Blood and Marrow Transplantation
Jane C. Shivnan
I. History
A. Beginnings of Blood and Marrow Transplantation (BMT): The earliest recorded attempt to use bone marrow therapeutically was in 1891, when bone marrow was administered by mouth to patients suffering from anemia and leukemia. It wasn’t until the explosion of the first atomic bomb in New Mexico in 1945, however, that a concerted effort was made to understand the principles of bone marrow replacement. Work in the 1950s and 1960s helped define appropriate preparative regimens and methods of bone marrow collection and administration. The 1970s saw a focus on the application of human leukocyte antigen (HLA) typing to BMT, and the use of immunosuppressive medications to prevent and control a serious BMT complication, graft-versus-host disease (GVHD).
B. Expansion of Transplantation Technology: The clinical availability of cyclosporine-A in 1983, enhanced HLA-typing methods, improved antibiotics and antiviral medications, availability of specialized blood products for transfusional support, and other supportive treatments made the 1980s a decade in which the application of this technology grew exponentially. Further refinement of GVHD prophylaxis and treatment, as well as the use of growth factors and other biologic response modifiers, supported the increased use of bone marrow for the treatment of malignancies and disorders of the immune system. The 1990s brought a significant advance with the application of pheresis technology to the collection of peripheral blood stem cells (PBSCs). This allowed transplantation to proceed without the risks of a bone marrow harvest, and often with a more rapid engraftment of hematopoietic cells. Additional advances included the extension of transplantation technology to unrelated and HLA-mismatched donors, and the increased banking and use of a rich source of hematopoietic stem cells, umbilical cord blood (UCB).
C. Future of BMT: Current research in transplantation includes investigation of the “mini” (nonmyeloablative) allogeneic BMT, designed to create a chimeric bone marrow with both host and donor cells. Donor lymphocyte infusions (DLI) and tumor vaccines in conjunction with BMT are also under investigation. These techniques have in common a focus on the graft-versus-tumor immune system response that helps prevent relapse after allogeneic BMT. Improving preparative regimens to increase relapse-free survival and minimize toxicity continues to be a focus for BMT research. In the allogeneic BMT setting, manipulation of T-lymphocyte subpopulations in the graft and continued study of immunosuppressive regimens seek to decrease the risk of GVHD.
Changes in supportive therapies provide hope for prophylaxis and treatment of infectious complications and organ toxicities. The body of nursing research investigating short- and long-term quality of life for BMT recipients and caregivers, symptom management, and the use of alternative modalities such as massage therapy and acupressure is growing rapidly. These changes in BMT modalities and supportive care promise a future of safe, cost-effective, readily available immune system treatments for many cancers and inherited or acquired nonmalignant disorders.
Changes in supportive therapies provide hope for prophylaxis and treatment of infectious complications and organ toxicities. The body of nursing research investigating short- and long-term quality of life for BMT recipients and caregivers, symptom management, and the use of alternative modalities such as massage therapy and acupressure is growing rapidly. These changes in BMT modalities and supportive care promise a future of safe, cost-effective, readily available immune system treatments for many cancers and inherited or acquired nonmalignant disorders.
II. Definition
A. Blood and marrow transplantation is a complete or partial replacement of hematopoietic stem cells after an immunosuppressive and myeloablative preparative regimen (generally a timed sequence of high-dose chemotherapy with or without radiation therapy and immunosuppressives). It is a potentially curative treatment for a wide variety of malignant and nonmalignant disorders.
B. The source of hematopoietic stem cells and type of transplant selected are based on a number of factors, including diagnosis, the patient’s general state of health, and the availability of an HLA-matched familial related or unrelated bone marrow donor. Table 5-1 summarizes the advantages and disadvantages of the major types (autologous, syngeneic, and allogeneic) of transplantation.
III. Rationale for Use
A. The dose-limiting toxicity for many chemotherapeutic agents and for total body irradiation is bone marrow destruction, and the resulting life-threatening aplasia. By providing a source for new bone marrow cells, BMT facilitates the use of higher, potentially more curative doses of chemotherapy and radiation therapy in malignancies such as neuroblastoma.
TABLE 5-1 Types of Stem Cell Transplantation | ||||||||||||
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B. BMT can also be used to treat primary disorders of the bone marrow. BMT allows the replacement of diseased bone marrow with healthy cells in diseases such as aplastic anemia, thalassemia, myelofibrosis, and leukemia.
