George Santos and his contributions to the science of bone marrow transplantation

As I read the recent issue of The Cancer Letter, I could not help but reflect on the environment around bone marrow transplantation in the early 1970s.  

Don Thomas got much of the credit, but the other major leader in the field was George Santos—who was at Johns Hopkins. Don Thomas introduced the use of the radiation to ablate the leukemic bone marrow as the preparative regimen, but it was George Santos who introduced the use of high dose cyclophosphamide as a preparative regimen that did not require the two headed cobalt unit that Thomas had at the Mary Imogene Bassett hospital in Cooperstown.  

I invited them both to Roswell in about 1970 to critique our program—and both were pioneers.  Thomas got the Nobel prize because of the volume and innovation, but in many ways, Santos did as much for the advancement of the therapeutic technique.  

The other interesting thing about that time was that the chairman of Medicine at the University of Washington was an infectious disease guy (of FUO fame) by the name of Robert Petersdorf, who believed it was wrong to initiate antibiotic therapy, even in leukopenic patients, until you had the blood culture results back so that you could use targeted antibiotic treatment.  

Don Thomas had a team of investigators, including a Master’s level microbiologist named Riginald Clift, and they all made rounds on their patients at Swedish Hospital in Seattle and did not subscribe to the infectious disease practices of Petersdorf.  

Bone marrow transplants for malignancy are performed as highly intensive treatments to eliminate every possible malignant cell, particularly in leukemia and lymphoma. With this approach, we rescue patients from the toxicity to the bone marrow induced by cancer treatment. 

For example, in patients with acute lymphocytic leukemia who are in second remission, we can expect a 50% to 60% disease-free survival, with patients surviving from 15 to 16 years after the transplant. In patients with acute myelogenous leukemia who are in first remission, our data suggest a disease-free survival of close to 65% of patients thus treated. With chemo-therapy in first remission, however, results vary, with long-term survival ranging from 20% to 40%. Most physicians obtain only about a 20% long-term survival with chemotherapy alone.

In subsequent remissions in patients with acute myelogenous leukemia, the results with transplantation, while still encouraging, are not quite as good. In patients with chronic myelogenous leukemia, if the transplant is done during the chronic phase of the disease, one may expect from 50% to 65% disease-free survival, with patients in some series surviving 10 or 15 years. More recently, patients with non-Hodgkin’s lymphoma or Hodgkin’s disease, who are not curable by conventional methods, have had disease-free survival of from 50% to 60% with bone marrow transplants.

We have been using family members for donors of bone marrow; unfortunately, however, donors are not available for most patients. We are now trying another approach, that of using the patient’s own bone marrow, first purging it of any tumor cells. With this approach in acute myelogenous leukemia, we have done relatively well in patients in second and third remissions, achieving a 30% disease-free survival in over 60 patients.

The most exciting application of this approach has been in the treatment of the lymphomas. We have treated from 30 to 40 lymphoma patients (about 1,000 patients worldwide have been treated by this method), with the results suggesting that from 50% to 60% of patients will have long term, disease-free survival, with a good number being cured.  

George Santos, professor emeritus of oncology and medicine at the Johns Hopkins University School of Medicine, died Jan. 21 due to complications from cancer. He was 72.

A world-renowned expert in bone marrow transplantation, Santos founded the Johns Hopkins Oncology Center’s bone marrow transplant program and served as its director from 1968 until his retirement in 1994.

Among his extensive research and clinical accomplishments was development of the regimen to prepare patients for the procedure by using the anticancer drugs busulfan and cytoxan, which quickly became the worldwide standard. His animal studies in transplantation biology continue to serve as guides in the development of new therapeutic approaches.

“As one of the first Oncology Center faculty members, George Santos played a critical role in establishing the field of oncology as a specialty,” said Martin Abeloff, director of the Johns Hopkins Oncology Center. “I was privileged to have worked with him and learned from him as an oncology fellow and later as a colleague. Many of the great strides we have made today in bone marrow transplantation as therapy for cancer and other diseases can be directly traced to the early research of Dr. Santos.”