History of Hematopoietic Stem Cell Transplantation
Seminars in Oncology Nursing
Volume 25 • Number 2 • May, 2009
Copyright © 2009 Elsevier
History of Hematopoietic Stem Cell Transplantation
Susan A. Ezzone
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* Address correspondence to Susan Ezzone, MS, RN, CNP, AOCNP®, Nurse Practitioner, Blood and Marrow Stem Cell Transplantation Program, Ohio State University Medical Center, Arthur G. James Cancer Hospital & Solove Research Institute, Columbus, OH 43210
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E-mail address: susan.ezzone@osumc.edu
PII S0749-2081(09)00023-0
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Objectives
To provide an overview of the history of hematopoietic stem cell transplantation (HSCT).
Data Sources
Research studies, book chapters, websites, and articles.
Conclusion
The history of HSCT begins in the late 1950s. Although many treatment strategies have evolved, the basic concepts of transplantation remain the same.
Implications for Nursing Practice
An understanding of the history of HSCT and transplant nursing practice are important to broaden the knowledge of nurses caring for transplant patients.
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Key Words
History
bone marrow transplant
hematopoietic stem cell transplantation
indications
treatment
HEMATOPOIETIC stem cell transplantation (HSCT) has been used for many years for the treatment of a variety of malignant and non-malignant hematologic disorders, solid tumors, and autoimmune disorders. Although the basic rational for use of transplantation for a treatment option for many diseases remain the same, components of the transplant process have changed. Use of HSCT for the treatment of a variety of diseases has evolved with increasing complexity and variations of transplant treatment options.[1] This article describes some of the historical developments of HSCT over the years.
Over The Years
1950s
In the early years, bone marrow or spleen extract was injected or fed to the patient with a variety of conditions including anemia, leukemia, and chlorosis. Thomas et al[2] first reported the infusion of bone marrow in 1957 to patients who received radiation and chemotherapy. In 1957, several laboratory workers were treated with human bone marrow transplant (BMT) after exposure to radiation due to the Vinca nuclear reactor accident.[3] Although recovery of hematopoietic function did occur, it was unclear if long-lasting benefit was possible. These early experiences led to the use of HSCT to promote recovery of hematopoietic function after myeloablative chemotherapy and radiation therapy. During the late 1950s, Thomas et al[4] reported the use of total body irradiation and syngeneic transplantation for treatment of leukemia.
1960s
In the early 1960s a better understanding of human leukocyte typing (HLA) led to the use of allogeneic sibling donors for transplantation. At that time, the use of autologous transplantation was disappointing because of contamination with tumor cells. However, clinical trials continued to evaluate the use of autologous transplant for lymphohematopoietic malignancies. A review of approximately 200 transplants reported in the 1960s indicated that more than half of the patients failed to engraft post transplant.[5] The experience of poor outcomes post transplant led to a decline in the number of transplants performed. Emphasis was placed on developments in the areas of histocompatibility, conditioning regimens, and prevention and treatment of graft-versus-host disease (GVHD).
1970s
In the 1970s, efforts were made to improve supportive care measures such as the use of antibiotics and more effective conditioning regimens. Because of these improvements, interest in BMT for aplastic anemia and leukemia increased[6] and overall survival rates rose to more than 70%. By the late 1970s, Thomas et al[6] demonstrated the use of allogeneic bone marrow from an HLA identical sibling following administration of total body irradiation and cyclophosphamide.
1980s
A nuclear reactor accident in 1986 in Chernobyl resulted in marrow suppression of hundreds of persons in Russia. Marrow transplantation was used as a treatment for hematologic recovery.[7] Initial bone marrow recovery occurred and there were only two long-term survivors reported. Many persons died of nonhematologic toxicity of radiation exposure, including burns.
Interest in BMT continued to grow and by 1986 approximately 5,000 transplants were performed each year at more than 200 transplant centers.[8] Emphasis began to focus on establishment of criteria for performing a BMT, including patient risk factors, disease status, type of transplant, and presence of infection or other toxicities. The use of a chemotherapy-based preparative regimen of busulfan and cyclophosphamide was used to replace the use of total body irradiation with busulfan and cyclophosphamide.[9] During the 1980s, knowledge of the cryopreservation and storage of autologous stem cells grew. The use of autologous BMT became common for treatment of a variety of hematologic diseases and solid tumors. Interest in the use of the stem cell collected from the peripheral blood was introduced in the mid to late 1980s.[10] Stem cells were found to circulate in the peripheral blood following administration of colony stimulating factors with or without chemotherapy. [11] , [12] In the late 1980s, Kessinger et al[13] introduced the use of the peripheral blood stem cells for allogeneic transplant. Advantages to the use of stem cells collected from the peripheral blood were described as faster neutrophil and platelet recovery and decreased need for supportive care such as intravenous antibiotics and blood transfusions.[12]
In 1986, the National Bone Marrow Transplant Donor Registry was developed in the United States. Similar types of registries exist in other countries throughout the world.[14]. The registry, now called the National Marrow Donor Program, serves to seek and identify unrelated stem cell donors for patients who do not have a related suitable HLA match and to coordinate the collection of peripheral blood or bone marrow stem cells. Interest in use of the umbilical cord blood (UCB) as a source of stem cells for unrelated, related, or autologous transplant grew through the late 1980s.
