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December 2013, Supplement to Volume 17, Number 6

 

Article

Autologous Hematopoietic Stem Cell Transplantation for Patients With Multiple Myeloma: An Overview for Nurses in Community Practice

Teresa Miceli, RN, BSN, OCNฎ, Kathryn Lilleby, RN, Kimberly Noonan, RN, ANP-BC, Sandra Kurtin, RN, MS, AOCNฎ, ANP-C, Beth Faiman, MSN, APRN-BC, AOCNฎ, and Patricia A. Mangan, MSN, APRN-BC

 

Autologous hematopoietic stem cell transplantation (AHSCT) is approved for the treatment of select solid tumors, autoimmune disorders, and most hematologic malignancies. Multiple myeloma (MM) is the most common indication for AHSCT. Despite improvement in response and survival rates in the era of novel agents, AHSCT remains an important treatment option for patients with MM who are eligible. Clinical management of patients with MM requires a multidisciplinary approach that incorporates healthcare professionals in a number of clinical settings as well as caregivers and the patient. Patients about to undergo AHSCT are generally referred to tertiary care centers that specialize in ASCT. Pre- and post-transplantation treatments and long-term follow-up often are managed by a community-based referring oncologist in collaboration with the transplantation team. Oncology nurses play an integral role in the care of patients with MM in each clinical setting. This article aims to provide non-transplantation oncology nurses with guidelines for education, clinical management, and support of patients with MM undergoing AHSCT with a primary focus on the pre- and post-transplantation period.

 

Hematopoietic stem cell transplantation (HSCT) is an accepted treatment for selected autoimmune and nonmalignant disorders, solid tumors, and hematologic malignancies. High-dose chemotherapy (HDC) is used in these settings to provide intensive cytotoxic therapy with the goal of eliminating malignant cells. However, the toxic effects of treatment are not specific to malignant cells alone, but affect all fast-growing cells. This results in expected side effects, most significantly bone marrow ablation (Antin & Yolin Raley, 2009). As such, reconstitution of the bone marrow and hematopoietic function using either autologous (patient’s own) or allogeneic (related or unrelated donor) stem cells is integral to the treatment process. In both procedures, stem cells are collected prior to receiving HDC, processed, stored, and then infused into the patient following HDC. Without stem cell “rescue” following HDC, patients would not recover bone marrow function, causing significant risk of mortality from life-threatening infection, bleeding, or anemia (Antin & Yolin Raley, 2009; Bensinger, 2009; Kumar, 2009; Rodriguez, 2010b). The general process for HSCT is found in Figures 1 and 2 and further discussed in Faiman, Miceli, Noonan, and Lilleby (2013), published on pages 33–41 of this supplement.

 

Multiple Myeloma Overview

 

Multiple myeloma (MM) is a malignant plasma cell disorder. Plasma cells produce immunoglobulin, which are proteins critical to the protective immune response. Immunoglobulins consist of a heavy chain (IgG, IgA, IgM, IgD, IgE) and a light chain (kappa or lambda) (Mangan, 2010). In MM, atypical plasma cells produce excess quantities of one of these proteins, referred to as paraproteins, monoclonal proteins, or M proteins. The patient-specific myeloma subtype is categorized by the involved immunoglobulin (heavy chain and light chain) (e.g., IgG kappa). Several factors are thought to play a role in the malignant transformation of plasma cells, including chromosome changes, molecular characteristics, and elements that affect the bone marrow microenvironment such as cytokine abnormalities. Many of these factors are thought to have prognostic significance (Palumbo & Anderson, 2011).

 

The diagnosis of MM is based on the presence of greater than 10% atypical plasma cells in the bone marrow, presence of a monoclonal protein in the peripheral blood and/or urine, and additional laboratory and clinical findings (Durie et al., 2006; Kyle et al., 2003). The common clinical manifestations of MM are the byproduct of excess paraprotein and its impact on the cellular environment and organs, and include anemia, fatigue, hypercalcemia, bone disease, bone pain, renal dysfunction, and decreased immune function (Kyle et al., 2003; Mangan, 2010).

