve in 24 to 48 hours. Common adverse effects include nausea, vomiting, facial flushing, hypertension, hypotension, bradycardia, tachycardia, cardiac arrhythmias, tachypnea, cough, chest tightness, fever, chills, and abdominal cramping. Patients typically report an unusual taste, emit a garlic-like breath, and urine or emesis may have an
Fig 3. Preparation by a nurse to administer stem cells. (Courtesy of Salick Health Care, Westlake Village, CA).
offensive smell, which may be attributed to the sulfur contained in DMSO. For patients with prolonged hypotension, increasing the rate of hydration while decreasing or stopping the stem cell administration may stabilize the patient. Vital signs should be monitored closely every 5 to 10 minutes until the patient is stable. Hypertension may be a delayed effect occurring 2 to 4 hours after infusion. Hemoglobinuria, hematuria, increased bilirubin or serum creatinine may occur immediately following infusion as a result of red cell contamination. However, this is not a serious problem and levels return to normal in a few days. Davis et al22 evaluated 37 adults who received 63 stem cell reinfusions. All patients were premedicared with dexamethasone, ondansetron, and lorazepam. Stem cell reinfusions were well-tolerated and most side effects resolved within 10 minutes after completion. The most frequent side effects during reinfusion were cough (46%), facial flushing (44%), nausea (23%), transient blood pressure changes (15%), hypotension (15%), bradycardia (11%), and chest pressure (12%). Hematuria was
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noted in 68% of patients after reinfusion and was significantly correlated with higher blood volumes. No cumulative adverse effects were noted. 22 Nursing research is important to characterize the scope and incidence of adverse effects during stem cell reinfusion. Nursing care during the reinfusion process combines clinical expertise and pychosocial skills to prevent or minimize complications and to prepare the patient and family for expected side effects that may occur. Nurses should administer prophylactic medications before reinfusion as ordered, monitor vital signs, fluid status, intake and output, provide comfort measures such as cool soaks for facial flushing, and assist in emotional support. Table 4 identifies the complications and interventions related to stem cell reinfusion. PRE-ENGRAFTMENT COMPLICATIONS The etiology of complications after BCT are the result of toxicities related to the preparative regimen and medications, graft failure, relapse, and in the allogeneic recipient, graft versus host disease (GVHD). Other factors that may contribute to the incidence of side effects include: age, performance status, disease, and infectious disease profile. Mucositis, hemorrhage cystitis, and hepatotoxicity are noted with cyclophosphamide, thiotepa, melphalan, and carmustine (BCNU). 23 High-dose treatment protocols consisting of cyclophosphamide (5,625 mg/m 2 total dose), cisplatin (165 mg/m 2 total dose), and BCNU (600 mg/m 2 total dose)
resulted in severe gut toxicity, pneumonitis, and significant neuro-physiological effects.23 Cutaneous toxicity is associated with high-dose carboplatin (1,500 to 2,000 mg/m 2) and ifosfamide (10 rag/m2). 24,25Cutaneous manifestations include pruritic maculopapular rash on the upper and lower extremities that progresses to a confluent rash with facial edema and swelling of the hands and feet. Gordon et a126 recently reported that the use of granulocyte-macrophage colony-stimulating factor was a significant factor in anticoagulant deficiency.
Infection BCT recipients experience profound neutropenia resulting in viral and fungal infections. Infection prophylaxis with antibiotics (eg, ciprofloxan), antiviral medications (eg, acyclovir), and antifungal medications (eg, fluconazole) is common. Other measures to prevent infection include special dietary modifications (low bacterial diet). Despite rigorous infection control measures, many patients require empiric broad spectrum antibiotic treatment for neutropenic fever. 11 Kolb et a127 identified the type and incidence of infection in 66 BCT recipients. Sixty-two of the 66 (94%) patients experienced at least one febrile episode, 53% reported fever of unknown origin, and 39% had bacteremia caused by gram positive staphylococci. Lung filtrates were noted in 5% of recipients and one patient had herpes zoster virus infection. Severe organ infections were rarely observed. No mortalities due to infection were noted.