1990s
Throughout the 1990s, the use of HSCT for treatment of a variety of diseases and conditions continued to grow. Both autologous and allogeneic stem cell transplant were used by many transplant centers throughout the world. Many different conditioning regimens were developed to treat a variety of diseases. The use of the unrelated donor as a source of stem cells for transplantation continued to grow because of improved understanding of HLA typing. In the late 1990s, non-myeloablative stem cell transplant (NST) was used as an alternative treatment option for hematologic diseases and solid tumors. [15] , [16] The conditioning regimens used for NST are less toxic, which results in minimal treatment-related hematologic toxicities such as neutropenia, anemia, and thrombocytopenia. Nonhematologic toxicities associated with NST are mild compared with the side effects associated with myeloablative transplant. Additionally, NST is better tolerated by the elderly patient or persons with comorbid conditions.
An increased interest in the use of UCB as a source of stem cells for transplantation grew in the 1990s. The UCB is a rich source of stem cells that may be used for unrelated, allogeneic, or autologous stem cell transplant in children and adults. This source of stem cells can be infused fresh or collected and stored for later use. The use of double UCB transplant has been used in some settings to increase the total stem cell dose infused. [17] , [18]
21st Century
Efforts continue to improve the prevention and treatment of GVHD. Use of HSCT for the treatment of a variety of malignant and non-malignant hematologic diseases and autoimmune conditions continues to grow. For example, one study evaluated the use of transplant for the treatment of multiple myeloma utilizing single versus double autologous HSCT.[19] In addition, clinical studies are being conducted to evaluate the efficacy of autologous followed by non-myeloablative allogeneic stem cell transplant for treatment of multiple myeloma.[20] The American Society of Blood and Marrow Transplant (ASBMT) published recommendations for the timing of transplant consultation.[21] These recommendations provide guidance related to the appropriateness of transplantation for some hematologic diseases. A National Institutes of Health Consensus Development Project has developed criteria for the diagnosis, management, and clinical trials of chronic GVHD.[22] Interest in the use of mesenchymal stem cells for treatment of acute GVHD has been studied,[23] and use of extracorpeal photopheresis in treatment of chronic GVHD has been evaluated, but ongoing research is needed. [24] , [25] Many innovative treatment strategies continue to be explored. Ongoing advancements in the understanding of HLA typing continue, and a description of the HLA nomenclature was recently published.[26]
When reflecting back over the years, it is interesting to note that many ideas learned in the late 1950s are still relevant today. In 1957, Thomas et al[2] demonstrated the influence of the immune system and hematologic status on outcomes of HSCT. It was recognized in the early days that the occurrence of GVHD contributed to the elimination of tumors. Today, ongoing clinical trials continue to investigate the graft-versus-tumor effect. Although much has been learned, many of the basic concepts of transplantation remain the same.
Standards of Care
Over the years, several professional organizations have developed standards of care for practice in the field of HSCT. The American Society of Clinical Oncology and the American Society of Hematology have collaborated on clinical care and research related to the treatment of cancer. Some of these efforts included the use of transplantation as a treatment option for a variety of hematologic and nonhematologic diseases. In the 1970s the International Bone Marrow Transplant Registry was formed to serve as a data bank for allogeneic and syngeneic transplant. The Autologous Bone Marrow Transplant Registry was formed in 1990 to encourage international data collection related to autologous transplantation. The ASBMT was initiated to promote advancement in the specialty of HSCT and to develop guidelines for transplant centers to use as criteria for standards of practice for autologous and allogeneic stem cell transplantation. The ASBMT has developed evidence-based reviews for acute lymphocytic leukemia, acute myelogenous leukemia, multiple myeloma, and diffuse B-cell lymphoma. [27] , [28] , [29] , [30] , [31] , [32] Similar organizations have been developed in Canada and Europe.[33] These professional organizations provide a forum for development of standards of practice related to the specialty of HSCT.
The Center for International Blood and Marrow Transplant Research (CIBMTR) was initiated in 1972 to collect and analyze data from transplant centers throughout the world. More than 390 transplant centers participate in submitting data to the CIBMTR for the purpose of analyzing outcomes of allogeneic and autologous transplant. This data bank serves as a resource for trends related to the use of HSCT for treatment of disease and includes data related to type of transplant, use of various preparative regimens, and patient-related demographic data. According to the most recent CIBMTR data (www.cibmtr.org), unrelated transplants are most often performed using peripheral blood stem cells, and the use of peripheral blood stem cells have increased significantly for autologous and allogeneic transplantation.
The Center for Disease Control has developed “Guidelines for Preventing Opportunistic Infections Among Hematopoietic Stem Cell Transplant Recipients.”[34] These guidelines were developed through efforts of the Center for Disease Control, Infectious Disease Society of America, and ASBMT. In addition, these organizations have developed recommendations for the vaccination of HSCT recipients.
The Foundation for the Accreditation of Cellular Therapy was originally formed in 1996 by the ASBMT and International Society for Cellular Therapy. The purpose of the Foundation for the Accreditation of Cellular Therapy is to offer voluntary inspection and accreditation of cell therapy programs. International standards in the field of cellular therapy have been developed which address the clinical and laboratory components of care related to cellular therapy. Additional information may be obtained through the web site (www.factwebsite.org).
Numerous nursing publications have addressed the development of standards for HSCT nursing practice. [35] , [36] , [37] , [38] , [39] , [40] The practice of transplant nursing continues to grow as a recognized specialty in the field of oncology nursing.
Conclusion
There has been considerable progress in the field of HSCT. [41] , [42] Although much has been learned, use of old and new insights in HSCT will continue to be combined to identify the most effective treatment options.
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Susan A. Ezzone, MS, RN, CNP, AOCNP®: Nurse Practitioner, Blood and Marrow Stem Cell Transplant Program, The Ohio State University Medical Center, Arthur G. James Cancer Hospital & Research Institute, Columbus, OH
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