When Dr. E. Donnall Thomas first pioneered bone marrow transplantation in the 1960s and 1970s, his goal was to treat patients with advanced leukemia — at the time, a nearly universal death sentence. Today, thousands of patients with blood cancers around the world are cured every year thanks to modern forms of transplantation, and the procedure is also used for dozens of other diseases besides leukemia, with many more in the research pipeline.
Most importantly for the future of cancer therapies, it was Thomas and his colleagues’ work developing bone marrow transplantation at the newly founded Fred Hutchinson Cancer Research Center that revealed the potential for the human immune system to eliminate cancer.
Although the researchers originally aimed to cure leukemia by eradicating patients’ malignant white blood cells with high doses of chemotherapy and radiation, and then replacing them with healthy donor cells, they found something unexpected — when a cancer patient received a transplant from an identical twin, their disease often roared back within mere months of
the transplant.
Read the rest of our series, originally published in Hutch Magazine in summer 2015:
One life — and a world of possibilities
The impact of bone marrow transplantation: One patient's story
'The successes kept you going'
Dr. Fred Appelbaum recounts 40 years of difficult and exhilirating advances in bone marrow transplantation
Bone marrow transplant ins and outs (graphic)
Steps in the transplant process, BMT timeline and more
Grateful survivors gather at BMT reunion
Transplant recipients, donors, families and caregivers shared stories, learned and celebrated
'This little bag of cells is going to save her life'
A girl and her mom remember a lifesaving transplant
But patients who received cells slightly different from their own — from donors such as siblings who were not genetically identical matches or even unrelated individuals — had much lower relapse rates. For these patients, the researchers found that the unrelated donated immune cells were better able to recognize their cancer as “foreign” and attack it.
That observation launched decades of intense exploration by research teams at the Hutch and around the world into the immune system’s tumor-fighting potential. Ultimately, it laid the groundwork for the now-burgeoning field of immunotherapy, which uses a variety of techniques to harness or enhance the power of immune cells or molecules to precisely target malignant cells, sparing healthy cells the toxic side effects associated with traditional cancer treatments.
Immunotherapies represent just one of the families of treatments that continue to ripple out of transplantation, extending the reach of this landmark approach and its cousins to more and more patients. Researchers (many of whom trained under Thomas early in their careers) have built upon the foundation of transplantation new houses of treatment and cures for other diseases also once thought incurable. Thanks to one man’s dedication and stubborn pursuit of a technique many believed unachievable, scientists are now working to reverse disease-causing genetic mutations, offer curative transplants to every blood cancer patient in need and cure most cancers with a single infusion of disease-fighting immune cells or molecules.
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Pioneering work by Dr. E. Donnall Thomas and his colleagues at Fred Hutch made bone marrow transplantation a curative therapy for patients with certain blood cancers. Over the years, their unique approach to refining the procedure and steadily building on discoveries has rippled into many other spheres of treatment — and continues to drive new ideas that could translate into therapies
for many more patients in need.
Today, blood stem cell transplants are used for numerous forms of leukemia and lymphoma as well as dozens of other diseases, including myelodysplastic syndromes (MDS), multiple myeloma, Wiskott-Aldrich syndrome, anemias and more, as well as for children with blood cancers. Researchers are also testing transplantation to treat autoimmune disorders such as Crohn’s disease.
Developed at Fred Hutch, these gentler versions of bone marrow transplantation brought the procedure’s curative power to an older population not previously eligible for the more toxic preparations of the traditional transplant.
This collection of techniques developed at the Hutch and at many other research centers around the world harnesses and boosts the body’s own ability to eliminate cancer cells and is based on Thomas’ original observations of the immune system’s power to fight cancer. Whether through immune molecules known as antibodies that can precisely recognize tumors, killer immune cells known as T cells engineered or selected for their ability to home directly to and destroy cancer cells, or vaccines that can trigger the patient’s immune system to prevent or treat cancer, immunotherapeutic approaches are already being used to treat certain cancers. And many more techniques currently being tested are poised to change how we treat — and cure — nearly all cancers.
Because transplantation destroys much of their immune systems, patients are especially susceptible to infections, many of which can be dangerous or even deadly. In an effort to improve transplant safety, Hutch teams have made seminal contributions to understanding how to detect, prevent and treat many of the viruses and fungi that can cause disease — work that also kicked off research that has impacted care for other immunocompromised people, including organ transplant recipients and patients with HIV.
What researchers have learned about both transplantation and stem cells has broadened the possibilities for modern gene therapy. Researchers at the Hutch and elsewhere are developing cutting-edge gene therapies that aim to reach directly into patients’ genomes and correct disease-causing mutations or snip out hidden viral DNA, thus curing genetic or viral diseases such as HIV, sickle cell disease, thalassemia, severe combined immunodeficiency (SCID) and Fanconi anemia.
Using stem cells from donated umbilical cords, which don’t need to be as stringently matched to the recipient as adult stem cells, cord blood transplantation broadens options for the thousands of cancer patients every year who can’t find a matched adult donor.
Methods developed to support transplant patients through the difficult procedure — like food safety guidelines for immunocompromised patients and the Hickman line, an extended-use catheter developed at the Hutch to deliver IV nutrition or chemotherapy and draw blood samples without requiring patients to undergo hundreds of individual needle sticks — have helped shape the standard
of care for patients undergoing many other forms of treatment beyond transplantation.
Rachel Tompa is a former staff writer at Fred Hutchinson Cancer Center. She has a Ph.D. in molecular biology from the University of California, San Francisco and a certificate in science writing from the University of California, Santa Cruz. Follow her on Twitter @Rachel_Tompa.
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Are you interested in reprinting or republishing this story? Be our guest! We want to help connect people with the information they need. We just ask that you link back to the original article, preserve the author’s byline and refrain from making edits that alter the original context. Questions? Email us at communications@fredhutch.org
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