 

Autologous Versus Allogeneic Hematopoietic Stem Cell Transplantation

 

MM is the second most common hematologic malignancy, but is the most common indication for autologous HSCT (AHSCT) (Pasquini & Wang, 2011). Multiple studies demonstrate a survival benefit associated with AHSCT; therefore, AHSCT is considered the standard of care for eligible patients (Attal, 1996; Giralt et al., 2009; Kumar, 2009). Allogeneic HSCT (allo-HSCT) differs from AHSCT in that marrow created by donor cells can promote new immune activity in the recipient, providing a graft-versus-host disease (or antimyeloma) effect. Allo-HSCT is associated with high treatment-related morbidity and mortality and should only be pursued in the setting of a clinical trial (Bensinger, 2009; Lokhorst et al., 2010). Therefore, the focus of these guidelines will be directed toward AHSCT.

 

Treatment From Induction to Post-Transplantation Recovery

 

When designing the plan of care for a patient with MM, all treatment options should be considered. Every newly diagnosed patient with MM, even those older than age 70 years, should be considered a candidate for an AHSCT. Eligibility criteria vary by institution. Referral to a transplantation center, most often based on proximity and insurance contracting, should be made early in the treatment process when considering AHSCT (National Comprehensive Cancer Network [NCCN], 2013; Palumbo et al., 2011). More than 150 medical institutions exist in the United States that perform AHSCT (Blood and Marrow Transplant Information Network, 2013; Center for International Blood and Marrow Transplantation, 2013). Each institution has specific protocols for pretransplantation screening, evaluation, consultation, and treatment planning. Transplantation eligibility is largely based on age, performance status, and desire to undergo the procedure (see Figure 3). The screening and approval process may take weeks to months. Ultimately, transplantation eligibility should be determined by a transplantation specialist.

 

Once a patient is diagnosed with active MM, the patient will initiate a treatment plan that includes chemotherapy. The goal is to effectively suppress the malignant clone and optimally reach a complete response prior to the collection of stem cells. Patients with MM who are eligible for transplantation should not receive regimens containing melphalan prior to stem cell collection because it can interfere with stem cell mobilization (Cavo et al., 2011; Giralt et al., 2009). Novel therapies (thalidomide, lenalidomide, pomalidomide, bortezomib, and carfilzomib), in combination with dexamethasone or standard chemotherapeutic agents, have demonstrated improved response rates (RR) and overall survival (OS) in patients with MM and are considered acceptable regimens prior to HSCT (Cavallo et al., 2011; Kyle & Rajkumar, 2009; Lacy et al., 2012; NCCN, 2013; Sonneveld, Asselbergs, et al., 2012). For those patients deemed transplantation ineligible, melphalan and other alkylating agents in combination with novel agents have shown significant responses and improved OS (Palumbo et al., 2011; Rajkumar et al., 2010; San Miguel et al., 2008). A number of clinical trials that include initial therapy, supportive care, maintenance, or treatment of relapse in the clinical trial setting currently are being conducted. Participation in clinical trials should be considered at all phases of treatment when possible.

 

AHSC collection and transplantation is a multistep process. The timing for stem cell collection is individualized based on the transplantation plan. For example, a patient may collect stem cells for storage purposes and continue with current therapy, or collect stem cells with the intent to proceed directly to AHSCT. Patients who previously collected and stored stem cells will proceed with HDC and AHSCT when clinically indicated without repeating the collection process. Certain side effects and clinical implications are common to therapies used at each stage of the process (see Table 1). Preparing for all phases of the transplantation process can be overwhelming for patients. Figure 4 and Appendix A provide considerations and Internet resources that may assist patients and caregivers.

 

Post-Transplantation Recovery

 

The post-transplantation period begins after recovery from acute toxicity of the HDC, including blood count recovery (Kelley, McBride, Randolph, & Leum, 2000; Williams, 2004). This period of time has become obscured because of the many discharge options and individualized practices at each transplantation center. Patient acuity at time of discharge is higher than in years past, and the care of the patient with MM who has received AHSCT often is complex (Bevans, 2009). The majority of post-transplantation care becomes the responsibility of nontransplantation practitioners and caregivers. Patients anticipate the return home from the transplantation center, but also may experience anxiety in the transition.

