Hematopoietic cell transplantation (HCT) has become the standard of care for numerous life-threatening illnesses. Here, we present a brief history of this evolving therapy, both worldwide and at City of Hope.
In 1976, a young college student diagnosed with life-threatening acute myelogenous leukemia, Mushtaque Jivani, was told by his doctor to prepare for inevitable death. On the advice of his physician cousin, Jivani traveled across the country to City of Hope in Duarte, Calif., to receive treatment in the center’s newly-established Bone Marrow Transplantation (BMT) Program. Because his prognosis was so poor, Jivani believed the highly investigational BMT procedure might be his only hope for survival. He became the sixth patient transplanted at City of Hope in 1976. One year later, Jivani celebrated the first anniversary of his transplantation by sharing a cake with the BMT Program’s three physicians and six nurses. His survival – the first at City of Hope – was a landmark occasion, symbolizing enormous hope in the battle against cancer and other life-threatening diseases.
Thirty-five years later, Mushtaque Jivani is noted as one of City of Hope’s longest-living survivors.
In 1976, with guidance from colleagues at the Fred Hutchinson Cancer Research Center, City of Hope developed its own BMT Program. The program’s first patient with advanced leukemia underwent transplantation on May 18, 1976. Six patients were treated with BMT that first year, including Mushtaque Jivani.
Since 1976, when the program was initiated by Karl G. Blume, M.D., and Ernest Beutler, M.D., City of Hope’s BMT Program has grown by leaps and bounds. Due to the efforts at City of Hope and other leading cancer centers, BMT is now considered the standard of care for numerous malignancies.
In 1978, Stephen J. Forman, M.D., joined the program from the University of Southern California. In 1980, John A. Zaia, M.D., came from Harvard to join the staff as director of Virology and Infectious Diseases. Zaia established himself as an integral part of the program’s efforts to understand the biology of cytomegalovirus (CMV)-related pneumonitis, which was a major limitation to the success of BMT, and later went on to develop the gene therapy program at City of Hope, focusing on treatment of HIV with genetically-modified stem cells and T cells.
First Encouraging Results Published
In 1980, City of Hope’s BMT program published in the New England Journal of Medicine its results of the first series of patients undergoing BMT, confirming and extending the observation that transplant could be curative for patients with leukemia. Over the next six years, the program increased the numbers of transplants and diseases it treated with transplantation, focusing its efforts on increasing survival rates by addressing the problems of leukemic recurrence, graft-versus-host disease (GVHD) and CMV infection.
In 1981, under the leadership of Blume and Forman, the National Cancer Institute (NCI) awarded City of Hope its first Program Project Grant in BMT. This three-year grant supported studies involved with clinical transplantation for leukemia and transfusion support, as well as studies in immune reconstitution, virology and GVHD.
Autologous transplantation (using the patient’s own stem cells) became recognized as an attractive treatment option because the patient's body could not reject its own cells as it would a donor’s cells. In cases where the marrow was not completely contaminated with disease, it was thought high-dose chemotherapy protocols, with or without radiation, could be used as conditioning, and the autologous transplants would have a reasonable chance of success. Researchers at City of Hope, led by Gerhard Schmidt, M.D., and Philip Bierman, M.D., developed these autologous transplantation protocols.
The first autologous transplants at City of Hope were performed in June 1986. Today, autologous stem cell transplantation is the most common form of HCT, used for a wide spectrum of diseases. Most autologous stem cells for today’s transplants are harvested from peripheral blood, eliminating the need to use bone marrow.
In 1987, Blume left City of Hope to develop a transplant program at Stanford University, and Forman assumed the position of director of City of Hope’s BMT Program. By that time, the program had outgrown its 11-bed unit and, with the generous support of Isadore Familian, the Sunny and Isadore Familian Children’s and Bone Marrow Transplantation Center opened in late 1989.
Previously, it was thought BMT recipients needed to have a related donor to avoid rejection of the transplant. For patients without siblings or close living relatives, or whose relatives were not sufficiently genetically matched, this posed a severe problem. The determining factor as to what constitutes a “match” is an HLA type. The HLA system is a group of genes producing six distinct antigens. Due to the limited numbers of HLA antigens in the human population, it was recognized that unrelated individuals could share HLA types. Therefore, HLA-matched unrelated donors (MUDs) could be used in HCT with a low probability of rejection. Now, there are national and international registries of volunteer donors. These have greatly expanded the number of patients who could benefit from having a MUD transplant.
In 1989, a patient with leukemia was the institution’s first matched unrelated donor transplant recipient. It was a dramatic event. The marrow, which was obtained from a donor in England, arrived at Los Angeles International Airport and was airlifted to City of Hope by a Los Angeles County Sheriff’s Department helicopter. Today, under the leadership of Auayporn Nademanee, M.D., director of the MUD Program, and David Senitzer, Ph.D., director of the Histocompatibility Laboratory, approximately one-half of allogeneic transplants performed at City of Hope involve volunteer donors who are not related to the patient.
In support of the many patients throughout the world who require MUD transplants, City of Hope’s Transfusion Medicine Program incorporates a strong focus on the recruitment of donors through the National Marrow Donor Program. City of Hope is also a collection center for donors whose marrow needs to be transported to other sites.
In 1990, the role of BMT in the treatment of cancer - and its importance to biology and medicine – was acknowledged when the scientific world awarded the Nobel Prize for Medicine to E. Donnall Thomas, M.D., who pioneered and performed the first BMT. With further developments in the science and its clinical applications, the field had established itself as a separate discipline. Thus, in 1994, Forman, Blume and Thomas co-edited the first textbook on BMT, titled "Bone Marrow Transplantation." The second, larger edition, titled "Hematopoietic Cell Transplantation," was published in 1999, and the third edition in 2004. This book is the definitive resource on every aspect of transplantation, with contributions from 104 internationally recognized experts, many of whom are physicians and scientists at City of Hope.
In 1991, City of Hope performed a transplant that received national attention when a young girl with leukemia underwent transplantation utilizing both umbilical cord cells and bone marrow from her younger sister, who was conceived because neither a family nor unrelated marrow donor could be found. This transplant provoked a national debate on the family’s decision, which led to a story on the cover of TIME magazine and other national publications. At the time of this writing, both girls are part of a loving family, each owing the other the opportunity for life.
In 1993, following the untimely death from cancer of Schmidt, the program established a lectureship in his memory: the Gerhard Schmidt Memorial Lecture in Transplantation Research and Medicine. Schmidt, who joined the program in 1977, was the director of the Histocompatibility Laboratory and established the Autologous Stem Cell Transplant Program. He was also the first director of the MUD Program. In addition to his laboratory and clinical contributions, he published one of the first studies on the quality of life of transplant survivors. The lectureship is awarded to investigators in the field and is delivered annually in association with the “Celebration of Life” HCT Reunion held each April on campus. Distinguished lecturers have included Beutler, John Zaia, M.D., Rainer Storb, M.D., Peter Parham, Ph.D., Ron Levy, M.D., Catherine Verfaillie, M.D., Stanley Riddell, M.D, and Nobel laureate David Baltimore, Ph.D.
In 1995, under the guidance of Director Joseph Rosenthal, M.D., City of Hope began to expand its Pediatric BMT Program, resulting in a significant increase in the number of children undergoing treatment for solid tumors, hematologic malignancies, genetic diseases and certain solid tumors. This growing program specializes in the use of transplantation in the treatment of leukemia, sarcomas and neuroblastomas.