A Lifetime Dedicated to Defeating Childhood Cancer

Richard J. O’Reilly, Chair of MSK’s Department of Pediatrics and Chief of the Pediatric Bone Marrow Transplant Service for more than 30 years, will be honored on May 19 at MSK’s 37th annual convocation with the inaugural Society Prize in Pediatric Oncology. The prize recognizes his seminal contributions to the field of pediatric oncology and the science and practice of stem cell transplantation, and his devotion to his patients and their families. Established to mark The Society of Memorial Sloan Kettering’s 70 years of support of MSK’s innovative medical research and its championship of programs benefiting the lives of children with cancer, the prize will be awarded annually.

Here, Dr. O’Reilly talks about his years as a physician and department chair.
 

MSK's Dr. Richard O'Reilly and pediatric patient
Dr. Richard O'Reilly

What inspired you to become a doctor?

My grandfather was a physician and a professor at what was then the Long Island College of Medicine and is now SUNY Downstate Medical Center. I never knew him, but when I’d go with my family to what was known as the Irish Riviera in Spring Lake, New Jersey, I’d hear the older ladies talking in reverent tones about my grandfather the doctor. So the idea of becoming a physician was something that occurred to me relatively early in life. 
 
What drew you to focus on childhood cancer?

A child I cared for as a medical student who died of leukemia.
 
You’ve spent much of your life involved in transplantation for cancer and other diseases. Do you remember the first transplant in which you participated?

I do indeed. It was in 1973, when we gave the first transplant of bone marrow from an unrelated donor to a patient. I collaborated with then-Sloan Kettering Institute Director Robert Good and Bo Dupont, who was then a Member in SKI’s Immunology Program.
 
Our patient was a little boy named Matthew who was born with severe combined immunodeficiency [SCID, pronounced “skid”]. People are probably familiar with SCID as the “bubble boy” disease. These children are unable to fight infections and usually don’t survive past their first year, unless they receive a transplant of bone marrow stem cells to replace their missing immune system.
 
An essential component of transplanting donor marrow or blood-forming stem cells into a recipient is to identify the most closely matched human leukocyte antigen (HLA) donor you can. Ideally, this is a brother or sister. But Matthew lacked a suitable family donor. Dr. Dupont proposed that a matched unrelated donor could also be used for a transplant. So we set Matthew up in a germ-free isolation room on the second floor of Memorial Hospital. He remained there for nearly three years.
 
During this time, Dr. Dupont was working on the genetics of transplantation and was developing more-precise methods for matching patients and donors. After more than a year of very hard work — and searching — he identified a woman in Denmark. We thought it would be straightforward, but as it turned out it took seven transplants, or grafts, until it finally worked.
 
The donor was wonderful. Initially, she made the donations in Denmark and they were flown to us here at MSK. But she came over for the final donation — the one that “took.”
 
What were your feelings when you knew the transplant had worked?

Beyond elation. Matthew had lived in a bubble his entire life and at last he walked out with his parents to see the whole team — no masks, no gowns, all smiles. Then his mom picked him up, hugged and kissed him free of all sterile procedures, and after many fond farewells, took him home. Dr. Dupont smiled and said, “Soon we’ll be able to find an unrelated donor for anyone.” Now thousands receive such transplants annually.
 
What came after that?

We started doing transplants principally in kids who had a disease called aplastic anemia. After we’d had some good experiences, in about 1976 we began doing transplants for leukemia.
 
Can you talk about the progress you’ve made in transplantation to minimize the side or late effects of the treatment and improve outcomes?

In order to replace diseased or damaged marrow with healthy blood-forming cells, we first have to give patients high doses of chemotherapy and/or radiation to destroy the cancer cells. In a child, radiation can result in growth disorders and hormonal disruptions.
 
So to reduce toxicity we teamed up with our colleagues in Medical Physics and Radiation Oncology and introduced a technique called hyperfractionated total body irradiation. This method of delivering radiotherapy allowed us to give smaller doses over several days rather than one massive dose. It both increases the antileukemia and antitumor effects of the radiation and decreases short- and long-term side effects.
 
We’ve subsequently made great progress, too, in preventing graft-versus-host disease, a major complication of marrow and peripheral blood stem cell transplants. It happens when the donor’s immune cells [T cells] attack cells in the recipient’s body and can be fatal. In 1981, we introduced an approach at MSK called T cell depletion in which T cells are selectively removed from donor blood stem cells prior to their infusion. This significantly diminishes the chance that these T cells will attack the patient. Following the transplant, fresh T cells develop from the donor’s blood stem cells, providing the patient with a new immune system.
 
