Mobilization of Hematopoietic Stem Cells for Use in Autologous Transplantation Hollie Devine, MSN, RN, CNP, D. Kathryn Tierney, RN, PhD, Kim Schmit-Pokorny, RN, MSN, OCN®, and Kathleen McDermott, RN, BSN, OCN® Autologous hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic approach for various malignant hematologic and lymphoid diseases. Hematopoietic stem cells (HSCs) may be collected from the blood or the bone marrow. HSCs are capable of self-renewal and give rise to progenitor cells, multipotent cells that differentiate and proliferate into the mature cells of the blood and immune system. HSCs and progenitor cells are released from the bone marrow into the peripheral blood through a process called mobilization. HSCs then are collected from the blood in a process called apheresis and cryopreserved for administration following the high-dose preparative regimen. This article reviews stem cell biology, current mobilization strategies, use of novel mobilization agents, and nursing care of patients during the mobilization phase of autologous HSCT. Understanding the biology and process of HSC mobilization is critical for transplantation nurses to deliver and coordinate care during this complex phase of autologous HSCT. utologous hematopoietic stem cell transplantation (HSCT) is a therapeutic approach that is potentially At a Glance curative for a number of malignant hematologic Mobilization of hematopoietic stem cells (HSCs) from the bone and lymphoid diseases. The three types of HSCT marrow into the peripheral blood is a multistep process involv- are allogeneic, autologous, and syngeneic. In allo- ing the interplay among chemokines, cytokines, cell adhesion Ageneic transplantation, the hematopoietic stem cells (HSCs) molecules, and the bone marrow microenvironment. are obtained from a human leukocyte antigen–matched sibling, The goal of stem cell collection is to mobilize a sufficient an unrelated volunteer donor, or cyropreserved umbilical cord number of HSCs that are capable of regenerating the full blood. In autologous HSCT, the HSCs are collected from the hematopoietic lineages and to achieve adequate engraftment bone marrow or the blood of the patient when the cancer is following autologous HSC transplantation. in remission or a state of minimal residual disease. The third type of HCT is a syngeneic transplantation, where the source Nurses need to understand stem cell biology and the mecha- of the graft is an identical twin. Peripheral blood HSCs have nisms of action of current mobilization strategies. largely replaced the use of bone marrow as the graft source for autologous HSCT. The benefits of using HSCs collected from mobilization techniques will be reviewed, including the use the blood compared to HSCs collected from the bone marrow of novel mobilization agents. The collection, processing, and include a shorter period of neutropenia, which translates into cryopreservation of HSCs will be outlined. reduced use of antibiotics, decreased risk of infection, shorter hospitalization, and reduced costs (Schmitz et al., 1996; Smith et al., 1997). Hollie Devine, MSN, RN, CNP, is an adult nurse practitioner and educator The focus of this article is the mobilization of HSCs for use for advanced practice nurses and physician assistants in the James Can- in autologous HSCT. The term mobilization is used to describe cer Hospital at the Ohio State University Medical Center in Columbus; the process by which HSCs are released from the bone marrow D. Kathryn Tierney, RN, PhD, is an oncology clinical nurse specialist at into the blood. The biology of HSCs and the mechanisms by Stanford University Medical Center in California; Kim Schmit-Pokorny, which HSCs remain in the bone marrow microenvironment or RN, MSN, OCN®, is a transplant manager at the University of Nebraska are released into the blood will be reviewed. To date, the two Medical Center in Omaha; and Kathleen McDermott, RN, BSN, OCN®, is principle means of mobilization are the use of cytokines alone a clinical research nurse at the Dana-Farber Cancer Institute in Boston, or the use of cytokines in combination with chemotherapy. MA. (First submission August 2009. Revision submitted September 2009. These mobilization strategies will be described. Strategies for Accepted for publication October 8, 2009.) individuals who do not collect a sufficient graft with current Digital Object Identifier: 10.1188/10.CJON.212-222 212 April 2010 • Volume 14, Number 2 • Clinical Journal of Oncology Nursing Stem Cell Biology As HSCs mature, they expresses specific combinations of cell surface proteins that serve as biochemical markers. These bio- The Hematopoietic System chemical markers identify the evolutionary stage of the blood cell, dictate the next steps in cell