The History of Blood and Marrow Transplantation

The History of Blood and Marrow Transplantation © 2014 BMT InfoNet

Research and Script: Susan K. Stewart

Narrator:  Thomas J. Stewart

Video Editor: Stephen J. Anderson

Audio recording:  Jim Reeves

Music Supervisor: Alex Reeves

Run Time:  24 minutes.

Summary: Great strides have been made in bone marrow, stem cell and cord blood transplantation. An increasing number of patients with blood disorders are now able to enjoy a second chance at life, thanks the efforts of doctors and patients who pioneered this life-saving treatment.

Update 2021:  This video identifies Nancy McClain, who was transplanted in 1963, as the longest living bone marrow transplant survivor. Since then, we have learned that a six-year-old child named Nancy Lowry was successfully transplanted with bone marrow from her identical twin sister three years earlier in 1960. Nancy Lowry, who went on to be a public health and school nurse, is alive and well today. 

Highlights:

• Allogeneic stem cell transplants (transplants using donor cells) can now be offered to more patients due to better donor matching and improvements in managing side effects of the treatment.
• More autologous stem cell transplants (transplants using the patient's own stem cells) are performed each year than allogeneic transplants.
• Research continues to improve outcomes after transplant and improve patients' quality of life.

Key Points:

00:21:   In 1955 Dr. E. Donnall Thomas began researching the possibility of using bone marrow transplantation to cure humans with life-threatening diseases.

02:03    The first successful bone marrow transplant took place in 1960, using bone marrow from an identical twin.

04:05    The first successful bone marrow transplant using marrow from a sibling who was NOT an identical twin occurred in 1968.

05:33     The first successful transplant using bone marrow from an unrelated donor took place in London, England in 1973.

07:15     The Anthony Nolan in London, England was the first registry in the world established to recruit unrelated bone marrow donors.

11:01      A registry to recruit bone marrow donors was established in the U.S in 1979.  Originally called the National Marrow Donor Registry, it is now called Be The Match.

11:35      Research began on autologous transplants (transplants using the patient’s own stem cells instead of donor cells) in the early 1980s, Autologous transplants are now performed more often than transplants using donor cells.

14:37:     In 1988, the first successful cord blood transplant was performed. 

16:46       BMT InfoNet was created in 1990 to provide patients with information and support before during and after transplant.

18:47       Advances such as better donor matching, less toxic chemotherapy before transplant, and use of half-matched related donors for transplant has made transplants safer and more widely available.

Transcription of Video:

00:21 [Narrator]   In 1955, Dr. E. Donnall Thomas began researching the possibility of using bone marrow transplantation to cure humans with life-threatening diseases. In 1955, a young doctor named E Donnall Thomas, became intrigued by the notion of bone marrow transplantation in humans. With funding from the Atomic Energy Commission, which was interested in finding a cure for people exposed to nuclear radiation, he set up a laboratory at the Mary Imogene Bassett Hospital in Cooperstown, New York. There, he and Dr. Joseph Ferebee began experimenting with bone marrow transplants in humans with advanced leukemia.

00:54   In 1958, Dr. George Mathé attempted to save workers at a nuclear reactor who were exposed to radiation, with a bone marrow transplant.  Three years later, an accident at the Vinca Nuclear Reactor, just outside Belgrade, Yugoslavia, exposed six workers to very high doses of radiation. One died, and the remaining five were transported to Paris where Dr. George Mathé transplanted them with bone marrow collected from five strangers who volunteered to help.

At the time, it was not understood that the donor needed to be a genetic match for the patient in order for the transplant to succeed. Although, all five patients survived later analysis cast doubt on whether their survival was actually due to the transplanted bone marrow.

In 1957, Dr. Thomas issued a report on the first group of patient he treated with high dose radiation and a bone marrow transplant in Cooperstown, New York. The results were disappointing. All had died within a hundred days of their transplant. Discouraged by these results, many scientists abandoned interest in human bone marrow transplantation, but not everyone.

02:03     First successful bone marrow transplant took place in 1963, using bone marrow from an identical twin.  [Note: the first successful transplant actually took place 3 years earlier than the transplant described below)

In 1960, a prominent hematologist in Boston named William Damashek, sent two of his young doctors to visit Dr. Thomas in Cooperstown. They spent a week in his laboratory learning how to perform a bone marrow transplant. One of those young doctors was Dr. Robert Kyle.