 

The International Myeloma Foundation Nurse Leadership Board has compiled a summary of guidelines, recommendations, and clinical management strategies intended to optimize the quality of life (QOL) of patients undergoing transplantation and to minimize adverse events during the immediate post-transplantation period. The goal is to assist the community-based healthcare team, including oncology healthcare providers, to ease the transition from transplantation center to community, relieve anxieties, and provide information to guide the recovery of the patient after AHSCT. While reviewing these guidelines, note that QOL may improve over time. In several studies, transplantation-related symptoms and QOL improved or surpassed the pretransplantation level when measured at 6–12 months (Chao et al., 1992; Lyons et al., 2011; McQuellon et al., 1998; Saleh & Brockopp, 2001; Schulmeister, Quiett, & Mayer, 2005). 

 

Considerations for the Nontransplantation Oncology Nurse

 

Discharge guidelines vary among transplantation centers, but generally include suggested management of psychological and physical needs of the patient. Although patients and their caregivers receive extensive education verbally and in writing prior to their discharge from the transplantation center, the amount of information may be overwhelming, and specific details forgotten. Therefore, ongoing educational reinforcement is essential for both patients and their caregivers. Familiarity with the discharge procedures and post-transplantation policies at the particular transplantation center from which the patient has been discharged will allow for reinforcement of key concepts when healthcare providers meet with patients and their families. If not provided to the patient at discharge, written instructions can be requested from the transplantation center to help guide care. Long-term survivorship issues also should be considered when caring for the patients with MM post-transplantation. Guidelines addressing fertility, sexuality, renal aspects, bone health, health maintenance, and mobility and safety can be found in a previous supplement to the Clinical Journal of Oncology Nursing from the International Myeloma Foundation Nurse Leadership Board (Bilotti et al., 2011; Bilotti, Gleason, & McNeill, 2011; Faiman, Mangan, Spong, & Tariman, 2011; Miceli, Colson, Faiman, Miller, & Tariman, 2011; Richards, Bertolotti, Doss, & McCullagh, 2011; Rome, Jenkins, & Lilleby, 2011).

 

Post-Transplantation Needs

 

The psychological impact of AHSCT should not be overlooked. Patients often describe the “let down” feeling after working hard before and during the transplantation, and many reflect on the events leading up to the transplantation and the details of the transplantation after being discharged. Transplantation recovery can be associated with physical setbacks as well as social strain on the caregiver and family. In fact, post-transplantation psychological issues may present greater challenges than the medical needs of the patient for the community-based healthcare team (Cooke, Gemmill, Kravits, & Grant, 2009).

 

The estimated rate of depression following stem cell transplantation ranges from 25%–50%. Depression affects physical health, can increase symptom-related distress, decrease survival, and has been associated with a higher incidence of suicide. Early identification of the symptoms of depression will allow the post-transplantation healthcare team to intervene early and refer the patient for more intensive services, such as psychiatric or social services and referral back to the transplantation center. In some cases, antidepressive medications may be necessary. Caregivers and family members should be made aware of the frequency of post-transplantation depression, signs and symptoms they should report, and how best to contact the appropriate healthcare provider (Cooke et al., 2009).

 

Post-Transplantation Symptom Management

 

Symptom management is vital for patients after stem cell transplantation. Persistent symptoms of HDC-related toxicity are common even after the patient has returned home (see Table 2).

 

Post-Transplantation Infection Risk and Prevention

 

Post-transplantation infection is a major cause of morbidity and mortality. Although the patient’s white blood cell count and absolute neutrophil count may be within the normal range, the cells are functionally abnormal, placing the patient at increased risk for infection. In addition, continued physical weakness and malnutrition make recovery from a new infection difficult. Therefore, prophylactic antibiotics to prevent post-transplantation infections, such as invasive pneumococcal infection and pneumocystis pneumonia, are recommended for as long as one year following AHSCT (Tomblyn et al., 2009). Early detection and prompt intervention for infection is essential in caring for patients with MM (Palumbo et al., 2012). Careful assessment of the skin, lungs, gastrointestinal, renal, and skeletal systems are needed in identifying infection. Vital signs should be monitored at each clinic visit and patients should monitor their own vital signs as instructed by their care provider. Potential post-transplantation infections and preventions are listed in Table 3.