Table 4. Common Complications of Stem Cell Reinfusion Complication Renal compromise
Fluid overload
DMSO toxicity
Symptoms
Cause
Clinical Management
Hemoglobinuria, hematuria, increased bilirubin and creatinine Cough
Red cell contamination of stem cell product
IV hydration before and after infusion
Draw baseline serum bilirubin and creatinine levels
Large volume of stem cell product
Diuretics
Garlic-like odor, taste, cough, offensive odor to emesis and urine Arrhythmias, chest tightness
Cryopreservative
None
Monitor I & O and vital signs with infusion of each bag of stem cell product Offer citrus fruit, reassure patient that odor and smell will abate in 24-28 h Frequent monitoring of vital signs, administer medications as indicated Premedication with antiemetics
Nausea, vomiting
Facial flushing Allergic reaction, fever, chills
Cardiac monitors
Dexamethasone, ondansetron, Iorazepam
Nursing Management
Lorazepam-closely observe patient for somnolence, apply cool soaks
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Although BCT recipients have a shorter period of thrombocytopenia and anemia as compared to BMT recipients, packed red blood cells and platelet transfusions are required until engraftment stabilizes. Most protocols require that blood products be irradiated with 2,500 cGy to prevent transfusion related GVHD. Some protocols require that leukocyte-reduced or leukocyte filters be used to prevent cytomegalovirus (CMV) infection while others mandate that CMV negative blood products be administered to patients who are CMV seronegative. Clinical trials are underway to assess the efficacy of recombinant growth factor epoefin alpha and human megakaryocyte to stimulate rapid return of erythrocytes and thrombocytes.
Mucositis Mucositis usually begins at the time of stem cell reinfusion, peaks 7 to 14 days later, and resolves with neutrophil recovery. There are no mechanisms to prevent mucositis but supportive care can minimize infection, pain, anorexia, bleeding, and airway obstruction. Of particular concern is herpes simplex infection, which can further compromise the patient. Aggressive oral hygiene is imperative. Common mouth care protocols include combinations of saline and baking soda rinses several times a day and brushing with a soft toothbrush after any food or emesis. Chlorhexidine rinses and clotrimazole or nystatin troches may be appropriate for antifungal management. Topical anesthetics provide some pain relief and promote compliance with mouth care. IV narcotics may be necessary. 28
Skin Toxicities BCT recipients are at risk for alterations in skin integrity from chemotherapy, radiation, medications, or diarrhea, and in the case of aUogeneic BCT, GVHD. Because the skin is the primary barrier against infection, particular attention must be given to recipients during the period of profound neutropenia. Because thiotepa is excreted through perspiration, skin toxicities may be minimized by having the patient shower or bathe several times a day and wear loose clothing to allow perspiration to dry. Bulsulfan can cause painful erythematous macules on the hands, feet, axiUae, and groin. The lesions may progress to bullae formation followed by desquamation. Local treatment with ice packs may relieve discomfort but opioids may be
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required. Silver sulfadiazine may be applied as a topical antibiotic. 29
Veno-occlusive Disease (VOD) VOD, well-documented in BMT, is rarely seen in the BCT recipient. However, this life-threatening disorder is being reported with increasing regularity in BCT. Risk factors are high-dose therapy particularly TBI, cyclophosphamide, bulsulfan, and carmustine, preexisting hepatitis, and infection. It is caused by damage to the endothelial cells in the hepatic sinus as a result of high-dose chemotherapy and radiation. This disorder is characterized by hepatomegaly, jaundice, and fluid retention. There is great variation in severity, it affects several organ systems, requires close attention, and its treatment is diverse and controversial. Markers for severe VOD are onset of jaundice approximately 5 days after BCT, bilirubin >10 mg/dL before day 10 after BCT or >20 mg/dL 20 days after BCT, weight gain >5% within 10 days of BCT, doubling of baseline creatinine, decrease in urine sodium excretion, and abdominal ascites. Encephalopathy can occur due to shunting of blood from the liver and inadequate metabolism of waste products and drugs. Common timings are lethargy, confusion, and disorientation. 3° Death in patients with severe VOD is usually caused by cardiopulmonary and renal compromise and occurs between 30 and 60 days after BCT. Treatments under investigation for VOD include the use of anticoagulants, fibrinolytics, fluid restriction, and intense supportive c a r e . 31 Careful patient selection and identification of appropriate conditioning regimens may be the most effective defense against VOD until an effective prophylaxis or treatment is found. Nursing assessment includes identification of agents used in the patient's conditioning regimen, baseline liver function studies, history, assessing the abdomen twice daily, assessment of the skin, eyes, and urine for evidence of jaundice, twice daily weights, measuring abdominal girth, monitoring postural blood pressure, intake and output, liver function tests, coagulation studies, and the administration of therapies.