Three years later, after moving to the Mayo Clinic in Rochester, Minnesota, he was asked to consult on a case involving a nine-year-old girl named Nancy King. Nancy suffered from a blood disorder called a plastic anemia, which left her fatigued and unable to fight infection.

She was being kept alive with blood transfusions and large dosages of prednisone, but her condition was rapidly deteriorating. While examining her, Dr. Kyle noticed another child in the room and inquired who she was. The prednisone had caused Nancy to have the moon face and weight gain often associated with prednisone. It wasn't immediately apparent to him that the child was Nancy's twin. Upon learning that the child was an identical twin, Dr. Kyle proposed a bone marrow transplant.

Up until this point, the only successful transplants in humans were syngeneic transplants, transplants using bone marrow from an identical twin. Dr. Kyle needed to confirm that the two girls were indeed identical twins.

[Nancy McLain] "They took skin from me, a little small section here, and they planted it on my twin sister and then grafted her skin onto me in the same spot. If that would grow and we, our skin wouldn't be rejected, then they knew definitely that we're identical twins."

[Narrator] In 1963, Nancy was transplanted with her sister, Bonnie's, bone marrow. Today, she is doing well and leading an active life.

04:05 [Narrator] The first successful bone marrow transplant using marrow from a sibling who was not an identical twin occurred in 1968. It was not until 1968, that bone marrow from a sibling who was not an identical twin was successfully transplanted into a patient. This type of transplant is called an allogeneic transplant. The patient was a baby named David, who had a rare immune deficiency disease that had taken the life of all 11 male children born on his mother's side of the family. His pediatrician believed that only a transplant could save him and reached out to the famous immunologist, Dr. Robert Goode, at the University of Minnesota, for help. A new blood test developed by Dr. Fritz Bach at the university of Wisconsin, gave Dr. Goode the tool he needed to determine if one of David's four sisters could serve as his bone marrow donor.

[David's Father]: "Dr. Good wants us saw at the hospital to be tested for possible bone marrow transplant, to see if we can save your brother's life.

[David's Sibling]: Will it hurt?

[David's Father]: I don't think so. I believe you'll be asleep.

 [David's Sibling]: Even if it does, I'm going.

 [David's Other Sibling]: If I can help David, I will.

 [David's Sibling]: Me too.  

[Narrator]: Nine year old Doreen proved to be the best match. On August 21, 1968, David was transplanted with Doreen's marrow. Finally, in December, David returned home to his family just in time for Christmas. David continued to thrive and is alive and well today.

05:33     The first successful transplant using bone marrow from an unrelated donor took place in  1973. Other successful transplants using marrow from a sibling who was not an identical twin, quickly followed. Despite these successes, only a third of patients who needed a transplant had a brother or sister who could serve as their donor.

After many failed attempts, in 1973, the first successful transplants using bone marrow from an unrelated donor were performed. The first one took place in London, England. A two-year-old boy named Simon Bostic was diagnosed with a rare blood disease called chronic granulomatous disorder or CGD. The same disease had killed his older brother, Andrew, two years earlier. Desperate not to lose another son, the Bostic family began searching for an unrelated bone marrow donor for Simon. His mother began by asking her friends to be tested. Then she was interviewed for an article in the local press.

[Simon Bostic]: "for some reason, this was picked up by the national newspapers in the UK and the tabloid press. It became a huge, huge thing. It was front page news, who can save this child? To cut a long story, short people started going to be tested to see whether they had the correct tissue typing, because it was the tissue typing that was incredibly rare. I had a tissue typing and I think one in 50,000. Very, very rare tissue typing, very rare tissue type indeed. This is what people went in over the course of the next few months to be tested for, which pretty amazing response."

On April 13, 1973, a team led by Professor John Hobbs at London's Westminster Children's Hospital transplanted Simon with Joan McFarlane's marrow.

07:15     The Anthony Nolan in England was the first registry established to recruit unrelated bone marrow donors. Simon's successful transplant encouraged Shirley Nolan the mother of a child with a rare genetic disease called Wiskott-Aldrich syndrome, to search for an unrelated donor for her son, Anthony. although a match was never found for him, her efforts led to the creation of the world's first bone marrow donor registry, which was named in his honor. Today, the Anthony Nolan based in London boasts more than half a million bone marrow donors.

07:57     First successful transplant in the U.S. with marrow from an unrelated donor took place in 1973. Later that year, a team of doctors at Memorial Sloan Kettering Cancer Center in New York, led by Dr. Richard O'Reilly, performed the first unrelated donor transplant in the US on a five-month old infant named Matthew. Matthew was born with severe combined immune deficiency syndrome and was immediately hospitalized in a sterile environment after birth until a bone marrow donor could be found for him.