 

Frequent and meticulous hand washing by the patients and those they come in contact with is very important to prevent the transfer of infection. Many transplantation centers recommend that patients wear a mask when coming into a clinic or hospital for appointments. Patients may be advised to avoid public places such as restaurants, movies, or shopping malls. The suspension of these precautions will vary by individual centers and should be discussed in detail with the transplantation center.

 

Recommendations concerning personal hygiene, home maintenance, and cleanliness also may be provided by the transplantation center to further reduce the risk of infection. Guidelines for laundering clothes and housekeeping, particularly facilities used by the patient, are commonly provided. Specific policies regarding personal hygiene also are often recommended. It must be kept in mind that the patient may not be able to perform some of these duties independently in the first months following HSCT, emphasizing the need to include caregivers in the education process (Antin & Yolin Raley, 2009). The role of caregivers in the recovery of patients with HSCT is discussed in greater detail by Kurtin, Lilleby, and Spong (2013) on pages 25–32 of this supplement.

 

Because of the risk of food-borne infection, specific nutritional and dietary guidelines may be mandated by the transplantation center. Nutritional recommendations and restrictions may begin at the start of HDC and continue after discharge. In general, the Advisory Committee on Immune Practices recommends foods that have been refrigerated, pasteurized, or well-cooked for patients during the post-transplantation period (Antin & Yolin Raley, 2009; Tomblyn et al., 2009).

 

Smoking tobacco is prohibited after an AHSCT for many reasons. People who smoke are at increased risk for developing pneumonia as well as pulmonary and cardiovascular toxicity related to AHSCT. Marijuana use is prohibited because of the heightened risk of fungal infection associated with inhalation. Alcohol consumption also is restricted because of its potential effect on the liver, platelets, and immune function (Sipsas & Kontoyiannis, 2008; Tichelli et al., 2008; Versteeg, Slot, van der Velden, & van der Weijden, 2008).

 

Post-Transplantation Immunizations

 

The transplantation process results in a loss of T and B lymphocytes which, in turn, causes loss of immune memory. Immune memory is shaped by the culmination of exposure to infectious agents, environmental antigens, and vaccines during a person’s lifetime (Kroger, Sumaya, Pickering, & Atkinson, 2011; Stadtmauer et al., 2011). Therefore, patients require reimmunization.

 

Post-transplantation immunizations vary by institution. Based on the Centers for Disease Control and Prevention and Advisory Committee on Immune Practices recommendations, non-live vaccines may be administered as early as three months post-transplantation. Live-attenuated vaccines may be administered two years following transplantation in immune-competent people (Tomblyn et al., 2009). An example of an immunization schedule can be found in Table 4.

 

Post-Transplantation Medication Considerations

 

Polypharmacy during transplantation is common and can be confusing. Therefore, many transplantation teams will provide patients and their families with a medication chart to help track and maintain the dose and the administration of scheduled and “as needed” medications. Pretransplantation and transplantation-specific medications are added, discontinued, and adjusted frequently according to the patient’s needs during the acute care phase of the transplantation. Hypertension and hyperglycemic management regimens, in particular, often require modifications during the transplantation process. A list of discharge medications should be provided to the patient as well as to the discharge facility or homecare agency and the patient’s referring oncologist involved in the patient’s care. Patients may be restricted from taking certain over-the-counter medications such as nonsteroidal anti-inflammatory drugs and supplements because of drug interactions, organ toxicity, or interference with therapy. Medications must be taken as prescribed and medication changes should be discussed with the staff at the transplantation center.

 

Disease Management Following Autologous Hematopoietic Stem Cell Transplantation

 

Although AHSCT remains an important treatment strategy for patients with MM, relapse of MM is inevitable for the majority of patients. The timing is unpredictable and relapse can occur at any time following AHSCT, ranging from months to years. Those considered at high risk based on stage of disease and cytogenetics are at greater risk of early relapse (Mikhael et al., 2013; Palumbo & Cavallo, 2012). Providing patients with the clear message is important so that when progression does occur, they understand that it does not necessarily indicate end of life, but, rather, a time for change in therapy. Determining the optimal time to next therapy remains a controversial issue following AHSCT, and several studies are ongoing. Data regarding the use of maintenance therapy following HSCT for MM continue to be reported. Attal et al. (2012) reported improvement in progression-free survival (PFS) following AHSCT using lenalidomide as maintenance therapy but no increase in OS. McCarthy et al. (2012) also reported an increase in PFS as well as a longer OS. Bortezomib can be used as maintenance post-transplantation as well, and may be associated with improvement in PFS (Sonneveld, Schmidt-Wolf, et al., 2012).