Nursing Management Nursing care during the engraftment recovery phase is directed at early detection of multiple complications and prompt intervention. The etiology of symptoms are often confounding and the
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patient's condition can change rapidly. Nurses must be skilled in assessing and managing toxic effects and provide psychosocial support. The engraftment phase of transplant is an intense time for the patient and family. Until techniques are significantly improved, professional health care teams need to support recipients with the use of prophylactic measures and astute patient assessment. 3°
Relapse Relapse is a significant problem after BCT and may be attributed to the reinfusion of malignant cells contained in the stem cell product or residual cancer cells not eradicated by the preconditioning regimen. 32 A number of investigational approaches are being employed to diminish recurrent disease. Posttransplant immunotherapy using active immunization is one approach that might eliminate any remaining tumor cells. Other options for treatment of recurrent disease after BCT include salvage chemotherapy, second transplants, withdrawal of immunosuppressive medications (in allogeneic BCT), cytokine therapy, donor leukocyte infusions, and monoclonal antibody therapy. 32,33 DISCHARGE CRITERIA
Discharge criteria for the BCT recipient, either from the hospital or to return to their referring physician, is highly variable and dependent on the condition of the recipient, 24-hour availability of the transplant team, the geographic proximity to the transplant facility, the availability of transportation to outpatient and emergency facilities, and the availability of a competent caregiver. Typically patients must be free of overwhelming clinical problems, be afebrile, and have a strong family caregiver to manage their c a r e . 4 LONG-TERM COMPLICATIONS The identification of long-term effects of BCT will be forthcoming as more BCT recipients become long-term survivors. Prolonged abnormalities in humoral and cell mediated immunity have been reported after BCT, and secondary complications such as varicella zoster infection, CMV infection, and others are not uncommon. Delayed engraftment and graft failure have also been documented. 13Although it is tempting to superimpose the long-term complications of BMT to BCT, one must carefully review the BMT literature to identify those complications related to TBI before
assigning these problems to BCT recipients who receive only chemotherapy. For example, in describing growth and development problems in pediatric BMT recipients, Sanders 34 found that complications were dependent on the child's age at time of transplant, prior cranial irradiation, and type, dose and duration of high-dose therapy. Children who received cyclophosphamide only in conditioning regimens had normal growth rates whereas children receiving TBI showed decreased growth rates. Cataract formation after BMT is caused by TBI or steroids to decrease the impact of GVHD. 35 Consequently, it is not likely that cataracts will be a notable complication in patients receiving chemotherapy only in conditioning regimens. Care and management of the BCT recipient does not end with successful engraftment and resolution of all complications. The outcome of transplantation is not always successful, and for patients with disease recurrence, palliative care, and bereavement support for families becomes an important focus. For patients who survive transplantation, there are numerous physical, psychological, quality of life, family caregiver burden, and economic issues to address. The BCT patient should be routinely monitored for potential late complications, relapse, and graft failure. ALLOGENEIC BCT
More than 250 allogeneic BCTs have been documented and this number is growing rapidly. The process, and patient and donor eligibility for allogeneic BCT are similar to allogeneic BMT. If the donor has adequate venous access, stem cells are collected through bilateral large bore catheters inserted in the antecubital fossas. Long-term, indwelling catheters are avoided to prevent risks of infection, pneumothorax, and the inconvenience of a catheter. The amount of stern cells collected are based on the recipient's size. If an ABO incompatibility exists between the patient and donor, the cells are processed to accommodate ABO incompatibility. Allogeneic BCT recipients receive prophylaxis and treatment for GVHD with cyclosporine and corticosteroids. Initial data report the incidence and severity of acute GHVD after allogeneic BCT not to be significantly different from that after marrow transplant. In a small cohort of 73 patients receiving HLA identical BCT and GVHD prophy-
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laxis, 56% of 23 evaluable patients developed some form of chronic GVHD. 36 Manifestations of chronic GVHD in allogeneic BCT recipients are being studied closely. Initial fears that chronic GVHD would present with even greater morbidity and mortality than in B M T recipients was based on the knowledge that peripheral blood contains approximately 20 times the number of T cells compared to marrow. Because donor T cells cause GVHD, it is postulated that chronic GVHD would be a major limitation to successful BCT. Early research is encouraging, but conflicting. Milfin et al, 37 reported that of 44 allogeneic BCTs, chronic GVHD occurred in 17 out of the 37 evaluable patients, but more long-term follow-up is needed. Another study of 21 patients reported that more than half presented with liver and skin chronic GVHD. 38 Donor safety is a major concern during cytokine mobilization.39 Transplant teams must assess the risks of subjecting healthy donors to the complications of cytokine therapy, the expense and compli-
cations of surgical catheter placement, and possible u n k n o w n late complications of therapy. Current studies do not confirm long-term effects of growth factors in healthy donors, but more research is needed in this area. 4° CONCLUSION
Although it is believed that BCT is less expensive, less toxic, and as beneficial as BMT, research is needed to document these potential advantages and predictions that BCT will replace B M T within the next 5 years. Currently, several randomized clinical trials are comparing BCT with BMT. Only the results of long-term trials will determine the optimal treatment based on decreased morbidity, mortality, disease-free survival, quality of life, and cost of care. Oncology nurses working with transplant recipients will need to keep abreast of changing technology as more patients receive hematologic transplants from new cell sources such as blood and umbilical cord.