Five months later, a Danish woman named Liz Larson was identified as a donor for Matthew through a tissue typing laboratory at Rigshospitalet in Copenhagen. Over a period of two years, she donated bone marrow for Matthew on six separate occasions. Finally, he was able to go home with his parents, but died a few years later of a secondary malignancy.

08:53:   Early efforts to successfully cure patients who had leukemia or lymphoma with a transplant mostly  failed.

Dr. Donnall Thomas, who had moved his research from Cooperstown to the US Public Health Service Hospital in Seattle continued testing bone marrow transplants on patients with advanced stage leukemia.

 Patients were irradiated in an underground bunker at a former military facility, then quickly transported back to the hospital where they were transplanted. Although in several cases, the transplant initially seemed successful, most patients died within a few months. Dr. Thomas began exploring the possibility of transplanting patients earlier in the course of their disease.

08:53:   A rare success treating childhood leukemia with a transplant. In 1976, a child named Nancy Vanerka was diagnosed with acute myelogenous leukemia on her ninth birthday. Her doctors held out little hope. Then one evening, while sitting in a local diner, Nancy's parents were given a glimmer of hope.

[Nancy Vanerka] "My parents went out to eat one night and they looked out the window and in the news stand, they saw the front page of the newspaper and it said that a young girl from our area was one of the first survivors of a bone marrow transplant. They were doing experimental transplants on AML, children with AML, at the Hutch. My parents brought that to our doctor and asked why he had not suggested it. He said that he didn't think I would ever get in remission. If I did, I'd only stay there for like four days. My parents insisted that my sister be tested and really a miracle. She matched me on all seven antigens."

 [Narrator]: The family flew to Seattle for the transplant. Nancy was one of only two patients on the transplant unit to survive that year.

11:01:   Successful transplant with unrelated donor marrow led to the establishment of the National Marrow Donor Registry. However, a few years later, Dr. Thomas was reporting increasing success in patients transplanted for leukemia. In 1979, his team performed a successful bone marrow transplant for a patient named Laura Graves using marrow from an unrelated donor. The success of that transplant spurred the creation of a US registry of bone marrow donors called the National Marrow Donor Registry. Today, the registry is called, Be The Match and includes more than 11 million volunteer donors.

11:35:  In the 1980s,  autologous bone marrow transplants (using the patient’s own bone marrow) were tested at several transplant centers for patients with leukemia, lymphoma and multiple myeloma. It was an option lymphoma patient, Steve Bauer, embraced in 1983 with little hesitation.

 [Steve Bauer]: "I first heard about autologous transplants from my oncologist after seven months of unsuccessful chemo treatments to combat my stage four non-Hodgkin's lymphoma. I did not receive much information about the transplant process, since the procedure was so new and there were no other readily available resources. Despite these uncertainties, I made a decision to go forward and knew that that was my best decision to make for opportunity to beat my cancer. I had proposed to my wife in January before my transplant decision in the summer of 1983. After my transplant was completed in August, we were married that following October of 1983 and have enjoyed 31 years of happy marriage since."

Today, more autologous transplants are performed each year than syngeneic and allogeneic transplants combined.

13:05     Young singer, Kyle Rocheleu, undergoes an autologous transplant, followed by an allogeneic transplant.  In 1985, a young singer named Kyle Rocheleau had just returned from a tour in Japan. It was not unusual for her to feel fatigued after a grueling schedule of performances, but this time, the fatigue persisted for weeks. After several blood tests and a bone marrow biopsy, Kyle could not believe the news. She had acute lymphoblastic leukemia.

[Kyle Rocheleau] "Denial. I thought they had the wrong marrow. I was absolutely certain that they'd made a mistake."

 [Narrator]: Doctors at UCLA Medical Center in Los Angeles immediately began searching for a bone marrow donor, but the national marrow donor registry was still in its infancy. None of its donors were a match. Out of options, the doctors performed an autologous bone marrow transplant on Kyle instead. The transplant brought her 18 months of good health before the leukemia returned.

 Once again, doctors launched a search for an unrelated donor. This time, she got lucky. A few months earlier, an employee at a blood bank in Northern California, decided to conquer her fear of needles by having a blood test so that she could join the bone marrow registry. She was a perfect match for Kyle. In 1988, Kyle underwent a life-saving bone marrow transplant and is alive and well today.