 

Conclusion

 

Care of the patient following AHSCT is complex, however, expected side effects of HDC usually are manageable. Although consistent objectives and goals are in place for AHSCT recipients, care must be individualized based on pretransplantation treatment toxicities and transplantation-related side effects. Community oncology professionals play a critical role in the collaborative management of the patient with MM throughout the treatment continuum. Consistent communication among the patient, the referring center, and the transplantation center is vital to ensure all testing, insurance approval, and support services are in place prior to starting the transplantation process. Post-transplantation guidelines are not standardized, and recommendations for post-transplantation care vary between transplantation centers. These factors add to the challenge of caring for the transplantation patient in a community-based setting.

 

All providers should assist in supporting the patient and family members through the transplantation journey. Discharge is an exciting time for the patient, but also can be physically challenging and emotionally overwhelming. Community providers are instrumental in monitoring and managing post-transplantation concerns. Understanding the AHSCT rationale, process, and needs of the patient post-transplantation will improve the QOL for the patient undergoing transplantation and impact OS. Maintaining a collaborative management approach with consistent communication between the transplantation center and community healthcare provider team will improve overall outcomes for patients undergoing transplantation.

 

The authors gratefully acknowledge Brian G.M. Durie, MD, Robert A. Kyle, MD, and Diane P. Moran, RN, MA, EdM, senior vice president of strategic planning at the International Myeloma Foundation, for their critical review of the manuscript.

 

Implications for Practice

 

ุ  Include healthcare professionals from a number of clinical settings to best address the multidisciplinary approach required to manage multiple myeloma.

 

ุ  Become familiar with the autologous hematopoietic stem cell transplantation process, as it remains an important treatment option for multiple myeloma.

 

ุ  Incorporate guidelines for post-transplantation management in the community setting to promote quality of life and improve survival for patients.

 

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Teresa Miceli, RN, BSN, OCNฎ, is a bone marrow transplantation nurse coordinator and assistant professor of nursing in the College of Medicine in the William von Liebig Transplant Center at the Mayo Clinic in Rochester, MN; Kathryn Lilleby, RN, is a clinical research nurse at the Fred Hutchinson Cancer Research Center in Seattle, WA; Kimberly Noonan, RN, ANP-BC, is an adult nurse practitioner at the Dana-Farber Cancer Institute in Boston, MA; Sandra Kurtin, RN, MS, AOCNฎ, ANP-C, is a nurse practitioner and clinical assistant professor of medicine in the Hematology/Oncology Division of the University of Arizona Cancer Center in Tucson; Beth Faiman, MSN, APRN-BC, AOCNฎ, is a nurse practitioner in the Taussig Cancer Center at the Cleveland Clinic in Ohio; and Patricia A. Mangan, MSN, APRN-BC is a nurse lead in the Department of Hematologic Malignancies and Bone Marrow and Stem Cell Transplant Programs in the Abramson Cancer Center at the University of Pennsylvania in Philadelphia. The authors received editorial support from Alita Anderson, MD, with Eubio Medical Communications, and Joyce Divine, PhD, with ScienceFirst LLC, in preparation of this article supported by Sanofi Oncology. The authors are fully responsible for content and editorial decisions about this article. Kurtin is a consultant for Celgene Corporation, Novartis Pharmaceuticals, Millennium: The Takeda Oncology Company, and Onyx Pharmaceuticals. Mangan has received honoraria from Celgene Corporation, Millennium: The Takeda Oncology Company, Onyx Pharmaceuticals, and Sanofi-Aventis. Miceli, Lilleby, Noonan, and Faiman have no financial relationships to disclose. The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers or editorial staff. Miceli can be reached at miceli.teresa@mayo.edu, with copy to editor at CJONEditor@ons.org. (Submitted July 2013. Revision submitted September 2013. Accepted for publication September 8, 2013.)

 

http://dx.doi.org/10.1188/13.CJON.S2.13-24