REFERENCES 1. GratwohlA, SchmitzN: First internationalsymposiumon allogeneic peripheral blood precursor cell transplants. Bone Marrow Transplant17:S1-$3, 1996 (suppl 1) 2. www.hhpt:CBRstore@aolCordBloodRegistry 3. Stetz M, McDonald JC, Comptom K: Needs and experience of family caregiver during marrow transplantation. OncolNurs Forum 23:1422-1427, 1996 4. BuchselPC, KapostayPM: Peripheral stem cell transplantation, in HubbardSM, GoodmanM, KnobtTK (eds): Oncology Nursing Update: Patient Treatmentand Support. Philadelphia, PA, Lippincott, 1995,pp 1-14 5. GorinNC: Cryopreservationand storage of stem cells, in Areman EM, Deeg HJ (eds): Bone Marrow and Stern Cell Processing:A Manualof CurrentTechniques.Philadelphia,PA, Davis, 1992pp 171-184 6. BensingerW: Peripheral blood stem cell transplantation, in Buchner CD (ed): Technical and Biological Comments of Marrow Transplantation.Boston,MA, KluwerAcademic, 1995, pp 216-254 7. Burns JM, TierneyDK, Long GD, et al: Criticalpathway for administeringhigh-dose chemotherapy followedby peripheral blood stem cell rescue in the outpatientsetting. OncolNurs Forum 22:1219-1224, 1995 8. KhimppTR: Complicationsof peripheral blood stem cell transplantation.SeminOnco122:263-270,1995 9. KingC: Peripheral sterncell transplantation:Past, present, and future, in Buchsel PC, Whedon MB (eds): Bone Marrow Transplantation:Administrativeand ClinicalStrategies. Boston, MA, Jones and Bartlett, 1995, pp 187-211 10. KessingerA, BishopM, AndersonJ, et al: Comparisonof subcutaneous and intravenous administrationof recombinant human granul0cyte macrophage colony stimulating factor for
peripheral blood stem cell mobilization.Hematology 4:81-84, 1995 11. Walker F, Roethke S, Martin G: An overview of the rationale, process, and nursing implicationsof peripheral stem cell transplantation.CancerNurs 17:141-148, 1994 12. Rowe JM, Ciobanu N, Ascensao J: Recommended guidelines for the managementof autologous and allogeneic bone marrow transplantation. A report from the eastern cooperative oncologygroup (ECOG).Ann Intern Med 120:143158, 1994 13. GoldbergSL, ManganKF, KlumppTR, et al: Complications of peripheral blood stem cell (BCT) collections. Blood 82:631, 1993 (abstr, suppl 1) 14. Stephens LC, Haire WD, Schmit-PokornyK: Granulocyte macrophage colony stimulatingfactor: High incidence of apheresis catheter thrombosis during peripheral stem cell collection.Bone MarrowTransplant11:51-54, 1993 15. Hooper PJ, Santas EJ: Peripheral blood stem cell transplantation.OncolNuts Forum20:1215-1221, 1993 16. Shpall EJ, Jones RB: Mobilization and collection of peripheralbloodprogenitorcells for supportof high dose cancer therapy, in Forman S, Blume K, Thomas ED (eds): Bone Marrow Transplantation.Boston, MA, Blackwell Scientific, 1994, pp 913-918 17. Peters WP, Ross M, Vredenburg JJ, et aI: The use of intensive clinic support to permit outpatient autologous bone marrow transplantationfor breast cancer. Semin Oncol 21:2531, 1994 (suppl7) 18. Phillips GL: Conditioning regimens, in Deeg HJ, KlingemannHG, Phillips GL (eds): A Guide to Bone Marrow Transplantation(ed 2). Berlin,Germany,Springer-Verlag,1992, pp 67-88
