Confronted with a leukemia diagnosis that left him with few options, Mushtaque Jivani traveled halfway across the country in 1976 in search of hope. This hope came in the form of a completely new investigational therapy known as bone marrow transplantation.

The young man would receive the first successful transplant at City of Hope. Thirty-five years later, his survival remains a testament to the promise of medical research. And on Jan. 13, the center that saved his life reached a landmark of its own: 10,000 transplants.

To reach its 10,000th transplant, City of Hope had to embark on its own journey of scientific and medical discovery. This voyage was only possible through the bold first steps of pioneers in the field — men and women who believed the investigational treatment could save the lives of patients once told they could not be cured.

"These occasions provide an opportunity to pause and reflect," said Stephen J. Forman, M.D., Francis and Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation and chair of the Department of Hematology & Hematopoietic Cell Transplantation. "Day to day, our work is all about a single life at stake that we're trying to save.

"Reaching 10,000, you think about the many people, children and adults, who have benefited from City of Hope's nursing care and research — the many wonderful people who have come here, trusting us to care for them."

Today, physicians use the term hematopoietic cell transplantation, or HCT, to describe this therapy, which is used to treat patients with life-threatening cancers and other disorders of the blood and immune system. In the procedure, physicians seek to establish a new, disease-free blood and immune system by transplanting healthy blood stem cells into the body.

In the first procedures in the early 1960s, stem cells were collected exclusively from a donor's bone marrow. As medicine advanced, HCT added two different sources for stem cells: peripheral blood (from the bloodstream) and umbilical cord blood. Today, HCT describes any transplantation of the stem cells, regardless of the source.

Humble Beginnings

The City of Hope HCT story began more than 34 years ago in a three-bed unit led by two physicians — Karl Blume, M.D., who is now with Stanford University, and the late Ernest Beutler, M.D. — along with a few dedicated nurses. Guided by scientific diligence and persistence, they were one of the first teams anywhere to perform a successful transplant, proving that the therapy was lifesaving.

Now more than 30 physicians care for patients in an advanced 60-bed unit dedicated solely to the treatment of hematologic cancer in City of Hope Helford Clinical Research Hospital. Performing more transplants than any other center in the state, the program also is one of the world's largest and most successful.

"In the early days, this was a therapy of uncertain efficacy, done at a very small number of places. Our results helped validate that this could work to cure patients. Now it is a standard of care for the treatment of many diseases," said Forman, who joined City of Hope in 1978.

"Drs. Blume and Beutler were the real pioneers in this effort," he continued. "It is upon their shoulders that we now all stand."

The success of the City of Hope transplant program also has given hope to patients who lack a matching donor within their families.

These patients must rely on stem cells from unrelated donors, sometimes a world away. The procedure carries potential for dangerous complications, especially among the sickest patients. But the National Marrow Donor Program recently reported that City of Hope's Matched Unrelated Donor Program is the only one nationwide to achieve above-expected survival outcomes for five consecutive years.

"Caring for patients, we work as a team of physicians, nurses, scientists and other support staff, including those in transfusion medicine and the Histocompatibility Laboratory," said Auayporn P. Nademanee, M.D., director of the Matched Unrelated Donor Program and the Jan & Mace Siegel Professor in Hematology & Hematopoietic Cell Transplantation. "It allows us to anticipate — to say, 'Ah, something's going to happen tomorrow. Let's take care of the problem now.'"

The Influence of HCT

City of Hope research continues to lead to advances. New approaches to the transplant regimen improved cure rates, extended the procedure to older patients and expanded HCT to diseases beyond leukemia, lymphoma and multiple myeloma.

Through studies led by John A. Zaia, M.D., Aaron D. and Edith Miller Chair in Gene Therapy, and the late Gerhard Schmidt, M.D., City of Hope was among the first to develop a treatment to prevent cytomegalovirus, a potentially deadly infection to HCT patients.

Andrew A. Raubitschek, M.D., chair of the Department of Cancer Immunotherapeutics and Tumor Immunology, investigates a strategy called radioimmunotherapy, in which engineered immune molecules deliver targeted radiation directly to cancer cells. This approach has shown promise for lymphoma and is now being extended to leukemia.

Following on City of Hope’s remarkable transplant results for treatment of patients with HIV-related lymphoma, scientists also have adapted HCT to tackle HIV/AIDS. Zaia worked with John J. Rossi, Ph.D., Lidow Family Research Chair in the Department of Molecular and Cellular Biology, Amrita Krishnan, M.D., director of the Multiple Myeloma Program, and David DiGiusto, Ph.D., research professor in the Department of Virology, to develop a technique that couples HIV-fighting gene therapy with HCT in a bid to cure patients of HIV-related lymphoma while also blocking the virus that causes AIDS. A recent study from the City of Hope transplant program showed the anti-HIV genes persisted in patients up to two years after infusion.

Although HCT has come a long way, challenges remain. City of Hope laboratory and clinical scientists are driven to make HCT safer and more effective and help extend the length and quality of life of patients who turn to City of Hope for care.

Said Forman: "At the end of the day, all of our efforts are about our commitment to patients and their families — recognizing each of them as a dignified human being with a story to tell and a life to live. They also are our partners in developing new therapies for those who will come to us tomorrow for care. There’s an enormous number of people who are alive today because they were and are a part of something we did at City of Hope that was both bold and new. And that number continues to grow."