maturation, and serve as regulatory Hematopoiesis is a cell-renewal process that leads to the signals (Scholossman et al., 1997; Zola et al., 2005; Zola, Swart, constant manufacturing of functional differentiated blood cells Boumsell, & Mason, 2003; Zola, Swart, Nicholson, & Voss, 2007). from HSCs and progenitor cells (Lataillade, Domenech, & Le Flow cytometry through the use of fluorescent-labeled antibodies Bousse-Kerdiles, 2004). HSCs are cells that can differentiate into is a technique for analyzing multiple markers of individual cells. functional mature blood cells while maintaining an indefinite The cluster of differention or cluster of designation (CD) system capacity for self-renewal. HSCs have three general properties: is the nomenclature used to classify and analyze cell surface mol- they are capable of self-renewing, they are unspecialized, and ecules present on leukocytes. The CD marker is used to associate they give rise to specialized cells. HSCs are vital in that they as- cells with certain immune functions and properties (Scholoss- sist in regenerating cells damaged by disease, injury, and daily man et al., 1997; Zola et al., 2003, 2005, 2007). CD34 is a marker use (Stem Cell Information, 2006). A progenitor cell is a dividing of HSCs and is used clinically to separate HSCs from other types cell with capacity to differentiate. The developmental pathway of leukocytes (see Figure 2). As HSCs differentiate, they lose the of HSCs into functional blood cells involves loss of the poten- CD34 marker and acquire other biochemical markers specific to tial to proliferate, with progressive differentiation into specific a lineage. T cells will acquire CD4 or CD8 surface markers and B blood elements with defined functions. These fully differentiat- cells will acquire surface immunoglobulin markers and antigen- ed blood cells have finite life spans, requiring constant renewal specific receptors (Manz et al., 2004). Table 2 summarizes the from the HSC pool (Manz, Akashi, & Weissman, 2004). biochemical markers of the various blood cells. In the bone marrow microenvironment, stem cells may The biology of HSC mobilization is a complex process. For remain quiescent for long periods of time until they are acti- successful proliferation of later-stage myeloid and lymphoid vated for the purpose of homeostasis or tissue repair (Manz et cells to occur, the hematopoietic system needs several factors: a al., 2004). Inside the bone marrow reside long-term HSCs that consortium of HSCs, hematopoietic growth factors to stimulate have the capacity for self-renewal (see Figure 1). A subset of proliferation, and stromal cell interactions between HSCs and these long-term HSCs will differentiate into short-term HSCs, progenitor cells. which give rise to multipotent progenitors of either the myeloid or lymphoid cell lineages. The common lymphoid progenitor differentiates into precursors of the B and T lymphocyte and Bone Marrow Microenvironment natural killer lineages. The common myeloid progenitor gives Inside the bone marrow is a multifunctional network of cells rise to two types of progenitors; the granulocyte-monocyte and extracellular matrix that maintain HSC proliferation, differ- progenitor and a megakaryocyte-erythrocyte progenitor. The entiation, and survival. This network of cells and extracellular granulocyte-monocyte progenitor produces the granulocyte lin- matrix are known as the bone marrow microenvironment (see eages (which produce neutrophils, basophils, and eosinophils), Figure 3). Stromal cells are the layers of cells that support the the monocyte-macrophage lineages, and the dendritic cell lin- infrastructure of the bone marrow. Stromal cells assist in the eages. The megakaryocyte-erythrocyte progenitor produces the regulation of HSCs and are important cells for providing dif- erythroid-lineage cells and megakaryocytes (Manz et al., 2004). ferentiation signals to HSCs. Additionally, stromal cells direct Table 1 describes the function of each blood cell. the movement of HSCs out of the bone marrow and into the peripheral circulation (Lataillade et al., 2004). Stromal cells produce stromal-cell derived factor- CLP 1a (SDF-1a), a chemokine widely expressed by Pro-T T many tissues such as the ectoderm, endoderm, B Pro-B mesoderm, and mesenchymal cells (McGrath, NK LT-HSC ST-HSC MPP GMP Koniski, Maltby, McGann, & Palis, 1999). SDF-1a Granulocytes is a signaling molecule involved in the prolif- Monocytes eration, homing, and engraftment of HSCs and Dendritic cells CMP MEP leukocytes. Erythrocytes Platelets Mechanisms of Mobilization CLP—common lymphoid progenitor; CMP—common myeloid progenitor; GMP— In addition to HSCs and stromal cells, mobili- granulocyte-monocyte progenitor; LT-HSC—long-term hematopoietic