C. The observed graft-versus-tumor effect of transplanted allogeneic hematopoietic stem cells enhances the immune system’s ability to control residual malignant disease and prevent relapse.
D. The usefulness of BMT as an intensive treatment modality is demonstrated by the variety of diseases treated: hematologic malignancies, solid tumors, genetic disorders, immune deficiencies, and autoimmune disorders (Table 5-2).
IV. Biology of Therapy
A. It had long been surmised that a pluripotent hematopoietic stem cell exists, capable of repopulating bone marrow and producing all of the differentiated cells made by that organ. Advances in the identification of cells through immunoassays have shown that cells carrying CD34 antigens on their cell surfaces may be pluripotent hematopoietic stem cells. These cells are found in bone marrow, UCB, and, in small numbers, circulating in the peripheral bloodstream.
B. Destruction of the bone marrow may be done deliberately to treat a primary disorder of the bone marrow or may occur as a side effect of therapy aimed at destroying tumor cells. An infusion of stem cells from a source such as bone marrow, UCB, or peripheral blood allows repopulation of bone marrow and production of red blood cells, white blood cells, and platelets. Measurable numbers of differentiated cells usually reach the peripheral bloodstream within 1 to 4 weeks of infusion.
TABLE 5-2 Diseases Treated by BMT and PBSCT | ||||||||||||||||||||||||||||||||
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V. Process of BMT
A. Pretransplantation Evaluation and Consultation: Before beginning the actual process of BMT, it is important to make sure that the patient is able to withstand the rigors of BMT and that the patient understands and is willing to undergo this potentially life-threatening treatment.
1. Eligibility criteria: All patients undergoing BMT must meet specific eligibility criteria that help predict their ability to withstand this intensive treatment modality. Criteria will vary among institutions as well as for different diseases and treatment protocols, but generally include measures of organ function, disease status, and health (Table 5-3). Before starting the BMT, staff at the transplantation center collect and review patient data to ensure that the patient meets the clinical eligibility criteria for transplantation.
2. Insurance verification: Due to the high costs associated with this intensive treatment, verification of insurance coverage or adequate financial resources is also obtained. Frequently, the patient and family must find additional funding sources within their community to finance the cost of BMT. Although direct costs such as hospitalization, outpatient treatment, pharmacy charges, and blood products are often covered by insurance, indirect costs such as housing, travel, child care, living expenses away from home, loss of income of the patient and primary caregiver, and loss of income are generally borne by the patient and family.
3. Informed consent: The complexity and potential morbidity of the procedure must be explained to the patient as part of an informed consent process. A variety of teaching methods (videos, printed materials, discussion) are helpful in providing the patient with sufficient knowledge about the procedure, as well as its risks and potential benefits. The nurse plays an important role in reinforcing information and supporting the patient and family during this decision-making process.
B. Preparation for transplantation
1. Intravenous (IV) access is needed throughout the transplantation process for blood sampling, medication administration, parenteral
nutrition, and blood product administration. For patients undergoing PBSC transplantation, large-bore IV access is required for apheresis. Long-term indwelling catheters (eg, Hickman or Groshong), frequently with two or three lumens, are usually inserted before transplantation to support the need for IV access. The nurse should review the procedure for insertion and care of the catheter with the patient. Nosocomial bloodstream infections are a serious risk to BMT patients, and meticulous catheter care based on research findings and national guidelines is essential. Long-term indwelling catheters are usually inserted in an operating room or fluoroscopy procedure room under local anesthesia or IV conscious sedation.
nutrition, and blood product administration. For patients undergoing PBSC transplantation, large-bore IV access is required for apheresis. Long-term indwelling catheters (eg, Hickman or Groshong), frequently with two or three lumens, are usually inserted before transplantation to support the need for IV access. The nurse should review the procedure for insertion and care of the catheter with the patient. Nosocomial bloodstream infections are a serious risk to BMT patients, and meticulous catheter care based on research findings and national guidelines is essential. Long-term indwelling catheters are usually inserted in an operating room or fluoroscopy procedure room under local anesthesia or IV conscious sedation.
TABLE 5-3 Example of Eligibility Criteria for Transplant | ||||||||||||||||||||||
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