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19. Buchsel PC, Kelleher J: Bone marrow transplantation. Nurs Clin North Am 24:907-938, 1989 20. Algara M, Valls A, Vivancos P, et al: Outpatient total body irradiation for bone marrow transplantation. Bone Marrow Transplant 14:381-382, 1994 21. Dager R, Robertson KA, Lucas KG, et al: Outpatient total body irradiation for pediatric patients undergoing stem cell transplant. Blood 88:413a, 1996 (abstr, suppl 1) 22. Davis ME, Klemm I, Wiest D: Side effect associated with peripheral blood stem cell PBSC reinfusion. Proceedings Bone Marrow Transplant Conference, Dallas, TX, March 1997 23. Williams SF, Meyers SE: The University of Chicago experience with high-dose chemotherapy intensification and autologous stem cell rescue. Bone Marrow Transplant 10:38, 1992 (abstr) 24. Pittman KB, To KB, Bayly JL, et al: Cutaneous toxicity of high dose carboplatin, etoposide, and ifosfamide followed by autologous stem cell infusion. Bone Marrow Transplant 10:535-540, 1992 25. Beyer J, Grabbe K, Lenz V, et al: Cutaneous toxicity of high dose carboplatin, etoposide, and ifosfamide followed by autologous stem cell infusion. Bone Marrow Transplant 10:491-494, 1992 26. Gordon B, Haire W, Ruby E, et al: Factors predicting morbidity following hematopoietic stem cell transplantation. Bone Marrow Transplant 19:497-501, 1997 27. Kolb HJ: For the European group for blood and marrow transplantation working party for chronic leukemia. Blood 86:2041-2050, 1994 28. Lloid M: Oral medicine concerns of the BMT patient, in Buchsel PC, Whedon MB (eds): Bone Marrow Transplantation: Administrative and Clinical Strategies. Boston, MA, Jones and Bartlett, 1995, pp 257-276 29. Tenenbaum L, Leshin D: Alterations in the integumentary system, in Tenenbaum L (ed): Cancer Chemotherapy and Biotherapy: A Reference Guide (ed 2). Philadelphia, PA, Saunders, 1994, pp 287-302
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30. Ballard B: Renal and hepatic complications, in Whedon MB (ed): Bone Marrow Transplantation: Nursing Principles, Practices and Insights. Boston, MA, Jones and Bartlett, 1991, pp 240-261 31. McDonald GV: Venoocclusive disease of the liver following marrow transplantation, in Sullivan KM, Koppa S (eds): Marrow Transplant Review. Charlottesville, VA, Kluge Carden Jennings, 1994, pp 169-134 32. Lilleby K: Breast and ovarian cancer vaccine study: New hope for patients posttransplant. Puget Sound Oncol Nurs Soc 19:8-9, 1996 33. Arcse W, Iori AE Nucci G, et al: What does one do for the CML patient in relapse after allogeneic bone marrow transplantation? Leuk Lymphoma 12:231-219, 1993 34. Sanders J: Growth and development after bone marrow transplantation, in Forman S, Bhime K, Thomas ED (eds): Bone Marrow Transplantation. Boston, MA, Blackwell Scientific, 1994, pp 527-537 35. Deeg H: Delayed complications after bone marrow transplantation, in Forman S, Blume K, Thomas ED (eds): Bone Marrow Transplantation. Boston, MA, Blackwell Scientific, 1994, pp 376-403 36. Bensinger WI, Longin K, Applebanm E et al: Transplantation of allogeneic peripheral blood progenitor cells mobilized by human granulocyte colony-stimulating factor. Blood 85:16551658, 1995 37. Milfin G, Russell Nit, Hutchinson R, et al: Allogeneic peripheral blood stern cell transplantation for hematological malignancies--an analysis of kinetics of engraftment and GVHD risk. Bone Marrow Transplant 19:9-13, 1996 38. Urbam-Ispizua, Garcia-Conde J, Brunet F, et al: High incidence of chronic graft versus host disease (GVHD) after allogeneic peripheral blood progenitor cell transplantation. (PBPCT 1996 Abstr 2455) Blood 88:617a, 1996 (abstr, suppl 1) 39. Korbling M, Champlin R: Peripheral blood progenitor cell transplantation: A replacement for marrow auto- or allo-grafts. Stem Cells 14:185-195, 1996