And we’ve also worked to develop and improve the use of donor-derived immune T cells grown in tissue culture to fight life-threatening infections caused by viruses such as Epstein-Barr and cytomegalovirus, and to eradicate residual tumor cells that can trigger cancer relapse after a transplant.
 
As Chair of the Department of Pediatrics, what stand out to you as some of the most significant recent accomplishments of your colleagues?
 
First, let me say that I believe we have the finest and most experienced team anywhere. From our pediatric medical oncologists, surgeons, radiation oncologists, and nurses to our pediatric anesthesiologists, radiologists, administrative staff, child life specialists, and social workers, everybody works for a common goal: to treat the child with cancer, cure the child, and return the child to a normal life with as few side effects as possible.
 
We’ve seen enormous progress in the treatment of neuroblastoma [a tumor that arises from primitive cells of the sympathetic nervous system], particularly with [pediatric oncologist] Nai-Kong Cheung’s introduction of an antibody called 3F8 that targets a marker called GD2 on the surface of the tumor cells. Used in combination with chemotherapy and surgery, it has significantly improved cure rates for children with high-risk disease.
 
Dr. Cheung has also developed another monoclonal antibody called 8H9 that, when linked to a radioisotope, can deliver radiation specifically to central nervous system [CNS] tumors and can also eradicate neuroblastoma that has recurred in the CNS.

Pediatric oncologist Paul Meyers and his team, in collaboration with our orthopedic and oncologic surgeons, have also made significant advances in the diagnosis and treatment of sarcomas of bone, muscle, and connective tissue that affect children and young adults.
 
Working with [geneticist] Marc Ladanyi, Chief of our Molecular Diagnostics Service, and his group, the department has helped to identify the genes that distinguish these tumors and to characterize their impact on treatment responses. Sequential trials of novel drug combinations — now including agents that specifically target the fusion gene in Ewing sarcoma and a humanized form of the 3F8 antibody that is active against osteogenic sarcoma — are steadily increasing the number of children and young adults with advanced disease who achieve and sustain long-term remissions.
 
In the treatment of leukemia, early advances made by [pediatric hematologic oncologist] Peter Steinherz in the treatment of high-risk forms of acute lymphoblastic leukemia (ALL) mean that ALL can now be treated with less-toxic regimens. The leukemia team subsequently introduced clofarabine as well as molecularly targeted drugs, thereby enhancing treatment effectiveness with less toxicity. Pediatric oncologist Kevin Curran, in collaboration with [medical oncologist] Renier Brentjens and [immunologist] Michel Sadelain, has also introduced genetically engineered T cells expressing chimeric antigen receptors [CARs] in the treatment of otherwise resistant disease.
 
Our transplant team has also introduced new preparative regimens, new types of transplants and new methods for treating transplant-associated complications that now permit their application to anyone requiring a graft and have achieved long-term cure rates that rank the program as one of the two best in the nation.
 
The Long-Term Follow-Up Program established for children surviving cancer by [pediatric endocrinologist] Charles Sklar and extended into adulthood by [primary care physician] Kevin Oeffinger has led the way in the early recognition and management of the medical late effects of childhood cancer and its treatment. This, in turn, has fostered new therapeutic approaches designed to reduce late toxicities without compromising the potential for a cure. New programs initiated by Kenneth Offit, Chief of MSK’s Clinical Genetics Service, and [geneticist and pediatric oncologist] Michael Walsh to identify the genetic attributes of children that may contribute to these long-term risks may further improve selection of therapeutic approaches in the future.
 
Finally, but not the least of our achievements, are the brilliant surgical approaches led by Michael LaQuaglia. His skills and techniques have transformed and saved lives and minimized the chances for disease progression in thousands of children, particularly those who have been diagnosed with tumors that at other institutions are considered inoperable.
 
What have you cherished most about your years at MSK?

Naturally, my patients and their families. And my colleagues, certainly. They’re wonderfully brilliant and dedicated. They consider what they do a vocation, not a job. But at MSK, this commitment to patients is alive in every corner of this place — from the scientists in their labs to the people who clean patients’ rooms.
 
At this time in our history we can analyze the distinctive biology of cancers affecting different tissues in ways that were almost inconceivable when I was a medical student. I cherish the fact that at MSK, the possibility for substantive discoveries in cancer — and the commitment to translate these discoveries into new and better therapies — is both extraordinary and unique.