14:37     Umbilical cord blood becomes a new source of cells for transplant. Despite a growing number of volunteer bone marrow donors in the late 1980s, the number of people able to find a suitable donor remained small compared to the need. Dr. Hal Broxmeyer and his colleagues at Indiana University, believed that cells in the discarded placenta and umbilical cord of newborn babies could be an alternate source of cells for transplant.

In 1988, that theory was put to the test. A five-year-old child in North Carolina named Matthew Farrow was diagnosed with a blood disorder called Fanconi Anemia. Unable to find a matching bone marrow donor, Dr. Joanne Kurtzberg at Duke University Medical Center in North Carolina, proposed an experimental cord blood transplant. The cells would come from Matthew's soon to be born baby sister.

The Farrows agreed and arrangements were made for Matthew to have the first ever cord blood transplant at Hospital Saint-Louis in Paris, France, under the supervision of Dr. Eliane Gluckman, an expert in treating children with Fanconi anemia. He and his parents spoke no French. His mother created a set of flashcards with pictures to help him communicate what he needed to the hospital staff.

[Matthew Farrow] "I was five years old when the time came for my transplant. I remember actually being frightened, being unaware of what was actually going on, not only to be leaving the country, but also the loneliness that I was going to experience being in the hospital without my parents."

[Narrator] After six months, the Farrow family returned home and Matthew was finally able to enjoy normal childhood activities without taking extraordinary measures to guard against infection. Today, Matthew works at a cord blood bank where he helps recruit cord blood and counsels patients about this saving treatment.

16:46:    BMT InfoNet is established to meet the need for patient information. By 1990, the number of transplants performed annually had grown to 11,000, yet little information was available to patients, written in simple language, that explained to them what to expect. Transplant survivor Susan Stewart, launched BMT InfoNet to address that need.

 [Susan Stewart] "The reason that I started BMT InfoNet was because at the time of my transplant, there was no information available to the lay person about what to expect before, during or after transplant. We began as a newsletter and eventually expanded into offering books about transplantation, which are now used at most of the leading medical centers, as well as a peer support program that connects people who are about to go through transplant with someone who's already been through transplant and explains from the patient's perspective, what to expect."

18:47: [Narrator] High dose chemotherapy instead of radiation and better donor matching improves results after transplant. Since the early days of transplantation, many advances have made this life-saving therapy available to more and more patients. Pioneering work by Dr. George Santos at Johns Hopkins University Medical Center in Baltimore, now allows doctors to prepare many patients for transplant with chemotherapy instead of the more toxic total body irradiation.

Better donor matching and using stem cells collected from the bloodstream, instead of bone marrow is now possible. The advent of DNA technology has enabled doctors to more precisely match potential donors with patients and transplants are now performed not only with bone marrow and umbilical cord blood, but with cells collected directly from the bloodstream as well.

18:32:    Reduced intensity transplants make it possible for older patients to have a transplant.  A new type of transplant called non-myeloablative or reduced intensity transplant allows doctors to prepare patients for transplant with milder, less toxic dosages of chemotherapy. This less intensive pre-treatment makes it possible for older patients and those with other health issues to consider a transplant and for much of the procedure to be performed in an outpatient clinic.

19:58:   Transplants with related donors whose HLA is a half-match with the patient are now possible. New research also offers hope for some patients like African-Americans and those of Asian descent who still struggle to find a compatible donor. Haplo identical, or half matched transplants, can now be performed using cells from any first degree relative, a parent, a sibling, or the patient's child.

[Pamela Carroll, mother of transplant recipient] "He had a transplant from his dad, but that was the only choice. It was because he didn't match anybody else. We were it. It was mom or dad. Between the two of us, his dad was a closer match, not a match, but a closer match. That was just a chance we were willing to take. We went with his dad."

20:46: [Narrator]  BMT Clinical Trials Network searching for ways to make transplants safer and more effective. Challenges like graft-versus-host disease, which occurs in approximately 50% of patients who undergo an allogeneic transplant, still remain. For some patients, the transplant is only a short-term cure and the long-term effects of transplant on a patient's quality of life are only now beginning to be addressed.

The BMT Clinical Trials Network, a consortium of leading transplant centers, is conducting research to address these and many other transplant issues. Through the partnership of doctors and patients who take part in these clinical trials, we are rapidly learning how to make transplants safer and more effective, so that many more people have the opportunity to celebrate a second chance at life.