Chapters Transcript Video 50 Years | Stem Cell Transplantation at Dana-Farber Brigham Cancer Center Back in the beginning days of transportation in the early 1970s it was a very different entity that we see now because we had to learn everything from scratch. There was no procedure that had preceded us. We're very selective about who we transplanted in the early days. It was almost exclusively people with a plastic anemia and bone marrow failure. And we had a very serious concern that people above the age of 30 or 35 couldn't tolerate the intensity of the procedure. And so that was our upper limit. And of course we didn't have much of the medicines that we have. Now. The antibiotics were much more limited. The blood product support was much more limited. The analgesics, the the anti rejection drugs, things of that nature were very primitive at the time and it was it was a very difficult And at that time we had to transplant beds and the patients would be in the hospital for at least three months for their transplants. And so we did probably typical about 6-8 transplants a year opposed to today. Where we have over 150 transplant beds and we do over 500 transplants at that time. Most transplants have been al genetic transplants where you go where you would find an H. L. A compatible brother or sister that would be able to donate stem cells for patients. But only about 25% of patients will actually have a mad sibling. In the early eighties my lab got involved in developing monoclonal antibodies. The technology has just been developed. We were looking for ways of using these antibodies because the antibody could distinguish leukemia cells from normal cells, leukemia cells from normal stem cells. And we had the idea that we could use these in the laboratory to purge a patient's own bone marrow of any residual leukemia cells and then make those stem cells available for a stem cell transplant to that same patient that was extended to lymphoma. With different sets of antibodies, then extended to aml acute myeloid leukemia with different antibodies. And so we developed the whole stem cell transplant program that was based around these immunological methods. So we in fact set out to make monoclonal antibodies because I wanted to make the magic bullet to treat lymphoma on antibody to cure it. We had a problem. The bone marrow's Where we got the stem cells to do bone marrow transplants were contaminated by cancer cells. We developed laboratory techniques to cleanse the bone marrow. It took years to figure out how to do it. And we started in the 80s, but that's how autologous transplant happened with monoclonal antibodies. The Brigham and Women's Hospital in Dana Farber Cancer Institute each had their own transplant programs before in 1996 when we combined at that time we were able to bring together the power and strength of both institutions. And we went from being sort of an intermediate two intermediate sized transplant programs to one of the largest transplant programs in the world and that allows us to enroll more patients on clinical trials. We get answers to clinical questions more rapidly when you can treat more patients on the specific clinical trial. And that has a lot of benefit for the patients. And also for the investigators. At the time we were trying to reduce some of the transplant complications, particularly graft versus host disease by taking out the immune system before we gave it back to the patients. This was called T cell depletion. We took the T cells out and we found was that the that the the leukemias were relapsing at an unprecedented rate. So we inferred from that that the t cells were important. We would collect these immune cells and we would administer them to a patient who had had a prior transplant and then relapsed. And lo and behold they went into remission and that was called the donor lymphocyte infusion. So we were among the first to do that internationally and that led to a whole evolution and how we think about transplantation and ultimately this gave rise to what we now refer to as a reduced intensity conditioning transplant or a rick transplant where we give much lower doses of chemotherapy and we are much more dependent on the immune system to deal with it. And that resulted in our ability to move transplantation. Too much older group of people. Dana Farber has been at the forefront of efforts to prevent and treat graft versus host disease. Colleague Dr Ritz and his laboratory have really made great strides in understanding the immunological underpinnings of chronic graft versus host disease. In his lab, the mechanisms by which B cell immunology is important in chronic graft versus host disease were first elucidated. We then went on and did clinical trials using B cell depletion as a way of treating graft versus host disease. The success of those trials then led to the development of a brutal nib. The first FDA approved compound in the management of steroid resistant chronic graft versus host disease ill too is certainly something that has been a priority for the transplant group at Dana Farber. We explode the biology, we discovered the rationale for that. And then we actually brought it into the clinic to actually treat patients who have chronic graft versus host disease. And what we discovered was that the treatment is safe and it is resulting in an improvement in patients. When I started doing transplants. Well over 30 years ago, the only donors who were available for patients were their brothers or sisters who were exact matches but that's changed a huge amount over the past 30 years. We're now able to get matches from a whole variety of sources. Things have really changed in the last two decades. You know uh in this field because nowadays, you know, many of our transplant patients don't get very sick at all during the transplant. And some of the, you know, the patients can get through the whole thing without even being in the hospital and the progress that has happened with regard to how patients are cared for. I mean anti medics that have gotten so much better our knowledge and research regarding infection control in all the areas of trying to keep a patient and family safe. So we've come a long way with regard to the research and everything that the data. Barbara Brigham's cancer care program has developed that has really has improved patient's quality of life While they're going through this very stressful and challenging process. I think the last 10-20 years really saw a dramatic improvement in survival and outcomes for patients who undergo transplant. And a lot of that was driven by improvements in the toxicity of transplant. I think for the next 5, 10, 20 years and beyond. One of the things that we're going to be focusing on a lot is how to reduce the relapse rate and improve the actual cure rate for our patients. And That's something that a lot of the investigators at the Farber here are focused on in a variety of different ways over the last 50 years. We've seen so much progress in the field of stem cell transplant but we recognize that there's still a lot of work to be done. We are still confronted despite this lifesaving procedure with the risk of relapse. I think we have our work cut out for us but I think we also have a road map into the future in terms of what are the areas that we really want to focus on? Published November 29, 2022 Created by
